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  1. Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models.

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    Abdullahi, Dauda; Annuar, Azlina Ahmad; Mohamad, Masro; Aziz, Izzuddin; Sanusi, Junedah

    2017-01-01

    It has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

  2. Experimental autoimmune prostatitis induces microglial activation in the spinal cord.

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    Wong, Larry; Done, Joseph D; Schaeffer, Anthony J; Thumbikat, Praveen

    2015-01-01

    The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. © 2014 Wiley Periodicals, Inc.

  3. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

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    Kaufmann, Nathalie; Zeka, Bleranda; Schanda, Kathrin; Fujihara, Kazuo; Illes, Zsolt; Dahle, Charlotte; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID:26990978

  4. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

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    Oji, Satoru; Nicolussi, Eva-Maria; Kaufmann, Nathalie

    2016-01-01

    -IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms...

  5. Tobacco-induced neuronal degeneration via cotinine in rats subjected to experimental spinal cord injury.

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    Dalgic, Ali; Okay, Onder; Helvacioglu, Fatma; Daglioglu, Ergun; Akdag, Rifat; Take, Gulnur; Belen, Deniz

    2013-05-01

    Cigarette smoke contains over 4000 chemicals including well-characterized toxicants and carcinogens, among which is cotinine. Cotinine is the principal metabolite of nicotine that has adverse affects on the microcirculation via vasoconstriction, hypoxia and the wound-healing cascade. Its impact on spinal cord injury (SCI) has not been investigated yet. The aim of the present study is to investigate the cotinine effect on SCI. 48 male Wistar rats were divided into six groups as follows: sham-control, sham-trauma, vehicle-control, vehicle-trauma, cotinine-control, and cotinine-trauma. Initially, a defined concentration of cotinine blood level was maintained by daily intraperitoneal injection of cotinine for 14 days in the cotinine groups. The concentration was similar to the cotinine dose in the blood level of heavy smokers. Only ethyl alcohol was injected in the vehicle groups during the same period. Then, SCI was performed by a Tator clip. The cotinine groups were compared with rats subjected to vehicle and sham groups by immunohistochemical biomarkers such as glial fibrillary acidic protein (GFAP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP) expressions. Electron microscopic examination was also performed. GFAP-positive cells were noted to be localized around degenerated astrocytes. Marked vacuolization with perivascular and perineural edema was seen in the cotinin consumption groups. These findings showed the inhibition of regeneration after SCI. Similarly, vacuolization within myelin layers was noted in the cotinine groups, which was detected through reduced CNP expression. Cotinine, a main metabolite of nicotine, has harmful effects on SCI via GFAP and CNP expression. The findings of the present study support the hypothesis that tobacco causes neuronal degeneration via cotinine. Georg Thieme Verlag KG Stuttgart · New York.

  6. Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy

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    Victoria L. Newton

    2017-01-01

    Full Text Available Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ- induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ. At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy.

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

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

    2003-01-01

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

  8. Elevated Expression of Fractalkine (CX3CL1 and Fractalkine Receptor (CX3CR1 in the Dorsal Root Ganglia and Spinal Cord in Experimental Autoimmune Encephalomyelitis: Implications in Multiple Sclerosis-Induced Neuropathic Pain

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    Wenjun Zhu

    2013-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system (CNS disease resulting from a targeted autoimmune-mediated attack on myelin proteins in the CNS. The release of Th1 inflammatory mediators in the CNS activates macrophages, antibodies, and microglia resulting in myelin damage and the induction of neuropathic pain (NPP. Molecular signaling through fractalkine (CX3CL1, a nociceptive chemokine, via its receptor (CX3CR1 is thought to be associated with MS-induced NPP. An experimental autoimmune encephalomyelitis (EAE model of MS was utilized to assess time dependent gene and protein expression changes of CX3CL1 and CX3CR1. Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG and spinal cord (SC 12 days after EAE induction compared to controls. This increased expression correlated with behavioural thermal sensory abnormalities consistent with NPP. Furthermore, this increased expression correlated with the peak neurological disability caused by EAE induction. This is the first study to identify CX3CL1 signaling through CX3CR1 via the DRG /SC anatomical connection that represents a critical pathway involved in NPP induction in an EAE model of MS.

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

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    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 spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

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    Huie, J. Russell

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions. PMID:27721996

  11. Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

    Directory of Open Access Journals (Sweden)

    Sandra M. Garraway

    2016-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions.

  12. MR imaging with Gd-DTPA enhancement in experimental acute injury of the spinal cord

    International Nuclear Information System (INIS)

    Hackney, D.B.; Asato, R.; Joseph, P.M.; McGrath, J.T.; Grossman, R.I.; Shetty, A.

    1986-01-01

    The authors performed MR imaging with Gd-DTPA enhancement in adult male Sprague-Dawley rats, with experimentally induced acute spinal cored injuries. After epidural compression of the spinal cored the pathologic changes of acute cord contusion were allowed to develop for 30 minutes to 4 hours. MR imaging was then performed at 1.4 T. Both short spin-echo (TR = 400 msec, TE = 15-20 msec) and long spin-echo (TR = 2,000 msec, TE = 100 msec) images were obtained. After the initial imaging, Gd-DTPA (0.1 mmol/kg) and Evans blue dye were administered intravenously and imaging was repeated. Enhancement of normal central gray matter was consistently observed. However, neither pathologic enhancement on MR images nor extravasation of Evans blue dye on histologic inspection were identified

  13. Ca++ dependent bistability induced by serotonin in spinal motoneurons

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    Hounsgaard, J.; Kiehn, O.

