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Sample records for als mouse spinal

  1. Voltage-gated calcium channels are abnormal in cultured spinal motoneurons in the G93A-SOD1 transgenic mouse model of ALS.

    Science.gov (United States)

    Chang, Qing; Martin, Lee J

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motoneurons. Hyperexcitability and excitotoxicity have been implicated in the early pathogenesis of ALS. Studies addressing excitotoxic motoneuron death and intracellular Ca(2+) overload have mostly focused on Ca(2+) influx through AMPA glutamate receptors. However, intrinsic excitability of motoneurons through voltage-gated ion channels may also have a role in the neurodegeneration. In this study we examined the function and localization of voltage-gated Ca(2+) channels in cultured spinal cord motoneurons from mice expressing a mutant form of human superoxide dismutase-1 with a Gly93→Ala substitution (G93A-SOD1). Using whole-cell patch-clamp recordings, we showed that high voltage activated (HVA) Ca(2+) currents are increased in G93A-SOD1 motoneurons, but low voltage activated Ca(2+) currents are not affected. G93A-SOD1 motoneurons also have altered persistent Ca(2+) current mediated by L-type Ca(2+) channels. Quantitative single-cell RT-PCR revealed higher levels of Ca1a, Ca1b, Ca1c, and Ca1e subunit mRNA expression in G93A-SOD1 motoneurons, indicating that the increase of HVA Ca(2+) currents may result from upregulation of Ca(2+) channel mRNA expression in motoneurons. The localizations of the Ca1B N-type and Ca1D L-type Ca(2+) channels in motoneurons were examined by immunocytochemistry and confocal microscopy. G93A-SOD1 motoneurons had increased Ca1B channels on the plasma membrane of soma and dendrites. Ca1D channels are similar on the plasma membrane of soma and lower on the plasma membrane of dendrites of G93A-SOD1 motoneurons. Our study demonstrates that voltage-gated Ca(2+) channels have aberrant functions and localizations in ALS mouse motoneurons. The increased HVA Ca(2+) currents and PCCa current could contribute to early pathogenesis of ALS. PMID:27151771

  2. Inhibitory zinc-enriched terminals in mouse spinal cord

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  3. Glycoconjugates Distribution during Developing Mouse Spinal Cord Motor Organizers

    OpenAIRE

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

    2015-01-01

    Background: The aim of this research was to study the distribution and changes of glycoconjugates particularly their terminal sugars by using lectin histochemistry during mouse spinal cord development. Methods: Formalin-fixed sections of mouse embryo (10-16 fetal days) were processed for lectin histochemical method. In this study, two groups of horseradish peroxidase -labeled specific lectins were used: N-acetylgalactosamine, including Dolichos biflorus, Wisteria floribunda agglutinin (WFA), ...

  4. The wobbler mouse, an ALS animal model

    OpenAIRE

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now,...

  5. A Neonatal Mouse Spinal Cord Compression Injury Model.

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    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

  6. A Neural Model of Demyelination of the Mouse Spinal Cord

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    Petreska, Biljana; Yovel, Yossi

    2008-01-01

    This paper presents a neural network model of demyelination of the mouse motor pathways, coupled to a central pattern generation (CPG) model for quadruped walking. Demyelination is the degradation of the myelin layer covering the axons which can be caused by several neurodegenerative autoimmune diseases such as multiple sclerosis. We use this model - to our knowledge first of its kind - to investigate the locomotion deficits that appear following demyelination of axons in the spinal cord. Our...

  7. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...... similarities to ALS. The cellular effects of the wobbler mutation, cellular transport defects, neurofilament aggregation, neuronal hyperexcitability and neuroinflammation closely resemble human ALS. Now, 57 years after the first report on the wobbler mouse we summarize the progress made in understanding...

  8. [Gene expression profile of spinal ventral horn in ALS].

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    Yamamoto, Masahiko; Tanaka, Fumiaki; Sobue, Gen

    2007-10-01

    The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser-captured microdissection, gene expression profiles of degenerating spinal motor neurons as well as spinal ventral horn from autopsied patients with sporadic ALS were examined. Spinal motor neurons showed a distinct gene expression profile from the whole spinal ventral horn. Three percent of genes examined were significantly downregulated, and 1% were upregulated in motor neurons. In contrast with motor neurons, the total spinal ventral horn homogenates demonstrated 0.7% and 0.2% significant upregulation and downregulation of gene expression, respectively. Downregulated genes in motor neurons included those associated with cytoskeleton/axonal transport, transcription and cell surface antigens/receptors, such as dynactin 1 (DCTN1) and early growth response 3 (EGR3). In particular, DCTN1 was markedly downregulated in most residual motor neurons prior to the accumulation of pNF-H and ubiquitylated protein. Promoters for cell death pathway, death receptor 5 (DR5), cyclins C (CCNC) and A1 (CCNA), and caspases were upregulated, whereas cell death inhibitors, acetyl-CoA transporter (ACATN) and NF-kappaB (NFKB) were also upregulated. In terms of spinal ventral horn, the expression of genes related to cell surface antigens/receptors, transcription and cell adhesion/ECM were increased. The gene expression resulting in neurodegenerative and neuroprotective changes were both present in spinal motor neurons and ventral horn. Moreover, Inflammation-related genes, such as belonging to the cytokine family were not, however, significantly upregulated in either motor neurons or ventral horn. The sequence of motor neuron-specific gene expression changes from early DCTN1 downregulation to late CCNC upregulation in sporadic ALS can provide direct information on the genes leading to neurodegeneration and neuronal death, and are helpful

  9. [Gene expression profile of spinal ventral horn in ALS].

    Science.gov (United States)

    Yamamoto, Masahiko; Tanaka, Fumiaki; Sobue, Gen

    2007-10-01

    The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser-captured microdissection, gene expression profiles of degenerating spinal motor neurons as well as spinal ventral horn from autopsied patients with sporadic ALS were examined. Spinal motor neurons showed a distinct gene expression profile from the whole spinal ventral horn. Three percent of genes examined were significantly downregulated, and 1% were upregulated in motor neurons. In contrast with motor neurons, the total spinal ventral horn homogenates demonstrated 0.7% and 0.2% significant upregulation and downregulation of gene expression, respectively. Downregulated genes in motor neurons included those associated with cytoskeleton/axonal transport, transcription and cell surface antigens/receptors, such as dynactin 1 (DCTN1) and early growth response 3 (EGR3). In particular, DCTN1 was markedly downregulated in most residual motor neurons prior to the accumulation of pNF-H and ubiquitylated protein. Promoters for cell death pathway, death receptor 5 (DR5), cyclins C (CCNC) and A1 (CCNA), and caspases were upregulated, whereas cell death inhibitors, acetyl-CoA transporter (ACATN) and NF-kappaB (NFKB) were also upregulated. In terms of spinal ventral horn, the expression of genes related to cell surface antigens/receptors, transcription and cell adhesion/ECM were increased. The gene expression resulting in neurodegenerative and neuroprotective changes were both present in spinal motor neurons and ventral horn. Moreover, Inflammation-related genes, such as belonging to the cytokine family were not, however, significantly upregulated in either motor neurons or ventral horn. The sequence of motor neuron-specific gene expression changes from early DCTN1 downregulation to late CCNC upregulation in sporadic ALS can provide direct information on the genes leading to neurodegeneration and neuronal death, and are helpful

  10. Characterisation of the primary afferent spinal innervation of mouse uterus

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    Geraldine eHerweijer

    2014-07-01

    Full Text Available The primary afferent innervation of the uterus is incompletely understood. The aim of this study was to identify the location and characteristics of primary afferent neurons that innervate the uterine horn of mice and correlate the different morphological types of putative primary afferent nerve endings, immunoreactive to the sensory marker, calcitonin gene related peptide (CGRP. Using retrograde tracing, injection of 5-10µL of 1,1'-didodecyl-3,3,3,3'-tetramethylindocarbocyanine perchlorate (DiI into discrete single sites in each uterine horn revealed a biomodal distribution of sensory neurons in dorsal root ganglia (DRG with peak labelling occurring between T13-L3 and a second smaller peak between L6-S1. The mean cross sectional area of labelled cells was 463 µm2 +/- SEM. A significantly greater proportion of labelled neurons consisted of small cell bodies (<300 µm2 in the sacral spinal cord (S2 compared with peak labelling at the lumbar (L2 region. In both sections and whole mount preparations, immunohistochemical staining for CGRP revealed substantial innervation of the uterus by CGRP-positive nerve fibres located primarily at the border between the circular and longitudinal muscle layers (N=4. The nerve endings were classified into three distinct types: single, branching or complex, that often aligned preferentially in either the circular or longitudinal axis of the smooth muscles. Complex endings were often associated with mesenteric vessels. We have identified that the cell bodies of primary afferent neurons innervating the mouse uterus lie primarily in DRG at L2 and S1 spinal levels. Also, the greatest density of CGRP immunoreactivity lies within the myometrium, with at least three different morphological types of nerve endings identified. These findings will facilitate further investigations into the mechanisms underlying sensory transduction in mouse uterus.

  11. Functional effect of mouse embryonic stem cell implantation after spinal cord injury

    OpenAIRE

    Lee, Tae-Hoon

    2013-01-01

    We transplanted mouse embryonic stem cells (mESCs) to improve functional loss in a rat model of clip-compression spinal cord injury (SCI). The mouse embryonic stem cells were transplanted to injured cord 7 days after injury. We include minimizing the progression of secondary injury, manipulating the neuroinhibitory environment of the spinal cord, replacing lost tissue with transplanted cells and substantial improvement of motor. A number of potential approaches optimize functional recovery af...

  12. A Neonatal Mouse Spinal Cord Compression Injury Model

    OpenAIRE

    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 facili...

  13. Blood supply to the thoracolumbar spinal cord in the laboratory mouse using corrosion and dissection techniques.

    Science.gov (United States)

    Flesarova, Slavka; Mazensky, David; Teleky, Jana; Almasiova, Viera; Holovska, Katarina; Supuka, Peter

    2016-01-01

    Mice are used frequently as experimental models in the study of ischemic spinal cord injury. The aim of the present study was to describe the arterial blood supply to the thoracolumbar spinal cord in the mouse. The study was carried out on 20 adult mice using the corrosion and dissection technique. Dorsal intercostal arteries were found as branches of the thoracic aorta: as 7 pairs in 80% of cases, as 8 pairs in 15% of cases and as 9 pairs in 5% of cases. The paired lumbar arteries arising from the abdominal aorta were present as 5 pairs in all cases. Along the entire thoracic and lumbar spinal regions, we observed left-sided branches entering the ventral spinal artery in 64.2% and right-sided branches in 35.8% of cases. Along the entire thoracic and lumbar spinal regions, the branches entering the dorsal spinal arteries were left-sided in 60.8% of cases and right-sided in 39.2% of cases. We found some variations in the site of origin of the artery of Adamkiewicz and in the number of dorsal spinal arteries. Documenting the anatomical variations in spinal cord blood supply in the laboratory mouse will aid the planning of future experimental studies and in determining the clinical relevance of such studies.

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

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    Karen K Y Ling

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

  15. Akhirin regulates the proliferation and differentiation of neural stem cells in intact and injured mouse spinal cord.

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    Abdulhaleem, Felemban Athary M; Song, Xiaohong; Kawano, Rie; Uezono, Naohiro; Ito, Ayako; Ahmed, Giasuddin; Hossain, Mahmud; Nakashima, Kinichi; Tanaka, Hideaki; Ohta, Kunimasa

    2015-05-01

    Although the central nervous system is considered a comparatively static tissue with limited cell turnover, cells with stem cell properties have been isolated from most neural tissues. The spinal cord ependymal cells show neural stem cell potential in vitro and in vivo in injured spinal cord. However, very little is known regarding the ependymal niche in the mouse spinal cord. We previously reported that a secreted factor, chick Akhirin, is expressed in the ciliary marginal zone of the eye, where it works as a heterophilic cell-adhesion molecule. Here, we describe a new crucial function for mouse Akhirin (M-AKH) in regulating the proliferation and differentiation of progenitors in the mouse spinal cord. During embryonic spinal cord development, M-AKH is transiently expressed in the central canal ependymal cells, which possess latent neural stem cell properties. Targeted inactivation of the AKH gene in mice causes a reduction in the size of the spinal cord and decreases BrdU incorporation in the spinal cord. Remarkably, the expression patterns of ependymal niche molecules in AKH knockout (AKH-/-) mice are different from those of AKH+/+, both in vitro and in vivo. Furthermore, we provide evidence that AKH expression in the central canal is rapidly upregulated in the injured spinal cord. Taken together, these results indicate that M-AKH plays a crucial role in mouse spinal cord formation by regulating the ependymal niche in the central canal.

  16. Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro.

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    Corcoran, Jonathan; So, Po-Lin; Barber, Robert D; Vincent, Karen J; Mazarakis, Nicholas D; Mitrophanous, Kyriacos A; Kingsman, Susan M; Maden, Malcolm

    2002-10-01

    Retinoic acid, acting through the nuclear retinoic acid receptor beta2 (RARbeta2), stimulates neurite outgrowth from peripheral nervous system tissue that has the capacity to regenerate neurites, namely, embryonic and adult dorsal root ganglia. Similarly, in central nervous system tissue that can regenerate, namely, embryonic mouse spinal cord, retinoic acid also stimulates neurite outgrowth and RARbeta2 is upregulated. By contrast, in the adult mouse spinal cord, which cannot regenerate, no such upregulation of RARbeta2 by retinoic acid is observed and no neurites are extended in vitro. To test our hypothesis that the upregulation of RARbeta2 is crucial to neurite regeneration, we have transduced adult mouse or rat spinal cord in vitro with a minimal equine infectious anaemia virus vector expressing RARbeta2. After transduction, prolific neurite outgrowth occurs. Outgrowth does not occur when the cord is transduced with a different isoform of RARbeta nor does it occur following treatment with nerve growth factor. These data demonstrate that RARbeta2 is involved in neurite outgrowth, at least in vitro, and that this gene may in the future be of some therapeutic use. PMID:12235288

  17. Isolation of a Mouse Motoneuron-Enriched Fraction from Mouse Spinal Cord on a Density Barrier

    OpenAIRE

    John Graham

    2002-01-01

    After a combined enzymic and mechanical disruption of the spinal cord tissue, the low-density motoneurons band at the interface of a 1.06-g/ml barrier through which other contaminating cells sediment.

  18. Ex vivo infection of human embryonic spinal cord neurons prior to transplantation into adult mouse cord

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    Dénes Ádám

    2010-05-01

    Full Text Available Abstract Background Genetically modified pseudorabies virus (Prv proved suitable for the delivery of foreign genes to rodent embryonic neurons ex vivo and maintaining foreign gene expression after transplantation into spinal cord in our earlier study. The question arose of whether human embryonic neurons, which are known to be more resistant to Prv, could also be infected with a mutant Prv. Specifically, we investigated whether a mutant Prv with deleted ribonucleotide reductase and early protein 0 genes has the potential to deliver marker genes (gfp and β-gal into human embryonic spinal cord neurons and whether the infected neurons maintain expression after transplantation into adult mouse cord. Results The results revealed that the mutant Prv effectively infected human embryonic spinal cord neurons ex vivo and the grafted cells exhibited reporter gene expression for several weeks. Grafting of infected human embryonic cells into the spinal cord of immunodeficient (rnu-/rnu- mice resulted in the infection of some of the host neurons. Discussion These results suggest that Prv is suitable for the delivery of foreign genes into transplantable human cells. This delivery method may offer a new approach to use genetically modified cells for grafting in animal models where spinal cord neuronal loss or axon degeneration occurs.

  19. Aberrant LncRNA Expression Profile in a Contusion Spinal Cord Injury Mouse Model

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    Ya Ding

    2016-01-01

    Full Text Available Long noncoding RNAs (LncRNAs play a crucial role in cell growth, development, and various diseases related to the central nervous system. However, LncRNA differential expression profiles in spinal cord injury are yet to be reported. In this study, we profiled the expression pattern of LncRNAs using a microarray method in a contusion spinal cord injury (SCI mouse model. Compared with a spinal cord without injury, few changes in LncRNA expression levels were noted 1 day after injury. The differential changes in LncRNA expression peaked 1 week after SCI and subsequently declined until 3 weeks after injury. Quantitative real-time polymerase chain reaction (qRT-PCR was used to validate the reliability of the microarray, demonstrating that the results were reliable. Gene ontology (GO analysis indicated that differentially expressed mRNAs were involved in transport, cell adhesion, ion transport, and metabolic processes, among others. Kyoto Encyclopedia of Genes and Genomes (KEGG enrichment analysis showed that the neuroactive ligand-receptor interaction, the PI3K-Akt signaling pathway, and focal adhesions were potentially implicated in SCI pathology. We constructed a dynamic LncRNA-mRNA network containing 264 LncRNAs and 949 mRNAs to elucidate the interactions between the LncRNAs and mRNAs. Overall, the results from this study indicate for the first time that LncRNAs are differentially expressed in a contusion SCI mouse model.

  20. Spinal mechanism of standard analgesics: evaluation using mouse models of allodynia.

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    Tsukamoto, Mina; Kiso, Tetsuo; Shimoshige, Yukinori; Aoki, Toshiaki; Matsuoka, Nobuya

    2010-05-25

    Spinal neurotransmission plays an important role in the perception of pain signaling. In the present study, we investigated the spinal anti-nociceptive mechanism of current standard analgesics in mouse models of tactile allodynia induced by intrathecal administration of N-methyl-D-aspartic acid (NMDA), prostaglandin E2 (PGE2), and bicuculline. NMDA-induced allodynia is induced by postsynaptic NMDA receptor activation, while PGE2-induced allodynia is triggered by the enhancement of presynaptic glutamate release via EP1 receptor activation. In contrast, bicuculline induces allodynia by the blockade of gamma-aminobutyric acid (GABA)A receptor-mediated inhibitory system. As the clinically available analgesics, pregabalin (alpha2delta-subunit calcium channel ligand), ziconotide (N-type calcium channel blocker), mexiletine (sodium channel blocker), and duloxetine (serotonin and norepinephrine reuptake inhibitors) were evaluated in these neurochemically-induced allodynia models. Pregabalin almost completely alleviated NMDA-, PGE2-, and bicuculline-induced allodynia. Despite being classified as an agent with a similar molecular target mechanism, ziconotide could only alleviate PGE2-induced allodynia, but not NMDA- or bicuculline-induced allodynia, as did mexiletine and duloxetine. These results taken together suggest that ziconotide, mexiletine, and duloxetine suppress spinal hyperactivity via the presynaptic site mechanism. In contrast, pregabalin could suppress via the downstream step during spinal hyperactivation such as postsynaptic NMDA activation or dysfunction of GABAergic control in addition to presynaptic mechanism. In conclusion, present findings provide implication that the spinal anti-nociceptive mechanistic site of pregabalin is different from that of ziconotide, mexiletine, and duloxetine, and pregabalin could have a broader anti-nociceptive mechanism other than N-type calcium channel blockade. PMID:20188724

  1. Dopamine exerts activation-dependent modulation of spinal locomotor circuits in the neonatal mouse.

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    Humphreys, Jennifer M; Whelan, Patrick J

    2012-12-01

    Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This depression was D(2) but not D(1) receptor dependent and was not due exclusively to depression of excitatory drive to motoneurons. Furthermore, the depression in excitation was not dependent on network activity. We next compared the modulatory effects of DA on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting, and increased amplitude. Overall, these data demonstrate that DA can potentiate network activity while at the same time reducing the gain of recurrent excitatory feedback loops from motoneurons onto the network.

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

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

    2015-11-01

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

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

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

    2016-03-01

    Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. PMID:26839365

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  5. Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord

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    Kucharova Karolina

    2011-11-01

    Full Text Available Abstract Background Multiple sclerosis (MS is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination. Methods Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR. Results The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype. Conclusions Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result

  6. Novel mouse model of spinal cord injury-induced heterotopic ossification

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    Heejae Kang, BA

    2014-11-01

    Full Text Available Heterotopic ossification (HO develops in about 20% to 30% of patients with spinal cord injury (SCI and significantly impairs their rehabilitation. There is no effective prevention or treatment for this condition at this time. Our current understanding of its etiology and pathophysiology is limited partially due to the lack of clinically relevant animal models. In this study, we report a novel mouse model of SCI-induced HO by administering a subthreshold dose of bone morphogenetic protein (BMP-2 to muscles in mice after SCI. Microcomputed tomography scanning showed that an intramuscular injection of 0.25 micrograms of BMP-2 causes significant HO in mice with SCI but not in control (sham surgery mice. Our analysis of gene expression showed significantly increased BMP signaling in quadriceps following SCI, suggesting that BMP signaling may play a role in SCI-induced HO. Administering 0.25 micrograms of BMP-2 to the front arms of the mice with SCI also results in the development of significant HO but not in control mice. This suggests that SCI causes a systematic osteogenic effect, which is not limited to paralyzed limbs. This novel mouse model will serve as a powerful tool in exploring the molecular mechanisms of SCI-induced HO, which may lead to novel treatment for this disease.

  7. Simultaneous submicrometric 3D imaging of the micro-vascular network and the neuronal system in a mouse spinal cord

    CERN Document Server

    Fratini, Michela; Campi, Gaetano; Brun, Francesco; Tromba, Giuliana; Modregger, Peter; Bucci, Domenico; Battaglia, Giuseppe; Spadon, Raffaele; Mastrogiacomo, Maddalena; Requardt, Herwig; Giove, Federico; Bravin, Alberto; Cedola, Alessia

    2014-01-01

    Defaults in vascular (VN) and neuronal networks of spinal cord are responsible for serious neurodegenerative pathologies. Because of inadequate investigation tools, the lacking knowledge of the complete fine structure of VN and neuronal systems is a crucial problem. Conventional 2D imaging yields incomplete spatial coverage leading to possible data misinterpretation, whereas standard 3D computed tomography imaging achieves insufficient resolution and contrast. We show that X-ray high-resolution phase-contrast tomography allows the simultaneous visualization of three-dimensional VN and neuronal systems of mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, with neither contrast agent nor a destructive sample-preparation. We image both the 3D distribution of micro-capillary network and the micrometric nerve fibers, axon-bundles and neuron soma. Our approach is a crucial tool for pre-clinical investigation of neurodegenerative pathologies and spinal-cord-injuries. In particular, it s...

  8. Peripheral androgen receptor gene suppression rescues disease in mouse models of spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Lieberman, Andrew P; Yu, Zhigang; Murray, Sue; Peralta, Raechel; Low, Audrey; Guo, Shuling; Yu, Xing Xian; Cortes, Constanza J; Bennett, C Frank; Monia, Brett P; La Spada, Albert R; Hung, Gene

    2014-05-01

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

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

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    Andrew P. Lieberman

    2014-05-01

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

  10. Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Ling, Karen K Y; Gibbs, Rebecca M; Feng, Zhihua; Ko, Chien-Ping

    2012-01-01

    Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in >20 muscles in the SMNΔ7 SMA mouse model. We found that severe denervation (<50% fully innervated endplates) occurs selectively in many vulnerable axial muscles and several appendicular muscles at the disease end stage. Since these vulnerable muscles were located throughout the body and were comprised of varying muscle fiber types, it is unlikely that muscle location or fiber type determines susceptibility to denervation. Furthermore, we found a similar extent of neurofilament accumulation at NMJs in both vulnerable and resistant muscles before the onset of denervation, suggesting that neurofilament accumulation does not predict subsequent NMJ denervation. Since vulnerable muscles were initially innervated, but later denervated, loss of innervation in SMA may be attributed to defects in synapse maintenance. Finally, we found that denervation was amendable by trichostatin A (TSA) treatment, which increased innervation in clinically relevant muscles in TSA-treated SMNΔ7 mice. Our findings suggest that neuromuscular denervation in vulnerable muscles is a widespread pathology in SMA, and can serve as a preparation for elucidating the biological basis of synapse loss, and for evaluating therapeutic efficacy.

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

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    Jean-Luc Boulland

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

  12. Changes in Synapses and Axons Demonstrated by Synaptophysin Immunohistochemistry Following Spinal Cord Compression Trauma in the Rat and Mouse

    Institute of Scientific and Technical Information of China (English)

    GUI-LIN LI; MOHAMMAD FAROOQUE; JONAS ISAKSSON; YNGVE OLSSON

    2004-01-01

    and methods To evaluate synaptic changes using synaptophysin immunohistochemstry in rat and mouse, which spinal cords were subjected to graded compression trauma at the level of Th8-9. Results Normal animals showed numerous fine dots of synaptophysin immunoreactivity in the gray matter. An increase in synaptophysin immunoreactivity was observed in the neuropil and synapses at the surface of motor neurons of the anterior horns in the Th8-9 segments lost immunoreactivity at 4-hour point after trauma. The immunoreactive synapses reappeared around motor neurons at 9-day point. Unexpected accumulation of synaptophysin immunoreactivity occurred in injured axons of the white matter of the compressed spinal cord. Conclusion Synaptic changes were important components of secondary injuries in spinal cord trauma. Loss of synapses on motor neurons may be one of the factors causing motor dysfunction of hind limbs and formation of new synapses may play an important role in recovery of motor function. Synaptophysin immunohistochemistry is also a good tool for studies of axonal swellings in spinal cord injuries.

  13. Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset

    Energy Technology Data Exchange (ETDEWEB)

    Cistaro, Angelina; Fania, Piercarlo [Positron Emission Tomography Center IRMET S.p.A, Turin (Italy); Consuelo Valentini, Maria; Carrara, Giovanna [CTO Hospital, Department of Neuroradiology, Turin (Italy); Chio, Adriano; Calvo, Andrea; Moglia, Cristina; Montuschi, Anna [University of Turin, Department of Neuroscience, ALS Center, Turin (Italy); Nobili, Flavio [University of Genoa, Department of Neurosciences, Clinical Neurophysiology Unit, Ophthalmology and Genetics, Genoa (Italy); Morbelli, Silvia [University of Genoa, Department of Internal Medicine, Nuclear Medicine Unit, Genoa (Italy); Salmaso, Dario [Institute of Cognitive Sciences and Technologies, CNR, Padua (Italy); Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Padua (Italy); Karolinska Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy)

    2012-02-15

    To identify the neurobiological traits of amyotrophic lateral sclerosis (ALS) and to elucidate functional differences between ALS of spinal and bulbar onset. We hypothesized that glucose metabolism distribution might vary between groups. The study groups comprised 32 patients with ALS of either bulbar (n = 13) or spinal (n=19) onset and 22 subjects as controls. They were investigated by [{sup 18}F]fluorodeoxyglucose (FDG) positron emission tomography (FDG PET), comparing the patient groups with each other and with the controls by statistical parametric mapping. Highly significant relative increases in glucose metabolism distribution were found in the group comprising all 32 ALS patients as compared with the controls in the bilateral amygdalae, midbrain, pons and cerebellum. Relative hypermetabolism was also found in patients with spinal onset as compared with the controls in the right midbrain. In patients with bulbar onset compared with the controls and with patients with spinal onset, large relatively hypometabolic areas were found in the bilateral frontal cortex, right insula, anterior cingulate, precuneus and inferior parietal lobe. Patients with spinal onset had significantly higher scores in a neuropsychological test assessing verbal fluency compared with patients with bulbar onset. This large FDG PET investigation provided unprecedented evidence of relatively increased metabolism in the amygdalae, midbrain and pons in ALS patients as compared with control subjects, possibly due to local activation of astrocytes and microglia. Highly significant relative decreases in metabolism were found in large frontal and parietal regions in the bulbar onset patients as compared with the spinal onset patients and the controls, suggesting a differential metabolic and neuropsychological state between the two conditions. (orig.)

  14. Insulinlike growth factor (IGF)-1 administration ameliorates disease manifestations in a mouse model of spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Rinaldi, Carlo; Bott, Laura C; Chen, Ke-lian; Harmison, George G; Katsuno, Masahisa; Sobue, Gen; Pennuto, Maria; Fischbeck, Kenneth H

    2012-12-06

    Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by polyglutamine expansion in the androgen receptor. Patients develop slowly progressive proximal muscle weakness, muscle atrophy and fasciculations. Affected individuals often show gynecomastia, testicular atrophy and reduced fertility as a result of mild androgen insensitivity. No effective disease-modifying therapy is currently available for this disease. Our recent studies have demonstrated that insulinlike growth factor (IGF)-1 reduces the mutant androgen receptor toxicity through activation of Akt in vitro, and spinal and bulbar muscular atrophy transgenic mice that also overexpress a noncirculating muscle isoform of IGF-1 have a less severe phenotype. Here we sought to establish the efficacy of daily intraperitoneal injections of mecasermin rinfabate, recombinant human IGF-1 and IGF-1 binding protein 3, in a transgenic mouse model expressing the mutant androgen receptor with an expanded 97 glutamine tract. The study was done in a controlled, randomized, blinded fashion, and, to reflect the clinical settings, the injections were started after the onset of disease manifestations. The treatment resulted in increased Akt phosphorylation and reduced mutant androgen receptor aggregation in muscle. In comparison to vehicle-treated controls, IGF-1-treated transgenic mice showed improved motor performance, attenuated weight loss and increased survival. Our results suggest that peripheral tissue can be targeted to improve the spinal and bulbar muscular atrophy phenotype and indicate that IGF-1 warrants further investigation in clinical trials as a potential treatment for this disease.

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

    Directory of Open Access Journals (Sweden)

    Savina Apolloni

    2014-09-01

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

  16. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6.

    Science.gov (United States)

    Vangansewinkel, Tim; Geurts, Nathalie; Quanten, Kirsten; Nelissen, Sofie; Lemmens, Stefanie; Geboes, Lies; Dooley, Dearbhaile; Vidal, Pia M; Pejler, Gunnar; Hendrix, Sven

    2016-05-01

    An important barrier for axon regeneration and recovery after traumatic spinal cord injury (SCI) is attributed to the scar that is formed at the lesion site. Here, we investigated the effect of mouse mast cell protease (mMCP) 6, a mast cell (MC)-specific tryptase, on scarring and functional recovery after a spinal cord hemisection injury. Functional recovery was significantly impaired in both MC-deficient and mMCP6-knockout (mMCP6(-/-)) mice after SCI compared with wild-type control mice. This decrease in locomotor performance was associated with an increased lesion size and excessive scarring at the injury site. Axon growth-inhibitory chondroitin sulfate proteoglycans and the extracellular matrix components fibronectin, laminin, and collagen IV were significantly up-regulated in MC-deficient and mMCP6(-/-) mice, with an increase in scar volume between 23 and 32%. A degradation assay revealed that mMCP6 directly cleaves fibronectin and collagen IV in vitro In addition, gene expression levels of the scar components fibronectin, aggrecan, and collagen IV were increased up to 6.8-fold in mMCP6(-/-) mice in the subacute phase after injury. These data indicate that endogenous mMCP6 has scar-suppressing properties after SCI via indirect cleavage of axon growth-inhibitory scar components and alteration of the gene expression profile of these factors.-Vangansewinkel, T., Geurts, N., Quanten, K., Nelissen, S., Lemmens, S., Geboes, L., Dooley, D., Vidal, P. M., Pejler, G., Hendrix, S. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6.

  17. Abnormal growth of the corticospinal axons into the lumbar spinal cord of the hyt/hyt mouse with congenital hypothyroidism.

    Science.gov (United States)

    Hsu, Jung-Yu C; Stein, Stuart A; Xu, Xiao-Ming

    2008-11-01

    Thyroid hormone deficiency may cause severe neurological disorders resulting from developmental deficits of the central nervous system. The mutant hyt/hyt mouse, characterized by fetal-onset, life-long hypothyroidism resulting from a point mutation of the thyroid-stimulating hormone receptor of the thyroid gland, displays a variety of abnormalities in motor behavior that are likely associated with dysfunctions of specific brain regions and a defective corticospinal tract (CST). To test the hypothesis that fetal and neonatal hypothyroidism cause abnormal CST development, the growth of the CST was investigated in hypothyroid hyt/hyt mice and their euthyroid progenitors, the BALB/cByJ mice. Anterograde labeling with biotinylated dextran amine demonstrated a decrease in the number of CST axons in the hyt/hyt mouse at the first lumbar level at postnatal day (P) 10. After retrograde tracing with fast blue (FB), fewer FB-labeled neurons were found in the motor cortex, the red nucleus, and the lateral vestibular nucleus of the hyt/hyt mouse. At the fourth lumbar level, the hyt/hyt mouse also showed smaller CST cross-sectional areas and significantly lower numbers of unmyelinated axons, myelinated axons, and growth cones within the CST during postnatal development. At P10, the hyt/hyt mouse demonstrated significantly lower immunoreactivity of embryonic neural cell adhesion molecule in the CST at the seventh cervical level, whereas the expression of growth-associated protein 43 remained unchanged. Our study demonstrated an abnormal development of the CST in the hyt/hyt mouse, manifested by reduced axon quantity and retarded growth pattern at the lumbar spinal cord. PMID:18543337

  18. Liquid chromatography-electrospray linear ion trap mass spectrometry analysis of targeted neuropeptides in Tac1(-/-) mouse spinal cords reveals significant lower concentration of opioid peptides.

    Science.gov (United States)

    Saidi, Mouna; Beaudry, Francis

    2015-08-01

    Tachykinin and opioid peptides play a central role in pain transmission, modulation and inhibition. The treatment of pain is very important in medicine and many studies using NK1 receptor antagonists failed to show significant analgesic effects in humans. Recent investigations suggest that both pronociceptive tachykinins and the analgesic opioid systems are important for normal pain sensation. The analysis of opioid peptides in Tac1(-/-) spinal cord tissues offers a great opportunity to verify the influence of the tachykinin system on specific opioid peptides. The objectives of this study were to develop an HPLC-MS/MRM assay to quantify targeted peptides in spinal cord tissues. Secondly, we wanted to verify if the Tac1(-/-) mouse endogenous opioid system is hampered and therefore affects significantly the pain modulatory pathways. Targeted neuropeptides were analyzed by high performance liquid chromatography linear ion trap mass spectrometry. Our results reveal that EM-2, Leu-Enk and Dyn A were down-regulated in Tac1(-/-) spinal cord tissues. Interestingly, Dyn A was almost 3 fold down-regulated (p<0.0001). No significant concentration differences were observed in mouse Tac1(-/-) spinal cords for Met-Enk and CGRP. The analysis of Tac1(-/-) mouse spinal cords revealed noteworthy decreases of EM-2, Leu-Enk and Dyn A concentrations which strongly suggest a significant impact on the endogenous pain-relieving mechanisms. These observations may have insightful impact on future analgesic drug developments and therapeutic strategies.

  19. Calcium Imaging of Living Astrocytes in the Mouse Spinal Cord following Sensory Stimulation

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    Giovanni Cirillo

    2012-01-01

    Full Text Available Astrocytic Ca2+ dynamics have been extensively studied in ex vivo models; however, the recent development of two-photon microscopy and astrocyte-specific labeling has allowed the study of Ca2+ signaling in living central nervous system. Ca2+ waves in astrocytes have been described in cultured cells and slice preparations, but evidence for astrocytic activation during sensory activity is lacking. There are currently few methods to image living spinal cord: breathing and heart-beating artifacts have impeded the widespread application of this technique. We here imaged the living spinal cord by two-photon microscopy in C57BL6/J mice. Through pressurized injection, we specifically loaded spinal astrocytes using the red fluorescent dye sulforhodamine 101 (SR101 and imaged astrocytic Ca2+ levels with Oregon-Green BAPTA-1 (OGB. Then, we studied astrocytic Ca2+ levels at rest and after right electrical hind paw stimulation. Sensory stimulation significantly increased astrocytic Ca2+ levels within the superficial dorsal horn of the spinal cord compared to rest. In conclusion, in vivo morphofunctional imaging of living astrocytes in spinal cord revealed that astrocytes actively participate to sensory stimulation.

  20. Superoxide dismutase 1 and tgSOD1 mouse spinal cord seed fibrils, suggesting a propagative cell death mechanism in amyotrophic lateral sclerosis.

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    Ruth Chia

    Full Text Available BACKGROUND: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease that specifically affects motor neurons and leads to a progressive and ultimately fatal loss of function, resulting in death typically within 3 to 5 years of diagnosis. The disease starts with a focal centre of weakness, such as one limb, and appears to spread to other parts of the body. Mutations in superoxide dismutase 1 (SOD1 are known to cause disease and it is generally accepted they lead to pathology not by loss of enzymatic activity but by gain of some unknown toxic function(s. Although different mutations lead to varying tendencies of SOD1 to aggregate, we suggest abnormal proteins share a common misfolding pathway that leads to the formation of amyloid fibrils. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that misfolding of superoxide dismutase 1 leads to the formation of amyloid fibrils associated with seeding activity, which can accelerate the formation of new fibrils in an autocatalytic cascade. The time limiting event is nucleation to form a stable protein "seed" before a rapid linear polymerisation results in amyloid fibrils analogous to other protein misfolding disorders. This phenomenon was not confined to fibrils of recombinant protein as here we show, for the first time, that spinal cord homogenates obtained from a transgenic mouse model that overexpresses mutant human superoxide dismutase 1 (the TgSOD1(G93A mouse also contain amyloid seeds that accelerate the formation of new fibrils in both wildtype and mutant SOD1 protein in vitro. CONCLUSIONS/SIGNIFICANCE: These findings provide new insights into ALS disease mechanism and in particular a mechanism that could account for the spread of pathology throughout the nervous system. This model of disease spread, which has analogies to other protein misfolding disorders such as prion disease, also suggests it may be possible to design assays for therapeutics that can inhibit fibril propagation and

  1. Loss of ALS2/Alsin exacerbates motor dysfunction in a SOD1-expressing mouse ALS model by disturbing endolysosomal trafficking.

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    Shinji Hadano

    Full Text Available BACKGROUND: ALS2/alsin is a guanine nucleotide exchange factor for the small GTPase Rab5 and involved in macropinocytosis-associated endosome fusion and trafficking, and neurite outgrowth. ALS2 deficiency accounts for a number of juvenile recessive motor neuron diseases (MNDs. Recently, it has been shown that ALS2 plays a role in neuroprotection against MND-associated pathological insults, such as toxicity induced by mutant Cu/Zn superoxide dismutase (SOD1. However, molecular mechanisms underlying the relationship between ALS2-associated cellular function and its neuroprotective role remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we investigated the molecular and pathological basis for the phenotypic modification of mutant SOD1-expressing mice by ALS2 loss. Genetic ablation of Als2 in SOD1(H46R, but not SOD1(G93A, transgenic mice aggravated the mutant SOD1-associated disease symptoms such as body weight loss and motor dysfunction, leading to the earlier death. Light and electron microscopic examinations revealed the presence of degenerating and/or swollen spinal axons accumulating granular aggregates and autophagosome-like vesicles in early- and even pre-symptomatic SOD1(H46R mice. Further, enhanced accumulation of insoluble high molecular weight SOD1, poly-ubiquitinated proteins, and macroautophagy-associated proteins such as polyubiquitin-binding protein p62/SQSTM1 and a lipidated form of light chain 3 (LC3-II, emerged in ALS2-deficient SOD1(H46R mice. Intriguingly, ALS2 was colocalized with LC3 and p62, and partly with SOD1 on autophagosome/endosome hybrid compartments, and loss of ALS2 significantly lowered the lysosome-dependent clearance of LC3 and p62 in cultured cells. CONCLUSIONS/SIGNIFICANCE: Based on these observations, although molecular basis for the distinctive susceptibilities to ALS2 loss in different mutant SOD1-expressing ALS models is still elusive, disturbance of the endolysosomal system by ALS2 loss

  2. [Macrophages promote the migration of neural stem cells into mouse spinal cord injury site].

    Science.gov (United States)

    Cheng, Zhijian; Zhu, Wen; Li, Haopeng; He, Xijing

    2016-09-01

    Objective To explore the role of macrophages in the migration of neural stem cells (NSCs) in vivo and in vitro . Methods NSCs with green fluorescent protein (GFP) were isolated from GFP transgenic mice and the immunofluorescence cytochemical staining of nestin was used to identify NSCs. After spinal cord injury was induced, the tissue level of macrophage chemotactic protein-1 (MCP-1) mRNA was detected using quantitative real time PCR. The migration of GFP-NSCs was investigated 1 week after GFP-NSCs were injected into both sides of the damaged area. The effect of macrophage on the migration of NSCs in vitro was tested by Transwell(TM) system and the content of MCP-1 was detected by ELISA. Results NSCs highly expressed nestin. Compared with the control group, the level of MCP-1 mRNA significantly increased in the spinal cord injury group. The NSCs which were injected into the spinal cord migrated into the center of the injured site where F4/80 was highly expressed. Macrophages significantly increased the number of migrating NSCs in vitro and the secretion of MCP-1. Conclusion Macrophages induce NSC migrating into the spinal cord injury site possibly through promoting the secretion of MCP-1. PMID:27609570

  3. Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy

    OpenAIRE

    Azzouz, Mimoun; Le, Thanh; Ralph, G. Scott; Walmsley, Lucy; Monani, Umrao R.; Lee, Debbie C P; Wilkes, Fraser; Mitrophanous, Kyriacos A.; Kingsman, Susan M.; Burghes, Arthur H.M.; Mazarakis, Nicholas D.

    2004-01-01

    Spinal muscular atrophy (SMA) is a frequent recessive autosomal disorder. It is caused by mutations or deletion of the telomeric copy of the survival motor neuron (SMN) gene, leading to depletion in SMN protein levels. The treatment rationale for SMA is to halt or delay the degeneration of motor neurons, but to date there are no effective drug treatments for this disease. We have previously demonstrated that pseudotyping of the nonprimate equine infectious anemia virus (using the lentivector ...

  4. Myelinated fibers of the mouse spinal cord after a 30-day space flight.

    Science.gov (United States)

    Povysheva, T V; Rezvyakov, P N; Shaimardanova, G F; Nikolskii, E E; Islamov, R R; Chelyshev, Yu A; Grygoryev, A I

    2016-07-01

    Myelinated fibers and myelin-forming cells in the spinal cord at the L3-L5 level were studied in C57BL/6N mice that had spent 30 days in space. Signs of destruction of myelin in different areas of white matter, reduction of the thickness of myelin sheath and axon diameter, decreased number of myelin-forming cells were detected in "flight" mice. The stay of mice in space during 30 days had a negative impact on the structure of myelinated fibers and caused reduced expression of the markers myelin-forming cells. These findings can complement the pathogenetic picture of the development of hypogravity motor syndrome. PMID:27595822

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    that it is possible to evoke fictive locomotion in the adult decerebrate mouse in vivo using L-3,4-Dihydroxyphenylalanine methyl ester hydrochloride (L-DOPA) and 5-hydroxytryptophan (5HTP) following injection of the monoaminoxiadase inhibitor Nialamide. We investigate the effects of afferent stimulation...

  6. Pharmacokinetics, pharmacodynamics, and efficacy of a small-molecule SMN2 splicing modifier in mouse models of spinal muscular atrophy

    Science.gov (United States)

    Zhao, Xin; Feng, Zhihua; Ling, Karen K. Y.; Mollin, Anna; Sheedy, Josephine; Yeh, Shirley; Petruska, Janet; Narasimhan, Jana; Dakka, Amal; Welch, Ellen M.; Karp, Gary; Chen, Karen S.; Metzger, Friedrich; Ratni, Hasane; Lotti, Francesco; Tisdale, Sarah; Naryshkin, Nikolai A.; Pellizzoni, Livio; Paushkin, Sergey; Ko, Chien-Ping; Weetall, Marla

    2016-01-01

    Spinal muscular atrophy (SMA) is caused by the loss or mutation of both copies of the survival motor neuron 1 (SMN1) gene. The related SMN2 gene is retained, but due to alternative splicing of exon 7, produces insufficient levels of the SMN protein. Here, we systematically characterize the pharmacokinetic and pharmacodynamics properties of the SMN splicing modifier SMN-C1. SMN-C1 is a low-molecular weight compound that promotes the inclusion of exon 7 and increases production of SMN protein in human cells and in two transgenic mouse models of SMA. Furthermore, increases in SMN protein levels in peripheral blood mononuclear cells and skin correlate with those in the central nervous system (CNS), indicating that a change of these levels in blood or skin can be used as a non-invasive surrogate to monitor increases of SMN protein levels in the CNS. Consistent with restored SMN function, SMN-C1 treatment increases the levels of spliceosomal and U7 small-nuclear RNAs and corrects RNA processing defects induced by SMN deficiency in the spinal cord of SMNΔ7 SMA mice. A 100% or greater increase in SMN protein in the CNS of SMNΔ7 SMA mice robustly improves the phenotype. Importantly, a ∼50% increase in SMN leads to long-term survival, but the SMA phenotype is only partially corrected, indicating that certain SMA disease manifestations may respond to treatment at lower doses. Overall, we provide important insights for the translation of pre-clinical data to the clinic and further therapeutic development of this series of molecules for SMA treatment. PMID:26931466

  7. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model.

    Science.gov (United States)

    Azzouz, Mimoun; Ralph, G Scott; Storkebaum, Erik; Walmsley, Lucy E; Mitrophanous, Kyriacos A; Kingsman, Susan M; Carmeliet, Peter; Mazarakis, Nicholas D

    2004-05-27

    Amyotrophic lateral sclerosis (ALS) causes adult-onset, progressive motor neuron degeneration in the brain and spinal cord, resulting in paralysis and death three to five years after onset in most patients. ALS is still incurable, in part because its complex aetiology remains insufficiently understood. Recent reports have indicated that reduced levels of vascular endothelial growth factor (VEGF), which is essential in angiogenesis and has also been implicated in neuroprotection, predispose mice and humans to ALS. However, the therapeutic potential of VEGF for the treatment of ALS has not previously been assessed. Here we report that a single injection of a VEGF-expressing lentiviral vector into various muscles delayed onset and slowed progression of ALS in mice engineered to overexpress the gene coding for the mutated G93A form of the superoxide dismutase-1 (SOD1(G93A)) (refs 7-10), even when treatment was only initiated at the onset of paralysis. VEGF treatment increased the life expectancy of ALS mice by 30 per cent without causing toxic side effects, thereby achieving one of the most effective therapies reported in the field so far. PMID:15164063

  8. Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Azzouz, Mimoun; Le, Thanh; Ralph, G Scott; Walmsley, Lucy; Monani, Umrao R; Lee, Debbie C P; Wilkes, Fraser; Mitrophanous, Kyriacos A; Kingsman, Susan M; Burghes, Arthur H M; Mazarakis, Nicholas D

    2004-12-01

    Spinal muscular atrophy (SMA) is a frequent recessive autosomal disorder. It is caused by mutations or deletion of the telomeric copy of the survival motor neuron (SMN) gene, leading to depletion in SMN protein levels. The treatment rationale for SMA is to halt or delay the degeneration of motor neurons, but to date there are no effective drug treatments for this disease. We have previously demonstrated that pseudotyping of the nonprimate equine infectious anemia virus (using the lentivector gene transfer system) with the glycoprotein of the Evelyn-Rokitnicki-Abelseth strain of the rabies virus confers retrograde axonal transport on these vectors. Here, we report that lentivector expressing human SMN was successfully used to restore SMN protein levels in SMA type 1 fibroblasts. Multiple single injections of a lentiviral vector expressing SMN in various muscles of SMA mice restored SMN to motor neurons, reduced motor neuron death, and increased the life expectancy by an average of 3 and 5 days (20% and 38%) compared with LacZ and untreated animals, respectively. Further extension of survival by SMN expression constructs will likely require a knowledge of when and/or where high levels of SMN are needed. PMID:15599397

  9. Spinal Cord Ventral Horns and Lymphoid Organ Involvement in Powassan Virus Infection in a Mouse Model

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    Rodrigo I. Santos

    2016-08-01

    Full Text Available Powassan virus (POWV belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investigate POWV infection and pathogenesis. After footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. Immunohistochemistry and immunofluorescence revealed a very strong neuronal tropism of POWV infection. The central nervous system infection appeared as a meningoencephalitis with perivascular mononuclear infiltration and microglial activation in the brain, and a poliomyelitis-like syndrome with high level of POWV antigen at the ventral horn of the spinal cord. Pathological studies also revealed substantial infection of splenic macrophages by POWV, which suggests that the spleen plays a more important role in pathogenesis than previously realized. This report provides a detailed description of the neuroanatomical distribution of the lesions produced by POWV infection in C57BL/6 mice.

  10. Spinal Cord Ventral Horns and Lymphoid Organ Involvement in Powassan Virus Infection in a Mouse Model.

    Science.gov (United States)

    Santos, Rodrigo I; Hermance, Meghan E; Gelman, Benjamin B; Thangamani, Saravanan

    2016-01-01

    Powassan virus (POWV) belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investigate POWV infection and pathogenesis. After footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. Immunohistochemistry and immunofluorescence revealed a very strong neuronal tropism of POWV infection. The central nervous system infection appeared as a meningoencephalitis with perivascular mononuclear infiltration and microglial activation in the brain, and a poliomyelitis-like syndrome with high level of POWV antigen at the ventral horn of the spinal cord. Pathological studies also revealed substantial infection of splenic macrophages by POWV, which suggests that the spleen plays a more important role in pathogenesis than previously realized. This report provides a detailed description of the neuroanatomical distribution of the lesions produced by POWV infection in C57BL/6 mice. PMID:27529273

  11. Spinal Cord Ventral Horns and Lymphoid Organ Involvement in Powassan Virus Infection in a Mouse Model

    Science.gov (United States)

    Santos, Rodrigo I.; Hermance, Meghan E.; Gelman, Benjamin B.; Thangamani, Saravanan

    2016-01-01

    Powassan virus (POWV) belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investigate POWV infection and pathogenesis. After footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. Immunohistochemistry and immunofluorescence revealed a very strong neuronal tropism of POWV infection. The central nervous system infection appeared as a meningoencephalitis with perivascular mononuclear infiltration and microglial activation in the brain, and a poliomyelitis-like syndrome with high level of POWV antigen at the ventral horn of the spinal cord. Pathological studies also revealed substantial infection of splenic macrophages by POWV, which suggests that the spleen plays a more important role in pathogenesis than previously realized. This report provides a detailed description of the neuroanatomical distribution of the lesions produced by POWV infection in C57BL/6 mice. PMID:27529273

  12. Identification of different functional types of spinal afferent neurons innervating the mouse large intestine using a novel CGRPα transgenic reporter mouse.

    Science.gov (United States)

    Hibberd, Timothy J; Kestell, Garreth R; Kyloh, Melinda A; Brookes, Simon J H; Wattchow, David A; Spencer, Nick J

    2016-04-15

    Spinal afferent neurons detect noxious and physiological stimuli in visceral organs. Five functional classes of afferent terminals have been extensively characterized in the colorectum, primarily from axonal recordings. Little is known about the corresponding somata of these classes of afferents, including their morphology, neurochemistry, and electrophysiology. To address this, we made intracellular recordings from somata in L6/S1 dorsal root ganglia and applied intraluminal colonic distensions. A transgenic calcitonin gene-related peptide-α (CGRPα)-mCherry reporter mouse, which enabled rapid identification of soma neurochemistry and morphology following electrophysiological recordings, was developed. Three distinct classes of low-threshold distension-sensitive colorectal afferent neurons were characterized; an additional group was distension-insensitive. Two of three low-threshold classes expressed CGRPα. One class expressing CGRPα discharged phasically, with inflections on the rising phase of their action potentials, at low frequencies, to both physiological (30 mmHg) distensions. The second class expressed CGRPα and discharged tonically, with smooth, briefer action potentials and significantly greater distension sensitivity than phasically firing neurons. A third class that lacked CGRPα generated the highest-frequency firing to distension and had smaller somata. Thus, CGRPα expression in colorectal afferents was associated with lower distension sensitivity and firing rates and larger somata, while colorectal afferents that generated the highest firing frequencies to distension had the smallest somata and lacked CGRPα. These data fill significant gaps in our understanding of the different classes of colorectal afferent somata that give rise to distinct functional classes of colorectal afferents. In healthy mice, the majority of sensory neurons that respond to colorectal distension are low-threshold, wide-dynamic-range afferents, encoding both

  13. Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons

    Science.gov (United States)

    Mariqueo, Trinidad A.; Agurto, Adolfo; Muñoz, Braulio; San Martin, Loreto; Coronado, Cesar; Fernández-Pérez, Eduardo J.; Murath, Pablo; Sánchez, Andrea; Homanics, Gregg E.