    1985-01-01

    The plateau potential, responsible for the bistable state of spinal motoneurons, recently described in the decerebrate cat, was suggested to depend on serotonin (Hounsgaard et al. 1984). In an in vitro preparation of the spinal cord of the turtle we now show that serotonin, applied directly...... to the bath, transforms the intrinsic response properties of motoneurons, uncovering a plateau potential and voltage sensitive bistability. The changes induced by serotonin were blocked by Mn++, while the plateau potential and the bistability remained after application of tetrodotoxin. We conclude...... that serotonin controls the expression of a Ca++ dependent plateau potential in motoneurons....

  14. [Changes of somatosensory and transcranial magnetic stimulation motor evoked potentials in experimental spinal cord injury].

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    Hou, Yong; Nie, Lin; Liu, Li-hong; Shao, Jun; Yuan, Yong-jian

    2008-03-18

    To study the changes of somatosensory evoked potential (SEP) and transcranial magnetic simulation motor evoked potential (TMS-MEP) in experimental spinal cord injury (SCI). Thirty-two rabbits were randomly divided into 4 equal groups. All rabbits were anesthetized for 90 min. A group (Group A) underwent only laminectomy of T12 without SCI, stimulation with different intensities was used to induce SEP and TMS-MEP to determine the most appropriate stimulation intensity. The EPs were recorded before and after the operation. The other 3 groups underwent laminectomy of T12 to expose the dura, and a spinal cord compressing apparatus weighing 40 g was put on the intact dura and dorsal surface of spinal cord underneath for 5, 15, and 30 min respectively (Groups B, C, and D). SEP and TMS-MEP were detected after anesthesia, after exposure of spinal cord, and 5 and 30 min, 1 and 6 h, and 1, 3, and 7 d. The latency and amplitude of each wave were measured. The data were analyzed by analysis of variance, t-test and linear correlation. Tarlov behavior score was used to assess the motor function before the operation and 1, 3, and 7 days after SCI. It was found that 100% intensity stimulus obtained stable and reliable MEP waves. Anesthetic did not influence the EPs. The amplitude of SEP began to decrease 5 min after SCI and the latency began to increase 30 min after SCI. And both the amplitude and latency, especially the former, of MEP began to significantly change 5 min after SCI. The latency levels of SEP and MEP increased and the amplitude decreased after compression time-dependently during a certain range of time (all P TMS-MEP are very sensitive to SCI, in particular, the change of amplitude is more sensitive then the latency change and can more accurately reflect the degree of SCI. Combination of SEP and TMS-MEP objectively reflects the SCI degree. EP measurement, as a noninvasive technique, has great value in monitoring spinal cord function.

  15. Induced Pluripotent Stem Cell Therapies for Cervical Spinal Cord Injury

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    Doulames, Vanessa M.; Plant, Giles W.

    2016-01-01

    Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs) to date. Despite the increase in survival rates due to emergency medicine improvements, overall quality of life remains poor, with patients facing variable deficits in respiratory and motor function. Therapies aiming to ameliorate symptoms and restore function, even partially, are urgently needed. Current therapeutic avenues in SCI seek to increase regenerative capacities through trophic and immunomodulatory factors, provide scaffolding to bridge the lesion site and promote regeneration of native axons, and to replace SCI-lost neurons and glia via intraspinal transplantation. Induced pluripotent stem cells (iPSCs) are a clinically viable means to accomplish this; they have no major ethical barriers, sources can be patient-matched and collected using non-invasive methods. In addition, the patient’s own cells can be used to establish a starter population capable of producing multiple cell types. To date, there is only a limited pool of research examining iPSC-derived transplants in SCI—even less research that is specific to cervical injury. The purpose of the review herein is to explore both preclinical and clinical recent advances in iPSC therapies with a detailed focus on cervical spinal cord injury. PMID:27070598

  16. Angelica Sinensis attenuates inflammatory reaction in experimental rat models having spinal cord injury.

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    Xu, Jun; E, Xiao-Qiang; Liu, Hui-Yong; Tian, Jun; Yan, Jing-Long

    2015-01-01

    This study was aimed to evaluate the effect of Angelica Sinensis on experimental rat models in which spinal cord injury was induced by studying different factors. Different factors causing inflammation play a key role in pathophysiology of SCI. Here three groups of rats (n=15, each was used). These included a sham control group where only laminectomy was performed, SCI group where SCI was induced and AS/SCI group where although SCI was induced but Angelica Sinensis was also administered to study its effect and draw a comparison with control. The expression of I-kBα and NF-kB p65 was also studied using western blotting and after recording optical density (OD) values of western blots. MPO activity was used to measure the effect of 20 mg/kg Angelica Sinensis. The levels of proinflammatory cytokines TNF-α, IL-1β and IL-6 were also studied. As compared with SCI group and sham control it was observed that Angelica Sinensis significantly reduced the expression of I-kBα and NF-kB p65, (PSinensis in rat models can attenuate the secondary damage caused by SCI and thus help in controlling the pathology of SCI in rats.