    2014-01-01

    Ethanol increased the frequency of miniature glycinergic currents [miniature inhibitory postsynaptic currents (mIPSCs)] in cultured spinal neurons. This effect was dependent on intracellular calcium augmentation, since preincubation with BAPTA (an intracellular calcium chelator) or thapsigargin [a sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump inhibitor] significantly attenuated this effect. Similarly, U73122 (a phospholipase C inhibitor) or 2-aminoethoxydiphenyl borate [2-APB, an inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) inhibitor] reduced this effect. Block of ethanol action was also achieved after preincubation with Rp-cAMPS, inhibitor of the adenylate cyclase (AC)/PKA signaling pathway. These data suggest that there is a convergence at the level of IP3R that accounts for presynaptic ethanol effects. At the postsynaptic level, ethanol increased the decay time constant of mIPSCs in a group of neurons (30 ± 10% above control, n = 13/26 cells). On the other hand, the currents activated by exogenously applied glycine were consistently potentiated (55 ± 10% above control, n = 11/12 cells), which suggests that ethanol modulates synaptic and nonsynaptic glycine receptors (GlyRs) in a different fashion. Supporting the role of G protein modulation on ethanol responses, we found that a nonhydrolyzable GTP analog [guanosine 5′-O-(3-thiotriphosphate) (GTPγS)] increased the decay time constant in ∼50% of the neurons (28 ± 12%, n = 11/19 cells) but potentiated the glycine-activated Cl− current in most of the neurons examined (83 ± 29%, n = 7/9 cells). In addition, confocal microscopy showed that α1-containing GlyRs colocalized with Gβ and Piccolo (a presynaptic cytomatrix protein) in ∼40% of synaptic receptor clusters, suggesting that colocalization of Gβγ and GlyRs might account for the difference in ethanol sensitivity at the postsynaptic level. PMID:24572089

  14. Thermomineral water promotes axonal sprouting but does not reduce glial scar formation in a mouse model of spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Dubravka Aleksi; Milan Aksi; Nevena Divac; Vidosava Radonji; Branislav Filipovi; Igor Jakovevski

    2014-01-01

    Thermomineral water from the Atomic Spa Gornja Trepča has been used for a century in the treatment of neurologic disease. The thermomineral water contains microelements, including lithium and magnesium, which show neural regeneration-promoting effects after central nervous system injury. In this study, we investigated the effects of oral intake of thermomineral water from the Atomic Spa Gornja Trepča on nerve regeneration in a 3-month-old mouse model of spinal cord injury. The mice receiving oral intake of thermomineral water showed better locomo-tor recovery than those without administration of thermomineral water at 8 and 12 weeks after lower thoracic spinal cord compression. At 12 weeks after injury, sprouting of catecholaminergic axons was better in mice that drank thermomineral water than in those without administration of thermomineral water, but there was no difference in glial reaction to injury between mice with and without administration of thermomineral water. These ifndings suggest that thermomineral water can promote the nerve regeneration but cannot reduce glial scar formation in a mouse model of spinal cord injury.

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

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    Claire Bacon

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

  16. Motor cortex-periaqueductal gray-spinal cord neuronal circuitry may involve in modulation of nociception: a virally mediated transsynaptic tracing study in spinally transected transgenic mouse model.

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    Da-Wei Ye

    Full Text Available Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems. Recent evidence indicated that the melanocortin-4 receptor (MC4R in the periaqueductal gray played an important role in neuropathic pain. This study was designed to assess whether MC4R signaling existed in motor cortex-periaqueductal gray-spinal cord neuronal circuitry modulated the activity of sympathetic pathway by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV-614 was injected into the left gastrocnemius muscle in adult male MC4R-green fluorescent protein (GFP transgenic mice (n = 15. After a survival time of 4-6 days, the mice (n = 5 were randomly assigned to humanely sacrifice, and spinal cords and brains were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the left gastrocnemius muscle were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML, periaqueductal gray and motor cortex. Our findings support the hypothesis that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may participate in the modulation of the melanocortin-sympathetic signaling and contribute to the descending modulation of nociceptive transmission, suggesting that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may modulate the activity of sympathetic outflow sensitive to nociceptive signals.

  17. Changes of gene expression profiles in the cervical spinal cord by acupuncture in an MPTP-intoxicated mouse model: microarray analysis.

    Science.gov (United States)

    Choi, Yeong-Gon; Yeo, Sujung; Hong, Yeon-Mi; Kim, Sung-Hoon; Lim, Sabina

    2011-07-15

    It has been shown that acupuncture at acupoints GB34 and LR3 inhibits the degeneration of nigrostriatal neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. The degeneration of spinal cord was reported to be induced in the MPTP-treated pre-symptomatic mouse. In this study, the gene expression profile changes following acupuncture at the acupoints were investigated in the cervical spinal cord of an MPTP-induced parkinsonism model using a whole transcript array (Affymetrix GeneChip mouse gene 1.0 ST array). It was shown that 8 of the probes up-regulated in MPTP, as compared to the control, were down-regulated after acupuncture at the acupoints. Of these 8 probes, 6 probes (4 annotated genes in 6 probes: Ctla2a, EG383229, Ppbp and Ube2l6) were exclusively down-regulated by acupuncture at the specific acupoints except for 2 probes as these 2 probes were commonly down-regulated by acupuncture at both the acupoints and the non-acupoints. In addition, 11 of the probes down-regulated in MPTP, as compared to the control, were up-regulated by acupuncture at the acupoints. Of these 11 probes, 10 probes (5 annotated genes in 10 probes: EG665033, ENSMUSG00000055323, Obox6, Pbp2 and Tmem150) were exclusively up-regulated by acupuncture at the specific acupoints except for the Fut11 because the Fut11 was commonly up-regulated by acupuncture at both the acupoints and the non-acupoints. The expression levels of the representative genes in the microarray were validated by real-time RT-PCR. These data suggest that the expression of these exclusively regulated 16 probes (9 genes) may be, at least in part, affected by acupuncture at the acupoints in the cervical spinal cord which can be damaged by MPTP intoxication. PMID:21440609

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

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    Kouichi Isami

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

  19. Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose.

    Directory of Open Access Journals (Sweden)

    Svitlana Garbuzova-Davis

    Full Text Available BACKGROUND: Amyotrophic Lateral Sclerosis (ALS is a multicausal disease characterized by motor neuron degeneration in the spinal cord and brain. Cell therapy may be a promising new treatment for this devastating disorder. We recently showed that a single low dose (10(6 cells of mononuclear human umbilical cord blood (MNC hUCB cells administered intravenously to G93A mice delayed symptom progression and modestly prolonged lifespan. The aim of this pre-clinical translation study is to optimize the dose of MNC hUCB cells to retard disease progression in G93A mice. Three different doses of MNC hUCB cells, 10x10(6, 25x10(6 and 50x10(6, were administered intravenously into pre-symptomatic G93A mice. Motor function tests and various assays to determine cell effects were performed on these mice. METHODOLOGY/PRINCIPAL FINDINGS: Our results showed that a cell dose of 25x10(6 cells significantly increased lifespan of mice by 20-25% and delayed disease progression by 15%. The most beneficial effect on decreasing pro-inflammatory cytokines in the brain and spinal cord was found in this group of mice. Human Th2 cytokines were found in plasma of mice receiving 25x10(6 cells, although prevalent human Th1 cytokines were indicated in mice with 50x10(6 cells. High response of splenic cells to mitogen (PHA was indicated in mice receiving 25x10(6 (mainly and 10x10(6 cells. Significantly increased lymphocytes and decreased neutrophils in the peripheral blood were found only in animals receiving 25x10(6 cells. Stable reduction in microglia density in both cervical and lumbar spinal cords was also noted in mice administered with 25x10(6 cells. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that treatment for ALS with an appropriate dose of MNC hUCB cells may provide a neuroprotective effect for motor neurons through active involvement of these cells in modulating the host immune inflammatory system response.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-06

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

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

    Directory of Open Access Journals (Sweden)

    Andrea Luchetti

    2015-08-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA. PMID:26258776

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

    Science.gov (United States)

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

    2015-01-01

    Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA. PMID:26258776

  4. Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing

    Science.gov (United States)

    Pryce, Gareth; Baker, David; Selwood, David L.

    2016-01-01

    Multiple sclerosis (MS) is a debilitating immune-mediated neurological disorder affecting young adults. MS is primarily relapsing-remitting, but neurodegeneration and disability accumulate from disease onset. The most commonly used mouse MS models exhibit a monophasic immune response with fast accumulation of neurological damage that does not allow the study of progressive neurodegeneration. The chronic relapsing and secondary progressive EAE (pEAE) Biozzi ABH mouse model of MS exhibits a reproducible relapsing-remitting disease course that slowly accumulates permanent neurological deficit and develops a post-relapsing progressive disease that permits the study of demyelination and neurodegeneration. RNA sequencing (RNAseq) was used to explore global gene expression in the pEAE Biozzi ABH mouse. Spinal cord tissue RNA from pEAE Biozzi ABH mice and healthy age-matched controls was sequenced. 2,072 genes were differentially expressed (q<0.05) from which 1,397 were significantly upregulated and 675 were significantly downregulated. This hypothesis-free investigation characterised the genomic changes that describe the pEAE mouse model. The differentially expressed genes revealed a persistent immunoreactant phenotype, combined with downregulation of the cholesterol biosynthesis superpathway and the LXR/RXR activation pathway. Genes differentially expressed include the myelination genes Slc17a7, Ugt8A and Opalin, the neuroprotective genes Sprr1A, Osm and Wisp2, as well as genes identified as MS risk factors, including RGs14 and Scap2. Novel genes with unestablished roles in EAE or MS were also identified. The identification of differentially expressed novel genes and genes involved in MS pathology, opens the door to their functional study in the pEAE mouse model which recapitulates some of the important clinical features of progressive MS. PMID:27355629

  5. Morphological and function al changes in the blood-spinal cord barrier of rabbits in an experimental spinal cord presyrinx state

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Li; Haiying Liu; Qingjun Zhang

    2006-01-01

    BACKGROUND: Presyrinx state of spinal cord reflect the initial lesion of syringomyelia (SM).The early trals has proved that ischamia and edema are main pathological of presyrinx state. OBJECTIVE: To estabilsh SM model of rabbits for investigating the relationship between changes of morphous and function of blood-spinal cord barrier and the edema degree, histological changes in presyrinx state of SM,and to explore the mechanism of the presyrinx state of SM.DESIGN: Randomized controlled animal experiment.SETTING: Department of Neurosurgery,Fourth Hospital,Heibei Medical University.MATERIALS: Sixty Chinese healthy white rabbits,aged 3.5-4.5 months,weighing 1.5-2.0kg,were provided by Experimental Animal Center of Hehei Medical University[certification:(SYXK(Ji)2003-0026)].Evan's blue (EB)and dimethylformamide(DMF) were purchased from Jingmei Biotech Co.,Ltd RM2125 paraffin section cutter(Leica Company,Japan),H-7500 transmission electron microscope (Hitachi Company,Japan),PM-20 light microscope photograph system(Olympus Company,Japan).METHODS:The experiment was carried out in the Laboratory of Neurosurgery Department,Second Hospital of Hebei Medical University from January to June 2006.①All the rabbits were randomly divided into two groups:model group(n=40),control group(n=20).Rabbits in two groups were divided into five subgroups once again at five time points(1st , 3rd ,7th ,14th ,21st days,n=8 and n=4 at each time point in the model group and control group,respectively).Under ketamine anesthesia,0.6 mL Kaolin solution(250 g/L,37℃)was injected into the cisterna magna of rabbits in model group,while 0.6 mL physiological saline(37℃)was injected into the rabbits of control group.②On the 1st ,3rd ,7th ,14th , 21st days after kaolin injection,cervical cord samples were harvested after sacrifice of animal. Quantitative analysis on the function of blood-spinal cord barrier was performed by Evan's blue technique.Water content of spinal cord was measured by dry

  6. Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury.

    Science.gov (United States)

    Chamney, Carissa; Godar, Michelle; Garrigan, Ethan; Huey, Kimberly A

    2013-03-01

    Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non-skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine. We tested the hypothesis that glutamine preserves muscle function after SCI and that this is associated with increased heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα). Changes in plantarflexor force, fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFα muscle protein levels were measured 7 days after sham or spinal cord transection surgery in mice receiving daily placebo or glutamine. Compared with placebo, after SCI glutamine significantly attenuated the reductions in maximal isometric force (0.22 ± 0.01 versus 0.31 ± 0.03 N, respectively) and fatigue resistance (34 ± 4 versus 59 ± 4% of initial force, respectively). Glutamine significantly ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal cord transection was associated with decreased Hsp70 and Hsp25 with glutamine only (45 ± 3 and 44 ± 5% of placebo, respectively). Glutamine significantly reduced spinal cord transection-associated increases in IL-6 and TNFα compared with placebo (38 ± 6 and 37 ± 8% of placebo, respectively). Functionally, early reductions in contractile protein, force and fatigue resistance after SCI were reversed with glutamine. Spinal cord transection-associated reductions in Hsp70, Hsp25, IL-6 and TNFα with glutamine versus placebo suggest lower stress in the muscle, possibly related to a reduced need to produce glutamine. These findings support glutamine as a therapeutic intervention to accelerate recovery of muscle function after SCI.

  7. p62/SQSTM1 differentially removes the toxic mutant androgen receptor via autophagy and inclusion formation in a spinal and bulbar muscular atrophy mouse model.

    Science.gov (United States)

    Doi, Hideki; Adachi, Hiroaki; Katsuno, Masahisa; Minamiyama, Makoto; Matsumoto, Shinjiro; Kondo, Naohide; Miyazaki, Yu; Iida, Madoka; Tohnai, Genki; Qiang, Qiang; Tanaka, Fumiaki; Yanagawa, Toru; Warabi, Eiji; Ishii, Tetsuro; Sobue, Gen

    2013-05-01

    Polyglutamine (polyQ) diseases are inherited neurodegenerative disorders that are caused by the expansion of trinucleotide CAG repeats in the causative genes. Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease that is caused by the expansion of a polyQ tract within the androgen receptor (AR). p62 is a ubiquitin- and light-chain 3-binding protein that is known to regulate the degradation of targeted proteins via autophagy and inclusion formation. In this study, we examined the effects of p62 depletion and overexpression on cultured cells and in a transgenic mouse model that overexpressed the mutant AR. Here, we demonstrate that depletion of p62 significantly exacerbated motor phenotypes and the neuropathological outcome, whereas overexpression of p62 protected against mutant AR toxicity in SBMA mice. Depletion of p62 significantly increased the levels of monomeric mutant AR and mutant AR protein complexes in an SBMA mouse model via the impairment of autophagic degradation. In addition, p62 overexpression improved SBMA mouse phenotypes by inducing cytoprotective inclusion formation. Our results demonstrate that p62 provides two different therapeutic targets in SBMA pathogenesis: (1) autophagy-dependent degradation and (2) benevolent inclusion formation of the mutant AR.

  8. The use of PRV-Bartha to define premotor inputs to lumbar motoneurons in the neonatal spinal cord of the mouse.

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    Ksenija Jovanovic

    Full Text Available BACKGROUND: The neonatal mouse has become a model system for studying the locomotor function of the lumbar spinal cord. However, information about the synaptic connectivity within the governing neural network remains scarce. A neurotropic pseudorabies virus (PRV Bartha has been used to map neuronal connectivity in other parts of the nervous system, due to its ability to travel trans-neuronally. Its use in spinal circuits regulating locomotion has been limited and no study has defined the time course of labelling for neurons known to project monosynaptically to motoneurons. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the ability of PRV Bartha, expressing green and/or red fluorescence, to label spinal neurons projecting monosynaptically to motoneurons of two principal hindlimb muscles, the tibialis anterior (TA and gastrocnemius (GC. As revealed by combined immunocytochemistry and confocal microscopy, 24-32 h after the viral muscle injection the label was restricted to the motoneuron pool while at 32-40 h the fluorescence was seen in interneurons throughout the medial and lateral ventral grey matter. Two classes of ipsilateral interneurons known to project monosynaptically to motoneurons (Renshaw cells and cells of origin of C-terminals were consistently labeled at 40 h post-injection but also a group in the ventral grey matter contralaterally. Our results suggest that the labeling of last order interneurons occurred 8-12 h after motoneuron labeling and we presume this is the time taken by the virus to cross one synapse, to travel retrogradely and to replicate in the labeled cells. CONCLUSIONS/SIGNIFICANCE: The study establishes the time window for virally-labelling monosynaptic projections to lumbar motoneurons following viral injection into hindlimb muscles. Moreover, it provides a good foundation for intracellular targeting of the labeled neurons in future physiological studies and better understanding the functional organization of

  9. TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study showing TRPV1 related adaptations in the TRPV4 knockout mouse.

    Science.gov (United States)

    Janssen, Dick A W; Hoenderop, Joost G; Heesakkers, John P F A; Schalken, Jack A

    2016-10-01

    The role of transient receptor potential vanilloid subtype 4 (TRPV4) channels in urinary bladder afferent neural pathways was investigated using spinal c-fos measurements in mice. Anesthetized wild type and TRPV4 knockout (-/-) mice underwent noxious bladder distention and treatment with either intravesical instillation with lipopolysaccharide (LPS), or the TRPV1 agonist resiniferatoxin (RTX), vehicle or an intraperitoneal injected TRPV4 antagonist (HC067047). Mice underwent paraformaldehyde perfusion for rapid fixation and L6-S1 spinal cord sections were removed followed by immunohistochemical staining for c-fos. A number of c-fos expressing neurons in the dorsal horns of L6-S1 spinal cord transections were quantified. Groups were compared using univariate ANOVA. Even with the absence of bladder inflammation on H&E, the TRPV4 -/- mice still have a significant twofold higher c-fos expression (n = 39, SD 2) after noxious bladder distention compared to wild type mice (n = 20, SD 3). A twofold increase in c-fos expression was observed after LPS treatment in wild types (n = 42, SD 5), but no increase was seen in TRPV4 -/- mice (n = 42, SD 2). After desensitization of primary afferent C-nerve fibers with RTX, c-fos expression in TRPV4-/- mice decreased significantly (threefold) (n = 12, SD 4). Results imply that TRPV4 channels are important for bladder afferent signaling. TRPV4 -/- mice bladders generate more noxious sensory output, which is predominantly mediated through TRPV1 expressing high threshold nerve fibers. This study reveals TRPV1 related adaptive changes in afferent pathways of the TRPV4 -/- mouse. We propose that this effect is caused by a congenital impairment of low threshold nerves that mediate normal bladder filling sensations.

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

    OpenAIRE

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

    2016-01-01

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

  11. Polyethylene glycol-coupled IGF1 delays motor function defects in a mouse model of spinal muscular atrophy with respiratory distress type 1.

    Science.gov (United States)

    Krieger, Frank; Elflein, Nicole; Saenger, Stefanie; Wirthgen, Elisa; Rak, Kristen; Frantz, Stefan; Hoeflich, Andreas; Toyka, Klaus V; Metzger, Friedrich; Jablonka, Sibylle

    2014-05-01

    Spinal muscular atrophy with respiratory distress type 1 is a neuromuscular disorder characterized by progressive weakness and atrophy of the diaphragm and skeletal muscles, leading to death in childhood. No effective treatment is available. The neuromuscular degeneration (Nmd(2J)) mouse shares a crucial mutation in the immunoglobulin mu-binding protein 2 gene (Ighmbp2) with spinal muscular atrophy with respiratory distress type 1 patients and also displays some basic features of the human disease. This model serves as a promising tool in understanding the complex mechanisms of the disease and in exploring novel treatment modalities such as insulin-like growth factor 1 (IGF1) which supports myogenic and neurogenic survival and stimulates differentiation during development. Here we investigated the treatment effects with polyethylene glycol-coupled IGF1 and its mechanisms of action in neurons and muscles. Polyethylene glycol-coupled IGF1 was applied subcutaneously every second day from post-natal Day 14 to post-natal Day 42 and the outcome was assessed by morphology, electromyography, and molecular studies. We found reduced IGF1 serum levels in Nmd(2J) mice 2 weeks after birth, which was normalized by polyethylene glycol-coupled IGF1 treatment. Nmd(2J) mice showed marked neurogenic muscle fibre atrophy in the gastrocnemius muscle and polyethylene glycol-coupled IGF1 treatment resulted in muscle fibre hypertrophy and slowed fibre degeneration along with significantly higher numbers of functionally active axonal sprouts. In the diaphragm with predominant myogenic changes a profound protection from muscle fibre degeneration was observed under treatment. No effects of polyethylene glycol-coupled IGF1 were monitored at the level of motor neuron survival. The beneficial effects of polyethylene glycol-coupled IGF1 corresponded to a marked activation of the IGF1 receptor, resulting in enhanced phosphorylation of Akt (protein kinase B) and the ribosomal protein S6 kinase in

  12. C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD.

    Science.gov (United States)

    Liu, Yuanjing; Pattamatta, Amrutha; Zu, Tao; Reid, Tammy; Bardhi, Olgert; Borchelt, David R; Yachnis, Anthony T; Ranum, Laura P W

    2016-05-01

    To define how the C9orf72 GGGGCC expansion mutation causes ALS/FTD and to facilitate therapy development, a mouse model that recapitulates the molecular and phenotypic features of the disease is urgently needed. Two groups recently reported BAC mouse models that produce RNA foci and RAN proteins but, surprisingly, do not develop the neurodegenerative or behavioral features of ALS/FTD. We now report a BAC mouse model of C9orf72 ALS/FTD that shows decreased survival, paralysis, muscle denervation, motor neuron loss, anxiety-like behavior, and cortical and hippocampal neurodegeneration. These mice express C9orf72 sense transcripts and upregulated antisense transcripts. In contrast to sense RNA foci, antisense foci preferentially accumulate in ALS/FTD-vulnerable cell populations. RAN protein accumulation increases with age and disease, and TDP-43 inclusions are found in degenerating brain regions in end-stage animals. The ALS/FTD phenotypes in our mice provide a unique tool that will facilitate developing therapies targeting pathways that prevent neurodegeneration and increase survival. PMID:27112499

  13. EGFR inhibitor erlotinib delays disease progression but does not extend survival in the SOD1 mouse model of ALS.

    Directory of Open Access Journals (Sweden)

    Claire E Le Pichon

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease that causes progressive paralysis due to motor neuron death. Several lines of published evidence suggested that inhibition of epidermal growth factor receptor (EGFR signaling might protect neurons from degeneration. To test this hypothesis in vivo, we treated the SOD1 transgenic mouse model of ALS with erlotinib, an EGFR inhibitor clinically approved for oncology indications. Although erlotinib failed to extend ALS mouse survival it did provide a modest but significant delay in the onset of multiple behavioral measures of disease progression. However, given the lack of protection of motor neuron synapses and the lack of survival extension, the small benefits observed after erlotinib treatment appear purely symptomatic, with no modification of disease course.

  14. Androgen regulates development of the sexually dimorphic gastrin-releasing peptide neuron system in the lumbar spinal cord: evidence from a mouse line lacking androgen receptor in the nervous system.

    Science.gov (United States)

    Sakamoto, Hirotaka; Saito, Kazuhiro; Marie-Luce, Clarisse; Raskin, Kalina; Oti, Takumi; Satoh, Keita; Tamura, Kei; Sakamoto, Tatsuya; Mhaouty-Kodja, Sakina

    2014-01-13

    Androgens including testosterone, organize the nervous system as well as masculine external and internal genitalia during the perinatal period. Androgen organization involves promotion of masculine body features, usually by acting through androgen receptors (ARs). We have recently demonstrated that the gastrin-releasing peptide (GRP) system in the lumbar spinal cord also mediates spinal centers promoting penile reflexes during male sexual behavior in rats. Testosterone may induce sexual differentiation of this spinal GRP system during development and maintain its activation in adulthood. In the present study, we examined the role of ARs in the nervous system regulating the development of the sexually dimorphic GRP system. For this purpose, we used a conditional mouse line selectively lacking the AR gene in the nervous system. AR floxed males carrying (mutants) or not (controls) the nestin-Cre transgene were castrated in adulthood and supplemented with physiological amounts of testosterone. Loss of AR expression in the nervous system resulted in a significant decrease in the number of GRP neurons compared to control littermates. Consequently, the intensity of GRP axonal projections onto the lower lumbar and upper sacral spinal cord was greater in control males than in mutant males. These results suggest that ARs expressed in the nervous system play a significant role in the development of the GRP system in the male lumbar spinal cord. The AR-deletion mutation may attenuate sexual behavior and activity of mutant males via spinal GRP system-mediated neural mechanisms.

  15. Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    B. Heurich; N.B. El Idrissi; R.M. Donev; S. Petri; P. Claus; J. Neal; B.P. Morgan; V. Ramaglia

    2011-01-01

    Complement activation products are elevated in cerebrospinal fluid, spinal cord and motor cortex of patients with amyotrophic lateral sclerosis (ALS) but are untested in models. We determined complement expression and activation in the SOD1 G93A mouse model of familial ALS (fALS). At 126 days, C3 mR

  16. A novel acylaminoimidazole derivative, WN1316, alleviates disease progression via suppression of glial inflammation in ALS mouse model.

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    Kazunori Tanaka

    Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset motor neuron degenerative disease. Given that oxidative stress and resulting chronic neuronal inflammation are thought to be central pathogenic, anti-oxidative agents and modulators of neuronal inflammation could be potential therapies for ALS. We report here that the novel small molecular compound, 2-[mesityl(methylamino]-N-[4-(pyridin-2-yl-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316 selectively suppresses oxidative stress-induced cell death and neuronal inflammation in the late-stage ALS mice. WN1316 has high blood-brain-barrier permeability and water solubility, and boosts both neuronal apoptosis inhibitory protein (NAIP and NF-E2-related factor 2 (Nrf2 which governed glutathione (GSH-related anti-oxidation pathway protecting motor neurons against oxidative injuries. Post-onset oral administration of low dose (1-100 µg/kg/day WN1316 in ALS(SOD1(H46R and ALS(SOD1(G93A mice resulted in sustained improved motor function and post onset survival rate. Immunohistochemical analysis revealed less DNA oxidative damage and motor neuronal inflammation as well as repression of both microgliosis and astrocytosis, concomitant down regulation of interleukin-1β and inducible nitric oxide synthase, and preservation of the motoneurons in anterior horn of lumbar spinal cord and skeletal muscle (quadriceps femoris. Thus, WN1316 would be a novel therapeutic agent for ALS.

  17. Correlation of in vivo and ex vivo 1H-MRI with histology in two severities of mouse spinal cord injury

    Science.gov (United States)

    Noristani, Harun N.; Lonjon, Nicolas; Cardoso, Maïda; Le Corre, Marine; Chan-Seng, Emilie; Captier, Guillaume; Privat, Alain; Coillot, Christophe; Goze-Bac, Christophe; Perrin, Florence E.

    2015-01-01

    Spinal cord injury (SCI) is a debilitating neuropathology with no effective treatment. Magnetic resonance imaging (MRI) technology is the only method used to assess the impact of an injury on the structure and function of the human spinal cord. Moreover, in pre-clinical SCI research, MRI is a non-invasive method with great translational potential since it provides relevant longitudinal assessment of anatomical and structural alterations induced by an injury. It is only recently that MRI techniques have been effectively used for the follow-up of SCI in rodents. However, the vast majority of these studies have been carried out on rats and when conducted in mice, the contusion injury model was predominantly chosen. Due to the remarkable potential of transgenic mice for studying the pathophysiology of SCI, we examined the use of both in and ex vivo 1H-MRI (9.4 T) in two severities of the mouse SCI (hemisection and over-hemisection) and documented their correlation with histological assessments. We demonstrated that a clear distinction between the two injury severities is possible using in and ex vivo 1H-MRI and that ex vivo MR images closely correlate with histology. Moreover, tissue modifications at a remote location from the lesion epicenter were identified by conventional ex vivo MRI analysis. Therefore, in vivo MRI has the potential to accurately identify in mice the progression of tissue alterations induced by SCI and is successfully implemented by ex vivo MRI examination. This combination of in and ex vivo MRI follow-up associated with histopathological assessment provides a valuable approach for further studies intended to evaluate therapeutic strategies on SCI. PMID:25798092

  18. Testosterone treatment fails to accelerate disease in a transgenic mouse model of spinal and bulbar muscular atrophy

    Directory of Open Access Journals (Sweden)

    Erica S. Chevalier-Larsen

    2012-01-01

    Evidence from multiple animal models demonstrates that testosterone plays a crucial role in the progression of symptoms in spinal and bulbar muscular atrophy (SBMA, a condition that results in neurodegeneration and muscle atrophy in affected men. Mice bearing a transgene encoding a human androgen receptor (AR that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q mice reproduce several aspects of the human disease. We treated transgenic male AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males exhibited functional deficits when compared with non-transgenics, long-term testosterone treatment had no effect on motor function. Testosterone treatment also failed to affect cellular markers of disease, including inclusion formation (the accumulation of large nuclear aggregates of mutant AR protein and levels of unphosphorylated neurofilament heavy chain. These data suggest that the mechanism of disease in SBMA saturates at close to endogenous hormone levels and that individuals with SBMA who take, or have taken, testosterone for its putative therapeutic properties are unlikely to suffer adverse effects.

  19. Intracerebroventricular injection of encapsulated human mesenchymal cells producing glucagon-like peptide 1 prolongs survival in a mouse model of ALS.

    Directory of Open Access Journals (Sweden)

    Sarah Knippenberg

    Full Text Available BACKGROUND: As pharmacological therapies have largely failed so far, stem cell therapy has recently come into the focus of ALS research. Neuroprotective potential was shown for several types of stem and progenitor cells, mainly due to release of trophic factors. In the present study, we assessed the effects of intracerebroventricular injection of glucagon-like peptide 1 (GLP-1 releasing mesenchymal stromal cells (MSC in mutant SOD1 (G93A transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: To improve the neuroprotective effects of native MSC, they had been transfected with a plasmid vector encoding a GLP-1 fusion gene prior to the injection, as GLP-1 was shown to exhibit neuroprotective properties before. Cells were encapsulated and therefore protected against rejection. After intracerebroventricular injection of these GLP-1 MSC capsules in presymptomatic SOD1 (G93A mice, we assessed possible protective effects by survival analysis, measurement of body weight, daily monitoring and evaluation of motor performance by rotarod and footprint analyses. Motor neuron numbers in the spinal cord as well as the amount of astrocytosis, microglial activation, heat shock response and neuronal nitric oxide synthase (nNOS expression were analyzed by immunohistological methods. Treatment with GLP-1 producing MSC capsules significantly prolonged survival by 13 days, delayed symptom onset by 15 days and weight loss by 14 days and led to significant improvements in motor performance tests compared to vehicle treated controls. Histological data are mainly in favour of anti-inflammatory effects of GLP-1 producing MSC capsules with reduced detection of inflammatory markers and a significant heat shock protein increase. CONCLUSION/SIGNIFICANCE: Intracerebroventricular injection of GLP-1 MSC capsules shows neuroprotective potential in the SOD1 (G93A mouse model.

  20. Involvement of the histaminergic system in the nociceptin-induced pain-related behaviors in the mouse spinal cord.

    Science.gov (United States)

    Sakurada, Shinobu; Watanabe, Hiroyuki; Mizoguchi, Hirokazu; Yonezawa, Akihiko; Orito, Tohru; Katsuyama, Sou; Kuramasu, Atsuo; Sakurada, Chikai; Yanai, Kazuhiko; Sakurada, Tsukasa

    2004-11-01

    Intrathecal (i.t.) injection of nociceptin elicited a behavioral response mainly consisting of biting and licking, which were eliminated by the i.t. co-administration of opioid receptor-like-1 (ORL-1) receptor antagonists. The behavioral response induced by nociceptin was characteristically similar to that by i.t.-administered histamine, and was attenuated by i.t. co-administration of the H1 receptor antagonists, but not by the H2 receptor antagonists, whereas the H3 receptor antagonist promoted the nociceptin-induced behavior. H1 receptor knockout (H1R-KO) mice did not show the nociceptin-induced nociceptive behavior, which was observed in wild-type mice. Pretreatment with a histamine antiserum or a histidine decarboxylase inhibitor resulted in a significant reduction of the response to nociceptin. The previous studies showed that NK1 receptor antagonists and a novel substance P (SP)-specific antagonist given i.t. could reduce the behavioral response to nociceptin and histamine. On the other hand, the nociceptive response induced by nociceptin, but not histamine, was completely attenuated by the i.t. co-administration of agonists for GABAA and GABAB receptors. In contrast, the antagonists for GABAA and GABAB receptors injected i.t. showed same nociceptive response with nociceptin and histamine, and their nociceptive responses were significantly blocked by the i.t. co-administration of the H1 receptor antagonists, but not H2 receptor antagonists or ORL-1 receptor antagonists. The present results suggest that the activation of the ORL-1 receptor by nociceptin may induce the disinhibition of histaminergic neuron and enhance the release of histamine, which subsequently acts on the H1 receptor located on the SP-containing neurons to produce the spinal cord-mediated nociceptive response.

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

    Science.gov (United States)

    Gutierrez-Mecinas, Maria; Kuehn, Emily D; Abraira, Victoria E; Polgár, Erika; Watanabe, Masahiko; Todd, Andrew J

    2016-08-01

    The spinal dorsal horn processes somatosensory information before conveying it to the brain. The neuronal organization of the dorsal horn is still poorly understood, although recent studies have defined several distinct populations among the interneurons, which account for most of its constituent neurons. All primary afferents, and the great majority of neurons in laminae I-III are glutamatergic, and a major factor limiting our understanding of the synaptic circuitry has been the difficulty in identifying glutamatergic synapses with light microscopy. Although there are numerous potential targets for antibodies, these are difficult to visualize with immunocytochemistry, because of protein cross-linking following tissue fixation. Although this can be overcome by antigen retrieval methods, these lead to difficulty in detecting other antigens. The aim of this study was to test whether the postsynaptic protein Homer can be used to reveal glutamatergic synapses in the dorsal horn. Immunostaining for Homer gave punctate labeling when viewed by confocal microscopy, and this was restricted to synapses at the ultrastructural level. We found that Homer puncta were colocalized with the AMPA receptor GluR2 subunit, but not with the inhibitory synapse-associated protein gephyrin. We also examined several populations of glutamatergic axons and found that most boutons were in contact with at least one Homer punctum. These results suggest that Homer antibodies can be used to reveal the great majority of glutamatergic synapses without antigen retrieval. This will be of considerable value in tracing synaptic circuits, and also in investigating plasticity of glutamatergic synapses in pain states. PMID:27185486

  2. Ibn Jazlah and his 11th century accounts (Taqwim al-abdan fi tadbir al-insan) of disease of the brain and spinal cord. Historical vignette.

    Science.gov (United States)

    Tubbs, R Shane; Loukas, Marios; Shoja, Mohammadali M; Ardalan, Mohammad; Oakes, W Jerry

    2008-09-01

    The 11th century was culturally and medicinally one of the most exciting periods in the history of Islam. Medicine of this day was influenced by the Greeks, Indians, Persians, Coptics, and Syriacs. One of the most prolific writers of this period was Ibn Jazlah, who resided in Baghdad in the district of Karkh. Ibn Jazlah made many important observations regarding diseases of the brain and spinal cord. These contributions and a review of the life and times of this early Muslim physician are presented. PMID:18928231

  3. The calcium-binding protein Mtsl/S100A4 in normal, degenerating and demyelinated spinal cord of the adult mouse%The calcium-binding protein Mtsl/S100A4 in normal,degenerating and demyelinated spinal cord of the adult mouse

    Institute of Scientific and Technical Information of China (English)

    FANG Zhengyu; XIONG Liang; HUANG Xiaolin; ZHOU Ning; Kozlova-Aldskogius Elena

    2008-01-01

    目的:研究止常、退行性病变以及脱髓鞘小鼠脊髓内Mtsl/S100A4蛋白的表达模式,及其对胶质细胞反应的影响.方法:以野生型和Mtsl/S100A4基因敲除型小鼠为试验动物,采用背根损伤、坐骨神经损伤、溴乙啶局部微量注射的方法复制退行性病变及脱髓鞘脊髓动物模型,应用免疫荧光技术,检测S100A4、GFAP、NG2、Mac1的表达情况.结果:野生型小鼠脊髓内,仅白质星型胶质细胞表达S100A4蛋白,且主要分布于Lissauer束:背根或坐骨神经损伤后,白质星形胶质细胞内的S100A4及GFAP表达上调.野生型与S100A4基因敲除小鼠GFAP表达量无显著差异;溴乙啶注射7d后,野生型小鼠脊髓脱髓鞘区域内她S100A4呈云雾状分布,胶质细胞反应局限于注射侧,并且形成清晰的胶质瘢痕,而S100A4基凶敲除小鼠则未见上述病理变化.结论:S100A4蛋白在小鼠脊髓内的表达模式与大鼠相似;退行性变的脊髓内,细胞内上调的S100A4蛋白并不影响胶质细胞的反应;脱髓鞘脊髓内,细胞外的S100A4蛋白明显影响胶质细胞反应,包括胶质瘢痕的形成.%Objective:To investigate the expression pattern of Mtsl/S100A4 in mouse spinal cord;to investigate the effects of Mtsl/S100A4 on glial cell responses.Method:The study was carried out on Mtsl/S100A4 wild type and knock-out mice.The degenerative spinal cord model was established by dorsal root or sciatic nerve injury.The de-myelinated spinal cord model was established by ethidium bromide injections.Then the expressions of S100A4,GFA P,NG2 and Mael were measured.Result:The expressions of Mtsl/S100A4 in mice spinal cord were similar to that in rats.In WT mice this protein expressed in a thin layer of fiber bundles in the tract of Lissauer,and in white matter astrocytes.There was intracellular up-regulation of Mtsl/S100A4 in white matter astrocytes of WT mice after dorsal root or sciatic nerve injury,with no difference in glial cell response

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  5. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model.

    Science.gov (United States)

    Ari, Csilla; Poff, Angela M; Held, Heather E; Landon, Carol S; Goldhagen, Craig R; Mavromates, Nicholas; D'Agostino, Dominic P

    2014-01-01

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong

  6. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS mouse model.

    Directory of Open Access Journals (Sweden)

    Csilla Ari

    Full Text Available Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG, the main ingredient of the DP, and the ketogenic diet (KD, would increase motor function and survival in a mouse model of ALS (SOD1-G93A. ALS mice were fed standard rodent diet (SD, KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001 and 4.2% (p = 0.006, respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which

  7. Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Dahlke, Carolin; Saberi, Darius; Ott, Bastian;

    2015-01-01

    An abnormal density of Iba-1-positive microglial cells expressing pro-inflammatory tumor necrosis factor (TNF) alpha- and glial fibrillary acidic protein (GFAP)-positive activated astroglial cells was detected in the motor cortex region of the WR mouse 40 days postnatal (d.p.n.). Motor neurons in the same...... be an important contributing factor of motor neuron degeneration. This would appear to be confirmed by the fact that there was no conspicuous increase of microglial cells and astrocytes in the motor cortex of control mice at any time. Conclusions Activated microglial cells secrete a variety of pro...

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

    OpenAIRE

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

    2015-01-01

    Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidatin...

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

    Directory of Open Access Journals (Sweden)

    Coral-Ann B Lewis

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

  10. Intraspinal transplantation of mouse and human neural precursor cells

    OpenAIRE

    Weinger, Jason G.; Chen, Lu; Coleman, Ronald; Leang, Ronika; Plaisted, Warren C.; Loring, Jeanne F.; Lane, Thomas E

    2013-01-01

    This unit describes the preparation and transplantation of human neural precursor cells (hNPCs) and mouse neural precursor cells (mNPCs) into the thoracic region of the mouse spinal cord. The techniques in this unit also describe how to prepare the mouse for surgery by performing a laminectomy to expose the spinal cord for transplantation. Here we show NPCs genetically labeled with eGFP transplanted into the spinal cord of a mouse following viralmediated demyelination can efficiently be detec...

  11. YAC contigs of the Rab1 and wobbler (wr) spinal muscular atrophy gene region on proximal mouse chromosome 11 and of the homologous region on human chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Wedemeyer, N.; Lengeling, A.; Ronsiek, M. [Univ. of Bielefeld (Germany)] [and others

    1996-03-05

    Despite rapid progress in the physical characterization of murine and human genomes, little molecular information is available on certain regions, e.g., proximal mouse chromosome 11 (Chr 11) and human chromosome 2p (Chr2p). We have localized the wobbler spinal atrophy gene wr to proximal mouse Chr 11, tightly linked to Rab1, a gene coding for a small GTP-binding protein, and Glns-ps1, an intronless pseudogene of the glutamine synthetase gene. We have not used these markers to construct a 1.3-Mb yeast artificial chromosome (YAC) contig of the Rab1 region on mouse Chr 11. Four YAC clones isolated from two independent YAC libraries were characterized by rare-cutting analysis, fluorescence in situ hybridization (FISH), and sequence-tagged site (STS) isolation and mapping. Rab1 and Glns-ps1 were found to be only 200 kb apart. A potential CpG island near a methylated NarI site and a trapped exon, ETG1.1, were found over 250 kb from Rab1. Two overlapping YACs were identified that contained a 150-kb region of human Chr 2p, comprising the RAB1 locus, AHY1.1, and the human homologue of ETG1.1, indicating a high degree of conservation of this region in the two species. We mapped AHY1.1 and thus human RAB1 on Chr 2p13.4-p14 using somatic cell hybrids and a radiation hybrid panel, thus extending a known region of conserved synteny between mouse Chr 11 and human Chr 2p. Recently, the gene LMGMD2B for a human recessive neuromuscular disease, limb girdle muscular dystrophy type 2B, has been mapped to 2p13-p16. The conservation between the mouse Rab1 and human RAB1 regions will be helpful in identifying candidate genes for the wobbler spinal muscular atrophy and in clarifying a possible relationship between wr and LMGMD2B. 33 refs., 7 figs., 3 tabs.

  12. Spinal brucellosis.

    Science.gov (United States)

    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.

  13. Spinal Cord Stimulation

    DEFF Research Database (Denmark)

    Meier, Kaare

    2014-01-01

    Spinal cord stimulation (SCS) is a surgical treatment for chronic neuropathic pain that is refractory to other treatment. Originally described by Shealy et al. in 1967(1), it is used to treat a range of conditions such as complex regional pain syndrome (CRPS I)(2), angina pectoris(3), radicular...... pain after failed back surgery syndrome (FBSS)(4), pain due to peripheral nerve injury, stump pain(5), peripheral vascular disease(6) and diabetic neuropathy(7,8); whereas phantom pain(9), postherpetic neuralgia(10), chronic visceral pain(11), and pain after partial spinal cord injury(12) remain more...

  14. Optimised and rapid pre-clinical screening in the SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS).

    OpenAIRE

    Mead, Richard J.; Bennett, Ellen J.; Kennerley, Aneurin J; Paul Sharp; Claire Sunyach; Paul Kasher; Jason Berwick; Brigitte Pettmann; Guiseppe Battaglia; Mimoun Azzouz; Andrew Grierson; Shaw, Pamela J.

    2011-01-01

    The human SOD1(G93A) transgenic mouse has been used extensively since its development in 1994 as a model for amyotrophic lateral sclerosis (ALS). In that time, a great many insights into the toxicity of mutant SOD1 have been gained using this and other mutant SOD transgenic mouse models. They all demonstrate a selective toxicity towards motor neurons and in some cases features of the pathology seen in the human disease. These models have two major drawbacks. Firstly the generation of robust p...

  15. Spinal canal stenosis; Spinalkanalstenose

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Boutchakova, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany)

    2014-11-15

    Spinal stenosis is a narrowing of the spinal canal by a combination of bone and soft tissues, which can lead to mechanical compression of spinal nerve roots or the dural sac. The lumbal spinal compression of these nerve roots can be symptomatic, resulting in weakness, reflex alterations, gait disturbances, bowel or bladder dysfunction, motor and sensory changes, radicular pain or atypical leg pain and neurogenic claudication. The anatomical presence of spinal canal stenosis is confirmed radiologically with computerized tomography, myelography or magnetic resonance imaging and play a decisive role in optimal patient-oriented therapy decision-making. (orig.) [German] Die Spinalkanalstenose ist eine umschriebene, knoechern-ligamentaer bedingte Einengung des Spinalkanals, die zur Kompression der Nervenwurzeln oder des Duralsacks fuehren kann. Die lumbale Spinalkanalstenose manifestiert sich klinisch als Komplex aus Rueckenschmerzen sowie sensiblen und motorischen neurologischen Ausfaellen, die in der Regel belastungsabhaengig sind (Claudicatio spinalis). Die bildgebende Diagnostik mittels Magnetresonanztomographie, Computertomographie und Myelographie spielt eine entscheidende Rolle bei der optimalen patientenbezogenen Therapieentscheidung. (orig.)

  16. Adult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury

    OpenAIRE

    Neirinckx, Virginie; Agirman, Gulistan; Coste, Cécile; Marquet, Alice; Dion, Valérie; Rogister, Bernard; Franzen, Rachelle; Wislet, Sabine

    2015-01-01

    Introduction Stem cells from adult tissues were considered for a long time as promising tools for regenerative therapy of neurological diseases, including spinal cord injuries (SCI). Indeed, mesenchymal (MSCs) and neural crest stem cells (NCSCs) together constitute the bone marrow stromal stem cells (BMSCs) that were used as therapeutic options in various models of experimental SCI. However, as clinical approaches remained disappointing, we thought that reducing BMSC heterogeneity should be a...

  17. Neuroprotective Effect of Non-viral Gene Therapy Treatment Based on Tetanus Toxin C-fragment in a Severe Mouse Model of Spinal Muscular Atrophy

    Science.gov (United States)

    Oliván, Sara; Calvo, Ana C.; Rando, Amaya; Herrando-Grabulosa, Mireia; Manzano, Raquel; Zaragoza, Pilar; Tizzano, Eduardo F.; Aquilera, Jose; Osta, Rosario

    2016-01-01

    Spinal muscular atrophy (SMA) is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN) protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC), which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons “in vitro” and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3, and p62) and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild-type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln), TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease. PMID:27605908

  18. Axotomy of tributaries of the pelvic and pudendal nerves induces changes in the neurochemistry of mouse dorsal root ganglion neurons and the spinal cord.

    Science.gov (United States)

    McCarthy, Carly J; Tomasella, Eugenia; Malet, Mariana; Seroogy, Kim B; Hökfelt, Tomas; Villar, Marcelo J; Gebhart, G F; Brumovsky, Pablo R

    2016-05-01

    Using immunohistochemical techniques, we characterized changes in the expression of several neurochemical markers in lumbar 4-sacral 2 (L4-S2) dorsal root ganglion (DRG) neuron profiles (NPs) and the spinal cord of BALB/c mice after axotomy of the L6 and S1 spinal nerves, major tributaries of the pelvic (targeting pelvic visceral organs) and pudendal (targeting perineum and genitalia) nerves. Sham animals were included. Expression of cyclic AMP-dependent transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine hydroxylase (TH) and vesicular glutamate transporters (VGLUT) types 1 and -2 was analysed seven days after injury. L6-S1 axotomy induced dramatic de novo expression of ATF3 in many L6-S1 DRG NPs, and parallel significant downregulations in the percentage of CGRP-, TRPV1-, TH- and VGLUT2-immunoreactive (IR) DRG NPs, as compared to their expression in uninjured DRGs (contralateral L6-S1-AXO; sham mice); VGLUT1 expression remained unaltered. Sham L6-S1 DRGs only showed a small ipsilateral increase in ATF3-IR NPs (other markers were unchanged). L6-S1-AXO induced de novo expression of ATF3 in several lumbosacral spinal cord motoneurons and parasympathetic preganglionic neurons; in sham mice the effect was limited to a few motoneurons. Finally, a moderate decrease in CGRP- and TRPV1-like-immunoreactivities was observed in the ipsilateral superficial dorsal horn neuropil. In conclusion, injury of a mixed visceral/non-visceral nerve leads to considerable neurochemical alterations in DRGs matched, to some extent, in the spinal cord. Changes in these and potentially other nociception-related molecules could contribute to pain due to injury of nerves in the abdominopelvic cavity. PMID:25749859

  19. Identification and quantification of neuropeptides in naïve mouse spinal cord using mass spectrometry reveals [des-Ser1]-cerebellin as a novel modulator of nociception.

    Science.gov (United States)

    Su, Jie; Sandor, Katalin; Sköld, Karl; Hökfelt, Tomas; Svensson, Camilla I; Kultima, Kim

    2014-07-01

    Neuropeptide transmitters involved in nociceptive processes are more likely to be expressed in the dorsal than the ventral horn of the spinal cord. This study was designed to examine the relative distribution of neuropeptides between the dorsal and ventral spinal cord in naïve mice using liquid chromatography, high-resolution mass spectrometry. We identified and relatively quantified 36 well-characterized full-length neuropeptides and an additional 168 not previously characterized peptides. By extraction with organic solvents we identified seven additional full-length neuropeptides. The peptide [des-Ser1]-cerebellin (desCER), originating from cerebellin precursor protein 1 (CBLN1), was predominantly expressed in the dorsal horn. Immunohistochemistry showed the presence of CBLN1 immunoreactivity with a punctate cytoplasmic pattern in neuronal cell bodies throughout the spinal gray matter. The signal was stronger in the dorsal compared to the ventral horn, with most CBLN1 positive cells present in outer laminae II/III, colocalizing with calbindin, a marker for excitatory interneurons. Intrathecal injection of desCER induced a dose-dependent mechanical hypersensitivity but not heat or cold hypersensitivity. This study provides evidence for involvement of desCER in nociception and provides a platform for continued exploration of involvement of novel neuropeptides in the regulation of nociceptive transmission. Neuropeptides involved in nociceptive processes are more likely to be expressed in the dorsal than the ventral horn of spinal cord. Well-characterized full-length neuropeptides as well as uncharacterized neuropeptides were quantified by mass spectrometry. The CBLN1-derived peptide [des-Ser1]-cerebellin (desCER) is predominantly expressed in the dorsal horn, and intrathecal injection of desCER induced a dose-dependent mechanical hypersensitivity.

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

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

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

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

    Science.gov (United States)

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

    2014-06-15

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

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

    Science.gov (United States)

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

    2011-08-15

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

  3. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Injury Psychological Issues After Spinal Cord Injury Psychological Health After Spinal Cord Injury Psychological Health After Spinal Cord Injury The Psychologist's Role After ...

  4. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury Psychological Realities After Spinal Cord Injury Psychology of Spinal Cord Injury Rehabilitation Psychology of Spinal Cord Injury Rehabilitation How Psychologists Help ...

  5. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury Psychological Realities after Spinal Cord Injury Psychology of Spinal Cord Injury Rehabilitation Psychology of Spinal Cord Injury Rehabilitation How Psychologists Help ...

  6. Early detection of motor dysfunction in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis (ALS using home cage running wheels.

    Directory of Open Access Journals (Sweden)

    Ellen J Bennett

    Full Text Available The SOD1G93A mouse has been used since 1994 for preclinical testing in amyotrophic lateral sclerosis (ALS. Despite recent genetic advances in our understanding of ALS, transgenic mice expressing mutant SOD1 remain the best available, and most widely used, vertebrate model of the disease. We previously described an optimised and rapid approach for preclinical studies in the SOD1G93A mouse. Here we describe improvements to this approach using home cage running wheels to obtain daily measurements of motor function, with minimal intervention. We show that home cage running wheels detect reductions in motor function at a similar time to the rotarod test, and that the data obtained are less variable allowing the use of smaller groups of animals to obtain satisfactory results. This approach refines use of the SOD1G93A model, and reduces the number of animals undergoing procedures of substantial severity, two central principles of the 3Rs (replacement, reduction and refinement of animal use in research. The small group sizes and rapid timescales enable affordable large-scale therapeutic pre-screening in the SOD1G93A mouse, as well as rapid validation of published positive effects in a second laboratory, one of the major stumbling blocks in ALS preclinical therapy development.