  17. Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.

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    Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren

    2009-08-25

    Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.

  18. Vitamin A active metabolite, all-trans retinoic acid, induces spinal cord sensitization. II. Effects after intrathecal administration

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    Alique, M; Lucio, F J; Herrero, J F

    2006-01-01

    Background and purpose: In our previous study (see accompanying paper) we observed that all-trans retinoic acid (ATRA) p.o. induces changes in spinal cord neuronal responses similar to those observed in inflammation-induced sensitization. In the present study we assessed the it. effects of ATRA, and its mechanisms of action. Experimental approach: The effects of all drugs were studied after it. administration in nociceptive withdrawal reflexes using behavioural tests in awake male Wistar rats. Key results: The administration of ATRA in normal rats induced a dose-dependent enhancement of nociceptive responses to noxious mechanical and thermal stimulation, as well as responses to innocuous stimulation. The intensity of the responses was similar to that observed in non-treated animals after carrageenan-induced inflammation. The effect induced by ATRA was fully prevented by the previous administration of the retinoic acid receptor (RAR) pan-antagonist LE540 but not by the retinoid X receptor (RXR) pan-antagonist HX531, suggesting a selective action on spinal cord RARs. The COX inhibitor dexketoprofen and the interleukin-1 receptor antagonist IL-1ra inhibited ATRA effect. The results indicate that COX and interleukin-1 are involved in the effects of ATRA in the spinal cord, similar to that seen in inflammation. Conclusions and implications: In conclusion, ATRA induces changes in the spinal cord similar to those observed in inflammation. The sensitization-like effect induced by ATRA was mediated by RARs and associated with a modulation of COX-2 and interleukin-1 activities. ATRA might be involved in the mechanisms underlying the initiation and/or maintenance of sensitization in the spinal cord. PMID:16847438

  19. Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

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    Schiaveto-de-Souza, A.; Silva, C.A. da; Defino, H.L.A.; Bel, E.A.Del

    2013-01-01

    Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury

  20. Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

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    A. Schiaveto-de-Souza

    2013-12-01

    Full Text Available Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.

  1. Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

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    Schiaveto-de-Souza, A. [Departamento de Morfofisiologia, Universidade Federal do Mato Grosso do Sul, Campo Grande, MS (Brazil); Silva, C.A. da [Departamento de Morfologia,Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Defino, H.L.A. [Departamento de Orthopedia e Traumatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Bel, E.A.Del [Departamento de Morfologia,Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2013-04-12

    Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.

  2. A rat model of chronic syringomyelia induced by epidural compression of the lumbar spinal cord.

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    Lee, Ji Yeoun; Kim, Shin Won; Kim, Saet Pyoul; Kim, Hyeonjin; Cheon, Jung-Eun; Kim, Seung-Ki; Paek, Sun Ha; Pang, Dachling; Wang, Kyu-Chang

    2017-10-01

    OBJECTIVE There has been no established animal model of syringomyelia associated with lumbosacral spinal lipoma. The research on the pathophysiology of syringomyelia has been focused on Chiari malformation, trauma, and inflammation. To understand the pathophysiology of syringomyelia associated with occult spinal dysraphism, a novel animal model of syringomyelia induced by chronic mechanical compression of the lumbar spinal cord was created. METHODS The model was made by epidural injection of highly concentrated paste-like kaolin solution through windows created by partial laminectomy of L-1 and L-5 vertebrae. Behavioral outcome in terms of motor (Basso-Beattie-Bresnahan score) and urinary function was assessed serially for 12 weeks. Magnetic resonance images were obtained in some animals to confirm the formation of a syrinx and to monitor changes in its size. Immunohistochemical studies, including analysis for glial fibrillary acidic protein, NeuN, CC1, ED-1, and caspase-3, were done. RESULTS By 12 weeks after the epidural compression procedure, syringomyelia formation was confirmed in 85% of the rats (34 of 40) on histology and/or MRI. The syrinx cavities were found rostral to the epidural compression. Motor deficit of varying degrees was seen immediately after the procedure in 28% of the rats (11 of 40). In 13 rats (33%), lower urinary tract dysfunction was seen. Motor deficit improved by 5 weeks after the procedure, whereas urinary dysfunction mostly improved by 2 weeks. Five rats (13%, 5 of 40) died 1 month postoperatively or later, and 3 of the 5 had developed urinary tract infection. At 12 weeks after the operation, IHC showed no inflammatory process, demyelination, or accelerated apoptosis in the spinal cords surrounding the syrinx cavities, similar to sham-operated animals. CONCLUSIONS A novel experimental model for syringomyelia by epidural compression of the lumbar spinal cord has been created. The authors hope that it will serve as an important research

  3. Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish

    Science.gov (United States)

    Mokalled, Mayssa H.; Patra, Chinmoy; Dickson, Amy L.; Endo, Toyokazu; Stainier, Didier Y. R.; Poss, Kenneth D.

    2016-01-01

    Unlike mammals, zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue and facilitate regeneration, a relatively unexplored process. Here, we performed a genome-wide profiling screen for secreted factors that are upregulated during zebrafish spinal cord regeneration. We find that connective tissue growth factor a (ctgfa) is induced in and around glial cells that participate in initial bridging events. Mutations in ctgfa disrupt spinal cord repair, while transgenic ctgfa overexpression and local human CTGF recombinant protein delivery accelerate bridging and functional regeneration. Our study reveals that CTGF is necessary and sufficient to stimulate glial bridging and natural spinal cord regeneration. PMID:27811277

  4. The effect of spinal manipulation on deep experimental muscle pain in healthy volunteers

    DEFF Research Database (Denmark)

    O'Neill, Søren; Ødegaard-Olsen, Øystein; Søvde, Beate

    2015-01-01

    individuals. METHODS AND MATERIALS: Local, para-spinal muscle pain was induced by injection of 0.5 ml sterile, hyper-tonic saline on two separate occasions 1 week apart. Immediately following the injection, treatment was administered as either a) HVLA-manipulation or b) placebo treatment, in a randomized...

  5. Neural control of locomotion and training-induced plasticity after spinal and cerebral lesions.

    Science.gov (United States)

    Knikou, Maria

    2010-10-01

    Standing and walking require a plethora of sensorimotor interactions that occur throughout the nervous system. Sensory afferent feedback plays a crucial role in the rhythmical muscle activation pattern, as it affects through spinal reflex circuits the spinal neuronal networks responsible for inducing and maintaining rhythmicity, drives short-term and long-term re-organization of the brain and spinal cord circuits, and contributes to recovery of walking after locomotor training. Therefore, spinal circuits integrating sensory signals are adjustable networks with learning capabilities. In this review, I will synthesize the mechanisms underlying phase-dependent modulation of spinal reflexes in healthy humans as well as those with spinal or cerebral lesions along with findings on afferent regulation of spinal reflexes and central pattern generator in reduced animal preparations. Recovery of walking after locomotor training has been documented in numerous studies but the re-organization of spinal interneuronal and cortical circuits need to be further explored at cellular and physiological levels. For maximizing sensorimotor recovery in people with spinal or cerebral lesions, a multidisciplinary approach (rehabilitation, pharmacology, and electrical stimulation) delivered during various sensorimotor constraints is needed. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Increased circulating rather than spinal cytokines accompany chronic pain behaviors in experimental bone cancer and arthritis

    Directory of Open Access Journals (Sweden)

    Line Pourtau

    2014-12-01

    Full Text Available Aim: Peripheral cytokines contribute to arthritis and bone cancer pain through sensory nerve actions. However, increased spinal cytokine and glial filament expression, coined neuroinflammation, has also been proposed to play a part in chronic pain. Therefore, spinal cord, dorsal root ganglia and circulating cytokines were compared in murine arthritis and bone cancer models in relationship to behavioral signs of pain. Methods: Exploratory behaviors were studied after intra-articular complete Freund's adjuvant or bone intramedullary sarcoma cell injection. Nervous tissue and blood cytokine expression were determined by real-time polymerase chain reaction (PCR and multiplex immunoassays, respectively. Results: PCR analysis did not reveal any hallmark of spinal neuroinflammation in spontaneously-behaving mice with cartilage or bone lesions. However, imposed paw stimulation during joint inflammation increased spinal interleukin-1β (IL-1β expression. Spontaneous paw guarding during rearing was displayed by animals with joint inflammation and bone destruction and was accompanied by increased circulating IL-6 and monocyte chemoattractant protein-1, respectively. In addition, dorsal root ganglia were found to constitutively express receptors for this chemotactic cytokine. Conclusion: Our findings indicate that spinal neuroinflammation is not a necessary condition for chronic pain and suggest that circulating cytokine action in dorsal root ganglia may contribute to experimental joint inflammation and bone cancer pain.

  7. Therapeutic effects of neurotrophic factors in experimental spinal cord injury models

    Directory of Open Access Journals (Sweden)

    Enomoto M

    2016-03-01

    Full Text Available Mitsuhiro Enomoto1,21Department of Orthopaedic and Spinal Surgery, Graduate School, 2Hyperbaric Medical Center, Tokyo Medical and Dental University, Tokyo, JapanAbstract: Neurotrophic factors (NFs play important roles in regenerative medicine approaches to mitigate primary and secondary damage after spinal cord injury (SCI because their receptors are still present in the injured spinal cord even though the expression of the NFs themselves is decreased. Several reports have shown that NF administration increases regenerative signaling after SCI, particularly by stimulating axonal growth. However, few NFs cross the blood–brain barrier, and most of them show low stability and limited diffusion within the central nervous system. To overcome this problem, transplantation strategies using genetically modified NF-secreting Schwann cells, neural and glial progenitor cells, and mesenchymal stem cells have been applied to animal models of SCI. In particular, multifunctional NFs that bind to TrkB, TrkC, and p75NTR receptors have been discovered in the last decade and utilized in preclinical cell therapies for spinal cord repair. To achieve functional recovery after SCI, it is important to consider the different effects of each NF on axonal regeneration, and strategies should be established to specifically harness the multifunctional properties of NFs. This review provides an overview of multifunctional NFs combined with cell therapy in experimental SCI models and a proposal to implement their use as a clinically viable therapy.Keywords: spinal cord injury, neurotrophic factor, multineurotrophin, regeneration, cell transplantation

  8. Comparing the Ease of Inducing Spinal Anaesthesia in the Sitting ...

    African Journals Online (AJOL)

    Under strict asepsis, spinal anaesthesia was established at a preferred intervertebral space (L2-L5), proportion of first attempt success, number of attempts, number of redirections, duration taken to establish spinal, complication were compared. Results: There were no statistical differences between the two groups in relation ...