  7. Spinal Hemangiomas

    Directory of Open Access Journals (Sweden)

    I.A. Norkin

    2010-06-01

    Full Text Available The given article considers the modern view on etiology, pathogenesis, classifications, clinical picture, diagnosis and treatment of spinal hemangiomas. Advantages of vertebroplasty over the other techniques of treatment of studied pathology are presented

  8. Spinal stenosis

    Science.gov (United States)

    ... make some changes in their activities or work. Spine surgery will often partly or fully relieve symptoms in ... disease of the bone Spinal fusion Patient Instructions Spine surgery - discharge Update Date 7/13/2015 Updated by: ...

  9. Spinal cysticercosis

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Desirée L Salazar

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

  11. Spinal vascular malformations; Spinale Gefaessmalformationen

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, U. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2012-05-15

    Spinal vascular malformations are a group of rare diseases with different clinical presentations ranging from incidental asymptomatic findings to progressive tetraplegia. This article provides an overview about imaging features as well as clinical and therapeutic aspects of spinal arteriovenous malformations, cavernomas and capillary telangiectasia. (orig.) [German] Spinale Gefaessmalformationen sind eine Gruppe seltener Erkrankungen mit unterschiedlichen klinischen Praesentationen, die vom asymptomatischen Zufallsbefund bis zur progredienten Tetraparese reichen. Dieser Artikel gibt einen Ueberblick ueber radiologische Befunde sowie klinische und therapeutische Aspekte von spinalen arteriovenoesen Malformationen, Kavernomen und kapillaeren Teleangiektasien. (orig.)

  12. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Substance Abuse and Spinal Cord Injury How Family Life Changes After Spinal Cord Injury How Family Life Changes After Spinal Cord Injury Empowering the Patient After Spinal ...

  13. RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns

    DEFF Research Database (Denmark)

    Doktor, Thomas Koed; Hua, Yimin; Andersen, Henriette Skovgaard;

    2016-01-01

    unknown. It is likely that aberrant splicing of genes expressed in motor neurons is involved in SMA pathogenesis, but increasing evidence indicates that pathologies also exist in other tissues. We present here a comprehensive RNA-seq study that covers multiple tissues in an SMA mouse model. We show...... are reversed. Finally, we report on missplicing of several Ca(2+) channel genes that may explain disrupted Ca(2+) homeostasis in SMA and activation of Cdk5....

  14. Perinatal modification of a sexually dimorphic motor nucleus in the spinal cord of the B6D2F1 house mouse.

    Science.gov (United States)

    Wagner, C K; Clemens, L G

    1989-04-01

    The sexually dimorphic dorsomedial nucleus (DM) of the spinal cord of mice is affected by gonadal steroids in adulthood and these effects are dependent upon genotype. Following castration of adult mice there is a decrease in DM cell size in DBA/2J and hybrid B6D2F1 strains and a decrease in the number of cells staining with thionin in C57B1/6J and B6D2F1 strains. The effects of androgens on development of the DM nucleus were examined in B6D2F1 mice, which exhibit both characteristics in adulthood. Testosterone propionate (TP) administered to females pre- or postnatally resulted in a significantly larger number of motoneurons in the region of the DM when compared to administration of the vehicle alone, while soma area remained unchanged. Adult males castrated on the day of birth had significantly fewer cells in the DM than did intact males. Differences in cell size between shams and castrates were dependent upon age. PMID:2780856

  15. Metabolic Therapy with Deanna Protocol Supplementation Delays Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model

    OpenAIRE

    Ari, Csilla; Poff, Angela M.; Held, Heather E.; Landon, Carol S.; Goldhagen, Craig R.; Mavromates, Nicholas; D’Agostino, Dominic P.

    2014-01-01

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic t...

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available Experts \\ Spinal Cord Injury 101 Topics Adult Injuries Spinal Cord Injury 101 Spinal Cord Injury 101 The Basics of Spinal Cord Injury Rehabilitation ... in countries outside the US ? A spinal cord injury affects the entire family FacingDisability is designed to ...

  17. RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns

    DEFF Research Database (Denmark)

    Doktor, Thomas Koed; Hua, Yimin; Andersen, Henriette Skovgaard;

    2016-01-01

    unknown. It is likely that aberrant splicing of genes expressed in motor neurons is involved in SMA pathogenesis, but increasing evidence indicates that pathologies also exist in other tissues. We present here a comprehensive RNA-seq study that covers multiple tissues in an SMA mouse model. We show...... is correlated with decreased snRNP assembly activity. In particular, the minor spliceosomal snRNPs are affected, and some U12-dependent introns have been reported to be aberrantly spliced in patient cells and animal models. SMA is characterized by loss of motor neurons, but the underlying mechanism is largely...... are reversed. Finally, we report on missplicing of several Ca(2+) channel genes that may explain disrupted Ca(2+) homeostasis in SMA and activation of Cdk5....

  18. Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse

    Directory of Open Access Journals (Sweden)

    Mark S. Nash

    2013-09-01

    Full Text Available CVD (cardiovascular disease represents a leading cause of mortality in chronic SCI (spinal cord injury. Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immuno-histochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin and increased NPY (neuropeptide-Y expression in the hypothalamic ARC (arcuate nucleus and PVN (paraventricular nucleus, 1-month post-SCI. Long-form leptin receptor (Ob-Rb, JAK2 (Janus kinase/STAT3 (signal transducer and activator of transcription 3/p38 and RhoA/ROCK (Rho-associated kinase signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3 inflammasome in VAT (visceral adipose tissue and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

  19. Toward a Broader View of Ube3a in a Mouse Model of Angelman Syndrome: Expression in Brain, Spinal Cord, Sciatic Nerve and Glial Cells.

    Directory of Open Access Journals (Sweden)

    Mark D Grier

    Full Text Available Angelman Syndrome (AS is a devastating neurodevelopmental disorder characterized by developmental delay, speech impairment, movement disorder, sleep disorders and refractory epilepsy. AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene. Ube3a is expressed nearly exclusively from the maternal chromosome in mature neurons. While imprinting in neurons of the brain has been well described, the imprinting and expression of Ube3a in other neural tissues remains relatively unexplored. Moreover, given the overwhelming deficits in brain function in AS patients, the possibility of disrupted Ube3a expression in the infratentorial nervous system and its consequent disability have been largely ignored. We evaluated the imprinting status of Ube3a in the spinal cord and sciatic nerve and show that it is also imprinted in these neural tissues. Furthermore, a growing body of clinical and radiological evidence has suggested that myelin dysfunction may contribute to morbidity in many neurodevelopmental syndromes. However, findings regarding Ube3a expression in non-neuronal cells of the brain have varied. Utilizing enriched primary cultures of oligodendrocytes and astrocytes, we show that Ube3a is expressed, but not imprinted in these cell types. Unlike many other neurodevelopmental disorders, AS symptoms do not become apparent until roughly 6 to 12 months of age. To determine the temporal expression pattern and silencing, we analyzed Ube3a expression in AS mice at several time points. We confirm relaxed imprinting of Ube3a in neurons of the postnatal developing cortex, but not in structures in which neurogenesis and migration are more complete. This furthers the hypothesis that the apparently normal window of development in AS patients is supported by an incompletely silenced paternal allele in developing neurons, resulting in a relative preservation of Ube3a expression during this crucial epoch of early development.

  20. Toward a Broader View of Ube3a in a Mouse Model of Angelman Syndrome: Expression in Brain, Spinal Cord, Sciatic Nerve and Glial Cells.

    Science.gov (United States)

    Grier, Mark D; Carson, Robert P; Lagrange, Andre Hollis

    2015-01-01

    Angelman Syndrome (AS) is a devastating neurodevelopmental disorder characterized by developmental delay, speech impairment, movement disorder, sleep disorders and refractory epilepsy. AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene. Ube3a is expressed nearly exclusively from the maternal chromosome in mature neurons. While imprinting in neurons of the brain has been well described, the imprinting and expression of Ube3a in other neural tissues remains relatively unexplored. Moreover, given the overwhelming deficits in brain function in AS patients, the possibility of disrupted Ube3a expression in the infratentorial nervous system and its consequent disability have been largely ignored. We evaluated the imprinting status of Ube3a in the spinal cord and sciatic nerve and show that it is also imprinted in these neural tissues. Furthermore, a growing body of clinical and radiological evidence has suggested that myelin dysfunction may contribute to morbidity in many neurodevelopmental syndromes. However, findings regarding Ube3a expression in non-neuronal cells of the brain have varied. Utilizing enriched primary cultures of oligodendrocytes and astrocytes, we show that Ube3a is expressed, but not imprinted in these cell types. Unlike many other neurodevelopmental disorders, AS symptoms do not become apparent until roughly 6 to 12 months of age. To determine the temporal expression pattern and silencing, we analyzed Ube3a expression in AS mice at several time points. We confirm relaxed imprinting of Ube3a in neurons of the postnatal developing cortex, but not in structures in which neurogenesis and migration are more complete. This furthers the hypothesis that the apparently normal window of development in AS patients is supported by an incompletely silenced paternal allele in developing neurons, resulting in a relative preservation of Ube3a expression during this crucial epoch of early development. PMID:25894543

  1. A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS.

    Science.gov (United States)

    Hatzipetros, Theo; Kidd, Joshua D; Moreno, Andy J; Thompson, Kenneth; Gill, Alan; Vieira, Fernando G

    2015-01-01

    The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers. PMID:26485052

  2. Spinal injury - resources

    Science.gov (United States)

    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 ...

  3. Quantitative evaluation of 3D mouse behaviors and motor function in the open-field after spinal cord injury using markerless motion tracking.

    Directory of Open Access Journals (Sweden)

    Alison L Sheets

    Full Text Available Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI. Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study's goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches. Three-dimensional movements of eight naïve, five mild, five moderate, and four severe SCI mice were recorded using 10 cameras (100 Hz. Background subtraction was used in each video frame to identify the animal's silhouette, and the 3D shape at each time was reconstructed using shape-from-silhouette. The reconstructed volume was divided into front and back halves using k-means clustering. The animal's front Center of Volume (CoV height and whole-body CoV speed were calculated and used to automatically classify animal behaviors including directed locomotion, exploratory locomotion, meandering, standing, and rearing. More detailed analyses of CoV height, speed, and lateral deviation during directed locomotion revealed behavioral differences and functional impairments in animals with mild, moderate, and severe SCI when compared with naïve animals. Naïve animals displayed the widest variety of behaviors including rearing and crossing the center of the open-field, the fastest speeds, and tallest rear CoV heights. SCI reduced the range of behaviors, and decreased speed (r = .70 p<.005 and rear CoV height (r = .65 p<.01 were significantly correlated with greater lesion size. This markerless tracking approach is a first step toward fundamentally changing how rodent movement studies are conducted. By providing scientists with sensitive, quantitative

  4. Spinal Cord Contusion

    Institute of Scientific and Technical Information of China (English)

    Gong Ju; Jian Wang; Yazhou Wang; Xianghui Zhao

    2014-01-01

    Spinal cord injury is a major cause of disability with devastating neurological outcomes and lim-ited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.

  5. 本体觉传入纤维在小鼠脊髓内的发育变化%DEVELOPMENTAL ALTERNATIONS IN PROPRIOCEPTIVE AFFERENT PROJECTIONS IN THE MOUSE SPINAL CORD

    Institute of Scientific and Technical Information of China (English)

    黄静; 冯枫; 刘翔宇; 李云庆; 武胜昔

    2006-01-01

    目的观察本体觉传入纤维在小鼠脊髓内投射和终止的发育变化. 方法采用小牛白蛋白(PV)免疫组织化学染色特异标记本体觉传入纤维,用免疫荧光单标记和双标记方法观察本体觉传入纤维在脊髓内的生长模式以及与运动神经元的关系.染色后的切片用激光共聚焦显微镜进行观察. 结果PV样免疫阳性(LI)本体觉纤维最早于胚胎(E)14 d出现在后索,E15时进入脊髓灰质.E16时,已有较多的PV-LI纤维到达中间带灰质和前角(VH).此后,随着发育阶段的增长,脊髓VH内PV-LI本体觉纤维和终末的数量和密度逐渐增加,并在生后早期P0-P7达到最高水平.P14后,上述本体觉纤维和终末的数量逐渐减少.本体觉传入纤维的终末在E17时开始与脊髓VH运动神经元形成密切的接触.结论本体觉传入纤维在脊髓内的定位模式形成于小鼠胚胎后期和生后早期,本研究结果为深入理解脊髓反射运动环路的发育特点提供了依据.%Objective To observe the developmental changes of projection and termination of proprioceptive afferent fibers in the mouse spinal cord. Methods Parvalbumin (PV) immunohistochemistry was used to label the proprioceptive afferents. Single and dual immunofluorescence histochemistry were used to examine the growth pattern of proprioceptive afferents and their relationships with motoneurons in the spinal ventral horn (VH). The stained sections were observed under a confocal laserscanning microscope. Results PV-like immunoreactive (LI) proprioceptive fibers first appeared in the dorsal column on embryonic (E) day 14, then entered the gray matter on El5 and reached the intermediate gray matter and VH more obviously on E16. The number and intensity of PV-LI proprioceptive afferent fibers and punctata increased in the VH with age and reached a maximum during earlier postnatal (P) period (P0-P7). After P14, the number and intensity of proprioceptive afferents gradually

  6. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Injury 101 The Basics of Spinal Cord Injury Rehabilitation The Basics of Spinal Cord Injury Rehabilitation Preventing Pressure Sores Preventing Pressure Sores Transition from ...

  7. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Workers Help Transitions How Social Workers Help Transitions Occupational Therapy After Spinal Cord Injury Occupational Therapy After Spinal Cord Injury How Occupational Therapists Work ...

  8. Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets.

    Science.gov (United States)

    Ganley, Robert P; Iwagaki, Noboru; del Rio, Patricia; Baseer, Najma; Dickie, Allen C; Boyle, Kieran A; Polgár, Erika; Watanabe, Masahiko; Abraira, Victoria E; Zimmerman, Amanda; Riddell, John S; Todd, Andrew J

    2015-05-13

    The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to "unclassified" cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.

  9. Estudio anatómico de la transferencia de los nervios accesorio y toracodorsal al nervio cubital en el gato Anatomic study of spinal accesory and thoracodorsal nerves transfer to ulnar nerve in cats

    Directory of Open Access Journals (Sweden)

    J.R. Martínez-Méndez

    2008-09-01

    Full Text Available Las lesiones del plexo braquial son una de las patologías más graves y con mayor número de secuelas del miembro superior. En el momento actual las transferencias nerviosas se encuentran en primera línea del armamento terapéutico para reconstruir funciones proximales del miembro superior. En el estudio que presentamos se realizaron 20 transferencias nerviosas al nervio cubital del gato común, tomando bien el nervio accesorio del espinal (10 casos o bien el nervio toracodorsal (10 casos. Como grupo control se utilizó el lado contralateral al intervenido. Durante el año siguiente, se evaluó la reinervación mediante estudios electromiográficos, histológicos de nervio y músculo, así como histoquímicos de médula espinal. Tras el análisis de los resultados encontramos que las motoneuronas de ambos nervios donantes son capaces de conseguir reinervaciones parciales del territorio cubital.A brachial plexus injury is one of the most severe pathologies of the upper limb, and also has severe sequels. In the actual state of the art, nerve transfers are being used as first line of therapeutic approach in the reconstruction of proximal functions of the upper limb. In this study 20 nerve transfers were made to the ulnar nerve of the cat, using the spinal accessory nerve (10 cases or the thoracodorsal nerve (10 cases. The opposite side was used as control. During next year, reinnervation was assessed by electromyography, nerve and muscle histology and histochemical evaluation of the spinal cord. We found that motoneurons of both donor nerves are able to make partial reinervation of the ulnar nerve territory.

  10. Optimised and rapid pre-clinical screening in the SOD1(G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS.

    Directory of Open Access Journals (Sweden)

    Richard J Mead

    Full Text Available The human SOD1(G93A transgenic mouse has been used extensively since its development in 1994 as a model for amyotrophic lateral sclerosis (ALS. In that time, a great many insights into the toxicity of mutant SOD1 have been gained using this and other mutant SOD transgenic mouse models. They all demonstrate a selective toxicity towards motor neurons and in some cases features of the pathology seen in the human disease. These models have two major drawbacks. Firstly the generation of robust preclinical data in these models has been highlighted as an area for concern. Secondly, the amount of time required for a single preclinical experiment in these models (3-4 months is a hurdle to the development of new therapies. We have developed an inbred C57BL/6 mouse line from the original mixed background (SJLxC57BL/6 SOD1(G93A transgenic line and show here that the disease course is remarkably consistent and much less prone to background noise, enabling reduced numbers of mice for testing of therapeutics. Secondly we have identified very early readouts showing a large decline in motor function compared to normal mice. This loss of motor function has allowed us to develop an early, sensitive and rapid screening protocol for the initial phases of denervation of muscle fibers, observed in this model. We describe multiple, quantitative readouts of motor function that can be used to interrogate this early mechanism. Such an approach will increase throughput for reduced costs, whilst reducing the severity of the experimental procedures involved.

  11. COMBINED LITHIUM AND VALPROATE TREATMENT DELAYS DISEASE ONSET, REDUCES NEUROLOGICAL DEFICITS AND PROLONGS SURVIVAL IN AN ALS MOUSE MODEL

    OpenAIRE

    FENG, H.-L.; Leng, Y.; MA, C.-H.; Zhang, J.; Ren, M; CHUANG, D.-M.

    2008-01-01

    Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar disorder, and have been shown to have neuroprotective properties in vivo and in vitro. A recent study demonstrated that combined treatment with lithium and VPA elicits synergistic neuroprotective effects against glutamate excitotoxicity in cultured brain neurons, and the synergy involves potentiated inhibition of glycogen synthase kinase-3 (GSK-3) activity through enhanced GSK-3 serine phosphorylation (Leng et al., J ...

  12. Spinal pain

    International Nuclear Information System (INIS)

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  13. Spinal pain

    Energy Technology Data Exchange (ETDEWEB)

    Izzo, R., E-mail: roberto1766@interfree.it [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: t.popolizio1@gmail.com [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: paoladaprile@yahoo.it [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)

    2015-05-15

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  14. Spinal infections

    Energy Technology Data Exchange (ETDEWEB)

    Tali, E. Turgut E-mail: turguttali@gazi.edu.tr

    2004-05-01

    Spinal infections can be thought of as a spectrum of disease comprising spondylitis, discitis, spondylodiscitis, pyogenic facet arthropathy, epidural infections, meningitis, polyradiculopathy and myelitis. Radiological evaluations have gained importance in the diagnosis, treatment planning, treatment and treatment monitoring of the spinal infections. Conventional radiographs are usually the initial imaging study. The sensitivity and specificity of the plain radiographs are very low. The sensitivity of CT is higher while it lacks of specificity. Conventional CT has played minor role for the diagnosis of early spondylitis and disc space infection and for follow-up, researches are going on the value of MDCT. MRI is as sensitive, specific and accurate as combined nuclear medicine studies and the method of choice for the spondylitis. Low signal areas of the vertebral body, loss of definition of the end plates and interruption of the cortical continuity, destruction of the cortical margins are typical on T1WI whereas high signal of affected areas of the vertebral body and disc is typical on T2WI. Contrast is mandatory and increases conspicuity, specificity, and observer confidence in the diagnosis and facilitates the treatment planning. Contrast enhancement is the earliest sign and pathognomonic in the acute inflammatory episode and even in the subtle infection then persists to a varying degree for several weeks or months. The outcome of the treatment is influenced by the type of infection and by the degree of neurologic compromise before treatment. There is an increasing move away from surgical intervention towards conservative therapy, percutaneous drainage of abscess or both. It is therefore critical to monitor treatment response, particularly in the immuno-deficient population.

  15. In vitro biocorrosion of Ti-6Al-4V implant alloy by a mouse macrophage cell line.

    Science.gov (United States)

    Lin, Hsin-Yi; Bumgardner, Joel D

    2004-03-15

    Corrosion of implant alloys releasing metal ions has the potential to cause adverse tissue reactions and implant failure. We hypothesized that macrophage cells and their released reactive chemical species (RCS) affect the alloy's corrosion properties. A custom cell culture corrosion box was used to evaluate how cell culture medium, macrophage cells and RCS altered the Ti-6Al-4V corrosion behaviors in 72 h and how corrosion products affected the cells. There was no difference in the charge transfer in the presence (75.2 +/- 17.7 mC) and absence (62.3 +/- 18.8 mC) of cells. The alloy had the lowest charge transfer (28.2 +/- 4.1 mC) and metal ion release (Ti < 10 ppb, V < 2 ppb) with activated cells (releasing RCS) compared with the other two conditions. This was attributed to an enhancement of the surface oxides by RCS. Metal ion release was very low (Ti < 20 ppb, V < 10 ppb) with nonactivated cells and did not change cell morphology, viability, and NO and ATP release compared with controls. However, IL-1beta released from the activated cells and the proliferation of nonactivated cells were greater on the alloy than the controls. In summary, macrophage cells and RCS reduced the corrosion of Ti-6Al-4V alloys as hypothesized. These data are important in understanding host tissue-material interactions.

  16. Mouse adenovirus type 1 infection of macrophages

    NARCIS (Netherlands)

    Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

  17. Granulocyte colony stimulating factor attenuates inflammation in a mouse model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Giniatullina Raisa

    2011-06-01

    Full Text Available Abstract Background Granulocyte colony stimulating factor (GCSF is protective in animal models of various neurodegenerative diseases. We investigated whether pegfilgrastim, GCSF with sustained action, is protective in a mouse model of amyotrophic lateral sclerosis (ALS. ALS is a fatal neurodegenerative disease with manifestations of upper and lower motoneuron death and muscle atrophy accompanied by inflammation in the CNS and periphery. Methods Human mutant G93A superoxide dismutase (SOD1 ALS mice were treated with pegfilgrastim starting at the presymptomatic stage and continued until the end stage. After long-term pegfilgrastim treatment, the inflammation status was defined in the spinal cord and peripheral tissues including hematopoietic organs and muscle. The effect of GCSF on spinal cord neuron survival and microglia, bone marrow and spleen monocyte activation was assessed in vitro. Results Long-term pegfilgrastim treatment prolonged mutant SOD1 mice survival and attenuated both astro- and microgliosis in the spinal cord. Pegfilgrastim in SOD1 mice modulated the inflammatory cell populations in the bone marrow and spleen and reduced the production of pro-inflammatory cytokine in monocytes and microglia. The mobilization of hematopoietic stem cells into the circulation was restored back to basal level after long-term pegfilgrastim treatment in SOD1 mice while the storage of Ly6C expressing monocytes in the bone marrow and spleen remained elevated. After pegfilgrastim treatment, an increased proportion of these cells in the degenerative muscle was detected at the end stage of ALS. Conclusions GCSF attenuated inflammation in the CNS and the periphery in a mouse model of ALS and thereby delayed the progression of the disease. This mechanism of action targeting inflammation provides a new perspective of the usage of GCSF in the treatment of ALS.

  18. Melittin restores proteasome function in an animal model of ALS

    Directory of Open Access Journals (Sweden)

    Lee Sang Min

    2011-06-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1 in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation. Melittin is a 26 amino acid protein and is one of the components of bee venom which is used in traditional Chinese medicine to inhibit of cancer cell proliferation and is known to have anti-inflammatory and anti-arthritic effects. The purpose of the present study was to determine if melittin could suppress motor neuron loss and protein misfolding in the hSOD1G93A mouse, which is commonly used as a model for inherited ALS. Meltittin was injected at the 'ZuSanLi' (ST36 acupuncture point in the hSOD1G93A animal model. Melittin-treated animals showed a decrease in the number of microglia and in the expression level of phospho-p38 in the spinal cord and brainstem. Interestingly, melittin treatment in symptomatic ALS animals improved motor function and reduced the level of neuron death in the spinal cord when compared to the control group. Furthermore, we found increased of α-synuclein modifications, such as phosphorylation or nitration, in both the brainstem and spinal cord in hSOD1G93A mice. However, melittin treatment reduced α-synuclein misfolding and restored the proteasomal activity in the brainstem and spinal cord of symptomatic hSOD1G93A transgenic mice. Our research suggests a potential functional link between melittin and the inhibition of neuroinflammation in an ALS animal model.

  19. Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Cheng Alice

    2011-07-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α is a principal regulator of mitochondrial biogenesis and oxidative metabolism. Results In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α. Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord. Conclusion Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy.

  20. Spinal Cord Infarction

    Science.gov (United States)

    ... treatments Functional and Dysfunctional Spinal Circuitry: Role for Rehabilitation and Neural Prostheses Summary of NINDS New Strategies in Spinal Cord Injury workshop held June, 2000. NINDS Workshop on Re- ...

  1. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  2. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... the use of electrical stimulation for spinal cord injuries? What is "Braingate" research? What is the status of stem-cell research? How would stem-cell therapies work in the treatment of spinal cord injuries? ...

  3. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... injury? What is the "Spinal Cord Injury Model Systems" program? ... family FacingDisability is designed to provide Internet-based information and support for people with spinal cord injuries ...

  4. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Patient Partnerships How Social Workers Help Transitions How Social Workers Help Transitions Occupational Therapy After Spinal Cord Injury Occupational Therapy After Spinal Cord Injury How Occupational Therapists Work How Occupational Therapists Work Occupational Therapy Enables Daily ...

  5. Spinal Muscular Atrophy

    Science.gov (United States)

    Spinal muscular atrophy (SMA) is a genetic disease that attacks nerve cells, called motor neurons, in the spinal cord. These cells communicate with your voluntary muscles - the ones you can control, like in your ...

  6. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans

    OpenAIRE

    Angeli, Claudia A.; Edgerton, V. Reggie; Gerasimenko, Yury P.; Harkema, Susan J.

    2014-01-01

    A diagnosis of motor complete spinal cord injury carries a dim prognosis for recovery. However, Angeli et al. show that epidural stimulation of the spinal cord can modulate the spinal circuitry to enable completely paralysed individuals to voluntarily control muscles of their legs and recover intentional movement years after injury.

  7. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Coping with a New Injury Adjusting to Social Life in a Wheelchair Adjusting to Social Life in a Wheelchair Substance Abuse and Spinal Cord ... Substance Abuse and Spinal Cord Injury How Family Life Changes After Spinal Cord Injury How Family Life ...

  8. Brain and Spinal Tumors

    Science.gov (United States)

    ... 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 ...

  9. Spinal Cord Injuries

    Science.gov (United States)

    ... forth between your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... down on the nerve parts that carry signals. Spinal cord injuries can be complete or incomplete. With a complete ...

  10. Spinal Cord Diseases

    Science.gov (United States)

    ... 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 ...

  11. PD-L1 is increased in the spinal cord and infiltrating lymphocytes in experimental allergic encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    Min Li; Qi Fang; Mingyuan Wang; Xueguang Zhang; Jiandong Jiang; Bing Fu; Jiechun Chen; Qun Xue; Wanli Dong; Yanzheng Gu; Lingtao Tang; Limin Xue

    2013-01-01

    Experimental al ergic encephalomyelitis is a mouse model of human multiple sclerosis with similar pathology and pathogenesis. Th1 cells play an important role in the pathogenesis of experimental al ergic encephalomyelitis. This study determined the potential effect of programmed celldeath 1 ligand 1 in the pathogenesis of experimental al ergic encephalomyelitis induced by injecting myelin oligodendrocyte glycoprotein, complete Freund’s adjuvant and Bordetel a pertussis toxin into C57BL/6J mice. Experimental al ergic encephalomyelitis mice developed disease and showed in-flammatory changes in the central nervous system by hematoxylin-eosin staining of spinal cord pathological sections, demyelination by Luxol fast-blue staining and clinical manifestations. The expression of programmed celldeath 1 ligand 1 in mice was detected by immunohistochemistry, flow cytometry and western blot analysis. The expression of programmed celldeath 1 ligand 1 in the spinal cord and splenocytes of mice was significantly increased compared with normal mice. Our findings suggest the involvement of programmed celldeath 1 ligand 1 in the pathogenesis of expe-rimental al ergic encephalomyelitis and suggest this should be studied in multiple sclerosis.

  12. 痛温觉和本体觉传入纤维在小鼠脊髓内的不同发育特点%ALTERNATIVE DEVELOPMENT OF NOCICEPTIVE AND PROPRIOCEPTIVE AFFERENT FIBERS IN THE MOUSE SPINAL CORD

    Institute of Scientific and Technical Information of China (English)

    冯枫; 黄静; 刘翔宇; 李云庆; 武胜昔

    2006-01-01

    The present study was designed to examine the developmental changes in projection and termination of nociceptive and proprioceptive afferent fibers in the spinal cord by labeling those two fibers with calcitonion gene-related peptide (CGRP) and parvalbumin (PV)separately in mouse embryos and neonatal pups aged embryonic day 15 to posanatal day 3 (E15 -P3). CGRP-like immunoreactive (LI)nociceptive fibers first appeared in the superficial dorsal horn (DH) at E16. The afferent projections extended laterally to the DH and entered into the deep portions of the DH at E17 and E18. After birth, the projection pattern of CGRP-LI fibers remained unchanged but the intensity of afferent terminals increased in the superficial laminae and their branching patterns became more complicated. In addition,CGRP-LI collaterals that projected into the contralateral DH were also examined after E16. Around birth, the contralateral projections were also found originated from the lateral part of the DH. PV-LI proprioceptive afferents were first observed entering the gray matter at E15 and reached the intermediate gray matter (IG) and the ventral horn (VH) more obviously on E16. The number and intensity of PV-LI fibers increased in the the VH with age and reached a maximum during earlier postnatal period ( P0-P3 ). The proprioceptive terminals seemed to form close relationship with motoneurons in the VH from E17. Our results indicate that the somatotopic organization of nociceptive and proprioceptive afferents in the spinal cord both are established during the late embryonic and early postnatal stages. These results help to understand the development of the sensory transmission in more details.%本研究通过采用钙基因相关肽(CGRP)和小牛白蛋白(PV)分别标记胚胎15d(E15)到生后3d(P3)小鼠脊髓的痛温觉和本体觉两种初级传入纤维,观察了这两种纤维在小鼠脊髓内投射和终止的发育变化.结果显示:CGRP样免疫阳性(LI)纤维最早于E16出现

  13. Early gene expression changes in spinal cord from SOD1G93A Amyotrophic Lateral Sclerosis animal model

    Directory of Open Access Journals (Sweden)

    Gabriela Pintar Oliveira

    2013-11-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is an adult-onset and fast progression neurodegenerative disease that leads to the loss of motor neurons. Mechanisms of selective motor neuron loss in ALS are unknown. The early events occurring in the spinal cord that may contribute to motor neuron death are not described, neither astrocytes participation in the pre-symptomatic phases of the disease. In order to identify ALS early events, we performed a microarray analysis employing a whole mouse genome platform to evaluate the gene expression pattern of lumbar spinal cords of transgenic SOD1G93A mice and their littermate controls at pre-symptomatic ages of 40 and 80 days. Differentially expressed genes were identified by means of the Bioconductor packages Agi4x44Preprocess and limma. FunNet web based tool was used for analysis of over-represented pathways. Furthermore, immunolabeled astrocytes from 40 and 80 days old mice were submitted to laser microdissection and RNA was extracted for evaluation of a selected gene by qPCR. Statistical analysis has pointed to 492 differentially expressed genes (155 up and 337 down regulated in 40 days and 1105 (433 up and 672 down in 80 days old ALS mice. KEGG analysis demonstrated the over-represented pathways tight junction, antigen processing and presentation, oxidative phosphorylation, endocytosis, chemokine signaling pathway, ubiquitin mediated proteolysis and glutamatergic synapse at both pre-symptomatic ages. Ube2i gene expression was evaluated in astrocytes from both transgenic ages, being up regulated in 40 and 80 days astrocytes enriched samples. Our data points to important early molecular events occurring in pre-symptomatic phases of ALS in mouse model. Early SUMOylation process linked to astrocytes might account to non autonomous cell toxicity in ALS. Further studies on the signaling pathways presented here may provide new insights to better understand the events triggering motor neuron death in this devastating

  14. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands...... and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus...

  15. Spinal injury in sport

    International Nuclear Information System (INIS)

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding

  16. Spinal injury in sport

    Energy Technology Data Exchange (ETDEWEB)

    Barile, Antonio [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)]. E-mail: antonio.barile@cc.univaq.it; Limbucci, Nicola [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Splendiani, Alessandra [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Gallucci, Massimo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Masciocchi, Carlo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)

    2007-04-15

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding.

  17. International Spinal Cord Injury

    DEFF Research Database (Denmark)

    Dvorak, M F; Itshayek, E; Fehlings, M G;

    2015-01-01

    of the completion of the intervention or surgical closure; (6) Surgical procedure-open reduction, (7) Surgical procedure-direct decompression of neural elements, and (8 and 9) Surgical procedure-stabilization and fusion (spinal segment number and level). All variables are coded using numbers or characters. Each...... spinal intervention and procedure is coded (variables 1 through 7) and the spinal segment level is described (variables 8 and 9). Sample clinical cases were developed to illustrate how to complete it. CONCLUSION: The International SCI Spinal Interventions and Surgical Procedures Basic Data Set...

  18. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... US ? A spinal cord injury affects the entire family FacingDisability is designed to provide Internet-based information ... spinal cord injuries and the members of their families. Our website has more than 1,500 videos ...

  19. Spinal arteriography: a primer

    Institute of Scientific and Technical Information of China (English)

    David A KUMPE

    2005-01-01

    Spinal arteriography is an esoteric procedure that is seldom performed by peripheral interventionalists. This presentation is intended to outline some of the essential points that the interventionalist performing the procedure should be aware of, especially about spinal dural arteriovenous fistulae (SDAVF).

  20. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Adjusting to Social Life in a Wheelchair Substance Abuse and Spinal Cord Injury Substance Abuse and Spinal Cord Injury How Family Life Changes ... Patient Partnerships How Social Workers Help Transitions How Social Workers Help ... advice, recommend or endorse health care products or services, or control the information found on external websites. ...

  1. Spinal pain in adolescents

    DEFF Research Database (Denmark)

    Aartun, Ellen; Hartvigsen, Jan; Wedderkopp, Niels;

    2014-01-01

    BACKGROUND: The severity and course of spinal pain is poorly understood in adolescents. The study aimed to determine the prevalence and two-year incidence, as well as the course, frequency, and intensity of pain in the neck, mid back, and low back (spinal pain). METHODS: This study was a school...

  2. Glioblastoma with spinal seeding

    Energy Technology Data Exchange (ETDEWEB)

    Fakhrai, N.; Fazeny-Doerner, B.; Marosi, C. [Clinical Div. of Oncology, Dept. of Medicine I, Univ. of Vienna (Austria); Czech, T. [Dept. of Neurosurgery, Univ. of Vienna (Austria); Diekmann, K. [Dept. of Radiooncology, Univ. of Vienna (Austria); Birner, P.; Hainfellner, J.A. [Clinical Inst. for Neurology, Univ. of Vienna (Austria); Prayer, D. [Dept. of Neuroradiology, Univ. of Vienna (Austria)

    2004-07-01

    Background: extracranial seeding of glioblastoma multiforme (GBM) is very rare and its development depends on several factors. This case report describes two patients suffering from GBM with spinal seeding. In both cases, the anatomic localization of the primary tumor close to the cerebrospinal fluid (CSF) was the main factor for spinal seeding. Case reports: two patients with GBM and spinal seeding are presented. After diagnosis of spinal seeding, both patients were highly symptomatic from their spinal lesions. Case 1 experienced severe pain requiring opiates, and case 2 had paresis of lower limbs as well as urinary retention/incontinence. Both patients were treated with spinal radiation therapy. Nevertheless, they died 3 months after diagnosis of spinal seeding. Results: in both patients the diagnosis of spinal seeding was made at the time of cranial recurrence. Both tumors showed close contact to the CSF initially. Even though the patients underwent intensive treatment, it was not possible to keep them in a symptom-free state. Conclusion: because of short survival periods, patients deserve optimal pain management and dedicated palliative care. (orig.)

  3. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Fertility After Spinal Cord Injury Coping with a New Injury Coping with a New Injury Adjusting to Social Life in a Wheelchair ... after an injury? What are the most promising new treatments for spinal cord injuries? What are the ...

  4. Mouse Adenovirus Type 1 Infection of Macrophages

    OpenAIRE

    Ashley, Shanna L.; Welton, Amanda R.; Harwood, Kirsten M.; van Rooijen, Nico; Spindler, Katherine R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus. Here we determined the extent and functional importance of macrophage infection by MAV-1. Bone marrow-derived macrophages expressed MAV-1 mRNAs and proteins upon ex vivo infection. Adherent perito...

  5. GNX-4728, a Novel Small Molecule Drug Inhibitor of Mitochondrial Permeability Transition, is Therapeutic in a Mouse Model of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Lee J Martin

    2014-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurological disorder in humans characterized by progressive degeneration of skeletal muscle and motor neurons in spinal cord, brainstem, and cerebral cortex causing skeletal muscle paralysis, respiratory insufficiency, and death. There are no cures or effective treatments for ALS. ALS can be inherited, but most cases are not associated with a family history of the disease. Mitochondria have been implicated in the pathogenesis but definitive proof of causal mechanisms is lacking. Identification of new clinically translatable disease mechanism-based molecular targets and small molecule drug candidates are needed for ALS patients. We tested the hypothesis in an animal model that drug modulation of the mitochondrial permeability transition pore (mPTP is therapeutic in ALS. A prospective randomized placebo-controlled drug trial was done in a transgenic mouse model of ALS. We explored GNX-4728 as a therapeutic drug. GNX-4728 inhibits mPTP opening as evidenced by increased mitochondrial calcium retention capacity both in vitro and in vivo. Chronic systemic treatment of G37R-human mutant superoxide dismutase-1 (hSOD1 transgenic mice with GNX-4728 resulted in major therapeutic benefits. GNX-4728 slowed disease progression and significantly improved motor function. The survival of ALS mice was increased significantly by GNX-4728 treatment as evidence by a nearly 2-fold extension of lifespan (360 days to 750 days. GNX-4728 protected against motor neuron degeneration and mitochondrial degeneration, attenuated spinal cord inflammation, and preserved neuromuscular junction innervation in the diaphragm in ALS mice. This work demonstrates that a mPTP-acting drug has major disease-modifying efficacy in a preclinical mouse model of ALS and establishes mitochondrial calcium retention, and indirectly the mPTP, as targets for ALS drug development.

  6. Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.

  7. Hexokinase I N-terminal based peptide prevents the VDAC1-SOD1 G93A interaction and re-establishes ALS cell viability

    Science.gov (United States)

    Magrì, Andrea; Belfiore, Ramona; Reina, Simona; Tomasello, Marianna Flora; Di Rosa, Maria Carmela; Guarino, Francesca; Leggio, Loredana; De Pinto, Vito; Messina, Angela

    2016-01-01

    Superoxide Dismutase 1 mutants associate with 20–25% of familial Amyotrophic Lateral Sclerosis (ALS) cases, producing toxic aggregates on mitochondria, notably in spinal cord. The Voltage Dependent Anion Channel isoform 1 (VDAC1) in the outer mitochondrial membrane is a docking site for SOD1 G93A mutant in ALS mice and the physiological receptor of Hexokinase I (HK1), which is poorly expressed in mouse spinal cord. Our results demonstrate that HK1 competes with SOD1 G93A for binding VDAC1, suggesting that in ALS spinal cord the available HK1-binding sites could be used by SOD1 mutants for docking mitochondria, producing thus organelle dysfunction. We tested this model by studying the action of a HK1-N-terminal based peptide (NHK1). This NHK1 peptide specifically interacts with VDAC1, inhibits the SOD1 G93A binding to mitochondria and restores the viability of ALS model NSC34 cells. Altogether, our results suggest that NHK1 peptide could be developed as a therapeutic tool in ALS, predicting an effective role also in other proteinopathies. PMID:27721436

  8. Spinal cord abscess

    Science.gov (United States)

    ... abscess: Back injuries or trauma, including minor ones Boils on the skin, especially on the back or ... of spinal cord abscess. Prevention Thorough treatment of boils, tuberculosis, and other infections decreases the risk. Early ...

  9. Spinal Cord Injury 101

    Science.gov (United States)

    ... 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 101

    Medline Plus

    Full Text Available ... family FacingDisability is designed to provide Internet-based information and support for people with spinal cord injuries ... health care products or services, or control the information found on external websites. The Hill Foundation is ...

  11. Spinal Cord Injury Map

    Science.gov (United States)

    ... Videos Videos by Topic and Question Videos by Family Relationship Videos by Experts Resources The Short List Government ... Home Videos by Topic and Question Videos by Family Relationship Videos by Spinal Cord Experts Resources Forums Peer ...

  12. Spinal cord trauma

    Science.gov (United States)

    ... Oh's Intensive Care Manual . 7th ed. Philadelphia, PA: Elsevier; 2014:chap 78. Bryce TN. Spinal cord injury. ... Physical Medicine and Rehabilitation . 5th ed. Philadelphia, PA: Elsevier; 2016:chap 49. Dalzell K, Nouri A, Fehlings ...

  13. Modeling spinal cord biomechanics

    Science.gov (United States)

    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.

  14. Androgens affect muscle, motor neuron, and survival in a mouse model of SOD1-related amyotrophic lateral sclerosis.

    Science.gov (United States)

    Aggarwal, Tanya; Polanco, Maria J; Scaramuzzino, Chiara; Rocchi, Anna; Milioto, Carmelo; Emionite, Laura; Ognio, Emanuela; Sambataro, Fabio; Galbiati, Mariarita; Poletti, Angelo; Pennuto, Maria

    2014-08-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of upper and lower motor neurons and skeletal muscle atrophy. Epidemiologic and experimental evidence suggest the involvement of androgens in ALS pathogenesis, but the mechanism through which androgens modify the ALS phenotype is unknown. Here, we show that androgen ablation by surgical castration extends survival and disease duration of a transgenic mouse model of ALS expressing mutant human SOD1 (hSOD1-G93A). Furthermore, long-term treatment of orchiectomized hSOD1-G93A mice with nandrolone decanoate (ND), an anabolic androgenic steroid, worsened disease manifestations. ND treatment induced muscle fiber hypertrophy but caused motor neuron death. ND negatively affected survival, thereby dissociating skeletal muscle pathology from life span in this ALS mouse model. Interestingly, orchiectomy decreased androgen receptor levels in the spinal cord and muscle, whereas ND treatment had the opposite effect. Notably, stimulation with ND promoted the recruitment of endogenous androgen receptor into biochemical complexes that were insoluble in sodium dodecyl sulfate, a finding consistent with protein aggregation. Overall, our results shed light on the role of androgens as modifiers of ALS pathogenesis via dysregulation of androgen receptor homeostasis.

  15. Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS.

    Directory of Open Access Journals (Sweden)

    Barkha P Patel

    Full Text Available Caloric restriction (CR extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS that shows increased free radical production. To investigate the long-term CR-induced pathology in G93A mice, we assessed the mitochondrial bioenergetic efficiency and oxidative capacity (CS--citrate synthase content and activity, cytochrome c oxidase--COX activity and protein content of COX subunit-I and IV and UCP3-uncoupling protein 3, oxidative damage (MDA--malondialdehyde and PC--protein carbonyls, antioxidant enzyme capacity (Mn-SOD, Cu/Zn-SOD and catalase, inflammation (TNF-alpha, stress response (Hsp70 and markers of apoptosis (Bax, Bcl-2, caspase 9, cleaved caspase 9 in their skeletal muscle. At age 40 days, G93A mice were divided into two groups: Ad libitum (AL; n = 14; 7 females or CR (n = 13; 6 females, with a diet equal to 60% of AL. COX/CS enzyme activity was lower in CR vs. AL male quadriceps (35%, despite a 2.3-fold higher COX-IV/CS protein content. UCP3 was higher in CR vs. AL females only. MnSOD and Cu/Zn-SOD were higher in CR vs. AL mice and CR vs. AL females. MDA was higher (83% in CR vs. AL red gastrocnemius. Conversely, PC was lower in CR vs. AL red (62% and white (30% gastrocnemius. TNF-alpha was higher (52% in CR vs. AL mice and Hsp70 was lower (62% in CR vs. AL quadriceps. Bax was higher in CR vs. AL mice (41% and CR vs. AL females (52%. Catalase, Bcl-2 and caspases did not differ. We conclude that CR increases lipid peroxidation, inflammation and apoptosis, while decreasing mitochondrial bioenergetic efficiency, protein oxidation and stress response in G93A mice.

  16. Human Neural Stem Cell Replacement Therapy for Amyotrophic Lateral Sclerosis by Spinal Transplantation

    OpenAIRE

    Hefferan, Michael P.; Jan Galik; Osamu Kakinohana; Gabriela Sekerkova; Camila Santucci; Silvia Marsala; Roman Navarro; Marian Hruska-Plochan; Karl Johe; Eva Feldman; Cleveland, Don W.; Martin Marsala

    2012-01-01

    BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension ...

  17. Congenital spinal malformations; Kongenitale spinale Malformationen

    Energy Technology Data Exchange (ETDEWEB)

    Ertl-Wagner, B.B.; Reiser, M.F. [Klinikum Grosshadern, Ludwig-Maximilians-Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2001-12-01

    Congenital spinal malformations form a complex and heterogeneous group of disorders whose pathogenesis is best explained embryologically. Radiologically, it is important to formulate a diagnosis when the disorder first becomes symptomatic. However, it is also crucial to detect complications of the disorder or of the respective therapeutic interventions in the further course of the disease such as hydromyelia or re-tethering after repair of a meningomyelocele. Moreover, once a congenital spinal malformation is diagnosed, associated malformations should be sought after. A possible syndromal classification such as in OEIS- or VACTERL-syndromes should also be considered. (orig.) [German] Kongenitale spinale Malformationen stellen eine komplexe Gruppe an Stoerungen dar, deren Genese sich am einfachsten aus der Embryologie heraus erklaeren laesst. Bei der klinisch-radiologischen Begutachtung ist zunaechst ihre korrekte Klassifikation im Rahmen der Erstdiagnose wichtig. Im weiteren Verlauf ist es jedoch zudem entscheidend, moegliche Komplikationen wie beispielsweise eine Hydromyelie oder ein Wiederanheften des Myelons nach Operation einer Spina bifida aperta zu erkennen. Zudem sollte bei der Diagnosestellung einer kongenitalen spinalen Malformation immer auch auf assoziierte Fehlbildungen, wie z.B. die Diastematomyelie oder das intraspinale Lipom bei der Spina bifida aperta, sowie auf eine moegliche syndromale Einordnung wie beispielsweise beim OEIS-oder VACTERL-Syndrom geachtet werden. (orig.)

  18. The Overexpression of TDP-43 Protein in the Neuron and Oligodendrocyte Cells Causes the Progressive Motor Neuron Degeneration in the SOD1 G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Lu, Yi; Tang, Chunyan; Zhu, Lei; Li, Jiao; Liang, Huiting; Zhang, Jie; Xu, Renshi

    2016-01-01

    The recent investigation suggested that the TDP-43 protein was closely related to the motor neuron degeneration in amyotrophic lateral sclerosis (ALS), but the pathogenesis contributed to motor neuron degeneration largely remained unknown. Therefore, we detected the alteration of TDP-43 expression and distribution in the adult spinal cord of the SOD1 G93A transgenic mouse model for searching the possible pathogenesis of ALS. We examined the TDP-43 expression and distribution in the different anatomic regions, segments and neural cells in the adult spinal cord at the different stages of the SOD1 wild-type and G93A transgenic model by the fluorescent immunohistochemical technology. We revealed that the amount of TDP-43 positive cell was cervical>lumbar>thoracic segment, that in the ventral horn was more than that in the dorsal horn, a few of TDP-43 protein sparsely expressed and distributed in the other regions, the TDP-43 protein weren't detected in the white matter and the central canal. The TDP-43 protein was mostly expressed and distributed in the nuclear of neuron cells and the cytoplasm of oligodendrocyte cells of the gray matter surrounding the central canal of spinal cord by the granular shape in the SOD1 wild-type and G93A transgenic mice. The amount of TDP-43 positive cell significantly increased at the onset and progression stages of ALS following with the increase of neuron death in spinal cord, particularly in the ventral horn of cervical segment at the progression stage. Our results suggested that the overexpression of TDP-43 protein in the neuron and oligodendrocyte cell causes the progressive motor neuron degeneration in the ALS-like mouse model. PMID:27570488

  19. Randomized clinical trial comparing spinal anesthesia with local anesthesia with sedation for loop colostomy closure Ensaio clínico randomizado comparando raquianestesia com anestesia local, associadas à sedação para o fechamento de colostomia em alça

    Directory of Open Access Journals (Sweden)

    Rone Antônio Alves de Abreu

    2010-09-01

    Full Text Available CONTEXT: Recent studies have shown that local anesthesia for loop colostomy closure is as safe as spinal anesthesia for this procedure. OBJECTIVES: Randomized clinical trial to compare the results from these two techniques. METHODS: Fifty patients were randomized for loop colostomy closure using spinal anesthesia (n = 25 and using local anesthesia (n = 25. Preoperatively, the bowel was evaluated by means of colonoscopy, and bowel preparation was performed with 10% oral mannitol solution and physiological saline solution for lavage through the distal colostomy orifice. All patients were given prophylactic antibiotics (cefoxitin. Pain, analgesia, reestablishment of peristaltism or peristalsis, diet reintroduction, length of hospitalization and rehospitalization were analyzed postoperatively. RESULTS: Surgery duration and local complications were greater in the spinal anesthesia group. Conversion to general anesthesia occurred only with spinal anesthesia. There was no difference in intraoperative pain between the groups, but postoperative pain, reestablishment of peristaltism or peristalsis, diet reintroduction and length of hospitalization were lower with local anesthesia. CONCLUSIONS: Local anesthesia plus sedation offers a safer and more effective method than spinal anesthesia for loop colostomy closure.CONTEXTO: Estudos recentes têm demonstrado que a anestesia local para o fechamento de colostomia em alça é tão segura quanto a raquianestesia para estes procedimentos. OBJETIVOS: Comparar os resultados do fechamento de colostomia em alça usando essas duas técnicas. MÉTODOS: Cinquenta pacientes foram randomizados para o fechamento de colostomia em alça sob raquianestesia (n = 25 e anestesia local (n = 25. No pré-operatório, o cólon foi avaliado por colonoscopia e o preparo intestinal foi realizado com solução oral de manitol a 10% e limpeza com solução salina fisiológica através do orifício distal da colostomia. Todos os

  20. Imaging in spinal trauma

    Energy Technology Data Exchange (ETDEWEB)

    Goethem, J.W.M. van [Universitair Ziekenhuis Antwerpen, University of Antwerp, Belgium, Department of Radiology, Edegem (Belgium); Algemeen Ziekenhuis Maria Middelares, Department of Radiology, Sint-Niklaas (Belgium); Maes, Menno; Oezsarlak, Oezkan; Hauwe, Luc van den; Parizel, Paul M. [Universitair Ziekenhuis Antwerpen, University of Antwerp, Belgium, Department of Radiology, Edegem (Belgium)

    2005-03-01

    Because it may cause paralysis, injury to the spine is one of the most feared traumas, and spinal cord injury is a major cause of disability. In the USA approximately 10,000 traumatic cervical spine fractures and 4000 traumatic thoracolumbar fractures are diagnosed each year. Although the number of individuals sustaining paralysis is far less than those with moderate or severe brain injury, the socioeconomic costs are significant. Since most of the spinal trauma patients survive their injuries, almost one out of 1000 inhabitants in the USA are currently being cared for partial or complete paralysis. Little controversy exists regarding the need for accurate and emergent imaging assessment of the traumatized spine in order to evaluate spinal stability and integrity of neural elements. Because clinicians fear missing occult spine injuries, they obtain radiographs for nearly all patients who present with blunt trauma. We are influenced on one side by fear of litigation and the possible devastating medical, psychologic and financial consequences of cervical spine injury, and on the other side by pressure to reduce health care costs. A set of clinical and/or anamnestic criteria, however, can be very useful in identifying patients who have an extremely low probability of injury and who consequently have no need for imaging studies. Multidetector (or multislice) computed tomography (MDCT) is the preferred primary imaging modality in blunt spinal trauma patients who do need imaging. Not only is CT more accurate in diagnosing spinal injury, it also reduces imaging time and patient manipulation. Evidence-based research has established that MDCT improves patient outcome and saves money in comparison to plain film. This review discusses the use, advantages and disadvantages of the different imaging techniques used in spinal trauma patients and the criteria used in selecting patients who do not need imaging. Finally an overview of different types of spinal injuries is given

  1. Imaging in spinal trauma

    International Nuclear Information System (INIS)

    Because it may cause paralysis, injury to the spine is one of the most feared traumas, and spinal cord injury is a major cause of disability. In the USA approximately 10,000 traumatic cervical spine fractures and 4000 traumatic thoracolumbar fractures are diagnosed each year. Although the number of individuals sustaining paralysis is far less than those with moderate or severe brain injury, the socioeconomic costs are significant. Since most of the spinal trauma patients survive their injuries, almost one out of 1000 inhabitants in the USA are currently being cared for partial or complete paralysis. Little controversy exists regarding the need for accurate and emergent imaging assessment of the traumatized spine in order to evaluate spinal stability and integrity of neural elements. Because clinicians fear missing occult spine injuries, they obtain radiographs for nearly all patients who present with blunt trauma. We are influenced on one side by fear of litigation and the possible devastating medical, psychologic and financial consequences of cervical spine injury, and on the other side by pressure to reduce health care costs. A set of clinical and/or anamnestic criteria, however, can be very useful in identifying patients who have an extremely low probability of injury and who consequently have no need for imaging studies. Multidetector (or multislice) computed tomography (MDCT) is the preferred primary imaging modality in blunt spinal trauma patients who do need imaging. Not only is CT more accurate in diagnosing spinal injury, it also reduces imaging time and patient manipulation. Evidence-based research has established that MDCT improves patient outcome and saves money in comparison to plain film. This review discusses the use, advantages and disadvantages of the different imaging techniques used in spinal trauma patients and the criteria used in selecting patients who do not need imaging. Finally an overview of different types of spinal injuries is given

  2. Role of tumor necrosis factor-α in spinal cord in the development of mouse bone cancer pain%脊髓水平肿瘤坏死因子-α在小鼠骨癌痛发生中的作用

    Institute of Scientific and Technical Information of China (English)

    高勤; 马正良; 张娟; 周晓芳; 王俊华; 顾小萍; 夏小萍

    2009-01-01

    Objective To explore the role of tumor necrosis factor-α(TNF-α)in spinal cord in the development of mouse bone cancer pain.Methods Forty eight C3H/He mice were divided randomly into tumor group and sham group.Each group was further divided into three subgroups according to the time-points at 7 th,10th and 14 th post-inoculating day (n=8).Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of fight femur to make model of bone can-cer pain.The sham grouP was inoculated with α-MEM containing no cell.Inoculated mice were killed according to the corre-sponding time-points.Reverse transcriptive polymerase chain reaction(RT-PCR)was applied to analysis the expression of TNF -α mRNA in spinal cord.Changes in pain behaviors including paw withdrawal mechanical threshold(PWMT)and paw with-drawal thermal latencv (PWTL) were observed before inoculation and at 3 rd,5th,7th,lOth and 14th post-inoculating day.Results After inoculation,coupled with pain aggravation,mRNA of TNF-α in spinal cord of tumor mice increased at each time-point(P<0.05).Conclusion TNF-α in spinal cord may participate in bone cancer pain.%目的 探讨脊髓水平肿瘤坏死因子-α(TNF-α)在小鼠骨癌痛中的作用.方法 48只G3H/He小鼠随机分为肿瘤组和假手术组,每组再次划分为术后7 d、10 d、14 d组(n=8).将含105个纤维肉瘤NCTC 2472细胞的最小必需培养基(α-MEM)注射到小鼠右侧股骨远端骨髓腔内,制作骨癌痛模型.假手术组注入不含肿瘤细胞的a-MEM.按照分组在相应时间点处死小鼠,用RT-PCR的方法检测脊髓腰膨大TNF-αmRNA水平,观察术前、术后3 d,5 d、7 d、10 d、14 d小鼠痛行为学的变化:机械痛缩足阈值(paw withdrawal mechanical threshold,PWMT)、热痛缩足潜伏期(paw withdrawal thermal latency,PWTL)和自发性抬足次数.结果 肿瘤细胞接种后,在各观察时间点,肿瘤组脊髓水平TNF-αmRNA表达较假手术组增高(P<0.05)并伴随痛觉过敏.结论 脊髓

  3. MRI of closed spinal dysraphisms

    Energy Technology Data Exchange (ETDEWEB)

    Badve, Chaitra A.; Khanna, Paritosh C.; Phillips, Grace S.; Thapa, Mahesh M.; Ishak, Gisele E. [Seattle Children' s Hospital and University of Washington Medical Center, Department of Radiology, Seattle, WA (United States)

    2011-10-15

    We present a pictorial review of MRI features of various closed spinal dysraphisms based on previously described clinicoradiological classification of spinal dysraphisms proposed. The defining imaging features of each dysraphism type are highlighted and a diagnostic algorithm for closed spinal dysraphisms is suggested. (orig.)