  9. Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats

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    Olavo Biraghi Letaif

    2015-10-01

    Full Text Available OBJECTIVES:To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion.METHODS:In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day.RESULTS:The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers.CONCLUSIONS:Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury.

  10. Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats.

    Science.gov (United States)

    Letaif, Olavo Biraghi; Cristante, Alexandre Fogaça; Barros Filho, Tarcísio Eloy Pessoa de; Ferreira, Ricardo; Santos, Gustavo Bispo dos; Rocha, Ivan Dias da; Marcon, Raphael Martus

    2015-10-01

    To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion. In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI) at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg) immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day. The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers. Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury.

  11. Peripheral formalin injection induces unique spinal cord microglial phenotypic changes

    Science.gov (United States)

    Fu, Kai-Yuan; Tan, Yong-Hui; Sung, Backil; Mao, Jianren

    2014-01-01

    Microglia are resident immune cells of brain and activated by peripheral tissue injury. In the present study, we investigated the possible induction of several microglial surface immunomolecules in the spinal cord, including leukocyte common antigen (LCA/CD45), MHC class I antigen, MHC class II antigen, Fc receptor, and CD11c following formalin injection into the rat’s hind paw. CD45 and MHC class I were upregulated in the activated microglia, which was evident on day 3 with the peak expression on day 7 following peripheral formalin injection. There was a very low basal expression of MHC class II, CD11c, and the Fc receptor, which did not change after the formalin injection. These results, for the first time, indicate that peripheral formalin injection can induce phenotypic changes of microglia with distinct upregulation of CD45 and MHC class I antigen. The data suggest that phenotypic changes of the activated microglia may be a unique pattern of central changes following peripheral tissue injury. PMID:19015000

  12. Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

    Science.gov (United States)

    Ramalho, Fernando S; Yamamoto, Aparecida Y; da Silva, Luis L; Figueiredo, Luiz T M; Rocha, Lenaldo B; Neder, Luciano; Teixeira, Sara R; Apolinário, Letícia A; Ramalho, Leandra N Z; Silva, Deisy M; Coutinho, Conrado M; Melli, Patrícia P; Augusto, Marlei J; Santoro, Ligia B; Duarte, Geraldo; Mussi-Pinhata, Marisa M

    2017-08-15

    We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar aplasia were observed. The spinal cord showed architectural distortion, severe neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons, and spinal cord samples were positive for ZIKV RNA. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  13. Biomechanical implications of lumbar spinal ligament transection.

    Science.gov (United States)

    Von Forell, Gregory A; Bowden, Anton E

    2014-11-01

    Many lumbar spine surgeries either intentionally or inadvertently damage or transect spinal ligaments. The purpose of this work was to quantify the previously unknown biomechanical consequences of isolated spinal ligament transection on the remaining spinal ligaments (stress transfer), vertebrae (bone remodelling stimulus) and intervertebral discs (disc pressure) of the lumbar spine. A finite element model of the full lumbar spine was developed and validated against experimental data and tested in the primary modes of spinal motion in the intact condition. Once a ligament was removed, stress increased in the remaining spinal ligaments and changes occurred in vertebral strain energy, but disc pressure remained similar. All major biomechanical changes occurred at the same spinal level as the transected ligament, with minor changes at adjacent levels. This work demonstrates that iatrogenic damage to spinal ligaments disturbs the load sharing within the spinal ligament network and may induce significant clinically relevant changes in the spinal motion segment.

  14. Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Xi-Tuan Ji

    Full Text Available Chemotherapy-induced neuropathic pain (CNP is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor; whereas minocycline (microglial specific inhibitor had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

  15. Spinal Cord Glioblastoma Induced by Radiation Therapy of Nasopharyngeal Rhabdomyosarcoma with MRI Findings: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Se Jin; Kim, In One [Dept. of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    Radiation-induced spinal cord gliomas are extremely rare. Since the first case was reported in 1980, only six additional cases have been reported.; The radiation-induced gliomas were related to the treatment of Hodgkin's lymphoma, thyroid cancer, and medullomyoblastoma, and to multiple chest fluoroscopic examinations in pulmonary tuberculosis patient. We report a case of radiation-induced spinal cord glioblastoma developed in a 17-year-old girl after a 13-year latency period following radiotherapy for nasopharyngeal rhabdomyosarcoma. MRI findings of our case are described.