  4. Spinal cord swelling and candidiasis

    Energy Technology Data Exchange (ETDEWEB)

    Ho, K.; Gronseth, G.; Aldrich, M.; Williams, A.

    1982-11-01

    Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was caused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunosuppressed cancer patient.

  5. Spinal actinomycosis: A rare disease

    Directory of Open Access Journals (Sweden)

    Dua Rakesh

    2010-01-01

    Full Text Available Actinomycosis is an indolent, slowly progressive infection caused by Actinomyces species. Of human actinomycosis, the spinal form is rare and actinomycosis-related spinal neurological deficit is uncommon. We report two cases with cervical and dorsal actinomycosis and one of them with spinal neurological deficit.

  6. Spinal cord swelling and candidiasis

    International Nuclear Information System (INIS)

    Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was cauused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunsupporessed cancer patient. (orig.)

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

    Science.gov (United States)

    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.

  8. [Spinal cord infarction].

    Science.gov (United States)

    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.

  9. Spinal leptomeningeal cysticercosis

    International Nuclear Information System (INIS)

    The spinal forms of neurocysticercosis are extremely rare, with a frequency under 1% in large series. The types of involvement are a) subarachnoid cysts and b) intramedullary lesions (less frequent). The authors report the case of a 56-year-old female with central nervous system infection by the larval form of Taenia Solium, which conduced to a hydrocephalus, treated by neurosurgical ventricular-peritoneal shunting. After 2 years, the patient consulted due to paraesthesia, spastic paraparesis and incontinence. MRI showed an homogeneous cystic mass compressing the spinal cord at D5-D6 level. Laminectomies were performed and the arachnoid membrane appeared thickened (arachnoiditis); the larval cyst was removed. Anatomo-pathologic exam revealed a leptomeningeal cysticercosis. The patient had a favorable clinical evolution without spinal compression sings or symptoms. (author)

  10. Congenital spinal malformations

    International Nuclear Information System (INIS)

    Congenital spinal malformations form a complex and heterogeneous group of disorders whose pathogenesis is best explained embryologically. Radiologically, it is important to formulate a diagnosis when the disorder first becomes symptomatic. However, it is also crucial to detect complications of the disorder or of the respective therapeutic interventions in the further course of the disease such as hydromyelia or re-tethering after repair of a meningomyelocele. Moreover, once a congenital spinal malformation is diagnosed, associated malformations should be sought after. A possible syndromal classification such as in OEIS- or VACTERL-syndromes should also be considered. (orig.)

  11. Spinal Neurocysticercosis: Case Report

    International Nuclear Information System (INIS)

    Neurocysticercosis (NCC) is the most frequent parasitic illness of the central nervous system caused by the larval form of Taenia solium and its considered to be endemic in Latin America. Its diagnosis is based on imaging findings and epidemiological data; although its diagnosis can be made through the detection of specific IgG antibodies, these tests have limited availability in our environment. Central nervous system involvement is generally observed in the brain parenchyma, and less commonly in the ventricular system and subarachnoid space; only infrequently is reported to involve the structures within the spinal canal, in this article we review a case of a patient with spinal cysticercal involvement.

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

    Directory of Open Access Journals (Sweden)

    Adam R Ferguson

    2012-10-01

    Full Text Available 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. The 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 with certain patterns of activity, 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. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. 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 spinal cord injury. We review these basic phenomena, discuss the cellular and molecular mechanisms, and discuss implications of these findings for improved rehabilitative therapies after spinal cord injury.

  13. Retinoic Acid Signaling during Early Spinal Cord Development

    OpenAIRE

    Ruth Diez del Corral; Morales, Aixa V

    2014-01-01

    Retinoic acid signaling is required at several steps during the development of the spinal cord, from the specification of generic properties to the final acquisition of neuronal subtype identities, including its role in trunk neural crest development. These functions are associated with the production of retinoic acid in specific tissues and are highly dependent on context. Here, we review the defects associated with retinoic acid signaling manipulations, mostly in chick and mouse models, tr...

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... 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 ...

  15. Spinal computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sartor, K.

    1980-10-01

    Computed tomography (CT) of the spine and spinal cord is gaining more and more importance as a valuable investigative method in neuroradiology. Performed as a noninvasive procedure, with or without intravenous contrast enhancement, it can be used to diagnose paravertebral soft tissue lesions, constrictive lesions of the bony spinal canal, structure changes of the vertebral column or of individual vertebrae, vascular intraspinal lesions, and intraspinal tumors with abnormally high or abnormally low attenuation values. Performed as an invasive procedure, after intrathecal introduction of metrizamide, spinal CT can in selected cases be used in conjunction with conventional metrizamide myelography as an additional procedure (secondary CT-myelography) or even as initial procedure ( primary CT-myelography), taking advantage of its unique properties, namely to provide a transverse axial image of the spine and related soft tissue structures and to detect even small differences in density. Further improvement of spinal CT, particularly the routine non-invasive demonstration of the intraspinal soft tissues, is to be expected.

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Home Videos by Topic and Question Videos by Family Relationship Videos by Spinal Cord Experts Resources Forums Peer Counseling Blog About Us Contact Donate Sitemap Privacy ... © 2011 – 2016 Hill Foundation for Families Living With Disabilities FacingDisability.com is an informational ...

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Home Videos by Topic and Question Videos by Family Relationship Videos by Spinal Cord Experts Resources Forums Peer Counseling Blog About Us Contact Donate Sitemap Privacy Statement Terms of Use © 2011 – 2016 Hill Foundation for Families Living With Disabilities FacingDisability.com is an informational ...

  18. Spinal Cord Injury

    Science.gov (United States)

    ... 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. ...

  19. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... 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 ...

  20. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tesla, Rachel; Wolf, Hamilton Parker; Xu, Pin; Drawbridge, Jordan; Estill, Sandi Jo; Huntington, Paula; McDaniel, Latisha; Knobbe, Whitney; Burket, Aaron; Tran, Stephanie; Starwalt, Ruth; Morlock, Lorraine; Naidoo, Jacinth; Williams, Noelle S; Ready, Joseph M; McKnight, Steven L; Pieper, Andrew A

    2012-10-16

    We previously reported the discovery of P7C3, an aminopropyl carbazole having proneurogenic and neuroprotective properties in newborn neural precursor cells of the hippocampal dentate gyrus. We have further found that chemicals having efficacy in this in vivo screening assay also protect dopaminergic neurons of the substantia nigra following exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a mouse model of Parkinson disease. Here, we provide evidence that an active analog of P7C3, known as P7C3A20, protects ventral horn spinal cord motor neurons from cell death in the G93A-SOD1 mutant mouse model of amyotrophic lateral sclerosis (ALS). P7C3A20 is efficacious in this model when administered at disease onset, and protection from cell death correlates with preservation of motor function in assays of walking gait and in the accelerating rotarod test. The prototypical member of this series, P7C3, delays disease progression in G93A-SOD1 mice when administration is initiated substantially earlier than the expected time of symptom onset. Dimebon, an antihistaminergic drug with significantly weaker proneurogenic and neuroprotective efficacy than P7C3, confers no protection in this ALS model. We propose that the chemical scaffold represented by P7C3 and P7C3A20 may provide a basis for the discovery and optimization of pharmacologic agents for the treatment of ALS.

  1. Spontaneous Functional Recovery from Incomplete Spinal Cord Injury

    DEFF Research Database (Denmark)

    Rasmussen, Rune; Carlsen, Eva Maria Meier

    2016-01-01

    Our interactions with the world occur via precise coordination of our motor system. Even a movement as seemingly simple as reaching for an object is a complex motor behavior that requires precise neuronal activity in supraspinal areas (Lemon, 2008) and spinal areas (Azim et al., 2014). Motor...

  2. Spinal Cord Injury: Facts and Figures at a Glance

    Science.gov (United States)

    ... 1,517,806 $1,071,309 Data Source: Economic Impact of SCI published in the journal Topics in Spinal Cord Injury Rehabilitation Volume 16 ... South, SRC 515, Birmingham, AL 35233-7330 For Statistics: (205) 934-3342; For Business: (205) 934-3320; TDD: (205) 934-4642; FAX: ( ...

  3. 骨癌痛小鼠脊髓水平CREB转录共激活因子1表达的变化%Changes in the expression of CREB-regulated transcription coactivator 1 in spinal cord in mouse model of bone cancer pain

    Institute of Scientific and Technical Information of China (English)

    杨许丽; 刘玥; 侯百灵; 刘明; 夏天娇; 孙蓓; 张羽; 冷鑫; 石林玉

    2014-01-01

    Objective To investigate the changes in the expression of CREB-regulated transcription coactivator 1 (CRTC1) in spinal cord during the development and maintenance of bone cancer pain in mice.Methods Forty six male C3H/HeJ mice were randomly divided into Sham group (n=23) and Tumor group (n=23).The mouse model of bone cancer pain was developed by intra-femur inoculation of α-minimal essence media (α-MEM) with osteolytic NCTC 2472 cells.The mice in sham group were inoculated with α-MEM without NCTC 2472 cells.Pain behaviors such as the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF) were assessed on 1 d before inoculation and on 4 d,7 d,10 d,14 d,21 d after inoculation.At each corresponding time point,three mice of each group were killed just after the pain behaviors assessment and the samples of spinal cord lumbar segment were obtained to detect the expression of CRTC1 using Western Blot.Results Compared with Sham group,PWMT((1.35±0.14) g,(1.10±0.28) g,(0.78±0.25) g,(0.47±0.16) g,(0.34±0.16)g) was significantly decreased (P<0.05) and NSF((3.12±0.74),(6.02±0.67),(7.42± 1.22),(10.824±0.98),(12.48±1.06)) was significantly increased (P<0.05) on 7 d,10 d,14 d and 21 d aftcr inoculation in Tumor group.Compared with baseline level,significant increase in the expression of CRTC1 in spinal cord was observed on 4 d in both Sham group and Tumor group (P<0.05).Compared with baseline level and Sham group,significant increase in the expression of CRTC1 in spinal cord was observed on 7 d,10 d,14 d and 21 d in Tumor group (P<0.05).Conclusion Expression of CRTC1 in spinal cord is up-regulated in mice with bone cancer pain,and this change may be involved in the development and maintenance of bone cancer pain.%目的 探讨骨癌痛小鼠脊髓水平CREB转录共激活因子1(CRTC1)表达的变化.方法 采用随机数字表法,46只C3H/HeJ雄性小鼠随机分为假手术组(Sham组,n=23)和肿瘤组(Tumor组,n=23),Tumor

  4. Differential diagnoses of spinal tumors; Differenzialdiagnose spinaler Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, U. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2011-12-15

    A wide variety of degenerative, inflammatory and vascular diseases can resemble the clinical presentation and imaging findings of spinal tumors. This article provides an overview of the most frequent diseases which are important to recognize for diagnostic imaging of the spine. (orig.) [German] Eine Vielzahl degenerativer, entzuendlicher und vaskulaerer Erkrankungen kann das klinische Bild und radiologische Befunde spinaler Tumoren imitieren. Dieser Artikel dient der Uebersicht ueber die haeufigsten dieser Erkrankungen, deren Kenntnis wichtig fuer die spinale Bildgebung ist. (orig.)

  5. Spinal trauma in children

    International Nuclear Information System (INIS)

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

  6. Primary spinal epidural lymphomas

    Directory of Open Access Journals (Sweden)

    Goutham Cugati

    2011-01-01

    Full Text Available An epidural location for lymphoma is observed in 0.1-6.5% of all the lymphomas. Primary spinal epidural lymphoma (PSEL is a subset of lymphomas, where there are no other recognizable sites of lymphomas at the time of diagnosis. The incidence of this subset of lymphomas is much less. It, however, is increasingly diagnosed, due to the increased use of more sensitive imaging modalities. For the electronic search, Pubmed was used to identify journals that enlisted and enumerated PSEL from 1961 to January 2011. The following combination of terms: "primary," "spinal," "epidural," and "lymphoma" were used. The most significant articles and their bibliographies were analyzed by the authors. The symptoms, pathogenesis, diagnostic workup, histopathology, treatment, and outcome have been analyzed in a systematic manner

  7. Spinal trauma in children

    Energy Technology Data Exchange (ETDEWEB)

    Roche, C.; Carty, H. [Radiology Dept., Royal Liverpool Children' s NHS Trust-Alder Hey (United Kingdom)

    2001-10-01

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

  8. A comprehensive assessment of the SOD1G93A low-copy transgenic mouse, which models human amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Abraham Acevedo-Arozena

    2011-09-01

    Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disorder that results in the death of motor neurons in the brain and spinal cord. The disorder generally strikes in mid-life, relentlessly leading to paralysis and death, typically 3–5 years after diagnosis. No effective treatments are available. Up to 10% of ALS is familial, usually autosomal dominant. Several causative genes are known and, of these, mutant superoxide dismutase 1 (SOD1 is by far the most frequently found, accounting for up to 20% of familial ALS. A range of human mutant SOD1 transgenic mouse strains has been produced, and these largely successfully model the human disease. Of these, the most widely used is the SOD1 mouse, which expresses a human SOD1 transgene with a causative G93A mutation. This mouse model is excellent for many purposes but carries up to 25 copies of the transgene and produces a great excess of SOD1 protein, which might affect our interpretation of disease processes. A variant of this strain carries a deletion of the transgene array such that the copy number is dropped to eight to ten mutant SOD1 genes. This ‘deleted’ ‘low-copy’ mouse undergoes a slower course of disease, over many months. Here we have carried out a comprehensive analysis of phenotype, including nerve and muscle physiology and histology, to add to our knowledge of this ‘deleted’ strain and give baseline data for future studies. We find differences in phenotype that arise from genetic background and sex, and we quantify the loss of nerve and muscle function over time. The slowly progressive pathology observed in this mouse strain could provide us with a more appropriate model for studying early-stage pathological processes in ALS and aid the development of therapies for early-stage treatments.

  9. Imaging of Spinal Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Lubdha M. Shah

    2011-01-01

    Full Text Available Metastases to the spine can involve the bone, epidural space, leptomeninges, and spinal cord. The spine is the third most common site for metastatic disease, following the lung and the liver. Approximately 60–70% of patients with systemic cancer will have spinal metastasis. Materials/Methods. This is a review of the imaging techniques and typical imaging appearances of spinal metastatic disease. Conclusions. Awareness of the different manifestations of spinal metastatic disease is essential as the spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT best delineates osseous integrity, while MRI is better at assessing soft tissue involvement. Physiologic properties, particularly in treated disease, can be evaluated with other imaging modalities such as FDG PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease.

  10. Transverse myelitis following spinal anesthesia

    Directory of Open Access Journals (Sweden)

    Jha Sanjeev

    2006-01-01

    Full Text Available Spinal anesthesia is widely used during surgical procedures. It is generally safe and the frequency of severe, permanent neurological complications associated with it has been reported to be extremely low. We report a patient, who developed paraplegia following spinal anesthesia. A 29-year-old male was referred with acute, flaccid, sensory motor paraplegia, with bladder and bowel involvement. He developed this immediately after an operation for inguinal hernia under spinal anesthesia. Spinal magnetic resonance imaging revealed hemorrhagic myelitis in the conus at D12. He was referred after he did not respond to intravenous methylprednisolone for 10 days. This case brings up the difficulty encountered in determination of the interspace used for spinal anesthesia and the potential for traumatic injury to the spinal cord. It also demonstrates the tragic outcome after a clinician violates some important, standard and established guidelines.

  11. Spinal brucellosis: a review

    Energy Technology Data Exchange (ETDEWEB)

    Chelli Bouaziz, Mouna; Ladeb, Mohamed Fethi; Chakroun, Mohamed; Chaabane, Skander [Institut M T Kassab d' orthopedie, Department of Radiology, Ksar Said (Tunisia)

    2008-09-15

    Brucellosis is a zoonosis of worldwide distribution, relatively frequent in Mediterranean countries and in the Middle East. It is a systemic infection, caused by facultative intra-cellular bacteria of the genus Brucella, that can involve many organs and tissues. The spine is the most common site of musculoskeletal involvement, followed by the sacroiliac joints. The aim of this study was to assess the clinical, biological and imaging features of spinal brucellosis. (orig.)

  12. Spinal brucellosis: a review

    International Nuclear Information System (INIS)

    Brucellosis is a zoonosis of worldwide distribution, relatively frequent in Mediterranean countries and in the Middle East. It is a systemic infection, caused by facultative intra-cellular bacteria of the genus Brucella, that can involve many organs and tissues. The spine is the most common site of musculoskeletal involvement, followed by the sacroiliac joints. The aim of this study was to assess the clinical, biological and imaging features of spinal brucellosis. (orig.)

  13. Infections in spinal instrumentation

    OpenAIRE

    Gerometta, Antoine; Olaverri, Juan Carlos Rodriguez; Bitan, Fabian

    2012-01-01

    Surgical-site infection (SSI ) in the spine is a serious postoperative complication. Factors such as posterior surgical approach, arthrodesis, use of spinal instrumentation, age, obesity, diabetes, tobacco use, operating-room environment and estimated blood loss are well established in the literature to affect the risk of infection. Infection after spine surgery with instrumentation is becoming a common pathology. The reported infection rates range from 0.7% to 11.9%, depending on the diagnos...

  14. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  15. Neurogenic bladder in spinal cord injury patients

    Directory of Open Access Journals (Sweden)

    Al Taweel W

    2015-06-01

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

  16. Increased aluminum content in the spinal cord of amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam and in the Kii Peninsula of Japan

    Energy Technology Data Exchange (ETDEWEB)

    Wakayama, Ikuro; Yoshida, Sohei [Wakayama Medical Coll. (Japan); Sasajima, Kazuhisa; Takada, Jitsuya; Yoshida, Koichi

    1994-07-01

    Aluminum content in the lumbar spinal cord of patients with amyotrophic lateral sclerosis(ALS) and Parkinsonism-dementia(PD) in the Kii Peninsula of Japan and in the island of Guam was measured using a particle induced X-ray emission analysis. We demonstrated that aluminum content was increased in the spinal cord of patients with ALS in two foci of the western Pacific, indicating aluminum to be a important factor in the process of spinal motor neuron degeneration. (author).

  17. Complications of spinal cord injury

    OpenAIRE

    Dursun, Erbil; Hamamci, Nigar; Ozbey, Aydan; Cakci, Aytul

    2004-01-01

    Spinal cord injury and its complications cause important physical, psychosocial and economical problems. The purpose of this study was to evaluate the complications resulting from spinal cord injury, to show their adverse effects on the rehabilitation program, and to make related clinicians to call attention especially to preventable complications. Sixty-two spinal cord injured patients were included in the study. All the patients were evaluated regarding age, gender, etiology, time since inj...

  18. Mouse adhalin

    DEFF Research Database (Denmark)

    Liu, L; Vachon, P H; Kuang, W;

    1997-01-01

    analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin was...... specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation in...

  19. Spinal angiography. Anatomy, technique and indications

    International Nuclear Information System (INIS)

    Spinal angiography is a diagnostic modality requiring detailed knowledge of spinal vascular anatomy. The cervical spinal cord is supplied by the vertebral arteries while segmental arteries which are preserved from fetal anatomy, supply the thoracic and lumbar regions. As spinal angiography carries the risk of paraplegia the indications have to be considered very carefully. Nevertheless, spinal angiography should be performed if there is reason to suspect a spinal vascular malformation from magnetic resonance imaging (MRI). (orig.)

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

    The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage fol owing spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Al en’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 wel recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additional y, anterior tibial muscle fibers slowly, but progressively, atrophied. Immunohistochemical staining showed that the absorbance values of calcitonin gene related pep-tide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic fibroblast 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 pep-tide 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.

  1. Sagittal Spinal Morphology in Highly Trained Adolescent Tennis Players

    Science.gov (United States)

    Muyor, José M.; Sánchez-Sánchez, Estefanía; Sanz-Rivas, David; López-Miñarro, Pedro A.

    2013-01-01

    Sports with a predominance of forward-bending and extension postures have been associated with alterations in the sagittal spinal curvatures and greater risk of spinal injury. Because, the tennis players adopt these postures, the aims of this study were: 1) to describe spinal curvatures and pelvic tilt in male and female highly trained adolescent tennis players during relaxed standing posture and with thoracic spine corrected (in prone lying on the floor); and 2) to determine the frequency of thoracic hyperkyphosis and lumbar hypo/hyper lordosis in these postures. Forty adolescent tennis players (24 male and 16 female) aged 13-18 years, participated voluntarily in this study. The Spinal Mouse system was used to measure sagittal spinal curvatures and pelvic tilt. The mean values in the relaxed standing posture were 43.83° ± 7.87° (thoracic kyphosis), - 27.58° ± 7.01° (lumbar lordosis), and 13.38° ± 5.57° (pelvic tilt) for male tennis players, respectively; and 36.13° ± 6.69° (thoracic kyphosis), - 32.69° ± 5.06° (lumbar lordosis), 20.94° ± 5.36° (pelvic tilt) for female tennis players (p tennis players showed a frequency of 62.5% and 93.8% (p = 0.032) for neutral thoracic kyphosis, and 83.3% and 93.8% (p = 0.062) in neutral lumbar lordosis, respectively. In conclusion, due to the high percentage of neutral spinal curvatures in both male and female tennis players, to practice tennis in these levels does not alter sagittal spinal morphology in the relaxed standing posture in adolescent highly trained tennis players. Key Points This study evaluated thoracic and lumbar spinal curvatures and pelvic tilt during several postures in young highly trained tennis players. Female tennis players showed statistically significant greater anterior pelvic tilt, lumbar lordosis and lower thoracic kyphosis than male tennis players. The high percentage of neutral thoracic kyphosis and lumbar lordosis posture in both groups of young tennis players in relaxed standing

  2. Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production.

    Science.gov (United States)

    McGivern, Jered V; Patitucci, Teresa N; Nord, Joshua A; Barabas, Marie-Elizabeth A; Stucky, Cheryl L; Ebert, Allison D

    2013-09-01

    Spinal muscular atrophy (SMA) is a genetic disorder caused by the deletion of the survival motor neuron 1 (SMN1) gene that leads to loss of motor neurons in the spinal cord. Although motor neurons are selectively lost during SMA pathology, selective replacement of SMN in motor neurons does not lead to full rescue in mouse models. Due to the ubiquitous expression of SMN, it is likely that other cell types besides motor neurons are affected by its disruption and therefore may contribute to disease pathology. Here we show that astrocytes in SMAΔ7 mouse spinal cord and from SMA-induced pluripotent stem cells exhibit morphological and cellular changes indicative of activation before overt motor neuron loss. Furthermore, our in vitro studies show mis-regulation of basal calcium and decreased response to adenosine triphosphate stimulation indicating abnormal astrocyte function. Together, for the first time, these data show early disruptions in astrocytes that may contribute to SMA disease pathology. PMID:23839956

  3. Complement Plays an Important Role in Spinal Cord Injury and Represents a Therapeutic Target for Improving Recovery following Trauma

    OpenAIRE

    Qiao, Fei; Atkinson, Carl; Song, Hongbin; Pannu, Ravinder; Singh, Inderjit; Tomlinson, Stephen

    2006-01-01

    Initiation of an inflammatory cascade following traumatic spinal cord injury (SCI) is thought to cause secondary injury and to adversely impact functional recovery, although the mechanisms involved are not well defined. We report on the dynamics of complement activation and deposition in the mouse spinal cord following traumatic injury, the role of complement in the development of SCI, and the characterization of a novel targeted complement inhibitor. Following traumatic injury, mice deficien...

  4. Erythropoietin attenuates the sequels of ischaemic spinal cord injury with enhanced recruitment of CD34+ cells in mice

    OpenAIRE

    Hirano, Koji; Wagner, Klaus; Mark, Peter; Pittermann, Erik; Gäbel, Ralf; Furlani, Dario; Li, Wenzhong; Vollmar, Brigitte; Yamada, Tomomi; Steinhoff, Gustav; Ma, Nan

    2012-01-01

    Abstract Erythropoietin has been shown to promote tissue regeneration after ischaemic injury in various organs. Here, we investigated whether Erythropoietin could ameliorate ischaemic spinal cord injury in the mouse and sought an underlying mechanism. Spinal cord ischaemia was developed by cross-clamping the descending thoracic aorta for 7 or 9 min. in mice. Erythropoietin (5000 IU/kg) or saline was administrated 30 min. before aortic cross-clamping. Neurological function was assessed using t...

  5. Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin.

    Science.gov (United States)

    Pivetta, Chiara; Esposito, Maria Soledad; Sigrist, Markus; Arber, Silvia

    2014-01-30

    Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement.

  6. Radiotherapy of presenile spinal osteoporosis

    International Nuclear Information System (INIS)

    Painfull conditions of presenile spinal osteoporosis may no longer respond to medication or physical therapy. Analgesic radiotherapy coupled with mild physical therapy and if necessary supported by orthopedic measures frequently results in pain relief and physical stability. Fifty-two cases of osteoporosis and osteoporotic spinal fractures illustrate how better longterm results are achieved by increasing the customary dosage and speeding up radiotherapy. (orig.)

  7. Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

    Science.gov (United States)

    Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

    2016-03-01

    Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. PMID:26754788

  8. Retraining the injured spinal cord

    Science.gov (United States)

    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.

  9. In Vivo Reprogramming for Brain and Spinal Cord Repair.

    Science.gov (United States)

    Chen, Gong; Wernig, Marius; Berninger, Benedikt; Nakafuku, Masato; Parmar, Malin; Zhang, Chun-Li

    2015-01-01

    Cell reprogramming technologies have enabled the generation of various specific cell types including neurons from readily accessible patient cells, such as skin fibroblasts, providing an intriguing novel cell source for autologous cell transplantation. However, cell transplantation faces several difficult hurdles such as cell production and purification, long-term survival, and functional integration after transplantation. Recently, in vivo reprogramming, which makes use of endogenous cells for regeneration purpose, emerged as a new approach to circumvent cell transplantation. There has been evidence for in vivo reprogramming in the mouse pancreas, heart, and brain and spinal cord with various degrees of success. This mini review summarizes the latest developments presented in the first symposium on in vivo reprogramming glial cells into functional neurons in the brain and spinal cord, held at the 2014 annual meeting of the Society for Neuroscience in Washington, DC. PMID:26730402

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

    Science.gov (United States)

    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

  11. Co-occurrence of TDP-43 mislocalization with reduced activity of an RNA editing enzyme, ADAR2, in aged mouse motor neurons.

    Science.gov (United States)

    Hideyama, Takuto; Teramoto, Sayaka; Hachiga, Kosuke; Yamashita, Takenari; Kwak, Shin

    2012-01-01

    TDP-43 pathology in spinal motor neurons is a neuropathological hallmark of sporadic amyotrophic lateral sclerosis (ALS) and has recently been shown to be closely associated with the downregulation of an RNA editing enzyme called adenosine deaminase acting on RNA 2 (ADAR2) in the motor neurons of sporadic ALS patients. Because TDP-43 pathology is found more frequently in the brains of elderly patients, we investigated the age-related changes in the TDP-43 localization and ADAR2 activity in mouse motor neurons. We found that ADAR2 was developmentally upregulated, and its mRNA expression level was progressively decreased in the spinal cords of aged mice. Motor neurons normally exhibit nuclear ADAR2 and TDP-43 immunoreactivity, whereas fast fatigable motor neurons in aged mice demonstrated a loss of ADAR2 and abnormal TDP-43 localization. Importantly, these motor neurons expressed significant amounts of the Q/R site-unedited AMPA receptor subunit 2 (GluA2) mRNA. Because expression of unedited GluA2 has been demonstrated as a lethality-causing molecular abnormality observed in the motor neurons, these results suggest that age-related decreases in ADAR2 activity play a mechanistic role in aging and serve as one of risk factors for ALS.

  12. Estudio anatómico de la transferencia de los nervios accesorio y toracodorsal al nervio cubital en el gato Anatomic study of spinal accesory and thoracodorsal nerves transfer to ulnar nerve in cats

    OpenAIRE

    J.R. Martínez-Méndez; A. Isla Guerrero; C. Pérez Conde; C Morales; C. Casado Pérez

    2008-01-01

    Las lesiones del plexo braquial son una de las patologías más graves y con mayor número de secuelas del miembro superior. En el momento actual las transferencias nerviosas se encuentran en primera línea del armamento terapéutico para reconstruir funciones proximales del miembro superior. En el estudio que presentamos se realizaron 20 transferencias nerviosas al nervio cubital del gato común, tomando bien el nervio accesorio del espinal (10 casos) o bien el nervio toracodorsal (10 casos). Como...

  13. "INTRAOPERATIVE SPINAL STIFFNESS MEASUREMENT IN MANAGEMENT OF SPINAL CANAL STENOSIS "

    Directory of Open Access Journals (Sweden)

    M. Karami

    2005-08-01

    Full Text Available In this study to determine whether spine stiffness is predictive of clinical results after lumbar spinal fusion for spinal stenosis, a total of 78 patients were measured intraoperatively with Kocher clamp manual distraction technique to determine motion segment stiffness then spinal fusion was performed for any loose segment. ‎Statistical analysis revealed that stiffness measurement correlate with clinical results of surgery. During a minimum of 2 years follow up after surgery, patients who had loose motion segment before or after decompression and were fused had the same level of satisfaction with surgical results as patients without loose segments and fusion. ‎We concluded that intraoperative spinal stiffness measurement provide a good indicator to spine fusion after lumbar canal stenosis ‎surgery.

  14. CD11d integrin blockade reduces the systemic inflammatory response syndrome after spinal cord injury

    OpenAIRE

    Bao, Feng; Brown, Arthur; Dekaban, Gregory A.; Omana, Vanessa; Weaver, Lynne C.

    2011-01-01

    Traumatic injury to the spinal cord triggers a systemic inflammatory response syndrome (SIRS), in which inflammatory cells from the circulation invade organs such as the liver, lung and kidney, leading to damage of these organs. Our previous study (Gris, et al, Exp. Neurol, 2008) demonstrated that spinal cord injury (SCI) activates circulating neutrophils that then invade the lung and kidney from 2 to 24 h after injury, increasing myeloperoxidase activity, cyclooxygenase-2 and matrix metallop...

  15. Ephrin-B3 decreases the survival of adult rat spinal cord-derived neural stem/progenitor cells in vitro and after transplantation into the injured rat spinal cord.

    Science.gov (United States)

    Fan, Xin Yan Susan; Mothe, Andrea J; Tator, Charles H

    2013-02-01

    Although transplantation of neural stem/progenitor cells (NSPC) encourages regeneration and repair after spinal cord injury (SCI), the survival of transplanted NSPC is limited. Ephrin-B3 has been shown to reduce the death of endogenous NSPC in the subventricular zone of the mouse brain without inducing uncontrolled proliferation. Due to similarities in the environment of the brain and spinal cord, we hypothesized that ephrin-B3 might reduce the death of both transplanted and endogenous spinal cord-derived NSPC. Both normal and injured (26 g clip compression) spinal cords were examined. Ephrin-B3-Fc was tested, and Fc fragments and phosphate-buffered saline (PBS) were used as controls. We found that EphA4 receptors were expressed by spinal cord-derived NSPC and expressed in the normal and injured rat spinal cord (higher expression in the latter). In vitro, ephrin-B3-Fc did not significantly reduce the survival of NSPC except at 1 μg/mL (Pinjured spinal cord compared with the infusion of PBS (Pinjured spinal cord, the infusion of either ephrin-B3-Fc or Fc fragments alone caused a 20-fold reduction in the survival of transplanted NSPC (P<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

  16. The spinal cord

    International Nuclear Information System (INIS)

    The spinal cord develops initially as an invagination of the thickened ectodermal neural plate to form the neural groove. This is then closed over by the neural folds, which fuse first in the thoracic region, then progressively rostrad and caudad to form the neural tube. The neural tube is completely formed by the fourth fetal week and is separated from the overlying ectoderm by intervening mesoderm, part of which has simultaneously segmented into somites to become the vertebral column. The cartilaginous and ossifying neural arches of the vertebral column are completely developed and fused by the third month of fetal life. The fetal spine can be detected by US by 12 weeks of gestational age

  17. Retinoic Acid Signaling during Early Spinal Cord Development

    Directory of Open Access Journals (Sweden)

    Ruth Diez del Corral

    2014-06-01

    Full Text Available Retinoic acid signaling is required at several steps during the development of the spinal cord, from the specification of generic properties to the final acquisition of neuronal subtype identities, including its role in trunk neural crest development. These functions are associated with the production of retinoic acid in specific tissues and are highly dependent on context. Here, we review the defects associated with retinoic acid signaling manipulations, mostly in chick and mouse models, trying to separate the different processes where retinoic acid signaling is involved and to highlight common features, such as its ability to promote transitions along the neuronal differentiation cascade.

  18. Depression and Spinal Cord Injury

    Science.gov (United States)

    ... of Washington-operated SCI Clinics: Harborview Medical Center Rehabilitation Medicine Clinic 325 9th Ave., Seattle WA 98104 Spinal Cord Injury Clinic nurses: 206-744-5862 University of Washington ...

  19. The City Mouse and the Country Mouse

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Once two mice (老鼠) were good friends. One lived in the city, the other lived in the country (乡村). After many years, the city mouse came to see the country mouse. The country mouse took him to his house in a field. He gave him the nicest food that he could find. The city mouse said,

  20. Radionuclide imaging of spinal infections

    Energy Technology Data Exchange (ETDEWEB)

    Gemmel, Filip [Ghent Maria-Middelares, General Hospital, Division of Nuclear Medicine, Ghent (Belgium); Medical Center Leeuwarden (MCL), Division of Nuclear Medicine, Henri Dunantweg 2, Postbus 888, Leeuwarden (Netherlands); Dumarey, Nicolas [Universite Libre de Bruxelles, Hopital Erasme, Division of Nuclear Medicine, Brussels (Belgium); Palestro, Christopher J. [Long Island Jewish Medical Center, Division of Nuclear Medicine, Long Island, NY (United States)

    2006-10-15

    The diagnosis of spinal infection, with or without implants, has been a challenge for physicians for many years. Spinal infections are now being recognised more frequently, owing to aging of the population and the increasing use of spinal-fusion surgery. The diagnosis in many cases is delayed, and this may result in permanent neurological damage or even death. Laboratory evidence of infection is variable. Conventional radiography and radionuclide bone imaging lack both sensitivity and specificity. Neither in vitro labelled leucocyte scintigraphy nor {sup 99m}Tc-anti-granulocyte antibody scintigraphy is especially useful, because of the frequency with which spinal infection presents as a non-specific photopenic area on these tests. Sequential bone/gallium imaging and {sup 67}Ga-SPECT are currently the radionuclide procedures of choice for spinal osteomyelitis, but these tests lack specificity, suffer from poor spatial resolution and require several days to complete. [{sup 18}F]Fluoro-2-deoxy-D-glucose (FDG) PET is a promising technique for diagnosing spinal infection, and has several potential advantages over conventional radionuclide tests. The study is sensitive and is completed in a single session, and image quality is superior to that obtained with single-photon emitting tracers. The specificity of FDG-PET may also be superior to that of conventional tracers because degenerative bone disease and fractures usually do not produce intense FDG uptake; moreover, spinal implants do not affect FDG imaging. However, FDG-PET images have to be read with caution in patients with instrumented spinal-fusion surgery since non-specific accumulation of FDG around the fusion material is not uncommon. In the future, PET-CT will likely provide more precise localisation of abnormalities. FDG-PET may prove to be useful for monitoring response to treatment in patients with spinal osteomyelitis. Other tracers for diagnosing spinal osteomyelitis are also under investigation, including

  1. Spinal dural arteriovenous fistulas; Spinale durale arteriovenoese Fisteln

    Energy Technology Data Exchange (ETDEWEB)

    Thron, A. [Abt. Neuroradiologie, Universitaetsklinikum der RWTH Aachen (Germany)

    2001-11-01

    The spinal dural arteriovenous fistula (SDAVF) is an important cause of a slowly progressive sensorimotor transverse lesion in mostly elderly patients. The disease affects men in 80% of the cases. Per year and per 1 Million inhabitants only 5-10 new cases of the disease have to be expected. Although rare, the serious disease should not be missed. Diagnosis can be made by MRI and spinal angiography. The result of treatment depends on early diagnosis. The arteriovenous shunt is located within the dural layer of the spinal canal. It connects branches of a radiculomeningeal artery with the veins of the spinal cord. Spinal cord supplying vessels are not primarily involved. Arterialisation of the venous part of the spinal cord circulation results in a chronic congestive myelopathy, which can well be demonstrated by MR imaging. The role of selective spinal angiography is to detect and exactly localize the site of the avshunt, which is rather difficult in some cases. Therapeutic alternatives are effective embolization of the fistula with liquid agents or surgical dysconnection. (orig.) [German] Die spinale durale arteriovenoese Fistel (SDAVF) ist eine wichtige Ursache fuer eine sich langsam, aber progredient entwickelnde Querschnittslaehmung des meist aelteren Patienten. 80% der Betroffenen sind Maenner. Die Erkrankungshaeufigkeit ist mit 5-10 Neuerkrankungen/1 Mio. Einwohner/Jahr zwar selten. Die unbehandelt ernste Prognose sowie die Tatsache, dass diese Erkrankung diagnostizierbar ist und der Erfolg der Behandlung von einer moeglichst fruehzeitigen Diagnosestellung abhaengt, machen sie jedoch zu einer wichtigen Erkrankung. Die der Erkrankung zugrundeliegende arteriovenoese Gefaessfehlverbindung ist in der Dura mater des Rueckenmarks gelegen. Ihre Ursache ist ungeklaert, sie ist vermutlich erworben wie die ihr aehnlichen arteriovenoesen Fisteln in der harten Hirnhaut des Schaedels. Im Gegensatz zu den angeborenen arteriovenoesen Gefaessmissbildungen zwischen

  2. Clinical picture of spinal tumors; Klinik spinaler Raumforderungen

    Energy Technology Data Exchange (ETDEWEB)

    Block, F. [Helios-Kliniken, Neurologische Klinik, Schwerin (Germany)

    2006-12-15

    Spinal tumors may present with symptoms such as pain and motor and sensory deficits. Sphincter dysfunction may also occur. The clinical picture depends upon the size and localization of the tumor in relation to the cross section and the height along the longitudinal axis of the spinal cord. Typical symptoms due to transverse damage of the spinal cord are complete lesion, Brown-Sequard syndrome, a lesion of the central spinal cord, and posterior cord syndrome. Tetraparesis, spastic, or flaccid paraparesis result from lesions at the cervical spine, thoracic spine, or below the first lumbar vertebral body, respectively. (orig.) Schmerzen, Paresen und Sensibilitaetsstoerungen stellen die wesentlichen und haeufigen Symptome spinaler Raumforderungen dar. Blasen- und Mastdarmstoerungen sind weitere moegliche Symptome. Ausdehnungen der Raumforderungen im Querschnitt und im Hinblick auf die Laengsachse des Rueckenmarks bestimmen das klinische Bild. Kompletter Querschnitt, Brown-Sequard-Syndrom, zentrale Rueckenmarkschaedigung und Hinterstrangsyndrom sind haeufige Auspraegungen entsprechend der Querschnittslaesion. Tetraparese, spastische oder schlaffe Paraparese resultieren aus Laesionen in Hoehe HWS, BWS bzw. unterhalb von LWK1. (orig.)

  3. Gene expression of inducible nitric oxide synthase in injured spinal cord tissue

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate gene expression of inducible nitric oxide synthase (iNOS) in injured spinal cord tissue of rats.Methods: Thirty-six adult Sprague-Dawley rats were divided randomly into six groups: a normal group and five injury groups, six animals in each group. Animals in the injury groups were killed at 2, 6, 12, 24, 48 hours after injury, respectively. A compression injury model of spinal cord was established according to Nystrom B et al, and gene expression of iNOS in spinal cord tissue was examined by means of reverse transcription polymerase chain reaction (RT-PCR).Results: Gene expression of iNOS was not detectable in normal spinal cord tissue but was seen in the injury groups. The expression was gradually up-regulated, reaching the maximum at 24 hours. The expression at 48hours began to decrease but was still significantly higher than that at 2 hours.Conclusions: iNOS is not involved in the normal physiological activities of spinal cord. Expression of iNOS is up-regulated in spinal cord tissue in response to injury and the up-regulation exists mainly in the late stage after injury. Over-expression of iNOS may contribute to the late injury of spinal cord.

  4. Wnt Signaling is Altered by Spinal Cord Neuronal Dysfunction in Amyotrophic Lateral Sclerosis Transgenic Mice

    OpenAIRE

    Yu, Li; Guan, Yingjun; Wu, Xin; Chen, Yanchun; Liu, Zhijun; Du, Hongmei; wang, xin

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive degeneration of the motor neurons in the cortex, brainstem, and spinal cord. The etiology and mechanisms of selective motor neuron loss in ALS remain unknown. Wnt signaling is involved in neurodegenerative processes but little is known about the kinetic changes in Wnt signaling during ALS progression. In this study we used transcriptional microarray analysis to examine the expression of Wnt...

  5. Spatial Elucidation of Spinal Cord Lipid- and Metabolite- Regulations in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Hanrieder, Jörg; Ewing, Andrew G.

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. We employed time of flight secondary ion mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite- regulations in post mortem human spinal cord tissue from ALS patients to investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate analysis of image and spectral data were performed on thoracic human spinal cord sections. Multivariate statistics of the image data allowed delineation of anatomical regions of interest based on their chemical identity. Spectral data extracted from these regions were compared using two different approaches for multivariate statistics, for investigating ALS related lipid and metabolite changes. The results show a significant decrease for cholesterol, triglycerides, and vitamin E in the ventral horn of ALS samples, which is presumably a consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid lysophosphatidylcholine and its fragments were increased in ALS ventral spinal cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell death. ToF-SIMS imaging is a promising approach for chemical histology and pathology for investigating the subcellular mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis.

  6. The intrathecal administration of losartan, an AT1 receptor antagonist, produces an antinociceptive effect through the inhibiton of p38 MAPK phosphorylation in the mouse formalin test.

    Science.gov (United States)

    Nemoto, Wataru; Ogata, Yoshiki; Nakagawasai, Osamu; Yaoita, Fukie; Tanado, Takeshi; Tan-No, Koichi

    2015-01-12

    We have recently reported that an intrathecal (i.t.) administration of angiotensin II (Ang II) into mice induces a nociceptive behavior accompanied by the activation of p38 MAPK signaling via AT1 receptors (Nemoto et al., 2013, Mol. Pain 9, 38). These results suggested that Ang II participates in the facilitation of nociceptive transmission in the spinal cord. In the present study, we used formalin test to examine the effect of i.t.-administered losartan, an AT1 receptor antagonist, and determine whether Ang II acts as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information. When administered i.t. 5 min before the injection of a 2% formalin solution into the plantar surface of the hindpaw, losartan (30-100 nmol) produced a dose-dependent and significant antinociceptive effect during both the first and second phases of the test. In the superficial dorsal horn of the spinal cord (laminae I and II), the fluorescence intensities for Ang II and phospho-p38 MAPK were both significantly increased on the ipsilateral side 3 min after the injection of formalin compared to saline-treated controls. Moreover, the increase of phospho-p38 MAPK fluorescence intensity was significantly inhibited by the i.t. administration of losartan (54.8 nmol) 5 min prior to formalin. These results indicate that losartan produces an antinociceptive effect through the inhibition of p38 MAPK phosphorylation in the mouse formalin test and that Ang II may act as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information.

  7. Spinal Cord Injury Model System Information Network

    Science.gov (United States)

    ... Go New to Website Managing Bowel Function After Spinal Cord Injury Resilience, Depression and Bouncing Back after SCI Getting ... the UAB-SCIMS Contact the UAB-SCIMS UAB Spinal Cord Injury Model System Newly Injured Health Daily Living Consumer ...

  8. Suicide in a spinal cord injured population

    DEFF Research Database (Denmark)

    Hartkopp, A; Brønnum-Hansen, Henrik; Seidenschnur, A M;

    1998-01-01

    To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI).......To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI)....

  9. MANAGEMENT OF LUMBAR SPINAL CANAL STENOSIS

    OpenAIRE

    Mukhergee G. S; Kiran Kumar L; Manikumar C. J

    2016-01-01

    BACKGROUND Spinal stenosis is one of the most common conditions in the elderly. It is defined as a narrowing of the spinal canal. The term stenosis is derived from the Greek word for narrow, which is “Stenos”. The first description of this condition is attributed to Antoine portal in 1803. Verbiest is credited with coining the term spinal stenosis and the associated narrowing of the spinal canal as its potential cause. [1-10] Kirkaldy–Willis subsequently described the de...

  10. Exciting innovations for the spinally injured

    OpenAIRE

    Hunt, K.J.; McLean, A.N.

    2002-01-01

    Spinal injury can be devastating, resulting, as it often does, in some paralysis and loss of sensation. Engineering plays an important role in spinal cord injury rehabilitation. Here, the authors survey current research into the uses of functional electrical stimulation to improve the quality of life of spinally injured people. Touching on the area of spinal cord repair and nerve regeneration, they also consider the question of whether technology can help paraplegics to take steps again.

  11. Radiosurgery of Spinal Meningiomas and Schwannomas

    OpenAIRE

    Kufeld, M; Wowra, B.; Muacevic, A.; Zausinger, Stefan; Tonn, Jörg-Christian

    2012-01-01

    Purpose of this study is to analyze local control, clinical symptoms and toxicity after image-guided radiosurgery of spinal meningiomas and schwannomas. Standard treatment of benign spinal lesions is microsurgical resection. While a few publications have reported about radiosurgery for benign spinal lesions, this is the first study analyzing the outcome of robotic radiosurgery for benign spinal tumors, treated exclusively with a non-invasive, fiducial free, single-fraction setup. Thirty-six p...

  12. Langerhans cell histiocytosis with multiple spinal involvement

    OpenAIRE

    Jiang, Liang; Liu, Xiao Guang; Zhong, Wo Quan; Ma, Qing Jun; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting; Liu, Zhong Jun

    2010-01-01

    To stress the clinical and radiologic presentation and treatment outcome of Langerhans cell histiocytosis (LCH) with multiple spinal involvements. A total of 42 cases with spinal LCH were reviewed in our hospital and 5 had multifocal spinal lesions. Multiple spinal LCH has been reported in 50 cases in the literature. All cases including ours were analyzed concerning age, sex, clinical and radiologic presentation, therapy and outcome. Of our five cases, three had neurological symptom, four sof...

  13. Recurrent Spinal Meningioma: A Case Report

    OpenAIRE

    Choi, Hoi Jung; Paeng, Sung Hwa; Kim, Sung Tae; Jung, Yong Tae

    2012-01-01

    Meningiomas are the second most common intradural spinal tumors accounting for 25% of all spinal tumors. Being a slow growing and invariably benign tumor, it responds favorably to surgical excision. In addition, spinal meningioma has low recurrence rates. However, we experienced a case of intradural extramedullary spinal meningioma which recurred 16 years after the initial surgery on a 64-year-old woman. She presented with progressive neurological symptoms and had a surgical history of remova...

  14. FAQs about Spinal Cord Injury (SCI)

    Science.gov (United States)

    ... of Care? Emergency Medical Services Hospital (Acute) Care Rehabilitation More FAQs about Spinal Cord Injury (SCI) If you or a loved one is ... spinal cord injury? What recovery is expected following spinal cord injury? Where is the ... on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant number 90SI5005). NIDILRR is a ...