  16. Magnetic resonance imaging of experimental spinal cord injury

    International Nuclear Information System (INIS)

    Nakamura, Tsutomu; Kumano, Kouichi; Kadoya, Satoru

    1989-01-01

    Correlation between pathological findings and magnetic resonance imaging (MRI) of experimental cord injury were investigated. Cord injuries were made on ten Wistar rats weighing 80-170 gm by epidural compression of the thoracic cord with a Biemer cerebral vascular clip for 5-20 seconds. Several hours after the procedure animals were examined by spin echo axial MR images with a pulse sequence of TR/TE=1000/36 msec. MR studies were repeated on 4 animals 3-7 days after the initial examination. Immediately after the latest MRI examination animals were sacrificed and fixed with 10% formalin. Three micron thickness paraffin sections stained with hematoxylin and eosin were evaluated under a microscope. The pathological finding was hemorrhagic necrosis with edema of various severity depending on duration of clip application. The hemorrhagic necrosis was observed either unilaterally or bilaterally to the cord. MR findings of the cord were of high intensity in five animals which were severely injured, while central low intensity of the injured cord appeared in three mildly injured animals. Of the remaining two animals which had mild injury, one showed unilateral high intensity, while no definitive change was demonstrated in the other. The high intensity in the MRI suggested edema associated with hemorrhagic necrosis rather than hemorrhage. The central low intensity appearing in the mildly injured cord might be hemorrhage in the gray matter. It is concluded that MRI was useful to diagnose not only the level and severity but also the pathological process in the injured cord, and thus to estimate the prognosis of the cord injuries. (author)

  17. Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

    Science.gov (United States)

    Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

    2007-01-01

    We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

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

    Science.gov (United States)

    Li, Y Q; Wong, C S

    2000-09-01

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

  19. Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

    Directory of Open Access Journals (Sweden)

    Srinivasu Kallakuri

    2015-01-01

    Full Text Available Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s of blast overpressure (OP induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.

  20. MRI in the early stage of spinal cord injury: does it have clinical relevance? An experimental study

    International Nuclear Information System (INIS)

    Hannmann, T.T.; Freund, M.

    2007-01-01

    Purpose: An experimental technique for producing a ventral spinal trauma which imitates a slipped intervertebral disc or a fractured vertebra was evaluated using magnetic resonance imaging and histology. The results were evaluated with respect to their clinical importance. Materials and Methods: A total of 69 Wistar rats were used for this study. An inflatable angioplasty balloon device was placed dorsally or ventrally to the spinal cord in order to produce a spinal trauma. 30 rats were used to compare neurological pathologies between ventral and dorsal trauma. 30 animals underwent graded ventral spinal cord compression. Magnetic resonance imaging was performed and the results were compared to histology. Results: Using this technique, the balloon device can be placed ventrally to the spinal cord. The compression time had a direct effect on changes on magnetic resonance images and edema in histology, but a longer compression time did not produce increased bleeding. The T2-weighted MRI scans showed hyperintense changes immediately after spinal compression. Therefore, they are the appropriate way for diagnosing acute spinal injuries. Although the T1-weighted MRI scans did not change after spinal compression, they are important for diagnosing epidural hematomas. (orig.)

  1. Spinal TNFα is necessary for inactivity-induced phrenic motor facilitation

    Science.gov (United States)

    Broytman, Oleg; Baertsch, Nathan A; Baker-Herman, Tracy L

    2013-01-01

    A prolonged reduction in central neural respiratory activity elicits a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF), a ‘rebound’ increase in phrenic burst amplitude apparent once respiratory neural activity is restored. iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize an early transient increase in phrenic burst amplitude and to form long-lasting iPMF following reduced respiratory neural activity. Upstream signal(s) leading to spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour necrosis factor-α (TNFα) is necessary for iPMF via an aPKC-dependent mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea; upon resumption of respiratory neural activity, a prolonged increase in phrenic burst amplitude (42 ± 9% baseline; P phrenic motor nucleus prior to neural apnoea blocked long-lasting iPMF (2 ± 8% baseline; P > 0.05). Intrathecal TNFα without neural apnoea was sufficient to elicit long-lasting phrenic motor facilitation (pMF; 62 ± 7% baseline; P < 0.05). Similar to iPMF, TNFα-induced pMF required spinal aPKC activity, as intrathecal delivery of a ζ-pseudosubstrate inhibitory peptide (PKCζ-PS) 35 min following intrathecal TNFα arrested TNFα-induced pMF (28 ± 8% baseline; P < 0.05). These data demonstrate that: (1) spinal TNFα is necessary for iPMF; and (2) spinal TNFα is sufficient to elicit pMF via a similar aPKC-dependent mechanism. These data are consistent with the hypothesis that reduced respiratory neural activity elicits iPMF via a TNFα-dependent increase in spinal aPKC activity. PMID:23878370

  2. Stimulation-induced optical signals in rat spinal cord slices

    Czech Academy of Sciences Publication Activity Database

    Kubinová, Šárka; Vargová, Lýdia; Syková, Eva

    2002-01-01

    Roč. 1, - (2002), s. 34 ISSN 0894-1491. [European Meeting on Glia l Cell Function in Health and Disease. Rome - Italy, 21.05.2002-25.05.2002] R&D Projects: GA MŠk LN00A065 Institutional research plan: CEZ:AV0Z5039906; CEZ:MSM 111300004; CEZ:MSM 5011112 Keywords : spinal cord Subject RIV: FH - Neurology Impact factor: 4.600, year: 2002

  3. Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysis

    Directory of Open Access Journals (Sweden)