  15. Genetics Home Reference: spinal muscular atrophy

    Science.gov (United States)

    ... accumulate and impair the normal function of motor neurons. Other types of spinal muscular atrophy that primarily affect the lower legs and feet and the lower arms and hands are caused by the dysfunction of neurons in the spinal cord. When spinal muscular atrophy ...

  16. Evaluation of spinal cord injury animal models

    Institute of Scientific and Technical Information of China (English)

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

    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.

  17. Functional outcome after a spinal fracture

    NARCIS (Netherlands)

    Post, Richard Bernardus

    2008-01-01

    This thesis takes a closer look at the functional outcome after a spinal fracture. An introduction to different aspects regarding spinal fractures is presented in Chapter 1. The incidence of traumatic thoracolumbar spinal fractures without neurological deficit in the Netherlands is approximately 1.2

  18. Unusual presentation of spinal lipomatosis

    Directory of Open Access Journals (Sweden)

    Stephenson W

    2014-09-01

    Full Text Available William Stephenson,1 Matthew J Kauflin2,3 1Primary Care, Huntington Veteran's Affairs Medical Center, Huntington, WV, USA; 2Department of Pharmacy, Grandview Medical Center, Dayton, Ohio, OH, USA; 3Ohio Northern University, Ada, Ohio, OH, USA Abstract: Spinal epidural lipomatosis (SEL is a rare condition characterized by overgrowth of normal adipose tissue in the extradural space within the spinal canal that can lead to significant spinal cord compression. It is most commonly reported in patients receiving chronic glucocorticoid therapy. Other causes can include obesity and hypercortisolism. Occasionally, idiopathic SEL will occur in patients with no known risk factors, but cases are more generally reported in obesity and males. We present the case of a 35 year-old non-obese woman found to have rapidly progressive SEL that was not associated with any of the common causes of the disorder. Keywords: lipomatosis, laminectomy, hypercortisolism

  19. Recurrent Primary Spinal Hydatid Cyst

    Directory of Open Access Journals (Sweden)

    Okan Turk

    2015-03-01

    Full Text Available Primary hydatid disease of spine is rare and spinal hydatitosis constitute only 1% of all hydatitosis. We report a case of recurrent primary intraspinal extradural hydatid cyst of the thoracic region causing progressive paraparesis. The patient was operated 16 years ago for primary spinal hydatid disease involvement and was instrumented dorsally for stabilization. The magnetic resonance imaging (MRI of thoracic spine showed a cystic lesion at T11-12 level and compressed spinal cord posterolaterally. Intraspinal cyst was excised through T11-12 laminectomy which made formerly. The early postoperative period showed a progressive improvement of his neurological deficit and he was discharged with antihelmintic treatment consisting of albendazole and amoxicillin-sulbactam combination. [Cukurova Med J 2015; 40(Suppl 1: 84-89

  20. Effects of novel subtype selective M-current activators on spinal reflexes in vitro: Comparison with retigabine.

    Science.gov (United States)

    Vicente-Baz, Jorge; Lopez-Garcia, Jose A; Rivera-Arconada, Ivan

    2016-10-01

    The activation of Kv7 channels and the resulting M-current is a powerful mechanism to control neuronal excitability with profound effects in pain pathways. Despite the lack of specific data on the expression and role of these channels in nociceptive processing, much attention has been paid at exploring their potential value as targets for analgesia. Here we have characterized the spinal actions of two novel subunit selective Kv7 activators, ICA-069673 and ML213, and compared their effects to those of retigabine that acts with similar affinity on all neuronal Kv7 channels. Spinal reflexes were recorded in a mouse spinal cord in vitro preparation to allow the testing of the compounds on native spinal pathways at known concentrations. As retigabine, novel compounds depressed spinal segmental transmission with particularly strong effects on wind up, showing an adequate pro-analgesic profile. ML213 presented the highest potency. In contrast to retigabine, the effects of ICA-069673 and ML213 were blocked by XE-991 even at the highest concentrations used, suggesting specific effect on Kv7 channels. In addition, the effects of ICA-069673 on repetitive stimulation are consistent with a mode of action involving state or activity dependent interaction with the channels. Compared to retigabine, novel Kv7 openers maintain strong depressant effects on spinal nociceptive transmission showing an improved specificity on Kv7 channels. The differential effects obtained with these Kv7 openers may indicate the existence of several Kv7 conformations in spinal circuits. PMID:27263036

  1. ECG in neonate mice with spinal muscular atrophy allows assessment of drug efficacy

    OpenAIRE

    Heier, Christopher R.; DiDonato, Christine J.

    2015-01-01

    Molecular technologies have produced diverse arrays of animal models for studying genetic diseases and potential therapeutics. Many have neonatal phenotypes. Spinal muscular atrophy (SMA) is a neuromuscular disorder primarily affecting children, and is of great interest in translational medicine. The most widely used SMA mouse models require all phenotyping to be performed in neonates since they do not survive much past weaning. Pre-clinical studies in neonate mice can be hindered by toxicity...

  2. Comparative Magnetic Resonance Imaging and Histopathological Correlates in Two SOD1 Transgenic Mouse Models of Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Ilaria Caron

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive and fatal disease due to motoneuron degeneration. Magnetic resonance imaging (MRI is becoming a promising non-invasive approach to monitor the disease course but a direct correlation with neuropathology is not feasible in human. Therefore in this study we aimed to examine MRI changes in relation to histopathology in two mouse models of ALS (C57BL6/J and 129S2/SvHsd SOD1G93A mice with different disease onset and progression. A longitudinal in vivo analysis of T2 maps, compared to ex vivo histological changes, was performed on cranial motor nuclei. An increased T2 value was associated with a significant tissue vacuolization that occurred prior to motoneuron loss in the cranial nuclei of C57 SOD1G93A mice. Conversely, in 129Sv SOD1G93A mice, which exhibit a more severe phenotype, MRI detected a milder increase of T2 value, associated with a milder vacuolization. This suggests that alteration within brainstem nuclei is not predictive of a more severe phenotype in the SOD1G93A mouse model. Using an ex vivo paradigm, Diffusion Tensor Imaging was also applied to study white matter spinal cord degeneration. In contrast to degeneration of cranial nuclei, alterations in white matter and axons loss reflected the different disease phenotype of SOD1G93A mice. The correspondence between MRI and histology further highlights the potential of MRI to monitor progressive motoneuron and axonal degeneration non-invasively in vivo. The identification of prognostic markers of the disease nevertheless requires validation in multiple models of ALS to ensure that these are not merely model-specific. Eventually this approach has the potential to lead to the development of robust and validated non-invasive imaging biomarkers in ALS patients, which may help to monitor the efficacy of therapies.

  3. Chemotherapeutic treatment for spinal tuberculosis

    NARCIS (Netherlands)

    van Loenhout-Rooyackers, JH; Verbeek, ALM; Jutte, PC

    2002-01-01

    AIM: To evaluate whether 6 months of chemotherapy for patients with spinal tuberculosis prevents relapse as effectively as more than 6 months of chemotherapy. METHOD: Literature review. Medline search including references, from January 1978 to November 2000. Inclusion criteria for publications: diag

  4. Spinal cord injury at birth

    DEFF Research Database (Denmark)

    Fenger-Gron, Jesper; Kock, Kirsten; Nielsen, Rasmus G;

    2008-01-01

    UNLABELLED: A case of perinatally acquired spinal cord injury (SCI) is presented. The foetus was vigorous until birth, the breech presented and delivery was performed by a non-traumatic Caesarean section. The infant displayed symptoms of severe SCI but diagnosis was delayed due to severe co...

  5. Spinal trauma. An imaging approach

    International Nuclear Information System (INIS)

    The diagnosis of trauma to the spine - where the slightest oversight may have catastrophic results - requires a thorough grasp of the spectrum of resultant pathology as well as the imaging modalities used in making an accurate diagnosis. In Spinal Trauma, the internationally renowned team of experts provides a comprehensive, cutting-edge exposition of the current vital role of imaging in the diagnosis and treatment of injuries to the axial skeleton. Beginning with a valuable clinical perspective of spinal trauma, the book offers the reader a unique overview of the biomechanics underlying the pathology of cervical trauma. Acute trauma topics include: - Optimization of imaging modalities - Malalignment - signs and significance - Vertebral fractures - detection and implications - Classification of thoraco-lumbar fractures - rationale and relevance - Neurovascular injury. Distilling decades of clinical and teaching expertise, the contributors further discuss the current role of imaging in special focus topics, which include: - The pediatric spine - Sports injuries - The rigid spine - Trauma in the elderly - Vertebral collapse, benign and malignant - Spinal trauma therapy - Vertebral fractures and osteoporosis - Neuropathic spine. All throughout the book, the focus is on understanding the injury, and its implications and complications, through 'an imaging approach'. Lavishly illustrated with hundreds of superb MR images and CT scans, and clear full-color drawings, the authors conclude with a look into the future, defining clinical trends and research directions. Spinal Trauma - with its broad scope, practical imaging approach, and current focus - is designed to enhance confidence and accuracy, making it essential reading for clinicians and radiologists at all levels. (orig.)

  6. Vestibulo-spinal reflex mechanisms

    Science.gov (United States)

    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.

  7. Inhibition of Epidermal Growth Factor Receptor Improves Myelination and Attenuates Tissue Damage of Spinal Cord Injury.

    Science.gov (United States)

    Zhang, Si; Ju, Peijun; Tjandra, Editha; Yeap, Yeeshan; Owlanj, Hamed; Feng, Zhiwei

    2016-10-01

    Preventing demyelination and promoting remyelination of denuded axons are promising therapeutic strategies for spinal cord injury (SCI). Epidermal growth factor receptor (EGFR) inhibition was reported to benefit the neural functional recovery and the axon regeneration after SCI. However, its role in de- and remyelination of axons in injured spinal cord is unclear. In the present study, we evaluated the effects of EGFR inhibitor, PD168393 (PD), on the myelination in mouse contusive SCI model. We found that expression of myelin basic protein (MBP) in the injured spinal cords of PD treated mice was remarkably elevated. The density of glial precursor cells and oligodendrocytes (OLs) was increased and the cell apoptosis in lesions was attenuated after PD168393 treatment. Moreover, PD168393 treatment reduced both the numbers of OX42 + microglial cells and glial fibrillary acidic protein + astrocytes in damaged area of spinal cords. We thus conclude that the therapeutic effects of EGFR inhibition after SCI involves facilitating remyelination of the injured spinal cord, increasing of oligodendrocyte precursor cells and OLs, as well as suppressing the activation of astrocytes and microglia/macrophages. PMID:26883518

  8. Pressure changes in spinal canal and evaluation of spinal cord injuries in spinal section subjected to impact

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To observe pressure changes in the spinal canal of the vertebrarium subjected to impact. From the point of view of impact, pressure changes and spinal cord injuries, the relationship between the type of spinal fracture and the severity of spinal cord injuries were analyzed and some experimental data were provided for early evaluation of severity of spinal cord injuries.   Methods: An experimental model of spinal burst fracture was made with Type BIM-I bio-impact machine and techniques of high velocity vertical loading in static pattern and stress shielding were adopted. Vertebral sections T10-L4 taken from fresh cadavers were impacted and pressure changes in the spinal canal were observed. The types and severity of spinal fracture were studied with gross and radiography examination.   Results: Great positive pressure wave (wave A) in the spinal canal of the 4 vertebral specimens with burst fracture was recorded. The peak value of pressure was correlated with the severity of posterior column injuries. Generally, the peak value of pressure was low in the samples with posterior column injuries, but high in the samples without injuries. The predominant features of fractures were burst fractures of vertebral body and severe destruction of the skeletal and fiber structure of the spinal canal. Positive and negative pressure waves (wave B) were recorded in 2 vertebral samples in which no significant abnormal changes were found by radiography examination, however, a little liquid effusion in the vertebral body was found by gross examination.   Conclusions: The type of pressure wave in the spinal canal is related to the deformation or the destruction of the spinal canal structure. The peak value of the pressure is non-linearly related to the obstruction in the spinal canal, but related to posterior column injuries.

  9. Changes of BB Isoenzyme of Creatine Kinase, CaATPase and Calpain in Experimental Autoimmune Encephalomyelitis Mouse Brain and Spinal Cord%实验性自身免疫性脑脊髓炎小鼠脑组织和脊髓中脑型肌酸激酶、钙泵和钙中性蛋白酶的变化

    Institute of Scientific and Technical Information of China (English)

    王沛; 郑荣远; 林福虹; 王赵伟; 厉芳; 张正学

    2011-01-01

    Aim: To investigate the changes ofBB isoenzyme of creatine kinase(CK-BB), CaATPase and calpain in experimental autoimmune encephalomyelitis(EAE) mouse brain and spinal cord. Methods: C57BL/6 mice were induced into the models of EAE with multiple sclerosis by myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) peptides. Behavioral changes of the EAE mice were observed and recorded. With HE staining, LFB myelin staining, the changes of the central nervous tissues, CK-BB, CaATPase and calpain activity were assayed in the peak incidence by using microplate reader and spectrophotometer (19 days after immunization). Results: Compared with the control group, the results of the EAE group were as follows :① Mean daily clinical scores and cumulative scores were mcreased(P<0.01).② HE staining: Central inflammatory cell infiltration became obvious(P<0.05).③ LFB Clinical Analysis of 15 Cases with Spontaneous Intracranial Hypotension HeadacheKEY WORDS spontaneous intracranial hypotension; headache; secondary headacheABSTRACT Aim: To explore the clinical features of spontaneous intracranial hypotension(SIH) headache.Methods: Clinical data of 15 cases of SIH headache were retrospectively analyzed. Results: 12 0f 15 caseswere acute onset, 9 were female. The ages of onset were from 28 t0 56 years. 93.33% cases had posturalheadache, with the common concomitant symptoms of nausea and vomit. The average cerebrospinal fluidpressure was (41.2 + 30.85)mmH20, which was higher in male than in female (P<0.05). Radionuclidecisternography and imaging were normal. All cases were cured after conservative treatment. Conclusion:Typical postural headache and cerebrospinal fluid pressure less than 60 mmH.O were the main features in SIHheadache, which were with favorable prognosis.%目的:观察实验性自身免疫性脑脊髓炎(EAE)小鼠模型脑组织和脊髓中脑型肌酸激酶(CK-BB)、钙泵(CaATPase) 和钙中性蛋白酶(calpain)的变化.方法:C57BL/6

  10. Loss of microRNA-124 expression in neurons in the peri-lesion area in mice with spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yu Zhao; Hui Zhang; Dan Zhang; Cai-yong Yu; Xiang-hui Zhao; Fang-fang Liu; Gan-lan Bian; Gong Ju; Jian Wang

    2015-01-01

    MicroRNA-124 (miR-124) is abundantly expressed in neurons in the mammalian central ner-vous system, and plays critical roles in the regulation of gene expression during embryonic neurogenesis and postnatal neural differentiation. However, the expression proifle of miR-124 after spinal cord injury and the underlying regulatory mechanisms are not well understood. In the present study, we examined the expression of miR-124 in mouse brain and spinal cord after spinal cord injury usingin situ hybridization. Furthermore, the expression of miR-124 was examined with quantitative RT-PCR at 1, 3 and 7 days after spinal cord injury. The miR-124 expression in neurons at the site of injury was evaluated by in situ hybridization combined with NeuN immunohistochemical staining. The miR-124 was mainly expressed in neurons through-out the brain and spinal cord. The expression of miR-124 in neurons significantly decreased within 7 days after spinal cord injury. Some of the neurons in the peri-lesion area were NeuN+/miR-124−. Moreover, the neurons distal to the peri-lesion site were NeuN+/miR-124+. These ifndings indicate that miR-124 expression in neurons is reduced after spinal cord injury, and may relfect the severity of spinal cord injury.

  11. Neuroimaging for spine and spinal cord surgery

    Energy Technology Data Exchange (ETDEWEB)

    Koyanagi, Izumi [Hokkaido Neurosurgical Memorial Hospital (Japan); Iwasaki, Yoshinobu; Hida, Kazutoshi

    2001-01-01

    Recent advances in neuroimaging of the spine and spinal cord are described based upon our clinical experiences with spinal disorders. Preoperative neuroradiological examinations, including magnetic resonance (MR) imaging and computerized tomography (CT) with three-dimensional reconstruction (3D-CT), were retrospectively analyzed in patients with cervical spondylosis or ossification of the posterior longitudinal ligament (130 cases), spinal trauma (43 cases) and intramedullary spinal cord tumors (92 cases). CT scan and 3D-CT were useful in elucidating the spine pathology associated with degenerative and traumatic spine diseases. Visualization of the deformity of the spine or fracture-dislocation of the spinal column with 3D-CT helped to determine the correct surgical treatment. MR imaging was most important in the diagnosis of both spine and spinal cord abnormalities. The axial MR images of the spinal cord were essential in understanding the laterality of the spinal cord compression in spinal column disorders and in determining surgical approaches to the intramedullary lesions. Although non-invasive diagnostic modalities such as MR imaging and CT scans are adequate for deciding which surgical treatment to use in the majority of spine and spinal cord disorders, conventional myelography is still needed in the diagnosis of nerve root compression in some cases of cervical spondylosis. (author)

  12. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves

    DEFF Research Database (Denmark)

    Rossini, P M; Burke, D; Chen, R;

    2015-01-01

    These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some ...

  13. Reduction of cytosolic phospholipase A2α upregulation delays the onset of symptoms in SOD1G93A mouse model of amyotrophic lateral sclerosis

    OpenAIRE

    Solomonov, Yulia; Hadad, Nurit; Levy, Rachel

    2016-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a fatal multifactorial neurodegenerative disease characterized by selective death of motor neurons in the cortex, brainstem, and spinal cord. Cytosolic phospholipase A2 alpha (cPLA2α) upregulation and activation in the spinal cord of patients with sporadic ALS and in the spinal cord of human mutant SOD1G93A (hmSOD1) transgenic mice were recently reported. Methods cPLA2α upregulation in the brainstem and spinal cord was reduced by brain infusio...

  14. Functional improvement in mouse models of familial amyotrophic lateral sclerosis by PEGylated insulin-like growth factor I treatment depends on disease severity.

    Science.gov (United States)

    Saenger, Stefanie; Holtmann, Bettina; Nilges, Mark R; Schroeder, Susanne; Hoeflich, Andreas; Kletzl, Heidemarie; Spooren, Will; Ostrowitzki, Susanne; Hanania, Taleen; Sendtner, Michael; Metzger, Friedrich

    2012-09-01

    Insulin-like growth factor I (IGF-I) has been successfully tested in the SOD1-G93A mouse model of familial amyotrophic lateral sclerosis (ALS) and proposed for clinical treatment. However, beneficial effects required gene therapy or intrathecal application. Circumventing the dosing issues we recently found that polyethylene glycol (PEG) modified IGF-I (PEG-IGF-I) modulated neuromuscular function after systemic application, and protected against disease progression in a motor neuron disease model. Here we investigated its effects in two SOD1-G93A mouse lines, the G1L with a milder and the G1H with a more severe phenotype. Results showed that in G1L mice, PEG-IGF-I treatment significantly improved muscle force, motor coordination and animal survival. In contrast, treatment of G1H mice with PEG-IGF-I or IGF-I even at high doses did not beneficially affect survival or functional outcomes despite increased signalling in brain and spinal cord by both agents. In conclusion, the data point towards further investigation of the therapeutic potential of PEG-IGF-I in ALS patients with less severe clinical phenotypes.

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

    OpenAIRE

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

    2010-01-01

    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...

  16. Intrinsic properties of mouse lumbar motoneurons revealed by intracellular recording in vivo

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Sukiasyan, Natalya; Zhang, Mengliang;

    2010-01-01

    for the possibility to evoke PICs. The data demonstrate that mouse spinal motoneurons share many of the same properties that have been demonstrated previously for cat, rat, and human motoneurons. The shorter AHP duration, steeper f-I slopes, and higher F(min) and F(max) than those in rats, cats, and humans are likely...

  17. Plastic Changes in the Spinal Cord in Motor Neuron Disease

    Directory of Open Access Journals (Sweden)

    Francesco Fornai

    2014-01-01

    Full Text Available In the present paper, we analyze the cell number within lamina X at the end stage of disease in a G93A mouse model of ALS; the effects induced by lithium; the stem-cell like phenotype of lamina X cells during ALS; the differentiation of these cells towards either a glial or neuronal phenotype. In summary we found that G93A mouse model of ALS produces an increase in lamina X cells which is further augmented by lithium administration. In the absence of lithium these nestin positive stem-like cells preferentially differentiate into glia (GFAP positive, while in the presence of lithium these cells differentiate towards a neuron-like phenotype (βIII-tubulin, NeuN, and calbindin-D28K positive. These effects of lithium are observed concomitantly with attenuation in disease progression and are reminiscent of neurogenetic effects induced by lithium in the subependymal ventricular zone of the hippocampus.

  18. Plastic changes in the spinal cord in motor neuron disease.

    Science.gov (United States)

    Fornai, Francesco; Ferrucci, Michela; Lenzi, Paola; Falleni, Alessandra; Biagioni, Francesca; Flaibani, Marina; Siciliano, Gabriele; Giannessi, Francesco; Paparelli, Antonio

    2014-01-01

    In the present paper, we analyze the cell number within lamina X at the end stage of disease in a G93A mouse model of ALS; the effects induced by lithium; the stem-cell like phenotype of lamina X cells during ALS; the differentiation of these cells towards either a glial or neuronal phenotype. In summary we found that G93A mouse model of ALS produces an increase in lamina X cells which is further augmented by lithium administration. In the absence of lithium these nestin positive stem-like cells preferentially differentiate into glia (GFAP positive), while in the presence of lithium these cells differentiate towards a neuron-like phenotype ( β III-tubulin, NeuN, and calbindin-D28K positive). These effects of lithium are observed concomitantly with attenuation in disease progression and are reminiscent of neurogenetic effects induced by lithium in the subependymal ventricular zone of the hippocampus. PMID:24829911

  19. Nonlinear optical techniques for imaging and manipulating the mouse central nervous system

    Science.gov (United States)

    Farrar, Matthew John

    The spinal cord of vertebrates serves as the conduit for somatosensory information and motor control, as well as being the locus of neural circuits that govern fast reflexes and patterned behaviors, such as walking in mammals or swimming in fish. Consequently, pathologies of the spinal cord -such as spinal cord injury (SCI)- lead to loss of motor control and sensory perception, with accompanying decline in life expectancy and quality of life. Despite the devastating effects of these diseases, few therapies exist to substantially ameliorate patient outcome. In part, studies of spinal cord pathology have been limited by the inability to perform in vivo imaging at the level of cellular processes. The focus of this thesis is to present the underlying theory for and demonstration of novel multi-photon microscopy (MPM) and optical manipulation techniques as they apply to studies the mouse central nervous system (CNS), with an emphasis on the spinal cord. The scientific findings which have resulted from the implementation of these techniques are also presented. In particular, we have demonstrated that third harmonic generation is a dye-free method of imaging CNS myelin, a fundamental constituent of the spinal cord that is difficult to label using exogenous dyes and/or transgenic constructs. Since gaining optical access to the spinal cord is a prerequisite for spinal cord imaging, we review our development of a novel spinal cord imaging chamber and surgical procedure which allowed us to image for multiple weeks following implantation without the need for repeated surgeries. We also have used MPM to characterize spinal venous blood flow before and after point occlusions. We review a novel nonlinear microscopy technique that may serve to show optical interfaces in three dimensions inside scattering tissue. Finally, we discuss a model and show results of optoporation, a means of transfecting cells with genetic constructs. Brief reviews of MPM and SCI are also presented.

  20. Management of postoperative spinal infections

    OpenAIRE

    Hegde, Vishal; Meredith, Dennis S; Kepler, Christopher K.; Huang, Russel C.

    2012-01-01

    Postoperative surgical site infection (SSI) is a common complication after posterior lumbar spine surgery. This review details an approach to the prevention, diagnosis and treatment of SSIs. Factors contributing to the development of a SSI can be split into three categories: (1) microbiological factors; (2) factors related to the patient and their spinal pathology; and (3) factors relating to the surgical procedure. SSI is most commonly caused by Staphylococcus aureus. The virulence of the or...

  1. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation.

    Directory of Open Access Journals (Sweden)

    Michael P Hefferan

    Full Text Available BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1 causes an inherited form of Amyotrophic Lateral Sclerosis (ALS. Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs into the lumbar spinal cord of SOD1(G93A rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension of lifespan. The aim of the present study was to analyze the degree of therapeutical effect of hNSCs once grafted into the lumbar spinal ventral horn in presymptomatic immunosuppressed SOD1(G93A rats and to assess the presence and functional integrity of the descending motor system in symptomatic SOD1(G93A animals. METHODS/PRINCIPAL FINDINGS: Presymptomatic SOD1(G93A rats (60-65 days old received spinal lumbar injections of hNSCs. After cell grafting, disease onset, disease progression and lifespan were analyzed. In separate symptomatic SOD1(G93A rats, the presence and functional conductivity of descending motor tracts (corticospinal and rubrospinal was analyzed by spinal surface recording electrodes after electrical stimulation of the motor cortex. Silver impregnation of lumbar spinal cord sections and descending motor axon counting in plastic spinal cord sections were used to validate morphologically the integrity of descending motor tracts. Grafting of hNSCs into the lumbar spinal cord of SOD1(G93A rats protected α-motoneurons in the vicinity of grafted cells, provided transient functional improvement, but offered no protection to α-motoneuron pools distant from grafted lumbar segments. Analysis of motor-evoked potentials recorded from the thoracic spinal cord of symptomatic SOD1(G93A rats showed a near complete loss of descending motor tract conduction, corresponding to a significant (50-65% loss of large caliber descending motor axons. CONCLUSIONS

  2. Testosterone Plus Finasteride Treatment After Spinal Cord Injury

    Science.gov (United States)

    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

  3. Acute Hydrocephalus Following Cervical Spinal Cord Injury

    OpenAIRE

    Son, Seong; Lee, Sang Gu; Park, Chan Woo; Kim, Woo Kyung

    2013-01-01

    We present a case of acute hydrocephalus secondary to cervical spinal cord injury in a patient with diffuse ossification of the posterior longitudinal ligament (OPLL). A 75-year-old male patient visited the emergency department with tetraparesis and spinal shock. Imaging studies showed cervical spinal cord injury with hemorrhage and diffuse OPLL from C1 to C4. We performed decompressive laminectomy and occipitocervical fusion. Two days after surgery, his mental status had deteriorated to drow...

  4. Nanomedicine for Treating Spinal Cord Injury

    OpenAIRE

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

    2013-01-01

    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 use...

  5. Neuronal degeneration in spinal multiple sclerosis

    OpenAIRE

    Bernhardt, Lydia

    2010-01-01

    To elucidate neuronal degeneration in spinal multiple sclerosis the spinal cord of 27 post mortem patients of the years 1997 to 2000 was investigated in comparison to 29 controls matched for sex, age and year of death. In addition to immunohistochemical examinations and demonstration of pathological cell changes, we also quantified the neurons of the cervical and thoracic spinal cord. In comparison to controls, MS-patients show a significant loss of 43% of the cervical neurons and a signif...

  6. Intracranial metastasis of spinal intramedullary anaplastic astrocytoma

    OpenAIRE

    Kataria, Rashim; Bhasme, Vishal; Chopra, Sanjeev; V D Sinha; Singhvi, Shashi

    2011-01-01

    Meningeal spread of spinal intramedullary astrocytoma into the cranium is rare. Only few case reports are available so far in the literature. We report a case of intramedullary high grade astrocytoma of the conus, developing intracranial metastasis after three months of partial excision of the spinal mass. The need for radical surgery, entire neuroaxis radiation, and adjuvant chemotherapy is suggested in the management of malignant spinal cord astrocytoma to prevent dissemination.

  7. Mobile myelographic filling defects: Spinal cysticercosis

    Energy Technology Data Exchange (ETDEWEB)

    Savoiardo, M.; Cimino, C.; Passerini, A.; La Mantia, L.

    1986-03-01

    Cysticercosis usually affects the brain and is easily demonstrated by CT. Spinal cysticercosis is much rarer and is usually diagnosed only at surgery. Myelographic demonstration of multiple rounded filling defects, some of which were mobile, allowed diagnosis of spinal extramedullary cysticercosis in an unsuspected case. The literature on spinal cysticercosis is briefly reviewed. Diagnosis is important in view of the recent development of medical treatment.

  8. Mobile myelographic filling defects: Spinal cysticercosis

    International Nuclear Information System (INIS)

    Cysticercosis usually affects the brain and is easily demonstrated by CT. Spinal cysticercosis is much rarer and is usually diagnosed only at surgery. Myelographic demonstration of multiple rounded filling defects, some of which were mobile, allowed diagnosis of spinal extramedullary cysticercosis in an unsuspected case. The literature on spinal cysticercosis is briefly reviewed. Diagnosis is important in view of the recent development of medical treatment. (orig.)

  9. MRI Findings in Spinal Canal Stenosis

    Directory of Open Access Journals (Sweden)

    Maryam Barzin

    2010-05-01

    Full Text Available Spinal canal stenosis results from progressive narrowing of the central spinal canal and the lateral recesses. Primary (congenital lumbar spinal stenosis is associated with achondroplastic dwarfism. The spinal canal may become narrowed by bulging or protrusion of the intervertebral disc annulus, herniation of the nucleus pulposus posteriorly, thickening of the posterior longitudinal ligament, hypertrophy of the facet joints, hypertrophy of the ligamentum flavum, epidural fat deposition, spondylosis of the intervertebral disc margins and uncovertebral joint hypertrophy in the neck. The central canal and the neurorecess may be compromised by tumor infiltration, such as metastatic disease, or by infectious spondylitis."nAP diameter of the normal adult cervical canal has a mean value of 17-18 mm at vertebral levels C3-5. The lower cervical canal measures 12-14 mm. Cervical stenosis is associated with an AP diameter of less than 10 mm. The thoracic spinal canal varies from 12 to 14 mm in diameter in the adult. The diameter of the normal lumbar spinal canal varies from 15 to 27 mm. Lumbar stenosis results from a spinal canal diameter of less than 12 mm in some patients; a diameter of 10 mm is definitely stenotic."nSpinal MRI is the most suitable technique for the diagnosis of spinal stenosis. The examination should be performed using thin sections (3 mm and high resolution, including the axial and sagittal planes using T1-weighted, proton-density, and T2-weighted techniques. The bony and osteophytic components are seen best using a T2-weighted gradient-echo technique."nOn MRI, findings of spinal stenosis have a variable presentation depending on the specific disease. The goal of spinal imaging is to localize the site and level of disease and to help differentiate between conditions in which patients require surgery or conservative treatment."nIn this presentation, different kinds of spinal canal stenosis and their MRI findings would be discussed.

  10. Moderate modulation of disease in the G93A model of ALS by the compound 2-(2-hydroxyphenyl)-benzoxazole (HBX).

    Science.gov (United States)

    Evans, Teresa M; Bhattacharya, Arunabh; Shi, Yun; Qi, Wenbo; Block, Travis J; Chaudhuri, Asish; Chaudhuri, Alakananda Ray; Hawker, Kara; Van Remmen, Holly

    2016-06-15

    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disease characterized by degeneration and death of motor neurons. Aberrant protein aggregation and oxidative stress are implicated in the etiology of ALS; thus preventing propagation of early aggregation events and oxidative damage could be an effective therapy. We tested the effect of dietary supplementation (initiated 40 days of age) with 2-(2-hydroxyphenyl)-benzoxazole (HBX), a compound with metal chelator and anti-aggregation properties, on disease onset, progression and lifespan in the G93A mouse model of ALS. Tests were not sufficiently powerful to detect any change to survival distribution of mice treated with HBX. However, the disease onset was delayed and max lifespan was increased in the treatment group. Additionally, disease progression was moderated as shown by reduced neuromuscular denervation measured by repetitive nerve stimulation. F2-isoprostanes, a marker of oxidative damage, are elevated in skeletal muscle from G93A mice at onset and this increase is prevented in HBX fed G93A mice. Furthermore, HBX treatment reduced mutant SOD1 protein aggregation in whole spinal cord of G93A mice at disease onset. Overall, our data suggests that HBX may be able to improve the degenerative symptoms of ALS through the prevention of oxidative damage and protein aggregation. Further studies are needed to uncover the mechanistic effects of HBX in ameliorating ALS pathology.

  11. MR imaging of spinal epidural sepsis

    International Nuclear Information System (INIS)

    Spinal epidural abscess is uncommonly found in adults and children. Early diagnosis and treatment improves prognosis and prevents serious neurologic sequelae. Four patients with spinal epidural infections were recently evaluated with MR and CT of the spine. In all cases, MR and CT localized the site of infection accurately and showed adjacent bony osteomyelitis. MR proved superior in characterizing infection (abscess vs. inflammatory edema) and demonstrating epidural involvement and spinal cord compression. In all cases, MR obviated the need for myelography. Early recognition by MR of spinal epidural sepsis led to expeditious treatment and better clinical outcome

  12. Spinal cord compression due to ethmoid adenocarcinoma.

    Science.gov (United States)

    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.

  13. Neuromesodermal progenitors and the making of the spinal cord

    Science.gov (United States)

    Henrique, Domingos; Abranches, Elsa; Verrier, Laure; Storey, Kate G.

    2016-01-01

    Neuromesodermal progenitors (NMps) contribute to both the elongating spinal cord and the adjacent paraxial mesoderm. It has been assumed that these cells arise as a result of patterning of the anterior neural plate. However, as the molecular mechanisms that specify NMps in vivo are uncovered, and as protocols for generating these bipotent cells from mouse and human pluripotent stem cells in vitro are established, the emerging data suggest that this view needs to be revised. Here, we review the characteristics, regulation, in vitro derivation and in vivo induction of NMps. We propose that these cells arise within primitive streak-associated epiblast via a mechanism that is separable from that which establishes neural fate in the anterior epiblast. We thus argue for the existence of two distinct routes for making central nervous system progenitors. PMID:26329597

  14. Changes in spinal range of motion after a flexibility training program in elderly women

    Directory of Open Access Journals (Sweden)

    Battaglia G

    2014-04-01

    Full Text Available Giuseppe Battaglia,1,2 Marianna Bellafiore,1,2 Giovanni Caramazza,2 Antonio Paoli,3 Antonino Bianco,1,2 Antonio Palma1,2 1Department of Law, Society, and Sport Sciences, University of Palermo, Palermo, Italy; 2Sicilian Regional Sports School of Italian National Olympic Committee (CONI, Sicily, Italy; 3Department of Biomedical Sciences, University of Padova, Padova, Italy Background: Aging-related reduced spinal mobility can interfere with the execution of important functional skills and activities in elderly women. Although several studies have shown positive outcomes in response to spinal flexibility training programs, little is known about the management of sets and repetitions in training protocols. The purpose of this study was to investigate the effects of an 8-week specific and standardized flexibility training program on the range of spinal motion in elderly women. Methods: Participants were recruited in a senior center of Palermo and randomly assigned in two groups: trained group (TG and control group (CG, which included 19 and 18 women, respectively. TG was trained for 8 weeks at two sessions/week. In particular, every session included three phases: warm up (~10 minutes, central period (~50 minutes, and cool down (~10 minutes. CG did not perform any physical activity during the experimental period. Spinal ranges of motion (ROM were measured from neutral standing position to maximum bending position and from neutral standing position to maximum extension position before and after the experimental period, using a SpinalMouse® device (Idiag, Volkerswill, Switzerland. Results: After the training period, TG showed an increase in spinal inclination by 16.4% (P<0.05, in sacral/hip ROM by 29.2% (P<0.05, and in thoracic ROM by 22.5% (P>0.05 compared with CG from maximum extension position to maximum bending position. We did not observe any significant difference in TG's lumbar ROM compared with CG after the training period (P>0.05. Conclusion

  15. Experimental study on spinal cord injury treated by embryonic spinal cord transplantation and greater omental transposition

    Institute of Scientific and Technical Information of China (English)

    Hao Dingjun(郝定均); Zheng Yonghong(郑永宏); Yuan Fuyong(袁福镛); He Liming; Wang Rong; Yuan Yong

    2004-01-01

    Objective: To observe the clinical efficacy of the embryonic spinal cellular transplantation and greater omental transposition for treatment of the spinal cord injury in 24 mongrel dogs. Methods: 24 adult mongrel dogs, weighing 10 ~ 13kg,bryonic spinal cellular transplantation and greater omental transposition group (group D). Each group consisted of 6 dogs. SEP(somatosensory evoked potential) and MEP (motor evoked potential) of the spinal cord were examed prior to the spinal cord injury and 2 months after the treatment to observe the changes of the animals' behavior. All dogs were killed 2 months after surgery and the spinal cord sections were obtained from T12 to L1 level for pathological analysis and observation under the electron microscope.Results: There was an obvious difference in the spinal somatosensory evoked potential and the motor evoked potential between the group D and the other three groups (group A, B, and C). Recovery of the behavior was noted. The spinal cells had survived for two months following the transplantation. Conclusion: Transplantation of the embryonic spinal cell and greater omentum for treatment of the spinal cord injury in dogs can gain a better outcome than the other groups in behavior and spinal somatosensory and motor evoked potential, but the further study is still essential to confirm its clinical efficacy.

  16. Involvement of spinal glutamate in nociceptive behavior induced by intrathecal administration of hemokinin-1 in mice.

    Science.gov (United States)

    Watanabe, Chizuko; Mizoguchi, Hirokazu; Bagetta, Giacinto; Sakurada, Shinobu

    2016-03-23

    The most recently identified tachykinin, hemokinin-1, was cloned from mouse bone marrow. While several studies indicated that hemokinin-1 is involved in pain and inflammation, the physiological functions of hemokinin-1 are not fully understood. Our previous research demonstrated that the intrathecal (i.t.) administration of hemokinin-1 (0.00625-1.6 nmol) dose-dependently induced nociceptive behaviors, consisting of scratching, biting and licking in mice, which are very similar with the nociceptive behaviors induced by the i.t. administration of substance P. Low-dose (0.0125 nmol) hemokinin-1-induced nociceptive behavior was inhibited by a specific NK1 receptor antagonist; however, high-dose (0.1 nmol) hemokinin-1-induced nociceptive behavior was not affected. In the present study, we found that the nociceptive behaviors induced by hemokinin-1 (0.1 nmol) were inhibited by the i.t. co-administration of MK-801 or D-APV, which are NMDA receptor antagonists. Moreover, we measured glutamate in the extracellular fluid of the mouse spinal cord using microdialysis. The i.t. administration of hemokinin-1 produced a significant increase in glutamate in the spinal cord, which was significantly reduced by co-administration with NMDA receptor antagonists. These results suggest that hemokinin-1-induced nociceptive behaviors may be mediated by the NMDA receptor in the spinal cord. PMID:26899156

  17. Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice.

    Science.gov (United States)

    Witts, Emily C; Nascimento, Filipe; Miles, Gareth B

    2015-10-01

    Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925-1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output. PMID:26311185

  18. ALS - resources

    Science.gov (United States)

    Resources - ALS ... The following organizations are good resources for information on amyotrophic lateral sclerosis : Muscular Dystrophy Association -- mda.org/disease/amyotrophic-lateral-sclerosis National Amyotrophic Lateral Sclerosis (ALS) Registry -- ...

  19. Gaze beats mouse

    DEFF Research Database (Denmark)

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

    2008-01-01

    pointing was faster than mouse pointing, while maintaining a similar error rate. EMG and mouse-button selection had a comparable performance. From analyses of completion time, throughput and error rates, we concluded that the combination of gaze and facial EMG holds potential for outperforming the mouse....

  20. Extensive molecular differences between anterior- and posterior-half-sclerotomes underlie somite polarity and spinal nerve segmentation

    Directory of Open Access Journals (Sweden)

    Keynes Roger J

    2009-05-01

    Full Text Available Abstract Background The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the full extent of molecular differences that underlie this polarity, we have undertaken a systematic comparison of gene expression between the two sclerotome halves in the mouse embryo. Results Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity. Conclusion We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.

  1. Psychological Aspects of Spinal Cord Injury

    Science.gov (United States)

    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)

  2. Subarachnoid disseminative hemangiopericytoma of the spinal cord

    Institute of Scientific and Technical Information of China (English)

    LIN Guo-zhong; WANG Zhen-yu; LI Zhen-dong; ZHONG Yan-feng; WANG Lei-ming

    2010-01-01

    @@ Hemangiopericytomas (HPCs) originating from central nervous system were increasingly reported recently.1 Intravertebral HPCs are predominantly epidural. Primary intradural HPCs of spinal cord are rare.2-5 Little subarachnoid dissemination has been reported. We reported a HPC of the cervical spinal cord with subarachnoid dissemination.

  3. Therapeutic approaches for spinal cord injury

    Directory of Open Access Journals (Sweden)

    Alexandre Fogaça Cristante

    2012-10-01

    Full Text Available 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.

  4. Therapeutic approaches for spinal cord injury.

    Science.gov (United States)

    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

  5. Remote cerebellar hemorrhage after lumbar spinal surgery

    Energy Technology Data Exchange (ETDEWEB)

    Cevik, Belma [Baskent University Faculty of Medicine, Department of Radiology, Fevzi Cakmak Cad. 10. sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: belmac@baskent-ank.edu.tr; Kirbas, Ismail; Cakir, Banu; Akin, Kayihan; Teksam, Mehmet [Baskent University Faculty of Medicine, Department of Radiology, Fevzi Cakmak Cad. 10. sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)

    2009-04-15

    Background: Postoperative remote cerebellar hemorrhage (RCH) as a complication of lumbar spinal surgery is an increasingly recognized clinical entity. The aim of this study was to determine the incidence of RCH after lumbar spinal surgery and to describe diagnostic imaging findings of RCH. Methods: Between October 1996 and March 2007, 2444 patients who had undergone lumbar spinal surgery were included in the study. Thirty-seven of 2444 patients were scanned by CT or MRI due to neurologic symptoms within the first 7 days of postoperative period. The data of all the patients were studied with regard to the following variables: incidence of RCH after lumbar spinal surgery, gender and age, coagulation parameters, history of previous arterial hypertension, and position of lumbar spinal surgery. Results: The retrospective study led to the identification of two patients who had RCH after lumbar spinal surgery. Of 37 patients who had neurologic symptoms, 29 patients were women and 8 patients were men. CT and MRI showed subarachnoid hemorrhage in the folia of bilateral cerebellar hemispheres in both patients with RCH. The incidence of RCH was 0.08% among patients who underwent lumbar spinal surgery. Conclusion: RCH is a rare complication of lumbar spinal surgery, self-limiting phenomenon that should not be mistaken for more ominous pathologic findings such as hemorrhagic infarction. This type of bleeding is thought to occur secondary to venous infarction, but the exact pathogenetic mechanism is unknown. CT or MRI allowed immediate diagnosis of this complication and guided conservative management.

  6. New products tissue-engineering in the treatment of spinal cord injury

    Science.gov (United States)

    Bolshakov, I. N.; Sergienko, V. I.; Kiselev, S. L.; Lagarkova, M. A.; Remigaylo, A. A.; Mihaylov, A. A.; Prokopenko, S. V.

    2015-11-01

    In the treatment of patients with complicated spinal cord injury the Russian Health spends about one million rubles for each patient in the acute and the interim period after the injury. The number of complicated spinal cord injury is different in geographical areas Russian Federation from 30 to 50 people per 1 million that is affected by the year 5600. Applied to the present surgical and pharmacological techniques provide unsatisfactory results or minimally effective treatment. Transplantation of 100 thousand neuronal mouse predecessors (24 rats) or human neuronal predecessors (18 rats) in the anatomical gap rat spinal cord, followed by analysis of neurological deficit. The neuro-matrix implantation in the rat spinal cord containing 100 thousand neuronal precursors hESC, repeatable control neuro-matrix transplantation, non-cell mass, eliminating neurological deficit for 14 weeks after transplantation about 5-9 points on the scale of the BBB. The cultivation under conditions in vitro human induced pluripotent stem cells on collagen-chitosan matrix (hIPSC) showed that neurons differentiated from induced pluripotent stem cells grown on scaffolds as compact groups and has no neurites. Cells do not penetrate into the matrix during long-term cultivation and formed near the surface of the spherical structures resembling neurospheres. At least 90% of the cells were positive for the neuronal marker tubulin b3. Further studies should be performed to examine the compatibility of neuronal cultures and matrices.

  7. A role for bombesin in sensory processing in the spinal cord.

    Science.gov (United States)

    O'Donohue, T L; Massari, V J; Pazoles, C J; Chronwall, B M; Shults, C W; Quirion, R; Chase, T N; Moody, T W

    1984-12-01

    Bombesin (BN)-containing neuronal processes were demonstrated in laminae I and II of the dorsal horn of the cat, rat, and mouse spinal cord by immunocytochemistry and radioimmunoassay. Dorsal rhizotomy in the cat resulted in a marked decrease in BN immunoreactivity in the dorsal horn indicating that BN is contained in primary sensory afferents. BN-binding sites were also localized in superficial laminae of the dorsal horn. The presence of both BN and BN-binding sites in the dorsal horn suggested that BN may be involved in sensory processing in the spinal cord. Consistent with this hypothesis, it was demonstrated that an injection of BN into the spinal cord caused a biting and scratching response indicative of sensory stimulation. The effect was similar to that observed after injection of substance P into the cord with the exception that the BN effect lasted about 100 times longer than that induced by substance P. Taken together, these data indicate that BN may be a neurotransmitter of primary sensory afferents to the spinal cord. PMID:6094746

  8. Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury.

    Directory of Open Access Journals (Sweden)

    Yan Sun

    Full Text Available Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2(+-GFP(+-oligodendrocyte precursor cells (OPCs, which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs, could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2(+-GFP(+-OPCs and transplanted them into the rats' cervical 4-5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2(+-GFP(+-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2(+-GFP(+-OPCs primarily differentiated into adenomatous polyposis coli (APC(+ oligodendrocytes (54.6±10.5%. The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E and electron microscopy demonstrated that the engrafted Olig2(+-GFP(+-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2(+-GFP(+-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS.

  9. Light distribution properties in spinal cord for optogenetic stimulation (Conference Presentation)

    Science.gov (United States)

    GÄ secka, Alicja; Bahdine, Mohamed; Lapointe, Nicolas; Rioux, Veronique; Perez-Sanchez, Jimena; Bonin, Robert P.; De Koninck, Yves; Côté, Daniel

    2016-03-01

    Optogenetics is currently one of the most popular technique in neuroscience. It enables cell-selective and temporally-precise control of neuronal activity. Good spatial control of the stimulated area and minimized tissue damage requires a specific knowledge about light scattering properties. Light propagation in cell cultures and brain tissue is relatively well documented and allows for a precise and reliable delivery of light to the neurons. In spinal cord, light must pass through highly organized white matter before reaching cell bodies present in grey matter, this heterogenous structure makes it difficult to predict the propagation pattern. In this work we investigate the light distribution properties through mouse and monkey spinal cord. The light propagation depends on a fibers orientation, leading to less deep penetration profile in the direction perpendicular to the fibers and lower attenuation in the direction parallel to the fibers. Additionally, the use of different illumination wavelengths results in variations of the attenuation coefficient. Next, we use Monte-Carlo simulation to study light transport. The model gives a full 3-D simulation of light distribution in spinal cord and takes into account different scattering properties related to the fibers orientation. These studies are important to estimate the minimum optical irradiance required at the fiber tip to effectively excite the optogenetic proteins in a desired region of spinal cord.

  10. Inhibition of the Ras/Raf/ERK1/2 Signaling Pathway Restores Cultured Spinal Cord-Injured Neuronal Migration, Adhesion, and Dendritic Spine Development.

    Science.gov (United States)

    Xu, Dongdong; Cao, Fujiang; Sun, Shiwei; Liu, Tao; Feng, Shiqing

    2016-08-01

    The Ras/Raf/ERK1/2 signaling pathway plays an important role in central and peripheral neurons in functions such as dendritic arborization, neuronal polarity, and axon assembly. However, emerging evidence also shows that up-regulation of this signaling pathway may lead to the development of spinal cord injury. The present study aimed to determine the effects of Ras/Raf/ERK1/2 signaling pathway inhibition on properties of spinal cord-injured neurons. First, neurons from spinal cord-injured C57BL/6 J mouse pups and sham-operated C57BL/6 J mouse pups were harvested. Then, immunofluorescence, western blotting, cell adhesion and cell migration assays, and DiI labeling were employed to investigate the effect of Ras/Raf/ERK1/2 signaling pathway inhibition on spinal cord-injured neurons. Immunofluorescence results of synapse formation indicated that the experimental spinal cord injury model was successfully established. Western blot results identified upregulated Erk phosphorylation in the spinal cord-injured neurons, and also showed that U0126 inhibited phosphorylation of Erk, which is a downstream kinase in the Ras/Raf signaling pathway. Additionally, cell migration and adhesion was significantly increased in the spinal cord-injured neurons. DiI labeling results also showed an increased formation of mature spines after inhibition of Ras/Raf/ERK1/2 signaling. Taken together, these results suggested that the Ras/Raf/ERK1/2 signaling pathway could serve as an effective treatment target for spinal cord injury.

  11. Proteomic assessment of a cell model of spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Lee Kelvin H

    2011-03-01

    Full Text Available Abstract Background Deletion or mutation(s of the survival motor neuron 1 (SMN1 gene causes spinal muscular atrophy (SMA, a neuromuscular disease characterized by spinal motor neuron death and muscle paralysis. Complete loss of the SMN protein is embryonically lethal, yet reduced levels of this protein result in selective death of motor neurons. Why motor neurons are specifically targeted by SMN deficiency remains to be determined. In this study, embryonic stem (ES cells derived from a severe SMA mouse model were differentiated into motor neurons in vitro by addition of retinoic acid and sonic hedgehog agonist. Proteomic and western blot analyses were used to probe protein expression alterations in this cell-culture model of SMA that could be relevant to the disease. Results When ES cells were primed with Noggin/fibroblast growth factors (bFGF and FGF-8 in a more robust neural differentiation medium for 2 days before differentiation induction, the efficiency of in vitro motor neuron differentiation was improved from ~25% to ~50%. The differentiated ES cells expressed a pan-neuronal marker (neurofilament and motor neuron markers (Hb9, Islet-1, and ChAT. Even though SMN-deficient ES cells had marked reduced levels of SMN (~20% of that in control ES cells, the morphology and differentiation efficiency for these cells are comparable to those for control samples. However, proteomics in conjunction with western blot analyses revealed 6 down-regulated and 14 up-regulated proteins with most of them involved in energy metabolism, cell stress-response, protein degradation, and cytoskeleton stability. Some of these activated cellular pathways showed specificity for either undifferentiated or differentiated cells. Increased p21 protein expression indicated that SMA ES cells were responding to cellular stress. Up-regulation of p21 was confirmed in spinal cord tissues from the same SMA mouse model from which the ES cells were derived. Conclusion SMN

  12. Ambulation and spinal cord injury.

    Science.gov (United States)

    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.

  13. Spinal morphine anesthesia and urinary retention.

    Science.gov (United States)

    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.

  14. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chul Min; Lee, Seung Hun [Dept. of Radiology, Hanyang University Hospital, Seoul (Korea, Republic of); Bae, Ji Yoon [Dept. of Pathology, National Police Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis.

  15. Multidetector-row CT for spinal diseases

    International Nuclear Information System (INIS)

    Multi-detector-row CT is called second stage helical CT because it produces multi-volume slices in a short time. We have observed sagittal, coronal images for spinal diseases by this CT. Thirty-three sagittal images out of 39 post-myelography for spinal diseases were good images of compression of the dural sac, and 8 coronal images post myelography were good images of compression of the dural sac and spinal nerve roots. We obtained 11 sagittal images for OPLL, and all images were nearly equal to that of tomography. However, spinal tumors and inflammatory diseases are more easily obtained using MRI. Multi-detector-row CT is useful for spinal degenerative diseases. (author)

  16. Oriental Medical Treatment of Lumbar Spinal Stenosis

    Directory of Open Access Journals (Sweden)

    Hae-Yeon Lee

    2003-12-01

    Full Text Available Lumbar spinal stenosis results from the progressive combined narrowing of the central spinal canal, the neurorecesses, and the neuroforaminal canals. In the absence of prior surgery, tumor, or infection, the spinal canal may become narrowed by bulging or protrusion of the intervertebral disc annulus, herniation of the nucleus pulposis posteriorly, thickening of the posterior longitudinal ligament, hypertrophy of the ligamentum flavum, epidural fat deposition, spondylosis of the intervertebral disc margins, or a combination of two or more of the above factors. Patients with spinal stenosis become symptomatic when pain, motor weakness, paresthesia, or other neurologic compromise causes distress. In one case, we administrated oriental medical treatment with acupuncture treatment and herb-medicine. Oriental medical treatment showed desirable effect on lumbar spinal stenosis.

  17. Retraction: "Inactivation of Ink4a/Arf Leads to Deregulated Expression of miRNAs in K-Ras Transgenic Mouse Model of Pancreatic Cancer" by Ali et al.

    Science.gov (United States)

    2016-10-01

    The above article, published online on June 21, 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Gary S. Stein, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation from Wayne State University involving the first author and the corresponding author that found Figure 5A to be inappropriately manipulated. Literature Cited Ali S, Banerjee S, Logna F, Bao B, Philip PA, Korc M, Sarkar FH. 2012. Inactivation of Ink4a/Arf leads to deregulated expression of miRNAs in K-Ras transgenic mouse model of pancreatic cancer. J Cell Physiol 227:3373-3380; doi: 10.1002/jcp.24036. PMID:27315161

  18. Retraction: "Inactivation of Ink4a/Arf Leads to Deregulated Expression of miRNAs in K-Ras Transgenic Mouse Model of Pancreatic Cancer" by Ali et al.

    Science.gov (United States)

    2016-10-01

    The above article, published online on June 21, 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Gary S. Stein, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation from Wayne State University involving the first author and the corresponding author that found Figure 5A to be inappropriately manipulated. Literature Cited Ali S, Banerjee S, Logna F, Bao B, Philip PA, Korc M, Sarkar FH. 2012. Inactivation of Ink4a/Arf leads to deregulated expression of miRNAs in K-Ras transgenic mouse model of pancreatic cancer. J Cell Physiol 227:3373-3380; doi: 10.1002/jcp.24036.

  19. Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy.

    Science.gov (United States)

    Sleigh, James N; Barreiro-Iglesias, Antón; Oliver, Peter L; Biba, Angeliki; Becker, Thomas; Davies, Kay E; Becker, Catherina G; Talbot, Kevin

    2014-02-15

    Spinal muscular atrophy (SMA) is characterized by the selective loss of spinal motor neurons owing to reduced levels of survival motor neuron (Smn) protein. In addition to its well-established role in assembling constituents of the spliceosome, diverse cellular functions have been proposed for Smn, but the reason why low levels of this widely expressed protein result in selective motor neuron pathology is still debated. In longitudinal studies of exon-level changes in SMA mouse model tissues, designed to determine the contribution of splicing dysfunction to the disease, we have previously shown that a generalized defect in splicing is unlikely to play a causative role in SMA. Nevertheless, we identified a small subset of genes that were alternatively spliced in the spinal cord compared with control mice before symptom onset, indicating a possible mechanistic role in disease. Here, we have performed functional studies of one of these genes, chondrolectin (Chodl), known to be highly expressed in motor neurons and important for correct motor axon outgrowth in zebrafish. Using in vitro and in vivo models of SMA, we demonstrate altered expression of Chodl in SMA mouse spinal motor neurons, show that Chodl has distinct effects on cell survival and neurite outgrowth and that increasing the expression of chodl can rescue motor neuron outgrowth defects in Smn-depleted zebrafish. Our findings thus link the dysregulation of Chodl to the pathophysiology of motor neuron degeneration in SMA.

  20. CT of metastatic spinal tumor

    International Nuclear Information System (INIS)

    CT findings of metastatic spinal tumor were classified into 6 types, i.e., consolidation, dissolution, mottle, doughnut, and ring types, and mixed type of these, and that of no findings. Some statistically significant relationship was found between prostatic cancer and consolidation type, and unknown primary cancer and dissolution type. Abnormal findings of bone scintigraphy was suspected to have metastatic spinal tumor by plain radiography and CT scan in 64/128 (50.0%) and 113/145 (78.6%), respectively. There was some relationship between plain radiographic findings and CT findings; between consolidation type of the former and consolidation type of the latter, dissolution type and dissolution type, compression fracture type and mixed type, the type of no findings and consolidation or mixed type. The most of lesions detected by CT as consolidation or mixed type were revealed by plain radiography. Changes in Ca ammount was not detected by plain radiography and CT scan if it was approximately less than 30% and 18% of the initial Ca respectively. (Ueda, J.)

  1. Nrf2 activation in astrocytes contributes to spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning.

    Science.gov (United States)

    Xu, Jiajun; Huang, Guoyang; Zhang, Kun; Sun, Jinchuan; Xu, Tao; Li, Runping; Tao, Hengyi; Xu, Weigang

    2014-08-01

    In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtime-polymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, γ-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury. HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in neurons. In

  2. [Spinal and spinal cord injuries. Therapeutic approach in Gabon].

    Science.gov (United States)

    Loembe, P M; Bouger, D; Dukuly, L; Ndong-Launay, M

    1991-01-01

    The authors present their experience with 81 cases (66.4%) of acute cervical spine injuries (C.S.I.) and 41 cases (33.6%) of acute thoracolumbar spine injuries (T.L.S.I.) treated by a multidisciplinary approach, at Jeanne Ebori Hospital (Libreville, Gabon) between the years 1981 and 1987. Traffic accidents were the leading cause of injury. The largest group consisted of patients in their third decade. The anatomic localizations were: upper cervical spine: 22 cases (27%); lower cervical spine: 56 (69%); upper thoracic spine: 11 (26.8%); lower thoracic spine or thoracolumbar area: 19 (46.3%); lumbar spine: 7 (17%). There were osteoligamental lesions in 3 cases (3.7%) of C.S.I. and 4 (9.7%) of T.L.S.I. Clinically, 44 patients (54.3%) with C.S.I. and 37 (90.2%) with T.L.S.I. had neurological deficits. Surgical indications depended upon the osseous as well as neurologic lesions. There were five important steps in the treatment of spinal injuries associated with neurological deficit: (1) immobilization, (2) medical stabilization, (3) spinal alignment (skeletal traction), (4) operative decompression if there was proven cord compression, and (5) spinal stabilization. Twenty patients (24.6%) with cervical injuries were treated conservatively (traction, collar, kinesitherapy); 53 (65.4%) underwent a surgical intervention (anterior approach - 21, posterior fusion - 30, combined approach - 2); and in 8 patients (9.8%) refraining from surgery seemed the best alternative. After lengthy multidisciplinary discussion, the authors elected not to operate on tetraplegic patients with respiratory problems that necessitated assisted ventilation, because of its fatal outcome. Of injuries to the thoracolumbar spine, 13 (31.7%) were treated conservatively (bedrest, orthopedic treatment). Twenty-eight patients (68.2%) with unstable thoracic and lumbar fractures associated with neurologic deficit required acute surgical intervention (stabilization with or without decompression of the neural

  3. Curcumin protects against ischemic spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Jinhua Zhang; Hao Wei; Meimei Lin; Chunmei Chen; Chunhua Wang; Maobai Liu

    2013-01-01

    Inducible nitric oxide synthase and N-methyl-D-aspartate receptors have been shown to participate in nerve cellinjury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneal y injected with curcumin. Reverse transcrip-tion-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tarlov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective ef-fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyl-D-aspartate receptor expression.

  4. Diagnosis and management of traumatic cervical central spinal cord injury: A review

    Directory of Open Access Journals (Sweden)

    Nancy E Epstein

    2015-01-01

    Full Text Available Background: The classical clinical presentation, neuroradiographic features, and conservative vs. surgical management of traumatic cervical central spinal cord (CSS injury remain controversial. Methods: CSS injuries, occurring in approximately 9.2% of all cord injuries, are usually attributed to significant hyperextension trauma combined with congenital/acquired cervical stenosis/spondylosis. Patients typically present with greater motor deficits in the upper vs. lower extremities accompanied by patchy sensory loss. T2-weighted magnetic resonance (MR scans usually show hyperintense T2 intramedullary signals reflecting acute edema along with ligamentous injury, while noncontrast computed tomography (CT studies typically show no attendant bony pathology (e.g. no fracture, dislocation. Results: CSS constitute only a small percentage of all traumatic spinal cord injuries. Aarabi et al. found CSS patients averaged 58.3 years of age, 83% were male and 52.4% involved accidents/falls in patients with narrowed spinal canals (average 5.6 mm; their average American Spinal Injury Association (ASIA motor score was 63.8, and most pathology was at the C3-C4 and C4-C5 levels (71%. Surgery was performed within 24 h (9 patients, 24-48 h (10 patients, or after 48 h (23 patients. In the Brodell et al. study of 16,134 patients with CSS, 39.7% had surgery. In the Gu et al. series, those with CSS and stenosis/ossification of the posterior longitudinal ligament (OPLL exhibited better outcomes following laminoplasty. Conclusions: Recognizing the unique features of CSS is critical, as the clinical, neuroradiological, and management strategies (e.g. conservative vs. surgical management: early vs. late differ from those utilized for other spinal cord trauma. Increased T2-weighted MR images best document CSS, while CT studies confirm the absence of fracture/dislocation.

  5. What is different about spinal pain?

    Directory of Open Access Journals (Sweden)

    Vernon Howard

    2012-07-01

    Full Text Available Abstract Background The mechanisms subserving deep spinal pain have not been studied as well as those related to the skin and to deep pain in peripheral limb structures. The clinical phenomenology of deep spinal pain presents unique features which call for investigations which can explain these at a mechanistic level. Methods Targeted searches of the literature were conducted and the relevant materials reviewed for applicability to the thesis that deep spinal pain is distinctive from deep pain in the peripheral limb structures. Topics related to the neuroanatomy and neurophysiology of deep spinal pain were organized in a hierarchical format for content review. Results Since the 1980’s the innervation characteristics of the spinal joints and deep muscles have been elucidated. Afferent connections subserving pain have been identified in a distinctive somatotopic organization within the spinal cord whereby afferents from deep spinal tissues terminate primarily in the lateral dorsal horn while those from deep peripheral tissues terminate primarily in the medial dorsal horn. Mechanisms underlying the clinical phenomena of referred pain from the spine, poor localization of spinal pain and chronicity of spine pain have emerged from the literature and are reviewed here, especially emphasizing the somatotopic organization and hyperconvergence of dorsal horn “low back (spinal neurons”. Taken together, these findings provide preliminary support for the hypothesis that deep spine pain is different from deep pain arising from peripheral limb structures. Conclusions This thesis addressed the question “what is different about spine pain?” Neuroanatomic and neurophysiologic findings from studies in the last twenty years provide preliminary support for the thesis that deep spine pain is different from deep pain arising from peripheral limb structures.

  6. Spinal cord evolution in early Homo.

    Science.gov (United States)

    Meyer, Marc R; Haeusler, Martin

    2015-11-01

    The discovery at Nariokotome of the Homo erectus skeleton KNM-WT 15000, with a narrow spinal canal, seemed to show that this relatively large-brained hominin retained the primitive spinal cord size of African apes and that brain size expansion preceded postcranial neurological evolution. Here we compare the size and shape of the KNM-WT 15000 spinal canal with modern and fossil taxa including H. erectus from Dmanisi, Homo antecessor, the European middle Pleistocene hominins from Sima de los Huesos, and Pan troglodytes. In terms of shape and absolute and relative size of the spinal canal, we find all of the Dmanisi and most of the vertebrae of KNM-WT 15000 are within the human range of variation except for the C7, T2, and T3 of KNM-WT 15000, which are constricted, suggesting spinal stenosis. While additional fossils might definitively indicate whether H. erectus had evolved a human-like enlarged spinal canal, the evidence from the Dmanisi spinal canal and the unaffected levels of KNM-WT 15000 show that unlike Australopithecus, H. erectus had a spinal canal size and shape equivalent to that of modern humans. Subadult status is unlikely to affect our results, as spinal canal growth is complete in both individuals. We contest the notion that vertebrae yield information about respiratory control or language evolution, but suggest that, like H. antecessor and European middle Pleistocene hominins from Sima de los Huesos, early Homo possessed a postcranial neurological endowment roughly commensurate to modern humans, with implications for neurological, structural, and vascular improvements over Pan and Australopithecus. PMID:26553817

  7. Spinal fractures resulting from traumatic injuries

    Institute of Scientific and Technical Information of China (English)

    Heidari Pedram; Zarei Mohammad Reza; Rasouli Mohammad Reza; Alexander R Vaccaro; Rahimi-Movaghar Vafa

    2010-01-01

    Objective:To illustrate mechanisms of spine fractures and the pattern of spinal injuries characterized by the major mechanisms in urban population of Iran.Methods:Data regarding spinal injuries including demographics,mechanism and level of spinal injury,abbreviated injury score,associated injuries and final fate of the patients were extracted from the Iranian national trauma registry database from 1999 to 2004.Results:A total of 619 patients with traumatic spine fractures were identified,of whom 68.5% were males.The peak frequency of these injuries occurred in the 21-40 year age-group.Accidental falls and road traffic crashes(RTCs)were the most common mechanisms of spinal fractures(47.2% and 44.1%,respectively).RTCs tended to occur in younger patients compared with accidental falls.The most common spinal region for spinal fracture was the lumbar spine(53.63%).Cervical spine fractures were significantly more common in RTCs,while lumbar spine fractures were more common in accidental falls(P<0.001).A total of 171(27.6%)patients had associated non-spinal injuries,of whom 127 had associated extremity injuries,and 55 had head injuries.Thirty-six(5.6%)patients had spinal cord injury(SCI).The injury severity score of the RTC group was significantly higher than that of accidental falls(P=0.002).Fifteen(4%)patients died of traumatic injuries.The rate of death was significantly higher in RTCs compared with accidental falls(5.1% vs 2.1%,P=0.039).Conclusions:The patterns of spinal fractures are similar to those reported from developed countries.RTCs tend to affect the younger age population and are associated with a higher degree of associated injuries and mortality than accidental falls.Therefore preventive strategies should be based on reduction of the number and severity of RTCs.

  8. Combining Adult Learning Theory with Occupational Therapy Intervention for Bladder and Bowel Management after Spinal Cord Injury: A Case Report.

    Science.gov (United States)

    Gallagher, Gina; Bell, Alison

    2016-01-01

    Bladder and bowel management is an important goal of rehabilitation for clients with spinal cord injury. Dependence is these areas have been linked to a variety of secondary complications, including decreased quality of life, urinary tract infections and pressure ulcers (Hammell, 2010; Hicken et al, 2001). Occupational therapists have been identified as important members of the health care team in spinal cord injury rehabilitation; however, specific roles and interventions have not been clearly described. This case report will describe occupational therapy interventions embedded with principles of adult learning theory to address bladder and bowel management with an adult client who sustained an incomplete thoracic level spinal cord injury. PMID:26694910

  9. Advance in spinal cord ischemia reperfusion injury: Blood-spinal cord barrier and remote ischemic preconditioning.

    Science.gov (United States)

    Yu, Qijing; Huang, Jinxiu; Hu, Ji; Zhu, Hongfei

    2016-06-01

    The blood-spinal cord barrier (BSCB) is the physiological and metabolic substance diffusion barrier between blood circulation and spinal cord tissues. This barrier plays a vital role in maintaining the microenvironment stability of the spinal cord. When the spinal cord is subjected to ischemia/reperfusion (I/R) injury, the structure and function of the BSCB is disrupted, further destroying the spinal cord homeostasis and ultimately leading to neurological deficit. Remote ischemic preconditioning (RIPC) is an approach in which interspersed cycles of preconditioning ischemia is followed by reperfusion to tissues/organs to protect the distant target tissues/organs against subsequent lethal ischemic injuries. RIPC is an innovation of the treatment strategies that protect the organ from I/R injury. In this study, we review the morphological structure and function of the BSCB, the injury mechanism of BSCB resulting from spinal cord I/R, and the effect of RIPC on it. PMID:27060223

  10. Post-traumatic recto-spinal fistula

    Energy Technology Data Exchange (ETDEWEB)

    Lantsberg, L.; Greenberg, G. [Department of Surgery A, Soroka University Medical Center, Beer-Sheva (Israel); Laufer, L.; Hertzanu, Y. [Department of Diagnostic Radiology, Soroka University Medical Center, Beer-Sheva (Israel)

    2000-01-01

    Acquired recto-spinal fistula has been described elsewhere as a rare complication of colorectal malignancy and Crohn's enterocolitis. We treated a young man who developed a recto-spinal fistula as a result of a high fall injury. The patient presented with meningeal signs, sepsis and perianal laceration. Computerized axial tomography revealed air in the supersellar cistern. Gastrografin enema showed that contrast material was leaking from the rectum into the spinal canal. Surgical management included a diverting sigmoid colostomy, sacral bone curettage and wide presacral drainage. To the best of our knowledge, rectospinal fistula of traumatic origin has not been previously reported in the English literature. (orig.)

  11. Costs and effects in lumbar spinal fusion

    DEFF Research Database (Denmark)

    Soegaard, Rikke; Christensen, Finn Bjarke; Christiansen, Terkel;

    2007-01-01

    consecutive patients with chronic low back pain, who were surgically treated from January 2001 through January 2003, was followed until 2 years postoperatively. Operations took place at University Hospital of Aarhus and all patients had either (1) non-instrumented posterolateral lumbar spinal fusion, (2...... posterolateral spinal fusion at DKK 94,396(95% CI 89,865;99,574) and instrumented posterolateral lumbar spinal fusion + anterior intervertebral support at DKK 120,759(95% CI 111,981;133,738). The net-benefit of the regimens was significantly affected by smoking and functional disability in psychosocial life...

  12. Spinal Deformity Associated with Chiari Malformation.

    Science.gov (United States)

    Kelly, Michael P; Guillaume, Tenner J; Lenke, Lawrence G

    2015-10-01

    Despite the frequency of Chiari-associated spinal deformities, this disease process remains poorly understood. Syringomyelia is often present; however, this is not necessary and scoliosis has been described in the absence of a syrinx. Decompression of the hindbrain is often recommended. In young patients (<10 years old) and/or those with small coronal Cobb measurements (<40°), decompression of the hindbrain may lead to resolution of the spinal deformity. Spinal fusion is reserved for those curves that progress to deformities greater than 50°. Further research is needed to understand the underlying pathophysiology to improve prognostication and treatment of this patient population.

  13. MR findings of the spinal epidural lesions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hun; Lee, Ho Kyu; Shin, Ji Hoon; Choi, Choong Gon; Suh, Dae Chul; Shin, Myung Jin; Rhim, Seung Chul [Ulsan Univ. College of Midicine, Seoul (Korea, Republic of); Park, Sung Tae [Dongguk Univ. College of Midicine, Kyungju (Korea, Republic of)

    2001-04-01

    The spinal canal takes the form of a series of cylinders designated by their relationship to the meninges and is divided by the dura mater into the epidural or extradural space and intradural space. The epidural space is composed of spinal ligaments, connective and areolar tissue, the epidural venous plexus, lymphatic channels and supporting elements, and various pathologic entities are found there. MR imaging can accurately depict the extent and characteristics of lesions, and in some cases specific diagnosis is possible. In this pictorial essay, we illustrate a variety of spinal epidural lesions and their MR findings.

  14. Nanomedicine for treating spinal cord injury

    Science.gov (United States)

    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.

  15. Kalsiyum Kanal Blokeri Verapamilin Spinal Reflekslere Etkisi

    OpenAIRE

    TAŞÇI, N.; GENÇ, O.

    2010-01-01

    Effects of calcium channel blocker verapamil on spinal reflexes were studied. Verapamil 5, 50, (iM locally. 10,20 mg/kg was administradet intraperitoneally and 10, 50, 100 (iM localyy. Experiments on adult spinal cats (n=10) were conducted. Animals weighing 1,5-3 kg were anesthetized with ketamine (45 mg/kg intramuscular) and artiflcally ventilated. Animals were spinalized at Cj level and a laminectomy was performed in the lumbosacral region. The ventral and dorsal roots of segment Lg were...

  16. Cellular Scaling Rules for Primate Spinal Cords

    OpenAIRE

    Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

    2010-01-01

    The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an expone...

  17. Neurological deficit following spinal anaesthesia: MRI and CT evidence of spinal cord gas embolism

    Energy Technology Data Exchange (ETDEWEB)

    Tedeschi, E. [Naples Univ. (Italy). Dept. of Biomorphological and Functional Sciences]|[Parco Comola-Ricci, Naples (Italy); Marano, I.; Savarese, F.; Brunetti, A.; Sodano, A. [Naples Univ. (Italy). Dept. of Biomorphological and Functional Sciences; Olibet, G. [Naples Univ. (Italy). Intensive Care Unit; Di Salvo, E. [Naples Univ. (Italy). Dept. of General and Transplant Surgery

    1999-04-01

    A 62-year-old diabetic woman developed permanent neurological deficits in the legs following spinal anaesthesia. MRI showed oedema in the spinal cord and a small intramedullary focus of signal void at the T10 level, with negative density at CT. Intramedullary gas bubbles have not been reported previously among the possible neurological complications of spinal anaesthesia; a combined ischaemic/embolic mechanism is hypothesised. (orig.) With 2 figs., 10 refs.

  18. Spinal cord decompression reduces rat neural cell apoptosis secondary to spinal cord injury*

    OpenAIRE

    Xu, Kan; Chen, Qi-xin; Li, Fang-cai; Chen, Wei-Shan; Lin, Min; Wu, Qiong-hua

    2009-01-01

    Objective: To determine whether spinal cord decompression plays a role in neural cell apoptosis after spinal cord injury. Study design: We used an animal model of compressive spinal cord injury with incomplete paraparesis to evaluate neural cell apoptosis after decompression. Apoptosis and cellular damage were assessed by staining with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) and immunostaining for caspase-3, Bcl-2 and Bax. Meth...

  19. Central nociceptive sensitization vs. spinal cord training: opposing forms of plasticity that dictate function after complete spinal cord injury

    OpenAIRE

    Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D; Grau, James W.

    2012-01-01

    The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive) stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI) field in...

  20. A Case of Extensive Spinal Cysticercosis Involving the Whole Spinal Canal in a Patient with a History of Cerebral Cysticercosis

    OpenAIRE

    Shin, Dong Ah; Shin, Hyun Chul

    2009-01-01

    Although cysticercosis is the most common parasitic disease affecting the central nervous system, spinal cysticercosis is rare. A rare form of spinal cysticercosis involving the whole spinal canal is presented. A 45-year-old Korean male had a history of intracranial cysticercosis and showed progressive paraparesis. Spinal magnetic resonance scan showed multiple cysts compressing the spinal cord from C1 to L1. Three different levels (C1-2, T1-3, and T11-L1) required operation. Histopathologica...

  1. Spinal imaging and image analysis

    CERN Document Server

    Yao, Jianhua

    2015-01-01

    This book is instrumental to building a bridge between scientists and clinicians in the field of spine imaging by introducing state-of-the-art computational methods in the context of clinical applications.  Spine imaging via computed tomography, magnetic resonance imaging, and other radiologic imaging modalities, is essential for noninvasively visualizing and assessing spinal pathology. Computational methods support and enhance the physician’s ability to utilize these imaging techniques for diagnosis, non-invasive treatment, and intervention in clinical practice. Chapters cover a broad range of topics encompassing radiological imaging modalities, clinical imaging applications for common spine diseases, image processing, computer-aided diagnosis, quantitative analysis, data reconstruction and visualization, statistical modeling, image-guided spine intervention, and robotic surgery. This volume serves a broad audience as  contributions were written by both clinicians and researchers, which reflects the inte...

  2. Spinal antinflammatory action of Diclofenac.

    Science.gov (United States)

    Sandri, Alberto

    2016-06-01

    Diclofenac is a non-steroidal antinflammatory drug (NSAID) that finds indication in the treatment of debilitating pathologies characterized by chronic pain sustained by inflammation, such as in rheumatic disease (rheumatoid arthritis or osteoarthritis) or periarthritis, bursitis, tendonitis, myositis and sciatica. Its properties differentiate it from other NSAIDs. In fact, diclofenac's increased effect on spinal nociception and chronic neuro-inflammatory pain may be referred to: 1) its synergistic effects on peroxisome proliferator-activated receptor-γ (PPAR- γ) activation and prostaglandin synthesis inhibition (COX-2 inhibition); 2) its capacity of suppressing neuronal hyperexcitability through the blockage of neuronal K+ channels in a concentration-dependant manner; and 3) its facility to cross the blood-brain barrier. PMID:27014880

  3. Pain in spinal cord injury.

    Science.gov (United States)

    Baastrup, Cathrine; Finnerup, Nanna Brix

    2012-01-01

    SUMMARY An important and detrimental effect of spinal cord injury (SCI) is pain, which develops in approximately two-thirds of all SCI patients, while approximately half of SCI patients develop chronic neuropathic pain (NP). Thus far, there is no cure for SCI NP, and oral pharmacological intervention is often inadequate, commonly resulting in a pain reduction of only 20-30%. In this short review, we will present an overview of the important features of SCI pain including taxonomy, epidemiology and classification, as well as a suggested oral pharmacological treatment strategy for SCI NP and the current evidence available from randomized placebo-controlled trials. Considerations and evidence for the nonpharmacological treatment of SCI will be discussed briefly. PMID:24654622

  4. Muscle after spinal cord injury

    DEFF Research Database (Denmark)

    Biering-Sørensen, Bo; Kristensen, Ida Bruun; Kjaer, Michael;

    2009-01-01

    The morphological and contractile changes of muscles below the level of the lesion after spinal cord injury (SCI) are dramatic. In humans with SCI, a fiber-type transformation away from type I begins 4-7 months post-SCI and reaches a new steady state with predominantly fast glycolytic IIX fibers...... years after the injury. There is a progressive drop in the proportion of slow myosin heavy chain (MHC) isoform fibers and a rise in the proportion of fibers that coexpress both the fast and slow MHC isoforms. The oxidative enzymatic activity starts to decline after the first few months post-SCI. Muscles...... from individuals with chronic SCI show less resistance to fatigue, and the speed-related contractile properties change, becoming faster. These findings are also present in animals. Future studies should longitudinally examine changes in muscles from early SCI until steady state is reached in order...

  5. The possible meaning of fractional anisotropy measurement of the cervical spinal cord in correct diagnosis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Budrewicz, Slawomir; Szewczyk, Pawel; Bladowska, Joanna; Podemski, Ryszard; Koziorowska-Gawron, Ewa; Ejma, Maria; Słotwiński, Krzysztof; Koszewicz, Magdalena

    2016-03-01

    Diagnosis of amyotrophic lateral sclerosis (ALS) is based on clinical criteria and electrophysiological tests (electromyography, and transcranial magnetic stimulation). In the search for ALS biomarkers, the role of imaging procedures is currently emphasized, especially modern MR techniques. MR procedures were performed on 15 ALS patients and a sex- and age-matched control group. The MR examinations were performed with a 1.5-T MR unit, and the protocol consisted of sagittal T1-weighed images, sagittal and axial T2-weighed images, and sagittal T2-weighed FAT SAT images followed by an axial diffusion tensor imaging (DTI) sequence of the cervical spinal cord. FA values in individual segments of the cervical spinal cord were decreased in the ALS group in comparison with the control group. After comparing FA values for anterior, posterior, and lateral corticospinal columns, the greatest difference was observed between the C2 and C5 segments. Spinal cord assessment with the use of FA measurements allows for confirmation of the motor pathways lesion in ALS patients. The method, together with clinical criteria, could be helpful in ALS diagnosis, assessment of clinical course, or even the effects of new drugs. The results also confirmed the theory of the generalized character of ALS. PMID:26590991

  6. Replacing the computer mouse

    OpenAIRE

    Dernoncourt, Franck

    2014-01-01

    In a few months the computer mouse will be half-a-century-old. It is known to have many drawbacks, the main ones being: loss of productivity due to constant switching between keyboard and mouse, and health issues such as RSI. Like the keyboard, it is an unnatural human-computer interface. However the vast majority of computer users still use computer mice nowadays. In this article, we explore computer mouse alternatives. Our research shows that moving the mouse cursor can be done efficiently ...

  7. An encyclopedia of mouse DNA elements (Mouse ENCODE)

    OpenAIRE

    Stamatoyannopoulos, John A; Guig?? Serra, Roderic; Djebali, Sarah; Lagarde, Julien; Adams, Leslie B.

    2012-01-01

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  8. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    Science.gov (United States)

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  9. Serotonergic modulation of spinal motor control

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; Cotel, Florence

    2015-01-01

    Serotonin (5-HT) is a monoamine that powerfully modulates spinal motor control by acting on intrasynaptic and extrasynaptic receptors. Here we review the diversity of 5-HT actions on locomotor and motoneuronal activities. Two approaches have been used on in vitro spinal cord preparations: either ...... and promotes the excitability of motoneurons, while stronger release inhibits rhythmic activity and motoneuron firing. This latter effect is responsible for central fatigue and secures rotation of motor units.......Serotonin (5-HT) is a monoamine that powerfully modulates spinal motor control by acting on intrasynaptic and extrasynaptic receptors. Here we review the diversity of 5-HT actions on locomotor and motoneuronal activities. Two approaches have been used on in vitro spinal cord preparations: either...

  10. An ergonomic task analysis of spinal anaesthesia.

    LENUS (Irish Health Repository)

    Ajmal, Muhammad

    2009-12-01

    Ergonomics is the study of physical interaction between humans and their working environment. The objective of this study was to characterize the performance of spinal anaesthesia in an acute hospital setting, applying ergonomic task analysis.

  11. Brain and Spinal Cord Tumors in Adults

    Science.gov (United States)

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

  12. Extramedullary haematopoeisis causing spinal cord compression

    Directory of Open Access Journals (Sweden)

    F Ismail

    2010-08-01

    Full Text Available Extramedullary haematopoeisis (EMH is a rare cause of spinal cord compression. However, in a patient with a haematological disorder and in particular thalassaemia, EMH with paraspinal masses should be considered and imaging planned appropriately.

  13. Spinal canal surrogate for testing intradural implants.

    Science.gov (United States)

    Oya, H; Howard, M A; Shurig, R; Gillies, G T

    2012-11-01

    We have designed, built and tested an anthropomorphic-scale surrogate spinal canal, for use in preliminary evaluations of the performance characteristics of a novel intradural spinal cord stimulator. The surrogate employs a silicone mock spinal cord with semi-major and semi-minor diameters of 10 and 6 mm, respectively, commensurate with those of actual thoracic-level spinal cord. The axial restoring force provided by the 300 µm thick silicone denticulate ligament constructs on the mock cord is ~ 0.32 N mm(-1) over a 1.5 mm range of displacement, which is within a factor of 2 of that measured by others in human cadaver specimens. Examples of testing protocols of prototype intradural stimulators that employ this device are discussed. PMID:22953718

  14. Investigation of spinal pathology in notalgia paresthetica.

    Science.gov (United States)

    Savk, Oner; Savk, Ekin

    2005-06-01

    A possible association of spinal pathology with notalgia paresthetica (NP) was investigated through clinical and radiographic evaluation. Forty-three NP patients underwent dermatologic and orthopedic examination accompanied by radiography of the spine. Sixty-one lesions in 43 patients were evaluated. In 34 patients, various vertebral pathologies were observed radiographically by a blinded investigator, and in 28 of these cases these changes were most prominent in the vertebrae which corresponded to a lesional dermatome. Thirty-seven lesions were accompanied by spinal changes decided to be relevant (60.7%). The striking correlation of NP localization with spinal pathology suggests that spinal nerve impingement may contribute to the pathogenesis of this entity. PMID:15928634

  15. APOPTOSIS AFTER SPINAL CORD INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To confirm the role played by apoptosis in spinal cord injury. Methods 36 rats models of spinal cord injury were made by Allen method. Histological examinations using HE staining and in situ end-labeling were used to observe apoptosis in spinal cord tissues from 1h to 21d after injury. Results HE staining sections showed hemorrhage and necrosis, neuronal degeneration and gliai cell proliferation. In situ end-labeling sections showed the appearance of apoptosis in both gray and white matter as well as in both central and surrounding region. The number of apoptotic cells increased from 12h after injury, increased to the peak at 4d and declined to normal at 21d. Conclu sion The results suggest that apoptosis, especially glial apoptosis, plays a role in the pathogenesis of spinal cord in jury.

  16. Application of Tuina Techniques to Spinal Diseases

    Institute of Scientific and Technical Information of China (English)

    FANG Min; SHEN Guo-quan; YAN Jun-tao; HAN Chou-ping

    2003-01-01

    @@ It's one of the earliest medical techniques to relieve pain, restore health and enjoy comfort with manipulations. Knowledge on spinal neck pain, shoulder pain, low back pain and leg pain can be traced back to the early stage of human evolution and upright position of two legs. Therefore the history of treating spinal diseases with Tuina or manipulations probably keeps the same pace with civilization.

  17. Imaging Techniques in Spinal Cord Injury

    OpenAIRE

    Ellingson, BM; Salamon, N.; Holly, LT

    2012-01-01

    © 2014 Elsevier Inc. Background Spinal imaging plays a critical role in the diagnosis, treatment, and rehabilitation of patients with spinal cord injury (SCI). In recent years there has been increasing interest in the development of advanced imaging techniques to provide pertinent microstructural and metabolic information that is not provided by conventional modalities. Methods This review details the pathophysiological structural changes that accompany SCI, as well as their imaging correlate...

  18. Early treatment of spinal cord injury

    OpenAIRE

    Feng, Ya-Ping

    2016-01-01

    With the rapid development of society, the incidence of spinal cord injury (SCI) is increasing year by year, and the treatment is very difficult with a high disability rate. Correct prehospital first aid transportation can greatly reduce secondary injury of spinal cord caused by improper transportation. Early application of high dose methylprednisolone, internal fixation by using screw-rod system, as well as intramedually and extramedually decompression can protect the residual neurolog...

  19. Central Diabetes Insipidus after Staged Spinal Surgery

    OpenAIRE

    Rosenbaum, Benjamin P.; Steinmetz, Michael P.

    2013-01-01

    Diabetes insipidus (DI) is described following penetrating spinal cord trauma but rarely following instrumented spinal fusion. More commonly, hyponatremia is seen following spine surgery, which may be iatrogenic, attributed to the syndrome of inappropriate antidiuretic hormone release. The authors present a case of a 57-year-old woman who underwent a planned two-stage operation for scoliotic deformity correction. On the third postoperative day, the patient developed hypernatremia (sodium leve...

  20. Male infertility in spinal cord trauma

    OpenAIRE

    Cristiano Utida; Jose C. Truzzi; Homero Bruschini; Rogerio Simonetti; Cedenho, Agnaldo P.; Miguel Srougi; Valdemar Ortiz

    2005-01-01

    Every year there are 10 thousand new cases of patients victimized by spinal cord trauma (SCT) in the United States and it is estimated that there are 7 thousand new cases in Brazil. Eighty percent of patients are fertile males. Infertility in this patient group is due to 3 main factors resulting from spinal cord lesions: erectile dysfunction, ejaculatory disorder and low sperm counts. Erectile dysfunction has been successfully treated with oral and injectable medications, use of vacuum device...

  1. A regeneration strategy for spinal cord injury

    OpenAIRE

    Nordblom, Jonathan

    2012-01-01

    A severe traumatic spinal cord injury (SCI) frequently leads to a devastating and permanent disability. Due to glial scarring and an inhibitory local environment, regrowth of disrupted axons in the injured spinal cord beyond a lesion is obstructed, thus preventing reconnection with neurons at the other side. Many experimental strategies have been presented to limit the damage and improve outcome after SCI, but few options are available for the patient. Neurons in the central nervous sys...

  2. Simulation and resident education in spinal neurosurgery

    Directory of Open Access Journals (Sweden)

    Parker E Bohm

    2015-01-01

    Results: A brief history of simulation in medicine is given, followed by current trends of spinal simulation utilization in residency programs. General themes from the literature are identified that are integral for implementing simulation into neurosurgical residency curriculum. Finally, various applications are reported. Conclusion: The use of simulation in spinal neurosurgery education is not as ubiquitous in comparison to other neurosurgical subspecialties, but many promising methods of simulation are available for augmenting resident education.

  3. Perturbed cholesterol homeostasis in aging spinal cord.

    Science.gov (United States)

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2016-09-01

    The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging. PMID:27459933

  4. Spinal infections in children: A review.

    Science.gov (United States)

    Tyagi, Rahul

    2016-12-01

    Spinal infections are uncommon but significant causes of morbidity and hospitalization in the paediatric population. These infections encompass a broad range of conditions, from discitis to osteomyelitis and spinal epidural and intramedullary abscesses. Paediatric spinal infections can be caused by a range of bacterial, viral, fungal and parasitic agents. Ultrastructural differences of the vertebrae and associated structures result in distinct mechanisms of pathogenesis of spinal infections in children compared to adults. The non-specific nature of symptoms produced by them can cause considerable diagnostic delays. Magnetic Resonance (MR) imaging can facilitate early identification of the disease, and distinguish it from other spinal pathologies. The association of antimicrobial resistant bacterial strains from some of the cases appears worrisome; as is the increasing incidence of Kingella kingae infections causing spinal infections. Rest and immobilization are the general treatment, and prompt initiation of antimicrobial therapy is warranted to ensure optimal clinical outcome. Most patients generally have a good prognosis; however, early identification and prompt initiation of antimicrobial therapy is essential to achieve the best therapeutic response. PMID:27408498

  5. Symptomatic spinal cord metastasis from cerebral oligodendroglioma.

    Science.gov (United States)

    Elefante, A; Peca, C; Del Basso De Caro, M L; Russo, C; Formicola, F; Mariniello, G; Brunetti, A; Maiuri, F

    2012-06-01

    Spinal subarachnoid spread is not uncommon in brain oligodendrogliomas; on the other hand, symptomatic involvement of the spinal cord and cauda is very rare, with only 16 reported cases. We report the case of a 41-year-old man who underwent resection of a low-grade frontal oligodendroglioma 4 years previously. He was again observed because of bilateral sciatic pain followed by left leg paresis. A spine MRI showed an intramedullary T12-L1 tumor with root enhancement. At operation, an intramedullary anaplastic oligodendroglioma with left exophytic component was found and partially resected. Two weeks later, a large left frontoparietal anaplastic oligodendroglioma was diagnosed and completely resected. The patient was neurologically stable for 8 months and died 1 year after the spinal surgery because of diffuse brain and spinal leptomeningeal spread. The review of the reported cases shows that spinal symptomatic metastases can occur in both low-grade and anaplastic oligodendrogliomas, even many years after surgery of the primary tumor; however, they exceptionally occur as first clinical manifestation or as anaplastic progression. The spinal seeding represents a negative event leading to a short survival.

  6. Spinal astrocytes produce and secrete dynorphin neuropeptides.

    Science.gov (United States)

    Wahlert, Andrew; Funkelstein, Lydiane; Fitzsimmons, Bethany; Yaksh, Tony; Hook, Vivian

    2013-04-01

    Dynorphin peptide neurotransmitters (neuropeptides) have been implicated in spinal pain processing based on the observations that intrathecal delivery of dynorphin results in proalgesic effects and disruption of extracellular dynorphin activity (by antisera) prevents injury evoked hyperalgesia. However, the cellular source of secreted spinal dynorphin has been unknown. For this reason, this study investigated the expression and secretion of dynorphin-related neuropeptides from spinal astrocytes (rat) in primary culture. Dynorphin A (1-17), dynorphin B, and α-neoendorphin were found to be present in the astrocytes, illustrated by immunofluorescence confocal microscopy, in a discrete punctate pattern of cellular localization. Measurement of astrocyte cellular levels of these dynorphins by radioimmunoassays confirmed the expression of these three dynorphin-related neuropeptides. Notably, BzATP (3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate) and KLA (di[3-deoxy-D-manno-octulosonyl]-lipid A) activation of purinergic and toll-like receptors, respectively, resulted in stimulated secretion of dynorphins A and B. However, α-neoendorphin secretion was not affected by BzATP or KLA. These findings suggest that dynorphins A and B undergo regulated secretion from spinal astrocytes. These findings also suggest that spinal astrocytes may provide secreted dynorphins that participate in spinal pain processing.

  7. The MOUSE Squad

    Science.gov (United States)

    Borja, Rhea R.

    2004-01-01

    This article presents a New York city after-school program started by MOUSE (Making Opportunities for Upgrading Schools and Education), a national nonprofit group that teaches students how to fix computers, and equips them with the communication and problem-solving skills to help them in the working world. The MOUSE program is part of a trend…

  8. Mouse genome database 2016.

    Science.gov (United States)

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data.

  9. Drug distribution in spinal cord during administration with spinal loop dialysis probes in anaesthetized rats

    DEFF Research Database (Denmark)

    Uustalu, Maria; Abelson, Klas S P

    2007-01-01

    over time. Then, the distribution of the different [(3)H]epibatidine concentrations along the spinal cord was studied. It was found that the percentage of [(3)H]epibatidine entering the spinal cord did not differ between different administered concentrations after a stabilization period of 60 min...

  10. The effect of spinal manipulative therapy on spinal range of motion

    DEFF Research Database (Denmark)

    Millan, Mario; Leboeuf-Yde, Charlotte; Budgell, Brian;

    2012-01-01

    Spinal manipulative therapy (SMT) has been shown to have an effect on spine-related pain, both clinically and in experimentally induced pain. However, it is unclear if it has an immediate noticeable biomechanical effect on spinal motion that can be measured in terms of an increased range of motion...

  11. Changes in lumbosacral spinal nerve roots on diffusion tensor imaging in spinal stenosis

    Directory of Open Access Journals (Sweden)

    Zhong-jun Hou

    2015-01-01

    Full Text Available Lumbosacral degenerative disc disease is a common cause of lower back and leg pain. Conventional T1-weighted imaging (T1WI and T2-weighted imaging (T2WI scans are commonly used to image spinal cord degeneration. However, these modalities are unable to image the entire lumbosacral spinal nerve roots. Thus, in the present study, we assessed the potential of diffusion tensor imaging (DTI for quantitative assessment of compressed lumbosacral spinal nerve roots. Subjects were 20 young healthy volunteers and 31 patients with lumbosacral stenosis. T2WI showed that the residual dural sac area was less than two-thirds that of the corresponding normal area in patients from L 3 to S 1 stenosis. On T1WI and T2WI, 74 lumbosacral spinal nerve roots from 31 patients showed compression changes. DTI showed thinning and distortion in 36 lumbosacral spinal nerve roots (49% and abruption in 17 lumbosacral spinal nerve roots (23%. Moreover, fractional anisotropy values were reduced in the lumbosacral spinal nerve roots of patients with lumbosacral stenosis. These findings suggest that DTI can objectively and quantitatively evaluate the severity of lumbosacral spinal nerve root compression.

  12. Spinal cord infarction: a rare cause of paraplegia.

    Science.gov (United States)

    Patel, Sonali; Naidoo, Khimara; Thomas, Peter

    2014-06-25

    Spinal cord infarction is rare and represents a diagnostic challenge for many physicians. There are few reported cases worldwide with a prevalence of 1.2% of all strokes. Circulation to the spinal cord is supplied by a rich anastomosis. The anterior spinal artery supplies the anterior two thirds of the spinal cord and infarction to this area is marked by paralysis, spinothalamic sensory deficit and loss of sphincter control depending on where the lesion is. Treatment of spinal cord infarction focuses on rehabilitation with diverse outcomes. This report presents a case of acute spinal cord infarction with acquisition of MRI to aid diagnosis.

  13. Surgical treatment of hydrocephalus and spinal dysraphism

    Institute of Scientific and Technical Information of China (English)

    Besnik Elshani; Basri Lenjani

    2014-01-01

    Objective:To identify during intrauterine congenital malformations;Surgery to dysraphism and hydrocephalus neurological benefit, the ability to live independently;Forecast possibility of lowering birth rates with congenital malformations.Methods:Epidemiological and congenital malformations of the spinal dysraphism were included in this prospective clinical study-research.Its forms were manifested by the appearance of hydrocephalus inNeurosurgicalClinic inPristina for the period2010-2012.All cases of spinal dysraphism operated in theNeurosurgery Clinic inPrishtina for the period2010-2012 were analyzed.Results:In theNeurosurgeryClinic atUCC since2010 to2012 are operated total55 cases of spinal dysraphism;The largest number of operations were recorded in2011 with20 operated cases or36.36%, while smaller in2010 with17 operated cases or30.91%,Number of patients varies by year, with some variations of the graph, where at the beginning of the graph have gradually increased over the years, following the continuous growing and finally landing back with graph;By sex and years, the largest number of cases in male gender with spinal dysraphism were registered in2012 with14 cases or37.8%, while the smallest number in2010 with11 cases or29.7%,Whereas the female gender, number of large backlog of cases was registered in2011 with8 cases or44.4%, while the smallest number in 2012 with4 cases or22.2%.Divided by types of spinal dysraphism total were identified:13 with spinal dysraphism meningocele or23.6% and42 spinal dysraphism myelomeningocele or76.4% of which were male dominance in relation to female sex ratio(M:F =40:15 occasions), by gender and spinal dysraphism species, the males are identified with many cases, the spinal dysraphism meningocele8 or20% and32 with spinal dysraphism myelomeningocele or80%,Eksterioizm Shanti where the body rejects foreign body system as the one we had at1 patient.Conclusions:Shant meningitis due to infection or eventual reduction in immune

  14. Engineering a new mouse model for vitiligo.

    Science.gov (United States)

    Manga, Prashiela; Orlow, Seth J

    2012-07-01

    Although the precise mechanisms that trigger vitiligo remain elusive, autoimmune responses mediate its progression. The development of therapies has been impeded by a paucity of animal models, since mice lack interfollicular melanocytes, the primary targets in vitiligo. In this issue, Harris et al. describe a mouse model in which interfollicular melanocytes are retained by Kit ligand overexpression and an immune response is initiated by transplanting melanocyte-targeting CD8+ T cells.

  15. Insights from Human/Mouse genome comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.

    2003-03-30

    Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

  16. Role of fetal surgery in spinal dysraphism

    Directory of Open Access Journals (Sweden)

    A Martina Messing-Jünger

    2013-01-01

    Full Text Available Open spinal dysraphism is a common and clinically challenging organo-genetic malformation. Due to the well-known multi-organ affection with significant implication on the lives of patients and their families, abortion after prenatal diagnosis became reality in most parts of the world. After publication of the Management of Myelomeningocele Study (MOMS results fetal surgery seems to be a new option and a broad discussion arose regarding advantages and risks of in utero treatment of spina bifida. This paper tries to evaluate objectively the actual state of knowledge and experience. This review article gives a historical overview as well as the experimental and pathophysiological background of fetal surgery in open spinal dysraphism. Additionally clinical follow-up experience of foetoscopically treated patients are presented and discussed. After carefully outweighing all available information on fetal surgery for spina bifida, one has to conclude, in accordance with the MOMS investigators, that in utero surgery cannot be considered a standard option at present time. But there is clear evidence of the hypothesis that early closure of the spinal canal has a positive influence on spinal cord function and severity of Chiari malformation type II, has been proven. A persisting problem is the fetal risk of prematurity and the maternal risk of uterus damage. There is also evidence that due to technical restrictions, fetal closure of the spinal canal bears unsolved problems leading to a higher postnatal incidence of complication surgery. Finally, missing long-term results make a definite evaluation impossible so far. At the moment, fetal surgery in open spinal dysraphism is not a standard of care despite promising results regarding central nervous system protection due to early spinal canal closure. Many technical problems need to be solved in the future in order to make this option a safe and standard one.

  17. Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS

    OpenAIRE

    Omura, T; Omura, K.; Tedeschi, A; Riva, P; Painter, MW; L. Rojas; Martin, J.; Lisi, V; Huebner, EA; Latremoliere, A; Yin, Y.; Barrett, LB; Singh, B; Lee, S.; Crisman, T

    2015-01-01

    © 2015 Elsevier Inc. Axon regeneration in the CNS requires reactivating injured neurons' intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice a...

  18. Morphometric analysis of the cervical spinal canal on MRI.

    Science.gov (United States)

    Matveeva, Niki; Janevski, Petar; Nakeva, Natasha; Zhivadinovik, Julija; Dodevski, Ace

    2013-01-01

    Two useful numerical values, called the Torg ratio and the spinal canal diameter (SC diameter) are widely accepted as reliable morphometric determinants of spinal stenosis. The aims of the study were to examine morphometric determinants of the cervical spinal canal on MRI in both sexes and analyse them as reliable indicators of spinal stenosis. Measurements were made on 50 MR images (sagittal T2 weighted images from C3 to C7) of the cervical spine of patients from the Emergency Centre who had undertaken MRI of the cervical spine in addition to CT for various diagnostic indications. Torg ratio, used in evaluation of the spinal canal stenosis on plain x-ray radiographs, cannot be used as a spinal canal stenosis indicator due to the gender differences in the vertebral bodies' width. Sagittal canal diameters were more spread out in males than in females. MRI enables the value of the space available for the spinal cord, (SAC) to be determined, by subtracting the sagittal diameter of the spinal cord from the sagittal diameter of the spinal canal. Not gender, but individual and level differences in the SAC values were evident (cervical cord enlargement). SAC values relied more on the spinal canal than on the spinal cord, so that the differences in the dimensions of the spinal cord accounted for less variability in the SAC values. MR imaging of the cervical spine provides more accurate cervical canal and spinal cord measurements that could serve as morphometric determinants of the cervical canal stenosis. PMID:24280784

  19. Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in EAE mouse

    OpenAIRE

    Leung, Gary; Sun, WenJing; Zheng, Lingxing; Brookes, Sarah; Tully, Melissa; Shi, Riyi

    2010-01-01

    Oxidative stress is considered a major contributor in the pathology of multiple sclerosis (MS). Acrolein, a highly reactive aldehyde byproduct of lipid peroxidation, is thought to perpetuate oxidative stress. In this study, we aimed to determine the role of acrolein in an animal model of MS, experimental autoimmune enchephalomyelitis (EAE) mice. We have demonstrated a significant elevation of acrolein protein adduct levels in EAE mouse spinal cord. Hydralazine, a known acrolein scavenger, sig...

  20. Experimental Optic Neuritis Induced by a Demyelinating Strain of Mouse Hepatitis Virus▿

    OpenAIRE

    Shindler, Kenneth S.; Kenyon, Lawrence C; Dutt, Mahasweta; Hingley, Susan T.; Sarma, Jayasri Das

    2008-01-01

    Optic neuritis (ON), an inflammatory demyelinating optic nerve disease, occurs in multiple sclerosis (MS). Pathological mechanisms and potential treatments for ON have been studied via experimental autoimmune MS models. However, evidence suggests that virus-induced inflammation is a likely etiology triggering MS and ON; experimental virus-induced ON models are therefore required. We demonstrate that MHV-A59, a mouse hepatitis virus (MHV) strain that causes brain and spinal cord inflammation a...

  1. The primary locus of motor neuron death in an ALS–PDC mouse model

    OpenAIRE

    Lee, Grace; Chu, Tony; Shaw, Christopher A.

    2009-01-01

    A mouse model of amyotrophic lateral sclerosis–parkinsonism–dementia complex based on the consumption of cycad seed flour was used to determine whether the observed pathology of motor neuron loss begins in the distal axons or the spinal cord. Assessments of neuromuscular junction integrity and motor neurons were performed at multiple time points. Mice fed cycad pellets performed worse on the wire hang than controls. Microglial activation in cycad-fed mice was observed with motor neuron degene...

  2. Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

    Directory of Open Access Journals (Sweden)

    Jian-jun Sun

    2015-01-01

    Full Text Available This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133 + and CD133− cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133 + cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133− cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133 + astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133− astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.