    Aigner Ludwig

    2008-05-01

    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis (EAE induced by myelin oligodendrocyte protein (MOG in female Dark Agouti (DA rats is a chronic demyelinating animal model of multiple sclerosis (MS. To identify new candidate molecules involved in the evolution or repair of EAE-lesions we used Affymetrix oligonucleotide microarrays to compare the spinal cord transcriptome at the peak of EAE, during remission and at the first relapse with healthy DA rats. Methods Untreated DA rats and DA rats immunised with MOG protein were sacrificed at defined time points. Total RNA was isolated from spinal cord tissue and used for hybridization of Affymetrix rat genome arrays RG U34 A-C. Selected expression values were confirmed by RealTime PCR. Adult neural stem cells were incubated with recombinant secretory leukocyte protease inhibitor (SLPI. Proliferation was assessed by BrdU incorporation, cyclin D1 and HES1 expression by RealTime PCR, cell differentiation by immunofluorescence analysis and IkappaBalpha degradation by Western blot. Results Among approximately 26,000 transcripts studied more than 1,100 were differentially regulated. Focussing on functional themes, we noticed a sustained downregulation of most of the transcripts of the cholesterol biosynthesis pathway. Furthermore, we found new candidate genes possibly contributing to regenerative processes in the spinal cord. Twelve transcripts were solely upregulated in the recovery phase, including genes not previously associated with repair processes. Expression of SLPI was upregulated more than hundredfold during EAE attack. Using immunohistochemistry, SLPI was identified in macrophages, activated microglia, neuronal cells and astrocytes. Incubation of adult neural stem cells (NSC with recombinant SLPI resulted in an increase of cell proliferation and of differentiation towards oligodendrocytes. These processes were paralleled by an upregulation of the cell-cycle promotor cyclin D1 and a

  4. Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries.

    Science.gov (United States)

    Etz, Christian D; Homann, Tobias M; Luehr, Maximilian; Kari, Fabian A; Weisz, Donald J; Kleinman, George; Plestis, Konstadinos A; Griepp, Randall B

    2008-06-01

    Spinal cord blood flow (SCBF) after sacrifice of thoracoabdominal aortic segmental arteries (TAASA) during thoracoabdominal aortic aneurysm (TAAA) repair remains poorly understood. This study explored SCBF for 72 h after sacrifice of all TAASA. Fourteen juvenile Yorkshire pigs underwent complete serial TAASA sacrifice (T4-L5). Six control pigs underwent anesthesia and cooling to 32 degrees C with no TAASA sacrifice. In the experimental animals, spinal cord function was continuously monitored using motor evoked potentials (MEPs) until 1h after clamping the last TAASA. Fluorescent microspheres enabled segmental measurement of SCBF along the entire spinal cord before, and 5 min, 1 h, 5 h, 24 h and 72 h after complete TAASA sacrifice. A modified Tarlov score was obtained for 3 days after surgery. All the pigs with complete TAASA sacrifice retained normal cord function (MEP) until 1h after TAASA ligation. Seven pigs (50%) with complete TAASA sacrifice recovered after 72 h; seven pigs suffered paraparesis or paraplegia. Intraoperatively, and until 1h postoperatively, SCBF was similar among the three groups along the entire cord. Postoperatively, SCBF did not decrease in any group, but significant hyperemia occurred at 5h in controls and recovery animals, but did not occur in pigs that developed paraparesis or paraplegia in the T8-L2 segments (p=0.0002) and L3-S segments (p=0.0007). At 24h, SCBF remained marginally lower from T8 caudally; at 72h, SCBF was similar among all groups along the entire cord. SCBF in the segments T8-L2 at 5h predicted functional recovery (p=0.003). This study suggests that critical spinal cord ischemia after complete TAASA sacrifice does not occur immediately (intraoperatively), but is delayed 1-5h or longer after clamping, and represents failure to mount a hyperemic response to rewarming and awakening. The short duration of low SCBF associated with spinal cord injury suggests that hemodynamic and metabolic manipulation lasting only 24-72 h may

  5. Cerebrospinal fluid pressures resulting from experimental traumatic spinal cord injuries in a pig model.

    Science.gov (United States)

    Jones, Claire F; Lee, Jae H T; Burstyn, Uri; Okon, Elena B; Kwon, Brian K; Cripton, Peter A

    2013-10-01

    Despite considerable effort over the last four decades, research has failed to translate into consistently effective treatment options for spinal cord injury (SCI). This is partly attributed to differences between the injury response of humans and rodent models. Some of this difference could be because the cerebrospinal fluid (CSF) layer of the human spine is relatively large, while that of the rodents is extremely thin. We sought to characterize the fluid impulse induced in the CSF by experimental SCIs of moderate and high human-like severity, and to compare this with previous studies in which fluid impulse has been associated with neural tissue injury. We used a new in vivo pig model (n = 6 per injury group, mean age 124.5 days, 20.9 kg) incorporating four miniature pressure transducers that were implanted in pairs in the subarachnoid space, cranial, and caudal to the injury at 30 mm and 100 mm. Tissue sparing was assessed with Eriochrome Cyanine and Neutral Red staining. The median peak pressures near the injury were 522.5 and 868.8 mmHg (range 96.7-1430.0) and far from the injury were 7.6 and 36.3 mmHg (range 3.8-83.7), for the moderate and high injury severities, respectively. Pressure impulse (mmHg.ms), apparent wave speed, and apparent attenuation factor were also evaluated. The data indicates that the fluid pressure wave may be sufficient to affect the severity and extent of primary tissue damage close to the injury site. However, the CSF pressure was close to normal physiologic values at 100 mm from the injury. The high injury severity animals had less tissue sparing than the moderate injury severity animals; this difference was statistically significant only within 1.6 mm of the epicenter. These results indicate that future research seeking to elucidate the mechanical origins of primary tissue damage in SCI should consider the effects of CSF. This pig model provides advantages for basic and preclinical SCI research due to its

  6. Spinal subarachnoid hemorrhage caused by scleroderma-induced aneurysm: a case report

    International Nuclear Information System (INIS)

    Mueller, J.; Neidl, K.; Contier-Dippel, B.; Huber, G.; Ernst, E.