  3. Nimodipine alleviates apoptosis-mediated impairments through the mitochondrial pathway after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yafei CAI; Rui FAN; Tianmiao HUA; Huiling LIU; Jing LI

    2011-01-01

    Spinal cord injury (SCI) remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine (an L-type Ca2+ channel antagonist) on functional recovery from SCI using Nystrom's method in a mouse model. Eighty-four mice were divided into three groups: control group in which only vertebral plates were cut off without causing any spinal injuries; SCI; and SCI with nimodipine treatment. We assessed the histopathology, apoptosis detection, cell cycle, mitochondrial transmembrane potential, bcl-2/bax and caspase-3 levels of tissue 8 h, 1 d, 3 d and 4 d after trauma to evaluate rehabilitation. Behavioral performances were also assessed before and after nimodipine treatment. Results from inclined plane tests, motor score assessment and histological observations indicated that mice in the nimodipine-treated group rehabilitated better than those in the SCI group. The ratio of apoptosis, caspase-3 and bax expression in the nimodipine-treated group were significantly lower than those in the SCI group. The mitochondrial membrane potential and bcl-2 expression were up-regulated in the nimodipine-treated group. Taken together, our results indicate that the inhibition of calcium flux by nimodipine could reduce apoptosis processes and tissue damage through a mitochondrial pathway after spinal cord trauma [Current Zoology 57 (3): 340-349, 2011].

  4. Prevention against diffuse spinal cord astrocytoma:can the Notch pathway be a novel treatment target?

    Institute of Scientific and Technical Information of China (English)

    Jian-jun Sun; Jin-long Mao; Xiao-hui Lou; Zhen-yu Wang; Ling-song Li; Hai-yan Yu; Yong-sheng Xu; Hai-bo Wu; Yi Luo; Bin Liu; Mei Zheng

    2015-01-01

    This study was designed to investigate whether the Notch pathway is involved in the develop-ment of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133+and CD133− cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7–11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133+ cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133− cell suspension, and Notch-immunopositive expres-sion was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133+ astro-cytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However,it should be emphasized that the sub-cortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133− astrocytoma cells. However, these ifndings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treat-ment target for diffuse spinal cord astrocytoma.

  5. Gene expression in the spinal cord in female lewis rats with experimental autoimmune encephalomyelitis induced with myelin basic protein.

    Directory of Open Access Journals (Sweden)

    Hayley R Inglis

    Full Text Available BACKGROUND: Experimental autoimmune encephalomyelitis (EAE, the best available model of multiple sclerosis, can be induced in different animal strains using immunization with central nervous system antigens. EAE is associated with inflammation and demyelination of the nervous system. Micro-array can be used to investigate gene expression and biological pathways that are altered during disease. There are few studies of the changes in gene expression in EAE, and these have mostly been done in a chronic mouse EAE model. EAE induced in the Lewis with myelin basic protein (MBP-EAE is well characterised, making it an ideal candidate for the analysis of gene expression in this disease model. METHODOLOGY/PRINCIPAL FINDINGS: MBP-EAE was induced in female Lewis rats by inoculation with MBP and adjuvants. Total RNA was extracted from the spinal cords and used for micro-array analysis using AffimetrixGeneChip Rat Exon 1.0 ST Arrays. Gene expression in the spinal cords was compared between healthy female rats and female rats with MBP-EAE. Gene expression in the spinal cord of rats with MBP-EAE differed from that in the spinal cord of normal rats, and there was regulation of pathways involved with immune function and nervous system function. For selected genes the change in expression was confirmed with real-time PCR. CONCLUSIONS/SIGNIFICANCE: EAE leads to modulation of gene expression in the spinal cord. We have identified the genes that are most significantly regulated in MBP-EAE in the Lewis rat and produced a profile of gene expression in the spinal cord at the peak of disease.

  6. Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    David J. Gifondorwa

    2012-01-01

    Full Text Available A prominent clinical feature of ALS is muscle weakness due to dysfunction, denervation and degeneration of motoneurons (MNs. While MN degeneration is a late stage event in the ALS mouse model, muscle denervation occurs significantly earlier in the disease. Strategies to prevent this early denervation may improve quality of life by maintaining muscle control and slowing disease progression. The precise cause of MN dysfunction and denervation is not known, but several mechanisms have been proposed that involve potentially toxic intra- and extracellular changes. Many cells confront these changes by mounting a stress response that includes increased expression of heat shock protein 70 (Hsp70. MNs do not upregulate Hsp70, and this may result in a potentially increased vulnerability. We previously reported that recombinant human hsp70 (rhHsp70 injections delayed symptom onset and increased lifespan in SOD1G93A mice. The exogenous rhHsp70 was localized to the muscle and not to spinal cord or brain suggesting it modulates peripheral pathophysiology. In the current study, we focused on earlier administration of Hsp70 and its effect on initial muscle denervation. Injections of the protein appeared to arrest denervation with preserved large myelinated peripheral axons, and reduced glial activation.

  7. Mouse models of congenital cataract.

    Science.gov (United States)

    Graw, J

    1999-06-01

    Mouse mutants affecting lens development are excellent models for corresponding human disorders. The mutant aphakia has been characterised by bilaterally aphakic eyes (Varnum and Stevens, J Hered 1968;59:147-50); the corresponding gene was mapped to chromosome 19 (Varnum and Stevens, Mouse News Lett 1975;53:35). Recent investigations in our laboratory refined the linkage of 0.6 cM proximal to the marker D19Mit10. Several candidate genes have been excluded (Chuk1, Fgf8, Lbp1, Npm3, Pax2, Pitx3). The Cat3 mutations are characterised by vacuolated lenses caused by alterations in the initial secondary lens fibre cell differentiation. Secondary malformations develop at the cornea and iris, but the retina remains unaffected. The mutation has been mapped to chromosome 10 close to the markers D10Mit41 and D10Mit95. Several candidate genes have been excluded (Dcn, Elk3, Ldc, Mell8, Tr2-11). The series of Cat2 mutations have been mapped close to the gamma-crystallin genes (Cryg; Löster et al., Genomics 1994;23:240-2). The Cat2nop mutation is characterised by a mutation in the third exon of Crygb leading to a truncated gamma B-crystallin and the termination of lens fibre cell differentiation. The Cat2 mutants are interesting models for human cataracts caused by mutations in the human CRYG genes at chromosome 2q32-35. PMID:10627821

  8. Central nociceptive sensitization vs. spinal cord training: Opposing forms of plasticity that dictate function after complete spinal cord injury

    Directory of Open Access Journals (Sweden)

    Adam R Ferguson

    2012-10-01

    Full Text Available The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome learning. Instrumental flexion training produces a central change in spinal plasticity that enables future spinal learning on both the ipsilateral and contralateral leg. However, if stimulation is given in a response-independent manner, the spinal cord develops central maladaptive plasticity that undermines future spinal learning on both legs. The present paper tests for interactions between spinal cord training and central nociceptive sensitization after complete spinal cord transection. We found that spinal training alters future central sensitization by intradermal formalin (24 h post-training. Conversely intradermal formalin impaired future spinal learning (24 h post-injection. Because the NMDA receptor has been implicated in formalin-induced central sensitization, we tested whether pretreatment with NMDA affects spinal learning. We found intrathecal NMDA impaired learning in a dose-dependent fashion, and that this effect endures for at least 24h. These data provide strong evidence for an

  9. Seminal plasma PSA in spinal cord injured men

    DEFF Research Database (Denmark)

    Brasso, K; Sønksen, J; Sommer, P;

    1998-01-01

    The aim of the study was to evaluate the impact of spinal cord injury on seminal plasma PSA concentration.......The aim of the study was to evaluate the impact of spinal cord injury on seminal plasma PSA concentration....

  10. Vocational Rehabilitation of Persons with Spinal Cord Injuries

    Science.gov (United States)

    Poor, Charles R.

    1975-01-01

    Reviews historical development of organized vocational rehabilitation programming for the spinal cord injured in the United States. Significant factors that affect vocational rehabilitation outcomes with spinal cord injured persons are listed and discussed. (Author)

  11. Primary spinal intradural hydatid cyst--a short report.

    Science.gov (United States)

    Pushparaj, K; Sundararajan, M; Madeswaran, K; Ambalavanan, S

    2001-06-01

    Primary spinal hydatid cysts are uncommon. Among these, intradural presentation is very rare. A case of primary spinal intradural hydatid cyst presenting as incomplete dorsal cord compression is reported here for its rarity. PMID:11447449

  12. Primary spinal intradural hydatid cyst--a short report.

    Directory of Open Access Journals (Sweden)

    Pushparaj K

    2001-04-01

    Full Text Available Primary spinal hydatid cysts are uncommon. Among these, intradural presentation is very rare. A case of primary spinal intradural hydatid cyst presenting as incomplete dorsal cord compression is reported here for its rarity.

  13. Primary spinal intradural hydatid cyst--a short report.

    OpenAIRE

    Pushparaj K; Sundararajan M; Madeswaran K; Ambalavanan S

    2001-01-01

    Primary spinal hydatid cysts are uncommon. Among these, intradural presentation is very rare. A case of primary spinal intradural hydatid cyst presenting as incomplete dorsal cord compression is reported here for its rarity.

  14. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    Science.gov (United States)

    ... myoclonic epilepsy spinal muscular atrophy with progressive myoclonic epilepsy Enable Javascript to view the expand/collapse boxes. ... All Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

  15. Mechanisms of symptomatic spinal cord ischemia after TEVAR

    DEFF Research Database (Denmark)

    Czerny, Martin; Eggebrecht, Holger; Sodeck, Gottfried;

    2012-01-01

    To test the hypothesis that simultaneous closure of at least 2 independent vascular territories supplying the spinal cord and/or prolonged hypotension may be associated with symptomatic spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR)....

  16. An interesting case of primary spinal arachnoiditis.

    LENUS (Irish Health Repository)

    Vaughan, Denis

    2012-02-27

    Spinal arachnoiditis describes inflammation of the meninges, subarachnoid space and, in most cases, also involve the pial layer. The vast majority of cases described are secondary and are preceded by a known event, for example,. trauma, infections or irritative substances. Here, we present the case of primary spinal arachnoiditis. A 35-year-old lady was referred to the neurosurgical services in Dublin, Ireland with a 15-month history of progressive, right lower limb weakness. Magnetic resonance imaging revealed cystic distortion of the lumbar spinal canal extending up to the conus. Initially, an L2-L4 laminectomy was performed revealing thickened and adherent arachnoid with a large cyst in the spinal canal. Four months after initial operation, the patient represented with bilateral lower limb weakness and loss of detrusor function. Repeat magnetic resonance imaging was performed, which showed the development of a syrinx in the patient\\'s thoracic spine. We then performed a T9-T10 laminectomy, midline myelotomy and insertion of a syringe-arachnoid shunt. Post-operative imaging showed resolution of the syrinx and a vast improvement in lower limb power. The patient also regained bladder control. In conclusion, spinal arachnoiditis is a clearly defined pathological and radiological entity with a highly variable clinical presentation. It is exceedingly difficult to treat as there is no recognised treatment currently, with most interventions aimed at symptomatic relief.

  17. Schwann cells for spinal cord repair

    Directory of Open Access Journals (Sweden)

    Oudega M.

    2005-01-01

    Full Text Available The complex nature of spinal cord injury appears to demand a multifactorial repair strategy. One of the components that will likely be included is an implant that will fill the area of lost nervous tissue and provide a growth substrate for injured axons. Here we will discuss the role of Schwann cells (SCs in cell-based, surgical repair strategies of the injured adult spinal cord. We will review key studies that showed that intraspinal SC grafts limit injury-induced tissue loss and promote axonal regeneration and myelination, and that this response can be improved by adding neurotrophic factors or anti-inflammatory agents. These results will be compared with several other approaches to the repair of the spinal cord. A general concern with repair strategies is the limited functional recovery, which is in large part due to the failure of axons to grow across the scar tissue at the distal graft-spinal cord interface. Consequently, new synaptic connections with spinal neurons involved in motor function are not formed. We will highlight repair approaches that did result in growth across the scar and discuss the necessity for more studies involving larger, clinically relevant types of injuries, addressing this specific issue. Finally, this review will reflect on the prospect of SCs for repair strategies in the clinic.

  18. [Cloning of gene fragment of estrogen receptor-beta and its expression in mouse embryo].

    Science.gov (United States)

    Zhang, Zi-Feng; Fan, Shao-Hua; Lu, Jun; Wu, Dong-Mei; Shan, Qun; Hu, Bin; Li, Fei; Zheng, Yuan-Lin

    2008-03-01

    In order to study the expression and regulation effects of estrogen receptor-beta (ERbeta) in the development of mouse embryo, the primer of ERbeta was designed, the ERbeta fragment was first obtained by RT-PCR and subcloned into plasmids pGEM- 3Z, then the recombinant plasmids were linearized with the restriction enzymes of EcoRand Hind. Using Sp6 and T7 RNA polymerase, the digoxigenin(dig) labeled sense and anti-sense probes were transcriped in vitro, respectively. Then the expression of ERbeta in mouse embryo was examined with the probes by whole-mount in situ hybridization. The results indicated that ERbeta is expressed in the brain, spinal neural tube, genital ridge, pericardium, limb bud and mandibular arch of 10.5 dpc embryo, and is also expressed in the telencephalon, mesencephalon, medulla oblongata, spinal cord and limb bud of 13.5 dpc embryo. These results suggest that ERbeta maybe play a role of regulation in sexual differentiation, primal differentiation of neural tube, further differentiation of three primary cerebral vesicles and spinal cord, generation and differentiation of bone and cartilage of limb bud, development of pericardium and configuration differentiation of mandibular in mouse embryo. PMID:18332005

  19. Dual action mechanisms of KK-3, a newly synthesized leu-enkephalin derivative, in the production of spinal analgesic effects.

    Science.gov (United States)

    Takahashi, M; Senda, T; Kaneto, H

    1990-04-01

    The action mechanism for the production of spinal analgesia of KK-3, tyrosyl-N-methyl-gamma-aminobutylyl-phenylalaninol, was examined by the tail pinch and tail flick methods. Intrathecal KK-3, 2.5, 5 and 10 nmol/mouse, dose-dependently produced an analgesic effect in both methods. In the tail pinch method, the analgesia was suppressed by 2 mg/kg but not by 1 mg/kg of naloxone; however, the analgesic effect was significantly antagonized by 1 and 2 mg/kg Mr2266, a kappa-antagonist. Meanwhile, both naloxone and Mr2266 failed to block the analgesic effect of KK-3 in the tail flick test. Intrathecal capsaicin, 0.3, 3 and 15 nmol/mouse, also produced a dose-dependent analgesic effect in the tail flick test, whereas no appreciable analgesia could be found in the tail pinch test. Neither naloxone nor Mr2266 blocked the analgesic effect of capsaicin. The results indicate that KK-3 may possess two separate pharmacological mechanisms for the production of analgesic effects on the spinal level: one is the depletion of substance P following its release from the spinal cord, and the other is the mediation through kappa-opioid receptors. PMID:2342228

  20. Making Human Neurons from Stem Cells after Spinal Cord Injury

    OpenAIRE

    Jun Yan; Leyan Xu; Welsh, Annie M; Glen Hatfield; Thomas Hazel; Karl Johe; Koliatsos, Vassilis E.

    2007-01-01

    Editors' Summary Background. Every year, spinal cord injuries, many caused by road traffic accidents, paralyze about 11,000 people in the US. This paralysis occurs because the spinal cord is the main communication highway between the body and the brain. Information from the skin and other sensory organs is transmitted to the brain along the spinal cord by bundles of neurons, nervous system cells that transmit and receive messages. The brain then sends information back down the spinal cord to ...

  1. Characteristics and rehabilitation for patients with spinal cord stab injury

    OpenAIRE

    Wang, Fangyong; Zhang, Junwei; Tang, Hehu; LI, XIANG; Jiang, Shudong; Lv, Zhen; Liu, Shujia; Chen, Shizheng; Liu, Jiesheng; Hong, Yi

    2015-01-01

    [Purpose] The objective of the study was to compare the incidence, diagnosis, treatment, and prognosis of patients with spinal cord stab injury to those with the more common spinal cord contusion injury. [Subjects] Of patients hospitalized in China Rehabilitation Research Center from 1994 to 2014, 40 of those having a spinal cord stab injury and 50 with spinal cord contusion were selected. [Methods] The data of all patients were analyzed retrospectively. The cases were evaluated by collecting...

  2. Transient Spinal Cord Ischemia as Presenting Manifestation of Polycythemia Vera

    Directory of Open Access Journals (Sweden)

    Sónia Costa

    2011-10-01

    Full Text Available Spinal arterial vascularization is supplied by a large anastomotic net, making spinal ischemic events far less common than ischemic cerebral strokes. Polycythemia vera, due to blood hyperviscosity and activated platelet aggregation, is associated with a higher risk of arterial and venous thrombotic events. We report a patient with spinal cord transient ischemic attacks, a rarely presenting manifestation, and polycythemia vera, which highlights the thrombotic potential of this disease, and the requirement of exhaustive diagnostic workout of a spinal ischemic event.

  3. Non-enhancing pilocytic astrocytoma of the spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Larson, David B. [University of Colorado Health Sciences Center, Department of Radiology A-030, Denver, CO (United States); Hedlund, Gary L. [Primary Children' s Medical Center, Department of Medical Imaging, Salt Lake, Utah (United States)

    2006-12-15

    Pilocytic astrocytomas are among the most common intramedullary spinal cord tumors in the pediatric age group. The presence of contrast enhancement is a major factor used to distinguish these tumors from other spinal cord lesions. We present a case of histologically proved non-enhancing intramedullary spinal cord pilocytic astrocytoma in a 12-year-old girl. This case represents an exception to the conventional wisdom that pediatric spinal neoplasms enhance with administration of intravenous contrast material. (orig.)

  4. Unusual presentation of a primary spinal Burkitt's lymphoma

    OpenAIRE

    WILKENING, A; Brack, M.; Brandis, A; Heidenreich, F; Dengler, R.; Weibenborn, K

    2001-01-01

    Primary CNS lymphomas are detected with increasing frequency in immunocompetent and immunodeficient persons. Primary involvement of the spinal roots has only rarely been reported. The unusual history is described of a patient with a primary spinal Burkitt's lymphoma initially presenting as an S1 syndrome showing lymphocytic pleocytosis in the CSF, leading to the misdiagnosis of meningoradiculitis. Repeated spinal MRI disclosed a spinal mass lesion and histological and imm...

  5. [Spinal sonography of a newborn infant with postpartal paraplegia].

    Science.gov (United States)

    Sauter, R; Klemm, T

    1988-01-01

    Cranial ultrasonography is a well established diagnostic procedure. In contrast ultrasonography of the spine and the spinal cord is less frequently used. It is indicated in infants with spinal dysraphism and may help to diagnose patients with meningomyelocele, spinal lipoma or cord tethering. We present a newborn with parplectic symptoms as a result of an epidural hematoma, which could be demonstrated exclusively by ultrasonography. We want to stress that spinal ultrasonography is a method of high clinical value.

  6. Cervical spinal canal narrowing and cervical neurologi-cal injuries

    OpenAIRE

    Zhang, Ling; Chen, Hai-Bin; Wang, Yi; ZHANG Li-ying; Liu, Jing-cheng; WANG Zheng-guo

    2012-01-01

    【Abstract】Cervical spinal canal narrowing can lead to injury of the spinal cord and neurological symptoms in-cluding neck pain, headache, weakness and parasthesisas. According to previous and recent clinical researches, we investigated the geometric parameters of normal cervical spinal canal including the sagittal and transverse diameters as well as Torg ratio. The mean sagittal diameter of cervical spinal canal at C 1 to C 7 ranges from 15.33 mm to 20.46 mm, ...

  7. Value of Micro-CT for Monitoring Spinal Microvascular Changes after Chronic Spinal Cord Compression

    Directory of Open Access Journals (Sweden)

    Hou-Qing Long

    2014-07-01

    Full Text Available Neurological degeneration can occur after compression of the spinal cord. It is widely accepted that spinal cord compression leads to ischemic lesions and ultimately neurological dysfunction due to a narrowed spinal canal. Therefore, an in-depth understanding of the pathogenesis of spinal cord compression injury is required to help develop effective clinical interventions. In the present study, we propose a new method of quantitative 3D micro-CT to observe microvascular events in a chronic spinal cord compression rat model. A total of 36 rats were divided into two groups: sham control group (n = 12 and compressive spinal cord injury group (n = 24. Rats were scarified at four weeks after surgery. In each group, CD34 micro-vessel immunohistochemical staining was performed in half of the animals, while micro-CT scanning was performed in the other half. Microvessel density (MVD was measured after immunohistochemical staining, while the vascular index (VI was measured in 3D micro-CT. In comparison with sham control, abnormal somatosensory evoked potentials (SEP can be seen in all 24 cases of the compression group, and VI shows the amount of microvessels reduced consistently and significantly (p < 0.01. A significant correlation is also found between MVD and VI (r = 0.95, p < 0.01. These data suggest that quantitative 3D micro-CT is a sensitive and promising tool for investigating microvascular changes during chronic compressive spinal cord injury.

  8. Expression of nerve growth factor in spinal dorsal horn following crushed spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: The aim of this study was to explore the expression of nerve growth factor(NGF) in spinal dorsal horn following crushed spinal cord injury. METHODS: The adult Srague-Dawley rat model of crushed spinal cord injury was established by the method in our laboratory, and intact spinal cord was used as control. The rats were sacrificed respectively after 24 hours, 7 days, and 21 days of operation, and the L3 spinal segments were removed out and fixed in 4% polyformaldehyde. The segments were sectioned into sections of 20 μm in thickness. The sections were stained with anti-NGF antibody by ABC method of immunohistochemistry technique. The immunoreactive intensity of NGF and the number of positive neurons as well as glial cells in dorsal horn were observed and counted under light microscope. RESULTS: The number of positive cells and immunoreactive intensity of NGF increased gradually in the dorsal horn at 24 hours, 7 days and 21 days following crushed spinal cord injury compared with control group (P<0.01). CONCLUSION: These results indicated that NGF plays an important role in the postoperative reaction during the early period of the crushed spinal cord injury.

  9. Concentration of nitric oxide (NO in spinal fluid of chronic spinal disease.

    Directory of Open Access Journals (Sweden)

    Yumite Y

    2001-08-01

    Full Text Available We studied total nitric oxide (nitrite + nitrate (NO levels in cerebrospinal fluid (CSF of chronic spinal diseases in nonsmokers (133 patients: 76 men and 57 women; mean age, 63 years; range, 15-92 years by the Griess method to clarify the role of NO in different spinal diseases. The extent of compression in terms of numbers of disc level at the compressed spinal nerve and neurological evaluation were also assessed according to the Japanese Orthopaedic Association scores. The spinal diseases included cervical myelopathy and radiculopathy (cervical disease group, ossification of yellow ligament (thoracic disease group, and lumbar disc herniation, lumbar canal stenosis and lumbar spondylolisthesis (lumbar disease group. NO levels in the spinal disease groups (4.98+/-2.28 micromol/l: mean +/- SD were significantly higher than that in the control group (2.53+/-0.94 micromol/l. An inverse correlation was detected between the elevated levels of NO and the grade of clinical symptoms in the cervical disorders. The number of disc level at the compressed spinal nerve was positively correlated with elevated NO levels in CSF in the cervical and lumbar disorder groups. These results indicate that nerve compression may elevate NO levels in CSF, and that NO concentration in the CSF might be a useful marker of damage to nervous system in spinal disorders.

  10. Mouse Phenome Database (MPD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

  11. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  12. Endogenous Two-Photon Excited Fluorescence Provides Label-Free Visualization of the Inflammatory Response in the Rodent Spinal Cord

    Science.gov (United States)

    Uckermann, Ortrud; Galli, Roberta; Beiermeister, Rudolf; Sitoci-Ficici, Kerim-Hakan; Later, Robert; Leipnitz, Elke; Neuwirth, Ales; Chavakis, Triantafyllos; Koch, Edmund; Schackert, Gabriele; Steiner, Gerald; Kirsch, Matthias

    2015-01-01

    Activation of CNS resident microglia and invasion of external macrophages plays a central role in spinal cord injuries and diseases. Multiphoton microscopy based on intrinsic tissue properties offers the possibility of label-free imaging and has the potential to be applied in vivo. In this work, we analyzed cellular structures displaying endogenous two-photon excited fluorescence (TPEF) in the pathologic spinal cord. It was compared qualitatively and quantitatively to Iba1 and CD68 immunohistochemical staining in two models: rat spinal cord injury and mouse encephalomyelitis. The extent of tissue damage was retrieved by coherent anti-Stokes Raman scattering (CARS) and second harmonic generation imaging. The pattern of CD68-positive cells representing postinjury activated microglia/macrophages was colocalized to the TPEF signal. Iba1-positive microglia were found in areas lacking any TPEF signal. In peripheral areas of inflammation, we found similar numbers of CD68-positive microglia/macrophages and TPEF-positive structures while the number of Iba1-positive cells was significantly higher. Therefore, we conclude that multiphoton imaging of unstained spinal cord tissue enables retrieving the extent of microglia activation by acquisition of endogenous TPEF. Future application of this technique in vivo will enable monitoring inflammatory responses of the nervous system allowing new insights into degenerative and regenerative processes. PMID:26355949

  13. Complement plays an important role in spinal cord injury and represents a therapeutic target for improving recovery following trauma.

    Science.gov (United States)

    Qiao, Fei; Atkinson, Carl; Song, Hongbin; Pannu, Ravinder; Singh, Inderjit; Tomlinson, Stephen

    2006-09-01

    Initiation of an inflammatory cascade following traumatic spinal cord injury (SCI) is thought to cause secondary injury and to adversely impact functional recovery, although the mechanisms involved are not well defined. We report on the dynamics of complement activation and deposition in the mouse spinal cord following traumatic injury, the role of complement in the development of SCI, and the characterization of a novel targeted complement inhibitor. Following traumatic injury, mice deficient in C3 had a significantly improved locomotor score when compared with wild-type controls, and analysis of their spinal cords revealed significantly more tissue sparing, with significantly less necrosis, demyelination, and neutrophil infiltration. Wild-type mice were also treated with CR2-Crry, a novel inhibitor of complement activation that targets to sites of C3 deposition. A single intravenous injection of CR2-Crry 1 hour after traumatic injury improved functional outcome and pathology to an extent similar to that seen in C3-deficient animals. CR2-Crry specifically targeted to the injured spinal cord in a distribution pattern corresponding to that seen for deposited C3. As immunosuppression is undesirable in patients following SCI, targeted CR2-Crry may provide appropriate bioavailability to treat SCI at a dose that does not significantly affect systemic levels of serum complement activity. PMID:16936276

  14. Endogenous Two-Photon Excited Fluorescence Provides Label-Free Visualization of the Inflammatory Response in the Rodent Spinal Cord

    Directory of Open Access Journals (Sweden)

    Ortrud Uckermann

    2015-01-01

    Full Text Available Activation of CNS resident microglia and invasion of external macrophages plays a central role in spinal cord injuries and diseases. Multiphoton microscopy based on intrinsic tissue properties offers the possibility of label-free imaging and has the potential to be applied in vivo. In this work, we analyzed cellular structures displaying endogenous two-photon excited fluorescence (TPEF in the pathologic spinal cord. It was compared qualitatively and quantitatively to Iba1 and CD68 immunohistochemical staining in two models: rat spinal cord injury and mouse encephalomyelitis. The extent of tissue damage was retrieved by coherent anti-Stokes Raman scattering (CARS and second harmonic generation imaging. The pattern of CD68-positive cells representing postinjury activated microglia/macrophages was colocalized to the TPEF signal. Iba1-positive microglia were found in areas lacking any TPEF signal. In peripheral areas of inflammation, we found similar numbers of CD68-positive microglia/macrophages and TPEF-positive structures while the number of Iba1-positive cells was significantly higher. Therefore, we conclude that multiphoton imaging of unstained spinal cord tissue enables retrieving the extent of microglia activation by acquisition of endogenous TPEF. Future application of this technique in vivo will enable monitoring inflammatory responses of the nervous system allowing new insights into degenerative and regenerative processes.

  15. Simultaneous Intracranial and Spinal Subdural Hematoma: Two Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Chung Dae; Song, Chang Joon; Lee, Jeong Eun; Choi, Seung Won [Chungnam National University, Daejeon (Korea, Republic of)

    2009-02-15

    Spinal subdural hematoma is a rare disease. Simultaneous intracranial and spinal subdural hematoma is extremely rare and only 14 such cases have been reported. We report here on two cases of simultaneous intracranial and spinal subdural hematoma that occurred following a fall-down head injury and intracranial surgery, and we discuss the pathogenesis of the disease.

  16. Turkish Adaptation of Spinal Cord Independence Measure--Version III

    Science.gov (United States)

    Kesiktas, Nur; Paker, Nurdan; Bugdayci, Derya; Sencan, Sureyya; Karan, Ayse; Muslumanoglu, Lutfiye

    2012-01-01

    Various rating scales have been used to assess ability in individuals with spinal cord injury. There is no specific functional assessment scale for Turkish patients with spinal cord injury. The Spinal Cord Independence Measure (SCIM) is a specific test, which has become popular in the last decade. A study was conducted to validate and evaluate the…

  17. Dynamics of intrinsic electrophysiological properties in spinal cord neurones

    DEFF Research Database (Denmark)

    Russo, R E; Hounsgaard, J

    1999-01-01

    The spinal cord is engaged in a wide variety of functions including generation of motor acts, coding of sensory information and autonomic control. The intrinsic electrophysiological properties of spinal neurones represent a fundamental building block of the spinal circuits executing these tasks...

  18. Spinal epidural empyema in two dogs

    International Nuclear Information System (INIS)

    Extensive, diffuse, epidural spinal cord compression was visualized myelographically in two dogs presented for rapid development of nonambulatory tetraparesis and paraplegia, respectively. Purulent fluid containing bacterial organisms was aspirated percutaneously under fluoroscopic guidance from the epidural space of each dog. One dog responded poorly to aggressive medical therapy, which included installation of an epidural lavage and drainage system. Both dogs were euthanized due to the severe nature of their disorder and the poor prognosis. Spinal epidural empyema (i.e., abscess) is a rare condition in humans and has not been reported previously in the veterinary literature. Spinal epidural empyema should be considered as a differential diagnosis in dogs presenting with painful myelopathies, especially when accompanied by fever

  19. SURGICAL TREATMENT OF METASTATIC SPINAL TUMOR

    Institute of Scientific and Technical Information of China (English)

    徐宏光; 王以朋; 邱贵兴; 叶启彬; 张嘉

    2002-01-01

    Objectives. To evaluate the effect of surgical treatment on metastatic spinal tumor. Methods. The results of surgical intervention for metastatic spinal tumor of 31 consecutive patients since October 1985 were reviewed. Results. The average survival time was 17.6 months (range from 3 months to 9 years), and 4 patients are still alive with an average survival time of 24.6 months (range, 14~ 84 months). No postoperative complication was noted. The preoperative symptoms were partially relieved and neurological functions were improved after surgery. Conclusions. Surgical treatment for metastatic spinal tumor could improve the life quality, but should be adopted cautiously. The surgical procedures such as decompression and internal fixation should be involved only when neurological deficits occurred. The surgery with postoperative complementary therapy may not only improve the life quality , but also extend the patients' life span.

  20. Spinal cord injury without radiographic abnormality

    Directory of Open Access Journals (Sweden)

    Singh Anil

    2006-01-01

    Full Text Available Spinal cord injury without radiological abnormality is rare in adults. Below we present a case report of 20 yrs old male with isolated cervical cord injury, without accompanying vertebral dislocation or fracture involving the spinal canal rim. He fell down on plain and smooth ground while carrying 40 kg weight overhead and developed quadriparesis with difficulty in respiration. Plain radiographs of the neck revealed no fractures or dislocations. MRI showed bulky spinal cord and an abnormal hyper intense signal on the T2W image from C2 vertebral body level to C3/4 intervertebral disc level predominantly in the anterior aspect of the cord The patient was managed conservatively with head halter traction and invasive ventilatory support for the initial 7 days period in the ICU. In our patient recovery was good and most of the neurological deficit improved over 4 weeks with conservative management.

  1. Applier tool for intradural spinal cord implants.

    Science.gov (United States)

    Oya, H; Reddy, C G; Dahdaleh, N S; Wilson, S; Howard, M A; Jeffery, N D; Utz, M; Gillies, G T

    2012-04-01

    We have designed, built and tested a novel device for placing intradural neurmodulator implants directly on the pial surface of the spinal cord. This applier tool is designed for ergonomic handling of delicate electro-mechanical devices such as the Iowa-Patch™ spinal cord stimulator implant, which is aimed at overcoming certain shortcomings in the performance of standard epidural stimulator devices. The applier is approximately 14 cm long, 6 mm in diameter, made of stainless steel components, and has simple and reliable mechanisms for the attachment and release of the implant from it. We describe the design of the device, details of its construction, and its performance during in vivo testing of somatosensory evoked potentials in an ovine model of intradural spinal cord stimulation. PMID:22339111

  2. SURGICAL TREATMENT OF METASTATIC SPINAL TUMOR

    Institute of Scientific and Technical Information of China (English)

    徐宏光; 王以朋; 等

    2002-01-01

    Objective:To evaluate the effect of surgical treatment on metastatic spinal tumor.Methods:The results of surgical intervention for metastatic spinal tumor of 31 consecutive patients since October 1985 were reviewed.Results:The average survival time was 17.6 months (range from 3 months to 9 years),and 4 patients are still alive with an average survival time of 24.6 months(range,14-84 months).No postoperative complication was noted.The preoperative symptoms were partially relieved and neurological functions were improved after surgery.Conclusions:Surgical treatment for metastatic spinal tumor could improve the life quality,but should be adopted cautiously.The surgical procedures such as decompression and internal fixation should be involved only when neurological deficits occurred.The surgery with postoperative complementary therapy may not only improve the life quality,but also extend the patients' life span.

  3. Primary multifocal gliosarcoma of the spinal cord

    Directory of Open Access Journals (Sweden)

    Ramesh M. Kumar

    2016-03-01

    Full Text Available Gliosarcoma (GS is a rare and exceedingly malignant neoplasm of the central nervous system. It displays clinical features similar to glioblastoma, yet is histologically unique as it harbors both gliomatous and sarcomatous cellular components. Involvement of the neuroaxis is predominantly limited to the cerebral parenchyma and meninges. Primary GS of the spinal cord is rarely encountered. We report a case of a 54 year old male who presented with 2 months of progressive, bilateral lower extremity sensory deficits. Magnetic resonance imaging of the neuro-axis revealed multiple intradural lesions involving the cervical and thoracic spinal cord without evidence of intracranial involvement. Surgical resection of a dural based, extramedullary cervical lesion and two exophytic, intramedullary thoracic lesions revealed gliosarcoma, WHO grade IV. The patient died approximately 11 months after presentation. This report confirms that GS is not limited to supratentorial involvement and can primarily affect the spinal cord.

  4. The transformation of spinal curvature into spinal deformity: pathological processes and implications for treatment

    Directory of Open Access Journals (Sweden)

    Hawes Martha C

    2006-03-01

    Full Text Available Abstract Background This review summarizes what is known about the pathological processes (e.g. structural and functional changes, by which spinal curvatures develop and evolve into spinal deformities. Methods Comprehensive review of articles (English language only published on 'scoliosis,' whose content yielded data on the pathological changes associated with spinal curvatures. Medline, Science Citation Index and other searches yielded > 10,000 titles each of which was surveyed for content related to 'pathology' and related terms such as 'etiology,' 'inheritance,' 'pathomechanism,' 'signs and symptoms.' Additional resources included all books published on 'scoliosis' and available through the Arizona Health Sciences Library, Interlibrary Loan, or through direct contact with the authors or publishers. Results A lateral curvature of the spine–'scoliosis'–can develop in association with postural imbalance due to genetic defects and injury as well as pain and scarring from trauma or surgery. Irrespective of the factor that triggers its appearance, a sustained postural imbalance can result, over time, in establishment of a state of continuous asymmetric loading relative to the spinal axis. Recent studies support the longstanding hypothesis that spinal deformity results directly from such postural imbalance, irrespective of the primary trigger, because the dynamics of growth within vertebrae are altered by continuous asymmetric mechanical loading. These data suggest that, as long as growth potential remains, evolution of a spinal curvature into a spinal deformity can be prevented by reversing the state of continuous asymmetric loading. Conclusion Spinal curvatures can routinely be diagnosed in early stages, before pathological deformity of the vertebral elements is induced in response to asymmetric loading. Current clinical approaches involve 'watching and waiting' while mild reversible spinal curvatures develop into spinal deformities with

  5. Langerhans cell histiocytosis with multiple spinal involvement.

    Science.gov (United States)

    Jiang, Liang; Liu, Xiao Guang; Zhong, Wo Quan; Ma, Qing Jun; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting; Liu, Zhong Jun

    2011-11-01

    To stress the clinical and radiologic presentation and treatment outcome of Langerhans cell histiocytosis (LCH) with multiple spinal involvements. A total of 42 cases with spinal LCH were reviewed in our hospital and 5 had multifocal spinal lesions. Multiple spinal LCH has been reported in 50 cases in the literature. All cases including ours were analyzed concerning age, sex, clinical and radiologic presentation, therapy and outcome. Of our five cases, three had neurological symptom, four soft tissue involvement and three had posterior arch extension. Compiling data from the eight largest case series of the spinal LCH reveals that 27.2% multiple vertebrae lesions. In these 55 cases, there were 26 female and 29 male with the mean age of 7.4 years (range 0.2-37). A total of 182 vertebrae were involved including 28.0% in the cervical spine, 47.8% in thoracic and 24.2% in the lumbar spine. Extraspinal LCH lesion was documented in 54.2% cases, visceral involvement in 31.1% and vertebra plana in 50% cases. Paravertebral and epidural extension were not documented in most cases. Pathological diagnosis was achieved in 47 cases including 8 open spine biopsy. The treatment strategy varied depending on different hospitals. One patient died, two had recurrence and the others had no evidence of the disease with an average of 7.2 years (range 1-21) of follow-up. Asymptomatic spinal lesions could be simply observed with or without bracing and chemotherapy is justified for multiple lesions. Surgical decompression should be reserved for the uncommon cases in which neurologic compromise does not respond to radiotherapy or progresses too rapidly for radiotherapy. PMID:20496040

  6. Reciprocal functional interactions between the brainstem and the lower spinal cord

    Directory of Open Access Journals (Sweden)

    Itaru eYazawa

    2014-05-01

    Full Text Available The interplay of the neuronal discharge patterns regarding respiration and locomotion was investigated using electrophysiological techniques in a decerebrate and arterially perfused in situ mouse preparation. The phrenic, tibial and/or peroneal nerve discharge became clearly organized into discharge episodes of increasing frequency and duration, punctuated by periods of quiescence as the perfusion flow rate increased at room temperature. The modulated sympathetic tone induced by the hyperoxic/normocapnic state was found to activate the locomotor pattern generator (LPG via descending pathways and generate a left and right alternating discharge during discharge episodes in the motor nerves. The rhythm coupling of respiration and locomotion occurred at a 1:1 frequency ratio. Although the phrenic discharge synchronized with the tibial discharge at all flow rates tested, the time lag between peaks of the two discharges during locomotion was ≈400 ms rather than ≈200 ms, suggesting spinal feedback via ascending pathways. The incidence of the phrenic and tibial discharge episodes decreased by ≈50% after spinalization at the twelfth thoracic vertebra and the respiratory rhythm was more regular. These results indicate that: (i locomotion can be generated in a hyperoxic/normocapnic state induced by specific respiratory conditions, (ii the central mechanism regarding entrainment of respiratory and locomotor rhythms relies on spinal feedback via ascending pathways, initiated by the activated LPG generating locomotion, and (iii the increase in respiratory rate seen during locomotion is caused not only by afferent mechanical and nociceptive inputs but also by impulses from the activated spinal cord producing a locomotor-like discharge via ascending pathways.

  7. SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Jung Hosung

    2011-02-01

    Full Text Available Abstract Background Stromal cell-derived factor-1 (SDF1 and its major signaling receptor, CXCR4, were initially described in the immune system; however, they are also expressed in the nervous system, including the spinal cord. After spinal cord injury, the blood brain barrier is compromised, opening the way for chemokine signaling between these two systems. These experiments clarified prior contradictory findings on normal expression of SDF1 and CXCR4 as well as examined the resulting spinal cord responses resulting from this signaling. Methods These experiments examined the expression and function of SDF1 and CXCR4 in the normal and injured adult mouse spinal cord primarily using CXCR4-EGFP and SDF1-EGFP transgenic reporter mice. Results In the uninjured spinal cord, SDF1 was expressed in the dorsal corticospinal tract (dCST as well as the meninges, whereas CXCR4 was found only in ependymal cells surrounding the central canal. After spinal cord injury (SCI, the pattern of SDF1 expression did not change rostral to the lesion but it disappeared from the degenerating dCST caudally. By contrast, CXCR4 expression changed dramatically after SCI. In addition to the CXCR4+ cells in the ependymal layer, numerous CXCR4+ cells appeared in the peripheral white matter and in the dorsal white matter localized between the dorsal corticospinal tract and the gray matter rostral to the lesion site. The non-ependymal CXCR4+ cells were found to be NG2+ and CD11b+ macrophages that presumably infiltrated through the broken blood-brain barrier. One population of macrophages appeared to be migrating towards the dCST that contains SDF1 rostral to the injury but not towards the caudal dCST in which SDF1 is no longer present. A second population of the CXCR4+ macrophages was present near the SDF1-expressing meningeal cells. Conclusions These observations suggest that attraction of CXCR4+ macrophages is part of a programmed response to injury and that modulation of the

  8. Effect of exercise on retrograde transport in a mouse model of amyotrophic lateral sclerosis

    OpenAIRE

    Whitney, Darryl Campbell

    2007-01-01

    The potential for exercise to improve function and delay disease progression in a mouse model of amyotrophic lateral sclerosis (ALS) has been examined in some detail. Recent studies have shown that retrograde transport is diminished throughout disease progression in this mouse model. The finding that exercise plus viral delivery of IGF-1 significantly improves lifespan of the G93A transgenic mouse highlights the need to investigate the mechanisms by which exercise may alter factors associated...

  9. Sleep disordered breathing following spinal cord injury

    DEFF Research Database (Denmark)

    Biering-Sørensen, Fin; Jennum, Poul; Laub, Michael

    2009-01-01

    with SCI, especially with regard to obstructive sleep apnea. In addition, there is a correlation between the incidence of sleep disturbances and the spinal cord level injured, age, body mass index, neck circumference, abdominal girth, and use of sedating medications. Regulation of respiration is dependent......Individuals with spinal cord injury (SCI) commonly complain about difficulty in sleeping. Although various sleep disordered breathing definitions and indices are used that make comparisons between studies difficult, it seems evident that the frequency of sleep disorders is higher in individuals...

  10. Multiple, primary spinal-paraspinal hydatid cysts

    Energy Technology Data Exchange (ETDEWEB)

    Sener, R.N.; Calli, C.; Kitis, O.; Yalman, O. [Dept. of Radiology, Ege University Hospital, Izmir (Turkey)

    2001-11-01

    A patient is presented with widespread primary hydatid cysts in spinal-paraspinal locations, secondary to Echinococcus granulosus. An alternative mechanism to explain how the embryos gained access to the body is proposed: The embryos penetrated the intestinal muscle and may have directly entered into the inferior vena cava system through small venous connections between this system and portal circulation. Various conditions in daily life associated with Valsalva maneuver might have caused such an atypical passage of the embryos to the inferior caval system toward the retroperitoneum and spinal-paraspinal structures via lumber epidural venous plexuses. (orig.)

  11. Pictorial essay: MR imaging in spinal dysraphism

    International Nuclear Information System (INIS)

    Prior to the advent of MR, the diagnostic armamentarium for spinal dysraphism included plain films, myelography and CT myelography. There were significant limitations to these modalities, such as high false negative rates for plain radiographs, requirement of general anesthesia for myelography (as the majority of patients are children), and high radiation exposure. MR is a single, safe investigation that can provide relevant information regarding the entire craniospinal axis. MR effectively demonstrates a wide variety of dysraphic abnormalities and effectively screens children for occult spinal dysraphism. (author)

  12. Taltirelin improves motor ataxia independently of monoamine levels in rolling mouse nagoya, a model of spinocerebellar atrophy.

    Science.gov (United States)

    Nakamura, Tomoka; Honda, Motoko; Kimura, Satoko; Tanabe, Mitsuo; Oda, Sen-ichi; Ono, Hideki

    2005-12-01

    To examine the relationship between motor ataxia and monoamine levels in the central nervous system, the contents and concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the cerebellum, brain stem and spinal cord were measured in rolling mouse Nagoya (RMN), a murine model of spinocerebellar atrophy. The tissue weight of the cerebellum and spinal cord, but not that of the brain stem was significantly lower in RMN than in the control group. In RMN, the NA content of the brain stem and spinal cord, but not the cerebellum were decreased relative to the control, and the concentration of NA in the spinal cord was also lower, but not significant. The DA and 5-HT contents in each tissue did not differ from those of the control, but the concentrations of monoamines, except for DA, were elevated in the brain stem and spinal cord in RMN. In particular, the concentrations of NA, DA and 5-HT in the cerebellum were significantly increased in RMN. Repeated administration of tartilerin hydrate, an analog of thyrotropin-releasing hormone, improved the ataxia of RMN, and elicited no obvious changes in either monoamine content or concentration of cerebellum, brain stem and spinal cord. These results indicate that the concentration of DA, as well as NA and 5-HT, increased in the RMN cerebellum, and that tartilerin improves the motor function of these mice via mechanisms other than changes in the levels of NA, DA and 5-HT in the central nervous system.

  13. The neurobiology of the spinal cord in experimental parkinsonism and Parkinson's disease.

    Science.gov (United States)

    Ferrucci, Michela; Biagioni, Francesca; Vivacqua, Giorgio; Busceti, Carla Letizia; Bartalucci, Alessia; Soldani, Paola; D'Este, Loredana; Fumagalli, Lorenzo; Fornai, Francesco

    2013-12-01

    The neurobiology of non-motor symptoms in Parkinson's disease (PD) reveals a number of unexpected areas which once were not recognized a priori as part of the neuropathology underlying PD. These areas may belong either to central nervous system or periphery. Among central areas major efforts in the last decade led to recognize a number of brain nuclei as part of the disease spreading or disease onset in PD patients. Unexpectedly recent evidence deriving from pathological studies in PD patients and corroborated by experimental models of PD provided clear evidence that the spinal cord is often recruited in PD pathology. Such an involvement is intriguing since the major degenerative disease of the spinal cord (amyotrophic lateral sclerosis) features the involvement of dopaminergic neurons of the substantia nigra pars compacta, while some environmental (parkinsonism, ALS, and dementia of Guam) and genetic (Kufor-Rakeb syndrome) diseases are known to be characterized by mixed degeneration of pyramidal and extrapyramidal regions. Thus, the clear-cut between degeneration of dopaminergic neurons in the substantia nigra and the loss of pyramidal motor system appears now more as a continuum of   degeneration which converge in abnormal activity and cell pathology of motor neurons as a final common pathway. Among motor neurons, visceral efferent cells of the spinal cord are involved and provide a robust neurobiological findings which may justify a variety of non-motor autonomic symptoms which characterize PD. Neurodegeneration in the spinal cord extends to the dorsal horn of the grey matter posing an intriguing link between PD and sensory alterations. The present manuscript reviews the involvement of multiple regions of the spinal cord in PD and experimental parkinsonism in the attempt to provide both a neurobiological background to understand non motor symptoms and to provide the anatomical basis for disease spreading. PMID:24873929

  14. 77 FR 18857 - Final Environmental Impact Statement and Record of Decision for Alabama Beach Mouse General...

    Science.gov (United States)

    2012-03-28

    ... species. On August 9, 2011, we published a notice of availability for a draft EIS (76 FR 48879) for a 90... Mouse General Conservation Plan for Incidental Take on the Fort Morgan Peninsula, Baldwin County, AL... Alabama beach mouse (Peromyscus polionotus ammobates). For record of decision (ROD) availability,...

  15. Spinal myoclonus following a peripheral nerve injury: a case report

    Directory of Open Access Journals (Sweden)

    Erkol Gokhan

    2008-08-01

    Full Text Available Abstract Spinal myoclonus is a rare disorder characterized by myoclonic movements in muscles that originate from several segments of the spinal cord and usually associated with laminectomy, spinal cord injury, post-operative, lumbosacral radiculopathy, spinal extradural block, myelopathy due to demyelination, cervical spondylosis and many other diseases. On rare occasions, it can originate from the peripheral nerve lesions and be mistaken for peripheral myoclonus. Careful history taking and electrophysiological evaluation is important in differential diagnosis. The aim of this report is to evaluate the clinical and electrophysiological characteristics and treatment results of a case with spinal myoclonus following a peripheral nerve injury without any structural lesion.

  16. Novalis Stereotactic Radiosurgery for Spinal Dural Arteriovenous Fistula

    Science.gov (United States)

    Sung, Kyoung-Su; Song, Young-Jin

    2016-01-01

    The spinal dural arteriovenous fistula (SDAVF) is rare, presenting with progressive, insidious symptoms, and inducing spinal cord ischemia and myelopathy, resulting in severe neurological deficits. If physicians have accurate and enough information about vascular anatomy and hemodynamics, they achieve the good results though the surgery or endovascular embolization. However, when selective spinal angiography is unsuccessful due to neurological deficits, surgery and endovascular embolization might be failed because of inadequate information. We describe a patient with a history of vasospasm during spinal angiography, who was successfully treated by spinal stereotactic radiosurgery using Novalis system. PMID:27446527

  17. Melatonin lowers edema after spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Cheng Li; Xiao Chen; Suchi Qiao; Xinwei Liu; Chang Liu; Degang Zhu; Jiacan Su; Zhiwei Wang

    2014-01-01

    Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial ifbrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spinal cord by edema might be related to the expression of aquaporin-4 and glial ifbrillary acidic protein.

  18. Spinal cord compression by spontaneous spinal subdural haematoma in polycythemia vera.

    OpenAIRE

    Kalina, P.; Drehobl, K. E.; Black, K; Woldenberg, R.; Sapan, M.

    1995-01-01

    A woman with an eight-year history of polycythemia vera presented with numbness and weakness of both legs. A large spinal haematoma was revealed on magnetic resonance imaging which was treated clinically and which subsequently resolved.

  19. Diagnósticos de enfermagem e proposta de intervenções para pacientes com lesão medular Diagnósticos de enfermería y propuesta de intervenciones para pacientes con lesión medular Nursing diagnoses and interventions proposal al for patients with spinal cord lesion

    Directory of Open Access Journals (Sweden)

    Clélia Regina Cafer

    2005-12-01

    la unidad de estudio, con la finalidad de identificar los diagnósticos de enfermería. Las intervenciones fueron propuestas por las autoras y sometidas a la evaluación de dos especialistas. RESULTADOS: Fueron identificados 15 diagnósticos de enfermería prevalentes, para los cuales se propusieron 26 intervenciones de enfermería. CONCLUSIÓN: Los resultados del estudio servirán de subsidio a las enfermeras para el cuidado de pacientes con lesión medular, auxiliándolos y contribuyendo en su autonomía, a través de las intervenciones propuestas.INTRODUCTION: Spinal cord lesions constitute very serious events that occur mostly among young people. Providing care to these patients is a complex task because they are greatly dependent on nursing staff and require a very carefully designed plan of care. The purpose of this study was to contribute ways to design a quality plan of care to attend these patients. OBJECTIVES: To identify nursing diagnoses according to the NANDA for patients with spinal cord lesions from an Orthopedic and Trauma Unit, and to propose appropriate nursing interventions according to the NIC. METHODS: This study used a descriptive and prospective research design. The sample consisted of 10 patients with spinal cord lesions. Data were colleted from January, 2000 to July, 2002 using a specific assessment tool. Data analysis led the researchers to propose nursing diagnoses which were validated by two clinical nursing specialists. RESULTS: Fifteen prevalent nursing diagnoses were identified and 26 nursing interventions were proposed. CONCLUSION: The results can be used to assist nurse to provide quality care for patients with spinal cord lesions, so as to improve the patients independence.

  20. Profound Intraoperative Metabolic Acidosis and Hypotension in a Child Undergoing Multilevel Spinal Fusion

    Directory of Open Access Journals (Sweden)

    Mohanad Shukry

    2009-01-01

    Full Text Available The prone position may cause cardiovascular system depression. Yet, the mechanisms involved and preemptive measures are not well understood (Edgcombe et al. (2008. During spinal surgery in the prone position, hypotension may occur. Implicated factors include prolonged abdominal compression impeding venous return resulting in increased blood loss, decreased cardiovascular reserve, and the use of total intravenous anesthesia (TIVA which has been shown to blunt the sympathetic response more than inhalation anesthesia. We present a case of hypotension during spinal surgery with all its challenges. Hypotension and acidosis persisted despite all supporting measures, and only to improve with supine positioning. Differential diagnosis for such an event are discussed. Although abdominal compression may not be obvious before the start of surgery, compressing the spine during surgery may lead to abdominal compression and hypoperfusion to abdominal organs.

  1. AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Desport Estelle

    2012-08-01

    Full Text Available Abstract Definition of the disease AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig light chains (LC (most commonly of lambda isotype usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils. Epidemiology AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. Clinical description The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. Diagnostic methods The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and

  2. Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury**

    Institute of Scientific and Technical Information of China (English)

    Tiansheng Sun; Chaoqun Ye; Jun Wu; Zhicheng Zhang; Yanhua Cai; Feng Yue

    2013-01-01

    A large body of evidence shows that spinal circuits are significantly affected by training, and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection. However, after incomplete lesions, the effect of treadmil training has been debated, which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects. In this study, rats with moderate spinal cord contusion were sub-jected to either step training on a treadmil or used in the model (control) group. The treadmil training began at day 7 post-injury and lasted 20 ± 10 minutes per day, 5 days per week for 10 weeks. The speed of the treadmil was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat. After 3 weeks of step training, the step training group exhibited a sig-nificantly greater improvement in the Basso, Beattie and Bresnahan score than the model group. The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury, while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups. These results suggest that treadmil training significantly improves functional re-covery and neural plasticity after incomplete spinal cord injury.

  3. Effects of hip joint angle changes on intersegmental spinal coupling in human spinal cord injury

    OpenAIRE

    Knikou, M

    2005-01-01

    Pathological expression of movement and muscle tone in human upper motor neuron disorders has been partly associated with impaired modulation of spinal inhibitory mechanisms, such as reciprocal or presynaptic inhibition. In addition, input from specific afferent systems contributes significantly to spinal reflex circuits coupled with posture or locomotion. Accordingly, the objectives of this study were to identify the involved afferents and their relative contribution to soleus H-reflex modul...

  4. Analysis of the host transcriptome from demyelinating spinal cord of murine coronavirus-infected mice.

    Directory of Open Access Journals (Sweden)

    Ruth Elliott

    Full Text Available Persistent infection of the mouse central nervous system (CNS with mouse hepatitis virus (MHV induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.

  5. Lower motor neuron dysfunction in ALS.

    Science.gov (United States)

    de Carvalho, Mamede; Swash, Michael

    2016-07-01

    In the motor system there is a complex interplay between cortical structures and spinal cord lower motor neurons (LMN). In this system both inhibitory and excitatory neurons have relevant roles. LMN loss is a marker of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Conventional needle electromyography (EMG) does not allow LMN loss to be quantified. Measurement of compound muscle action potential (CMAP) amplitude or area, and the neurophysiological index, provide a surrogate estimate of the number of functional motor units. Increased motor neuronal excitability is a neurophysiological marker of ALS in the context of a suspected clinical and electrophysiological diagnosis. In the LMN system, fasciculation potentials (FPs) are the earliest changes observed in affected muscles, a feature of LMN hyperexcitability. Reinnervation is best investigated by needle EMG although other methods can be explored. Moreover needle EMG give information about the temporal profile of the reinnervation process, important ancillary data. Quantitative motor unit potential analysis is a valuable method of evaluating reinnervation. The importance of FPs has been recognized in the Awaji criteria for the electrodiagnosis of ALS, criteria that are a sensitive adjunct to the revised El Escorial criteria. Finally, functionality of LMN's, and perhaps excitability studies in motor nerves, aids understanding of the disease process, allowing measurement of potential treatment effects in clinical trials. Other investigational techniques, such as electrical impedance myography, muscle and nerve ultrasound, and spinal cord imaging methods may prove useful in future. PMID:27117334

  6. THE DIAGNOSIS OF MAGNETIC RESONANCE IMAGING FOR SPINAL CAVERNOUS ANGIOMAS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To assess the characteristics of magnetic resonance imaging (MRI) for spinal cavernous angiomas.Methods The examinations of plain scan and contrast enhanced scan of magnetic resonance (MR) were performed in three patients with spinal cavernous angiomas.Results The focus of two cases was located in thorax segment of the spinal cord and one in lower cervical segment.All focuses were single and the shape of spinal cord was normal or slightly thick. MRI characteristic of spinal cavernous angiomas was just like popcorn or mulberry with a jumbled gobbet signal. Low and short T2 signal appeared around the focus. In all cases, there were no obvious contrast enhanced signal in 2 cases and one case with moderate contrast enhanced signal. The diameter of hemorrhage was smaller than that of the spinal cord.Conclusion MRI has higher sensitivity and specificity in the diagnosis of spinal cavernous angioma.

  7. Spinal cord injury reveals multilineage differentiation of ependymal cells.

    Directory of Open Access Journals (Sweden)

    Konstantinos Meletis

    2008-07-01

    Full Text Available Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury.

  8. Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord.

    Science.gov (United States)

    Grimm, Jimm; Sahgal, Arjun; Soltys, Scott G; Luxton, Gary; Patel, Ashish; Herbert, Scott; Xue, Jinyu; Ma, Lijun; Yorke, Ellen; Adler, John R; Gibbs, Iris C

    2016-04-01

    A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation. PMID:27000514

  9. Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord.

    Science.gov (United States)

    Grimm, Jimm; Sahgal, Arjun; Soltys, Scott G; Luxton, Gary; Patel, Ashish; Herbert, Scott; Xue, Jinyu; Ma, Lijun; Yorke, Ellen; Adler, John R; Gibbs, Iris C

    2016-04-01

    A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation.

  10. Mechanical characterization of the injured spinal cord after lateral spinal hemisection injury in the rat.

    Science.gov (United States)

    Saxena, Tarun; Gilbert, Jeremy; Stelzner, Dennis; Hasenwinkel, Julie

    2012-06-10

    The glial scar formed at the site of traumatic spinal cord injury (SCI) has been classically hypothesized to be a potent physical and biochemical barrier to nerve regeneration. One longstanding hypothesis is that the scar acts as a physical barrier due to its increased stiffness in comparison to uninjured spinal cord tissue. However, the information regarding the mechanical properties of the glial scar in the current literature is mostly anecdotal and not well quantified. We monitored the mechanical relaxation behavior of injured rat spinal cord tissue at the site of mid-thoracic spinal hemisection 2 weeks and 8 weeks post-injury using a microindentation test method. Elastic moduli were calculated and a modified standard linear model (mSLM) was fit to the data to estimate the relaxation time constant and viscosity. The SLM was modified to account for a spectrum of relaxation times, a phenomenon common to biological tissues, by incorporating a stretched exponential term. Injured tissue exhibited significantly lower stiffness and elastic modulus in comparison to uninjured control tissue, and the results from the model parameters indicated that the relaxation time constant and viscosity of injured tissue were significantly higher than controls. This study presents direct micromechanical measurements of injured spinal cord tissue post-injury. The results of this study show that the injured spinal tissue displays complex viscoelastic behavior, likely indicating changes in tissue permeability and diffusivity.

  11. [Magnetic resonance tomography in late sequelae of spinal and spinal cord injuries].

    Science.gov (United States)

    Kravtsov, A K; Akhadov, T A; Sachkova, I Iu; Belov, S A; Chernenko, O A; Panova, M M

    1993-01-01

    Magnetic-resonance tomography (MRT) helped obtain a high-resolution image characterized by high sensitivity in respect of soft tissue contrast visualization and providing direct imaging of the spinal cord and its radicles. This method is useful in the diagnosis of injuries to the spine and cord. A total of 64 patients of both sexes aged 6 to 67 were examined. The primary diagnosis of traumatic changes in the spine and cord was confirmed by MRT in only 62% of cases. Two groups of patients were singled out: with acute and chronic injuries, subdivided into subgroups with and without spinal cord dysfunction. The detected changes were divided into extramedullary (traumatic disk hernias, compression of the cord or radicles with a dislocated bone fragment, epidural hematoma) and intramedullary (edema, hemorrhages, spinal cord disruption); MRT diagnosis of intramedullary changes is particularly important, more so in the absence of bone injuries. In remote periods after the trauma the clinical picture was determined by spinal canal stenosis, cicatricial atrophic and adhesive changes eventually blocking the liquor space. Intramedullary changes presented as spinal cord cysts or syringomyelia. A classification of the detected changes by the types of injuries and their aftereffects is presented in the paper. The authors emphasize the desirability of MRT in spinal injuries with signs of cord dysfunction. PMID:7801568

  12. Spinal dural arteriovenous fistula: clinical and radiological findings in 54 patients; Die spinale durale arteriovenoese Fistelerkrankung (SDAVF): klinische und radiologische Befunde von 54 Patienten

    Energy Technology Data Exchange (ETDEWEB)

    Koch, C.; Kucinski, T.; Eckert, B.; Zeumer, H. [Abt. fuer Neuroradiologie, Universitaetsklinikum Hamburg Eppendorf (Germany); Roether, J. [Klinik fuer Neurologie, Universitaetsklinikum Hamburg Eppendorf (Germany)

    2003-08-01

    Signalanhebung des Myelons (100%) mit lokaler Schwellung (74%), Schrankenstoerung (79%) und erweiterten perimedullaeren Gefaessen (89%), die myelographisch in 78% der Faelle nachgewiesen wurden. Krankheitsbeweisend ist die Angiographie mit zumeist thorakaler Lokalisation der Fistel (69%), mehr als einer fistelzufuehrenden Arterie (67%) und venoeser Drainage nach kaudal und rostral (63%). Schlussfolgerungen: Die spinale MRT ist zum Nachweis der krankheitsrelevanten Befunde, die auf eine SDAVF hindeuten, sensitiver und spezifischer als die Myelographie und damit Untersuchungsmethode der ersten Wahl. Zur definitiven Krankheitsdiagnose ist die spinale Angiographie erforderlich. (orig.)

  13. Spinal cord stimulation in chronic pain syndromes

    NARCIS (Netherlands)

    ten Vaarwerk, IAM; Staal, MJ

    1998-01-01

    Spinal cord stimulation (SCS) has been used for more than 30 years now, and although it has shown to be effective under certain well-described conditions of chronic pain, conclusive evidence on its effectiveness is still sparse. There is a need for more prospective and methodological good studies, i

  14. Neurological complications in adult spinal deformity surgery.

    Science.gov (United States)

    Iorio, Justin A; Reid, Patrick; Kim, Han Jo

    2016-09-01

    The number of surgeries performed for adult spinal deformity (ASD) has been increasing due to an aging population, longer life expectancy, and studies supporting an improvement in health-related quality of life scores after operative intervention. However, medical and surgical complication rates remain high, and neurological complications such as spinal cord injury and motor deficits can be especially debilitating to patients. Several independent factors potentially influence the likelihood of neurological complications including surgical approach (anterior, lateral, or posterior), use of osteotomies, thoracic hyperkyphosis, spinal region, patient characteristics, and revision surgery status. The majority of ASD surgeries are performed by a posterior approach to the thoracic and/or lumbar spine, but anterior and lateral approaches are commonly performed and are associated with unique neural complications such as femoral nerve palsy and lumbar plexus injuries. Spinal morphology, such as that of hyperkyphosis, has been reported to be a risk factor for complications in addition to three-column osteotomies, which are often utilized to correct large deformities. Additionally, revision surgeries are common in ASD and these patients are at an increased risk of procedure-related complications and nervous system injury. Patient selection, surgical technique, and use of intraoperative neuromonitoring may reduce the incidence of complications and optimize outcomes. PMID:27250041

  15. Spinal intramedullary metastatic medulloblastoma. Case report.

    Science.gov (United States)

    Zumpano, B J

    1978-04-01

    Metastatic spread of medulloblastoma along the neuraxis by leptomeningeal seeding through the cerebrospinal fluid pathways is well known. The occurrence of extracranial metastases outside the neuraxis has been well established, but the occurrence of intramedullary spinal cord metastases not related to surface seeding is rare. A histologically documented case of the latter type is described. PMID:632889

  16. Spinal cord stimulation: Background and clinical application

    DEFF Research Database (Denmark)

    Meier, Kaare

    2014-01-01

    a number of contacts capable of delivering a weak electrical current to the spinal cord, evoking a feeling of peripheral paresthesia. With correct indication and if implanted by an experienced implanter, success rates generally are in the range of about 50–75%. Common indications include complex regional...

  17. Staging Childhood Brain and Spinal Cord Tumors

    Science.gov (United States)

    ... tests to check the brain, spinal cord, and nerve function. The exam checks a person’s mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro ...

  18. Anorgasmia in anterior spinal cord syndrome.

    OpenAIRE

    Berić, A; Light, J K

    1993-01-01

    Three male and two female patients with anorgasmia and dissociated sensory loss due to an anterior spinal cord syndrome are described. Clinical, neurophysiological and quantitative sensory evaluation revealed preservation of the large fibre dorsal column functions from the lumbosacral segments with concomitant severe dysfunction or absence of the small fibre neospinothalamic mediated functions. These findings indicate a role for the spinothalamic system in orgasm.

  19. Computed tomographic metrizamide myelography in spinal disease

    Energy Technology Data Exchange (ETDEWEB)

    Isu, T.; Ito, T.; Iwasaki, Y.; Tsuru, M. (Hokkaido Univ., Sapporo (Japan). School of Medicine); Kitaoka, K.

    1981-03-01

    Methods: Either EMT Head Scanner, CT 1010 (slice thickness 10 mm) or EMI Body Scanner, CT 5005 (slice thickness 13 mm) was used. The concentration of metrizamide was 170 - 250 mgI/ml and the amount was 7 - 10 ml. Either lumbar puncture or lateral C sub(1 - 2) puncture was made. Materials: 26 cases were included in this study. 1) disc disease: 11 cases, 2) spinal cord tumor: 6 cases, 3) Arnold-Chiari malformation: 3 cases, 4) atlantoaxial dislocation: 3 cases, 5) ossification of the posterior longitudinal ligament (associated with ossification of the ligamentum flavum): 2 cases (1 case), 6) spinal foreign body (acupuncture needle): 1 case. Results: 1) CT metrizamide myelography visualizes the subarachnoid space and makes it possible to know the lesion in the spinal canal in relation to the spinal cord in transverse plane. 2) It is difficult to determine the exact level of the lesion in axial plane. 3) The present technique does not allow to visualize the root sleeves. 4) It is difficult to delineate a compression of the subarachnoid space by small localized lesions (esp., disc diseases) due to overlapping the patent adjacent subarachnoid space within a slice 10 mm to 13 mm thick.

  20. Testing haptic sensations for spinal anesthesia.

    LENUS (Irish Health Repository)

    2011-01-01

    Having identified key determinants of teaching and learning spinal anesthesia, it was necessary to characterize and render the haptic sensations (feeling of touch) associated with needle insertion in the lower back. The approach used is to match recreated sensations (eg, "pop" through skin or dura mater) with experts\\' perceptions of the equivalent clinical events.

  1. Parents with a spinal cord injury

    DEFF Research Database (Denmark)

    Rasul, A; Biering-Sørensen, F

    2016-01-01

    STUDY DESIGN: This is a cross-sectional questionnaire. OBJECTIVES: The objective of this study was to describe the impact of parenting young children with a spinal cord injury (SCI) on various life situations (for example, personal, vocational and social). SETTING: Community; Denmark. METHODS...

  2. Solitary fibrous tumour of the spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Mordani, J.P. [City General Hospital, Stoke-on-Trent (United Kingdom). Dept. of Radiology; Haq, I.U. [North Staffordshire Royal Infirmary, Stoke-on-Trent (United Kingdom). Dept. of Neuroradiology; Singh, J. [North Staffordshire Royal Infirmary, Stoke-on-Trent (United Kingdom). Dept. of Neurosurgery

    2000-09-01

    We report an intramedullary primary solitary fibrous tumour of the cervical spinal cord in a 33-year-old man. The tumour predominantly consisted of monomorphic spindle cells with a storiform pattern. MRI demonstrated an inhomogeneously enhancing cervical intramedullary tumour. The patient was well without recurrence 18 months after surgery. (orig.)

  3. Teaching and learning spinal anaesthesia: anaesthetists' attitudes.

    LENUS (Irish Health Repository)

    Breen, Dorothy

    2010-12-01

    To identify the determinants of learning for one medical procedural skill, spinal anaesthesia, by eliciting the opinions of anaesthetists in Ireland and Hungary. This objective is one component of a research project, Medical Competence Assessment Procedure (MedCAP) funded by the EU Leonardo da Vinci Lifelong Learning Programme.

  4. Pulmonary sequelae after electron spinal irradiation

    International Nuclear Information System (INIS)

    We measured pulmonary function in 21 patients, after craniospinal irradiation with a posterior spinal electron beam. The median age at treatment was 7.5 years. Nine patients (43%) demonstrated abnormal pulmonary function tests, five with restrictive changes, one with isolated diminished diffusion capacity, and three with obstructive disease. These changes were mild and predominantly asymptomatic

  5. Male infertility in spinal cord trauma

    Directory of Open Access Journals (Sweden)

    Cristiano Utida

    2005-08-01

    Full Text Available Every year there are 10 thousand new cases of patients victimized by spinal cord trauma (SCT in the United States and it is estimated that there are 7 thousand new cases in Brazil. Eighty percent of patients are fertile males. Infertility in this patient group is due to 3 main factors resulting from spinal cord lesions: erectile dysfunction, ejaculatory disorder and low sperm counts. Erectile dysfunction has been successfully treated with oral and injectable medications, use of vacuum devices and penile prosthesis implants. The technological improvement in penile vibratory stimulation devices (PVS and rectal probe electro-ejaculation (RPE has made such procedures safer and accessible to patients with ejaculatory dysfunction. Despite the normal number of spermatozoa found in semen of spinal cord-injured patients, their motility is abnormal. This change does not seem to be related to changes in scrotal thermal regulation, frequency of ejaculation or duration of spinal cord damage but to factors related to the seminal plasma. Despite the poor seminal quality, increasingly more men with SCT have become fathers through techniques ranging from simple homologous insemination to sophisticated assisted reproduction techniques such as intracytoplasmic sperm injection (ICSI.

  6. Congenital spine anomalies: the closed spinal dysraphisms

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Erin Simon [University of Pennsylvania, Department of Radiology, The Children' s Hospital of Philadelphia, Perelman School of Medicine, Philadelphia, PA (United States); Rossi, Andrea [G. Gaslini Children' s Hospital, Department of Radiology, Genoa (Italy)

    2015-09-15

    The term congenital spinal anomalies encompasses a wide variety of dysmorphology that occurs during early development. Familiarity with current terminology and a practical, clinico-radiologic classification system allows the radiologist to have a more complete understanding of malformations of the spine and improves accuracy of diagnosis when these entities are encountered in practice. (orig.)

  7. Imaging of demyelinating and neoplastic diseases of the spinal cord; Bildgebung bei demyelinisierenden und tumoroesen Erkrankungen des Rueckenmarks

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Mang, C. [Institut fuer CT und MRT Gaenserndorf, Gaenserndorf (Austria)

    2010-12-15

    The clinical symptoms of myelopathy are variable and non-specific. Demyelinating as well as neoplastic spinal cord diseases can cause paresthesia, progressive sensomotoric deficits and bowel and bladder dysfunction. Imaging of the spine, especially with magnetic resonance imaging (MRI), is an essential component in the diagnostic assessment of myelopathy and makes a substantial contribution to achieving the correct diagnosis. Although intramedullary neoplasms are far less common than demyelinating spinal cord diseases, radiologists should be familiar with the three most common entities, astrocytoma, ependymoma and hemangioblastoma, which represent over 70% of all spinal cord neoplasms. An early diagnosis and therapy is essential with neoplastic and demyelinating spinal cord diseases to hold residual neurological deficits as low as possible. (orig.) [German] Die klinische Symptomatik von Myelopathien ist aeusserst variabel und unspezifisch. Sowohl demyelinisierende als auch tumoroese Rueckenmarkerkrankungen koennen Paraesthesien, progrediente sensomotorische Ausfaelle und eine Sphinkterdysfunktion hervorrufen. Bildgebende Untersuchungen, und hier allen voran die MRT, sind ein unerlaesslicher Bestandteil zur Abklaerung von Myelopathien und tragen wesentlich zur korrekten Diagnose bei. Intramedullaere Tumoren sind zwar weitaus seltener als demyelinisierende Rueckenmarkerkrankungen, dennoch sollte der Radiologe mit den Bildmerkmalen der 3 haeufigsten Tumorarten, dem Astrozytom, Ependymom und Haemangioblastom vertraut sein, die ueber 70% aller Rueckenmarktumoren verursachen. Eine moeglichst fruehe Diagnostik und Therapie sind bei tumoroesen und demyelinisierenden Rueckenmarkerkrankungen essenziell, um bleibende neurologische Defizite moeglichst gering zu halten. (orig.)

  8. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

    Directory of Open Access Journals (Sweden)

    Urszula eSlawinska

    2014-08-01

    Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

  9. An approach for ergonomic design of mouse wheel

    Institute of Scientific and Technical Information of China (English)

    Gao Sande; Nakana Keijiro; and Huang Loulin

    2012-01-01

    A new method for ergonomic design of a computer mouse is proposed in this paper. In the method, the movements of joints and tip of the forefinger during operating a mouse was captured by a high-speed video camera. The captured videos were ana- lyzed and an algorithm was developed to decide the size and location of the mouse wheel according to ergonomic principles. The al- gorithm was then coded in a software package with Visual C++ and OpenGL languages. Results of the calculation and simulation agreed well with those of the experiments. The software can also be used for shape design of mouse body, buttons and their layouts.

  10. Management of postoperative instrumented spinal wound infection

    Institute of Scientific and Technical Information of China (English)

    FANG Xiu-tong; Kirkham B.Wood

    2013-01-01

    Background Wound infection following spinal instrumented surgery is a frequent complication.The optimal treatment of acute deep wound infection following spinal instrumentation fusion remains controversial because of variability in cohort identification,definition of an infection,and the instrument used to measure outcomes.This retrospective study evaluated the clinical curative effect for postoperative spinal infection after instrumented spine fusion with extensive debridement,or implant removal.Methods From January 2004 to October 2009,851 patients were identified who underwent surgical treatment of spinal diseases.The medical records of patients who developed infections were reviewed in detail.Results Of 851 patients,41 (4.9%) developed an infection.Thirty-three were acute,and eight were delayed.Acute infected cases were managed with antibiotic therapy,and aggressive debridement of the wound and soft tissues leaving all instrumentation in situ in all but one patient.The most common symptoms of acute infection included:posterior incisional drainage (26 of 33 patients),back pain (22 of 33 patients) and fever (13 of 33 patients).Among patients with delayed onset infection,five of eight patients had local pain,four of eight patients had incision drainage,and one patient had a prolonged period of intermittent fever.The most frequent causative organism for postoperative spinal infection following spine surgery is Staphylococcus aureus.Pseudarthrosis was noted in long-term follow-up in four of 41 patients.Conclusions We recommend irrigation and debridement,no instrumentation removal,and,if necessary,repeat debridement followed by delayed primary closure for the treatment of acute deep infection with instrumentation.

  11. MR determination of neonatal spinal canal depth

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen, E-mail: owenarthurs@uk2.net [Centre for Cardiovascular MR, Great Ormond Street Hospital for Children, London WC1N 3JH (United Kingdom); Thayyil, Sudhin, E-mail: s.thayyil@ucl.ac.uk [Academic Neonatology, Institute for Women' s Health, London WC1E 6AU (United Kingdom); Wade, Angie, E-mail: a.wade@ucl.ac.uk [Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London (United Kingdom); Chong, W.K., E-mail: Kling.Chong@gosh.nhs.uk [Paediatric Neuroradiology, Great Ormond Street Hospital for Children, London (United Kingdom); Sebire, Neil J., E-mail: Neil.Sebire@gosh.nhs.uk [Histopathology, Great Ormond Street Hospital for Children, London WC1E 6AU (United Kingdom); Taylor, Andrew M., E-mail: a.taylor76@ucl.ac.uk [Centre for Cardiovascular MR, Cardiorespiratory Unit, Great Ormond Street Hospital for Children and UCL Institute of Cardiovascular Science, London WC1E 6AU (United Kingdom)

    2012-08-15

    Objectives: Lumbar punctures (LPs) are frequently performed in neonates and often result in traumatic haemorrhagic taps. Knowledge of the distance from the skin to the middle of the spinal canal (mid-spinal canal depth - MSCD) may reduce the incidence of traumatic taps, but there is little data in extremely premature or low birth weight neonates. Here, we determined the spinal canal depth at post-mortem in perinatal deaths using magnetic resonance imaging (MRI). Patients and methods: Spinal canal depth was measured in 78 post-mortem foetuses and perinatal cases (mean gestation 26 weeks; mean weight 1.04 kg) at the L3/L4 inter-vertebral space at post-mortem MRI. Both anterior (ASCD) and posterior (PSCD) spinal canal depth were measured; MSCD was calculated and modelled against weight and gestational age. Results: ASCD and PSCD (mm) correlated significantly with weight and gestational age (all r > 0.8). A simple linear model MSCD (mm) = 3 Multiplication-Sign Weight (kg) + 5 was the best fit, identifying an SCD value within the correct range for 87.2% (68/78) (95% CI (78.0, 92.9%)) cases. Gestational age did not add significantly to the predictive value of the model. Conclusion: There is a significant correlation between MSCD and body weight at post-mortem MRI in foetuses and perinatal deaths. If this association holds in preterm neonates, use of the formula MSCD (mm) = 3 Multiplication-Sign Weight (kg) + 5 could result in fewer traumatic LPs in this population.

  12. Update on treatment options for spinal brucellosis.

    Science.gov (United States)

    Ulu-Kilic, A; Karakas, A; Erdem, H; Turker, T; Inal, A S; Ak, O; Turan, H; Kazak, E; Inan, A; Duygu, F; Demiraslan, H; Kader, C; Sener, A; Dayan, S; Deveci, O; Tekin, R; Saltoglu, N; Aydın, M; Horasan, E S; Gul, H C; Ceylan, B; Kadanalı, A; Karabay, O; Karagoz, G; Kayabas, U; Turhan, V; Engin, D; Gulsun, S; Elaldı, N; Alabay, S

    2014-02-01

    We evaluated the efficacy and tolerability of antibiotic regimens and optimal duration of therapy in complicated and uncomplicated forms of spinal brucellosis. This is a multicentre, retrospective and comparative study involving a total of 293 patients with spinal brucellosis from 19 health institutions. Comparison of complicated and uncomplicated spinal brucellosis was statistically analysed. Complicated spinal brucellosis was diagnosed in 78 (26.6%) of our patients. Clinical presentation was found to be significantly more acute, with fever and weight loss, in patients in the complicated group. They had significantly higher leukocyte and platelet counts, erythrocyte sedimentation rates and C-reactive protein levels, and lower haemoglobulin levels. The involvement of the thoracic spine was significantly more frequent in complicated cases. Spondylodiscitis was complicated, with paravertebral abscess in 38 (13.0%), prevertebral abscess in 13 (4.4%), epidural abscess in 30 (10.2%), psoas abscess in 10 (3.4%) and radiculitis in 8 (2.7%) patients. The five major combination regimens were: doxycycline 200 mg/day, rifampicin 600 mg/day and streptomycin 1 g/day; doxycycline 200 mg/day, rifampicin 600 mg/day and gentamicin 5 mg/kg; doxycycline 200 mg/day and rifampicin 600 mg/day; doxycycline 200 mg/day and streptomycin 1 g/day; and doxycycline 200 mg/day, rifampicin 600 mg/day and ciprofloxacin 1 g/day. There were no significant therapeutic differences between these antibiotic groups; the results were similar regarding the complicated and uncomplicated groups. Patients were mostly treated with doxycycline and rifampicin with or without an aminoglycoside. In the former subgroup, complicated cases received antibiotics for a longer duration than uncomplicated cases. Early recognition of complicated cases is critical in preventing devastating complications. Antimicrobial treatment should be prolonged in complicated spinal brucellosis in particular.

  13. [Spinal cord injury in patients over 65 years of age].

    Science.gov (United States)

    Varela-Lage, Cristina; Alcobendas-Maestro, Mónica; Luque-Ríos, Inmaculada; Esclarín-De Ruz, Ana; Talavera-Díaz, Francisco; Ceruelo-Abajo, Silvia

    2015-06-01

    Introduccion. La poblacion de mayores de 65 años activos fisicamente continua en aumento, lo que condiciona un mayor riesgo de caidas y de lesion medular en un rango de edad con importante presencia de patologia cronica. Objetivo. Revisar la incidencia, el tipo de lesion, las complicaciones asociadas y los resultados funcionales de las lesiones medulares ocurridas en pacientes mayores de 65 años. Pacientes y metodos. Estudio descriptivo retrospectivo en lesionados medulares agudos mayores de 65 años ingresados en el Hospital Nacional de Paraplejicos desde enero de 2010 hasta diciembre de 2011. Las variables del estudio fueron datos demograficos y de lesion, antecedentes personales, complicaciones ocurridas durante el ingreso y capacidad funcional al alta medida con las escalas Spinal Cord Independence Measure (SCIM III) y Walking Index Spinal Cord Injury (WISCI). Resultados. Se incluyeron 111 individuos con una media de edad de 72,5 años. La incidencia anual fue de 17,3 pacientes/100 ingresos. El 33,3% eran lesiones cervicales y fueron incompletas el 66,7%. La etiologia medica fue mas frecuente que la traumatica. El 5% no presentaba otras enfermedades intercurrentes. El 97% sufrio algun tipo de complicacion. La media alcanzada para la SCIM III fue de 42 puntos y el 35% consiguio capacidad de marcha. Conclusiones. En los ultimos años se ha producido un aumento de lesion medular en mayores de 65 años, en los que la etiologia traumatica no es superior a la medica; mas frecuentemente son lesiones incompletas que asocian mayor comorbilidad que la poblacion general, y se consiguen resultados funcionales mas pobres a pesar de las mejoras neurologicas.

  14. Hyperbaric oxygen preconditioning induces tolerance against spinal cord ischemia in rabbits%高压氧预处理诱导兔脊髓缺血耐受现象产生

    Institute of Scientific and Technical Information of China (English)

    董海龙; 熊利泽; 朱正华

    2000-01-01

    @@ INTRODUCTION Paraplegia is a severe complication of desendingthoracic aneurysm (TA) and thora coabdominal anerysm(TAA) repair[1]. This complication is caused by spin al cord ischemia secondary to aortic clamping. Many methods and drugs have been suggeste d to protect against ischemic spinal cord injury[2-4] but the efficacy is still under dispute. Therefore, it is necessary to find some effective methods or dru gs to effectively protect against spinal cord ischemic injury.

  15. Mouse bladder wall injection.

    Science.gov (United States)

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  16. Manipulation of Mouse Embryonic Stem Cells for Knockout Mouse Production

    OpenAIRE

    Limaye, Advait; Hall, Bradford; Kulkarni, Ashok B.

    2009-01-01

    The establishment of mouse embryonic stem (ES) cell liness has allowed for the generation of the knockout mouse. ES cells that are genetically altered in culture can then be manipulated to derive a whole mouse containing the desired mutation. To successfully generate a knockout mouse, however, the ES cells must be carefully cultivated in a pluripotent state throughout the gene targeting experiment. This unit describes detailed step-by-step protocols, reagents, equipment, and strategies needed...

  17. Burn mouse models

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2014-01-01

    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third...

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

    Science.gov (United States)

    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.

  19. Induction of long-term potentiation and long-term depression is cell-type specific in the spinal cord.

    Science.gov (United States)

    Kim, Hee Young; Jun, Jaebeom; Wang, Jigong; Bittar, Alice; Chung, Kyungsoon; Chung, Jin Mo

    2015-04-01

    The underlying mechanism of chronic pain is believed to be changes in excitability in spinal dorsal horn (DH) neurons that respond abnormally to peripheral input. Increased excitability in pain transmission neurons, and depression of inhibitory neurons, are widely recognized in the spinal cord of animal models of chronic pain. The possible occurrence of 2 parallel but opposing forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) was tested in 2 types of identified DH neurons using whole-cell patch-clamp recordings in mouse spinal cord slices. The test stimulus was applied to the sensory fibers to evoke excitatory postsynaptic currents in identified spinothalamic tract neurons (STTn) and GABAergic neurons (GABAn). Afferent conditioning stimulation (ACS) applied to primary afferent fibers with various stimulation parameters induced LTP in STTn but LTD in GABAn, regardless of stimulation parameters. These opposite responses were further confirmed by simultaneous dual patch-clamp recordings of STTn and GABAn from a single spinal cord slice. Both the LTP in STTn and the LTD in GABAn were blocked by an NMDA receptor antagonist, AP5, or an intracellular Ca chelator, BAPTA. Both the pattern and magnitude of intracellular Ca after ACS were almost identical between STTn and GABAn based on live-cell calcium imaging. The results suggest that the intense sensory input induces an NMDA receptor-dependent intracellular Ca increase in both STTn and GABAn, but produces opposing synaptic plasticity. This study shows that there is cell type-specific synaptic plasticity in the spinal DH. PMID:25785524

  20. Radiotherapy of spinal cord gliomas. A retrospective mono-institutional analysis

    Energy Technology Data Exchange (ETDEWEB)

    Corradini, Stefanie; Hadi, Indrawati; Ganswindt, Ute; Belka, Claus; Niyazi, Maximilian [University of Munich, Department of Radiation Oncology, Munich (Germany); Hankel, Vinzent [Marienhospital Stuttgart, Department of Radiation Oncology, Stuttgart (Germany); Ertl, Lorenz [Staedtisches Klinikum Muenchen Harlaching, Department of Radiology, Neuroradiology, and Nuclear Medicine, Munich (Germany); University of Munich, Department of Neuroradiology, Munich (Germany)

    2016-03-15

    Behandlungsstrategie. Ziel dieser retrospektiven Studie war es, die patienten- sowie tumorbezogenen Charakteristika auszuwerten und den Einsatz sowie die Rolle der Strahlentherapie (RT) bei der Behandlung von spinalen Gliomen zu untersuchen. Es wurden retrospektiv die Daten von allen Patienten mit spinalen Gliomen untersucht, welche von 2003 bis 2013 an der Klinik fuer Strahlentherapie der LMU Muenchen behandelt wurden. Es erfolgte die Auswertung der patienten- sowie tumor- und therapiebezogenen Charakteristika. Das Gesamtueberleben (OS) wurde nach Kaplan-Meier geschaetzt. Univariate Analysen wurden mittels Log-Rank-Test durchgefuehrt. Die Daten von 16 Patienten wurden analysiert. Darunter waren sieben primaere spinale Gliome und acht Abtropfmetastasen intrakranieller Gliome. Das mediane Follow-up betrug 42 Monate. Alle Patienten erhielten eine RT mit einer medianen Gesamtdosis von 45,0 Gy. In 62,5 % erfolgte eine simultane Radiochemotherapie mit Temozolomid. Das mediane OS fuer die gesamte Kohorte lag bei 6 Monaten (95 %-KI 0,0-27,5). Patienten mit der Diagnose eines primaeren spinalen Glioms hatten ein signifikant besseres OS als Patienten mit zerebralen Abtropfmetastasen (p < 0,001). Ebenso war eine Tumorresektion mit einem signifikanten Ueberlebensvorteil assoziiert (p = 0,001). Bezueglich der RT zeigte sich eine Dosis-Wirkungs-Beziehung ab einer Dosis von ≥ 45 Gy, welche mit einem verbesserten OS im Vergleich zu einer Bestrahlungsdosis von < 45 Gy korrelierte (p < 0,001). Die simultane Chemotherapie hatte keinen Einfluss auf das OS. Schlussfolgerung Trotz der Fortschritte im Bereich der multimodalen Therapie ist die Prognose spinaler Gliome mit einem medianen OS von nur 6 Monaten immer noch schlecht. Obwohl die Aussagekraft der Ergebnisse durch die relativ kleine Anzahl an Patienten begrenzt ist, stellt diese Studie einen wichtigen Beitrag zur spaerlichen Datenlage dar. Die vorliegenden Studienergebnisse sind ausserdem eine der groessten Fallsammlungen zur simultanen

  1. Spinal cord compression due to epidural extramedullary haematopoiesis in thalassaemia: MRI

    International Nuclear Information System (INIS)

    Spinal epidural extramedullary haematopoiesis is very rare in thalassaemia. A 27-year-old man with thalassaemia intermedia presented with symptoms and signs of spinal cord compression. MRI showed a thoracic spinal epidural mass, representing extramedullary haematopoietic tissue, compressing the spinal cord. Following radiotherapy, serial MRI revealed regression of the epidural mass and gradual resolution of spinal cord oedema. (orig.)

  2. Granulocyte-colony stimulating factor (G-CSF improves motor recovery in the rat impactor model for spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Tanjew Dittgen

    Full Text Available Granulocyte-colony stimulating factor (G-CSF improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function.

  3. A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe Spinal Muscular Atrophy Transgenic Mice

    OpenAIRE

    Zhou, Haiyan; Janghra, Narinder; Mitrpant, Chalermchai; Dickinson, Rachel L.; Anthony, Karen; Price, Loren; Eperon, Ian C.; Wilton, Stephen D; Morgan, Jennifer; Muntoni, Francesco

    2013-01-01

    In the search for the most efficacious antisense oligonucleotides (AOs) aimed at inducing SMN2 exon 7 inclusion, we systematically assessed three AOs, PMO25 (−10, −34), PMO18 (−10, −27), and PMO20 (−10, −29), complementary to the SMN2 intron 7 splicing silencer (ISS-N1). PMO25 was the most efficacious in augmenting exon 7 inclusion in vitro in spinal muscular atrophy (SMA) patient fibroblasts and in vitro splicing assays. PMO25 and PMO18 were compared further in a mouse model of severe SMA. A...

  4. MicroRNA expression in the adult mouse central nervous system

    DEFF Research Database (Denmark)

    Bak, Mads; Silahtaroglu, Asli; Møller, Morten;

    2008-01-01

    distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......, hypothalamus, hippocampus, neocortex, olfactory bulb, eye, and pituitary gland. These findings suggest that a large number of mouse CNS-expressed miRNAs may be associated with specific functions within these regions. Notably, more than 50% of the identified mouse CNS-enriched miRNAs showed different expression......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

  5. Spinal cord motion. Influence of respiration and cardiac cycle

    Energy Technology Data Exchange (ETDEWEB)

    Winklhofer, S. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; Schoth, F. [RWTH Aachen University Hospital (Germany). Dept. of Diagnostic Radiology; Stolzmann, P. [University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; Krings, T. [Toronto Western Hospital, ON (Canada). Div. of Neuroradiology; Mull, M.; Wiesmann, M. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; Stracke, C.P. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; Alfried-Krupp-Hospital, Essen (Germany). Dept. of Neuroradiology

    2014-11-15

    To assess physiological spinal cord motion during the cardiac cycle compared with the influence of respiration based on magnetic resonance imaging (MRI) measurements. Anterior-posterior spinal cord motion within the spinal canal was assessed in 16 healthy volunteers (median age, 25 years) by cardiac-triggered and cardiac-gated gradient echo pulse sequence MRI. Image acquisition was performed during breath-holding, normal breathing, and forced breathing. Normal spinal cord motion values were computed using descriptive statistics. Breathing-dependent differences were assessed using the Wilcoxon signed-rank test and compared with the cardiac-based cord motion. A normal value table was set up for the spinal cord motion of each vertebral cervico-thoracic-lumbar segment. Significant differences in cord motion were found between cardiac-based motion while breath-holding and the two breathing modalities (P < 0.01 each). Spinal cord motion was found to be highest during forced breathing, with a maximum in the lower cervical spinal segments (C5; mean, 2.1 mm ± 1.17). Image acquisition during breath-holding revealed the lowest motion. MRI permits the demonstration and evaluation of cardiac and respiration-dependent spinal cord motion within the spinal canal from the cervical to lumbar segments. Breathing conditions have a considerably greater impact than cardiac activity on spinal cord motion.

  6. Gene therapy approaches for spinal cord injury

    Science.gov (United States)

    Bright, Corinne

    As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model. In order to develop a platform technology to treat spinal cord injury, several nonviral gene delivery systems and polymeric scaffolds were evaluated in vitro and in vivo. Nonviral vector trafficking was evaluated in primary neuronal culture to develop an understanding of the barriers to gene transfer in neurons and their supporting glia. Although the most efficient gene carrier in vitro differed from the optimal gene carrier in vivo, confocal and electron microscopy of these nonviral vectors provided insights into the interaction of these vectors with the nucleus. A novel pathway for delivering nanoparticles into the nuclei of neurons and Schwann cells via vesicle trafficking was observed in this study. Reporter gene expression levels were evaluated after direct and remote delivery to the spinal cord, and the optimal nonviral vector, dose, and delivery strategy were applied to deliver the gene encoding the basic fibroblast growth factor (bFGF) to the spinal cord. An injectable and biocompatible gel, composed of the amphiphillic polymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) was evaluated as a drug and gene delivery system in vitro, and combined with the optimized nonviral gene delivery system to treat spinal cord injury. Plasmid DNA encoding the bFGF gene and the therapeutic NEP1--40 peptide

  7. The Mouse SAGE Site: database of public mouse SAGE libraries.

    Science.gov (United States)

    Divina, Petr; Forejt, Jirí

    2004-01-01

    The Mouse SAGE Site is a web-based database of all available public libraries generated by the Serial Analysis of Gene Expression (SAGE) from various mouse tissues and cell lines. The database contains mouse SAGE libraries organized in a uniform way and provides web-based tools for browsing, comparing and searching SAGE data with reliable tag-to-gene identification. A modified approach based on the SAGEmap database is used for reliable tag identification. The Mouse SAGE Site is maintained on an ongoing basis at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic and is accessible at the internet address http://mouse.biomed.cas.cz/sage/.

  8. Mouse Leydig Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  9. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  10. Mouse-X

    OpenAIRE

    Tagg, Justin

    2014-01-01

    Mouse-X is a short Science Fiction film completed in 2014. It explores identity and reality through a powerful short story about a man trapped in a building with a thousand clones of himself, begging the question, 'Who are you, if you're not the only you?'

  11. Inhibition of spinal c-Jun-NH2-terminal kinase (JNK) improves locomotor activity of spinal cord injured rats.

    Science.gov (United States)

    Martini, Alessandra C; Forner, Stefânia; Koepp, Janice; Rae, Giles Alexander

    2016-05-16

    Mitogen-activated protein kinases (MAPKs) have been implicated in central nervous system injuries, yet the roles within neurodegeneration following spinal cord injury (SCI) still remain partially elucidated. We aimed to investigate the changes in expression of the three MAPKs following SCI and the role of spinal c-jun-NH2-terminal kinase (JNK) in motor impairment following the lesion. SCI induced at the T9 level resulted in enhanced expression of phosphorylated MAPKs shortly after trauma. SCI increased spinal cord myeloperoxidase levels, indicating a local neutrophil infiltration, and elevated the number of spinal apoptotic cells. Intrathecal administration of a specific inhibitor of JNK phosphorylation, SP600125, given at 1 and 4h after SCI, reduced the p-JNK expression, the number of spinal apoptotic cells and many of the histological signs of spinal injury. Notably, restoration of locomotor performance was clearly ameliorated by SP600125 treatment. Altogether, the results demonstrate that SCI induces activation of spinal MAPKs and that JNK plays a major role in mediating the deleterious consequences of spinal injury, not only at the spinal level, but also those regarding locomotor function. Therefore, inhibition of JNK activation in the spinal cord shortly after trauma might constitute a feasible therapeutic strategy for the functional recovery from SCI. PMID:27080425

  12. Effect of fetal spinal cord graft with different methods on axonal pathology after spinal cord contusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the effect of fetal spinal cord (FSC) graft with different methods on axonal pathology and neurological function recovery after spinal cord injury (SCI).   Methods: Forty Wistar rats were divided into 4 groups. In Group A, the spinal cord was injured and hemisected. In Group B, fetal spinal cord (FSC) was transferred into the injured site. In Group C, after having done as Group B, the upper and lower spinal nerve roots were anastomosed. And in Group D, after having done as Group B, the pedicled omentum was transferred into the hemisection cavity. At 6 weeks after operation, light and electronic microscopes were used to examine the axonal pathology. The neurological function was assessed with inclined plane tests in the open field. The number of axons was quantitated by a computer image analysis system.   Results: A greater loss of axons was observed in Group A than that of other groups at 6 weeks. The sequence of the reduced rate of the axons was as following, Group A>Group B>Group C>Group D (P<0.05). The remaining axons were paralleled with the significant improvement in neurological function recovery of the rats.   Conclusions: It indicates that FSC and pedicled omentum grafts after SCI can protect the axons and promote the neurological function recovery of the rats.

  13. Image-Guided Spinal Ablation: A Review.

    Science.gov (United States)

    Tsoumakidou, Georgia; Koch, Guillaume; Caudrelier, Jean; Garnon, Julien; Cazzato, Roberto Luigi; Edalat, Faramarz; Gangi, Afshin

    2016-09-01

    The image-guided thermal ablation procedures can be used to treat a variety of benign and malignant spinal tumours. Small size osteoid osteoma can be treated with laser or radiofrequency. Larger tumours (osteoblastoma, aneurysmal bone cyst and metastasis) can be addressed with radiofrequency or cryoablation. Results on the literature of spinal microwave ablation are scarce, and thus it should be used with caution. A distinct advantage of cryoablation is the ability to monitor the ice-ball by intermittent CT or MRI. The different thermal insulation, temperature and electrophysiological monitoring techniques should be applied. Cautious pre-procedural planning and intermittent intra-procedural monitoring of the ablation zone can help reduce neural complications. Tumour histology, patient clinical-functional status and life-expectancy should define the most efficient and least disabling treatment option. PMID:27329231

  14. Radiation tolerance of the cervical spinal cord

    International Nuclear Information System (INIS)

    A total of 109 patients were studied after receiving radiation therapy that included a dose to the spinal cord. In addition to irradiation of the primary site, 59 patients received radiation to the lower neck. Transverse myelopathy developed in three patients; all three had been treated with fields to the lower neck. The dose to the spinal cord at the site of junctional fields was thought to be considerably higher because of the beam divergence from multiple fields employed. The authors stress that prolonged fractionation of treatment, fixation of the head during treatment, precise dosimetry, and close surveillance of the patient are important factors in avoiding radiation myelitis. The authors also stress the importance of controlling divergence of multiple beams by employing appropriate shields

  15. Radiation tolerance of the cervical spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Y.H.; Fayos, J.V.

    1981-05-01

    A total of 109 patients were studied after receiving radiation therapy that included a dose to the spinal cord. In addition to irradiation of the primary site, 59 patients received radiation to the lower neck. Transverse myelopathy developed in three patients; all three had been treated with fields to the lower neck. The dose to the spinal cord at the site of junctional fields was thought to be considerably higher because of the beam divergence from multiple fields employed. The authors stress that prolonged fractionation of treatment, fixation of the head during treatment, precise dosimetry, and close surveillance of the patient are important factors in avoiding radiation myelitis. The authors also stress the importance of controlling divergence of multiple beams by employing appropriate shields.

  16. Combined spinal intramedullary arteriovenous malformation and lipomyelomeningocele

    Energy Technology Data Exchange (ETDEWEB)

    Weon, Y.C.; Roh, H.G.; Byun, H.S. [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology, Seoul (Korea); Chung, J.I. [Medimoa Hospital, Department of Radiology, Seoul (Korea); Eoh, W. [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea)

    2005-10-01

    Combined spinal arteriovenous malformation and lipomyelomeningocele are extremely rare. We present a rare combined case of a lipomyelomeningocele with an intramedullary arteriovenous malformation (AVM) occurred at the L3-L4 level in a 30-year-old man who suffered from low back pain radiating to the lower extremities, dysuria, and frequency for 5 years. The MR studies showed an intradural mass with high-signal intensity on both T1-weighted and T2-weighted images, intermingled with multiple signal-void structures. The mass extended extradurally toward a subcutaneously forming fatty mass on the patient's back. Spinal angiography showed an AVM supplied by the radiculopial branches of the lumbar arteries and drained by tortuous, dilated, perimedullary veins. Endovascular embolization and surgical resection were performed. (orig.)

  17. [Spinal muscular atrophy in Braunvieh calves].

    Science.gov (United States)

    Stocker, H; Ossent, P; Heckmann, R; Oertle, C

    1992-01-01

    Clinical, neurophysiological and histopathological findings of sixteen cases of spinal muscular atrophy in calves are described. The first clinical signs usually were noticed at 2-6 weeks of age. The animals showed weakness in the hindquarters, trembling and ultimate recumbency. There was a marked muscular atrophy in all four extremities. In addition, secondary bronchopneumonia was evident in 11 cases. Histopathological lesions consisted of degenerative changes in the neurons of the ventral horns and the axons of the spinal cord as well as degeneration of nerve axons in the extremities. Neurophysiological measurements revealed spontaneous activity in the muscles of the limbs. The conditions is autosomal recessive. So far 11 bulls have been identified and excluded from breeding.

  18. [Stereotactic body radiation therapy for spinal metastases].

    Science.gov (United States)

    Pasquier, D; Martinage, G; Mirabel, X; Lacornerie, T; Makhloufi, S; Faivre, J-C; Thureau, S; Lartigau, É

    2016-10-01

    After the liver and lungs, bones are the third most common sites of cancer metastasis. Palliative radiotherapy for secondary bone tumours helps relieve pain, improve the quality of life and reduce the risk of fractures. Stereotactic body radiotherapy can deliver high radiation doses with very tight margins, which has significant advantages when treating tumours close to the spinal cord. Strict quality control is essential as dose gradient at the edge of the spinal cord is important. Optimal schedule is not defined. A range of dose-fractionation schedules have been used. Pain relief and local control are seen in over 80%. Toxicity rates are low, although vertebral fracture may occur. Ongoing prospective studies will help clarify its role in the management of oligometastatic patients. PMID:27614511

  19. Combined Spinal Epdiural Anaesthesia: Single Space Technique

    Directory of Open Access Journals (Sweden)

    Khairat Mohd, Shigufta Qazi, Showkat Hussain

    2005-10-01

    Full Text Available A study of single space combined spinal epidural (CSE block was carried out in 30 patients forlower extremity orthopaedic surgery. Hyperbaric bupivacaine (0.5% was used for subarachanoidblock and (0.25% isobaric bupivacaine was given through epidural catheter for “top-up” doses tofacilitate surgery and for postoperative analgesia. Operative conditions were described as excellentin 73.33% patients, good in 23.33% patients and fair 3.33% patients. Similarly post operativeanalgesia was excellent in 70%, good in 26.66% and fair in 3.33% cases. Intra operative complicationslike hypotension < 80mm Hg occurred in 3.33% patients and < 90 mmHg in 10% patients. No postspinal headache or neurological complications were seen. CSE anaesthesia appears to combine thereliability of spinal and the flexibility of epidural block while their drawbacks are minimized.

  20. Magnetic Resonance Imaging in occult spinal dysraphism

    International Nuclear Information System (INIS)

    A prospective study was carried out in 100 cases of suspected occult spinal dysraphic anomalies with Magnetic Resonance Imaging (MRI) in order to determine its diagnostic efficacy as the initial imaging modality. MR imaging provided accurate preoperative information in 91 out of 92 cases (98.9%). Some of the unusual and interesting findings in the series were: presence of intrinsic cord abnormality in 19 out of 21 cases (90.4%) with a normal plain radiography, 4 cases of diastematomyelia with a dermoid in the dorsal and lumbar region associated with syringohydromyelia, intradural fibrous/glial bands, syringo-hydromyelia/myelomalacia of the conus with tethered cord syndrome having a normally paced conus, and myelocystocele. It is concluded that MRI is an excellent primary diagnostic tool, together with a plain radiography, for complete preoperative evaluation of mid-line spinal anomalies. 14 refs., 3 tabs., 7 figs