    1995-01-01

    We introduce a 58-year-old woman who suffered from progressive systemic scleroderma (PSS) associated with trigeminal sensory neuropathy for approximately 10 years. She then had a stroke from spinal subarachnoid hemorrhage (SSAH). Spinal digital subtraction angiography (DSA) revealed two aneurysms and smaller dilations of the afferent vessel that could also be seen by MRI. Three asymptomatic brain infarctions in different vascular regions could be revealed by CCT. The SSAH, ischemic lesions and aneurysms were probably caused by vasculitic affections induced by PSS. (orig.)

  7. Spinal subarachnoid hemorrhage caused by scleroderma-induced aneurysm: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, J. [Inst. fuer Neuroradiologie der Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Neidl, K. [Inst. fuer Neuroradiologie der Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Contier-Dippel, B. [Inst. fuer Neuroradiologie der Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Huber, G. [Inst. fuer Neuroradiologie der Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Ernst, E. [Neurologische Abt., Caritas Krankenhaus, Dillingen (Germany)

    1995-11-01

    We introduce a 58-year-old woman who suffered from progressive systemic scleroderma (PSS) associated with trigeminal sensory neuropathy for approximately 10 years. She then had a stroke from spinal subarachnoid hemorrhage (SSAH). Spinal digital subtraction angiography (DSA) revealed two aneurysms and smaller dilations of the afferent vessel that could also be seen by MRI. Three asymptomatic brain infarctions in different vascular regions could be revealed by CCT. The SSAH, ischemic lesions and aneurysms were probably caused by vasculitic affections induced by PSS. (orig.)

  8. Blocking weight-induced spinal cord injury in rats: effects of TRH or naloxone on motor function recovery and spinal cord blood flow

    International Nuclear Information System (INIS)

    Holtz, A.; Nystroem, B.; Gerdin, B.

    1989-01-01

    The ability of thyotropin releasing hormone (TRH) or naloxone to reduce the motor function deficit and to improve the spinal cord blood flow (SCBF) was investigated in a rat spinal cord compression injury model. Spinal cord injury was induced by compression for 5 min with a load of 35 g on a 2.2 x 5.0 mm sized compression plate causing a transient paraparesis. One group of animals was given TRH, one group naloxone and one group saline alone. Each drug was administered intravenously as a bolus dose of 2 mg/kg 60 min after injury followed by a continuous infusion of 2 mg/kg/h for 4 h. The motor performance was assessed daily on the inclined plant until Day 4, when SCBF was measured with the 14 C-iodoantipyrine autoradiographic method. It was found that neither TRH nor naloxone had promoted motor function recovery or affected SCBF 4 days after spinal cord injury. (author)

  9. Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT.

    Directory of Open Access Journals (Sweden)

    Ze-Min Ling

    Full Text Available Brachial plexus root avulsion (BPRA leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av treated with normal saline, Av+GM1 (treated with monosialoganglioside, and control. At time points of 3 day (d, 1 week (w, 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.

  10. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

    Science.gov (United States)

    Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

    2009-04-01

    Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

  11. Does experimental low back pain change posteroanterior lumbar spinal stiffness and trunk muscle activity? A randomized crossover study.

    Science.gov (United States)

    Wong, Arnold Y L; Parent, Eric C; Prasad, Narasimha; Huang, Christopher; Chan, K Ming; Kawchuk, Gregory N

    2016-05-01

    While some patients with low back pain demonstrate increased spinal stiffness that decreases as pain subsides, this observation is inconsistent. Currently, the relation between spinal stiffness and low back pain remains unclear. This study aimed to investigate the effects of experimental low back pain on temporal changes in posteroanterior spinal stiffness and concurrent trunk muscle activity. In separate sessions five days apart, nine asymptomatic participants received equal volume injections of hypertonic or isotonic saline in random order into the L3-L5 interspinous ligaments. Pain intensity, spinal stiffness (global and terminal stiffness) at the L3 level, and the surface electromyographic activity of six trunk muscles were measured before, immediately after, and 25-minute after injections. These outcome measures under different saline conditions were compared by generalized estimating equations. Compared to isotonic saline injections, hypertonic saline injections evoked significantly higher pain intensity (mean difference: 5.7/10), higher global (mean difference: 0.73N/mm) and terminal stiffness (mean difference: 0.58N/mm), and increased activity of four trunk muscles during indentation (Ppain subsided. While previous clinical research reported inconsistent findings regarding the association between spinal stiffness and low back pain, our study revealed that experimental pain caused temporary increases in spinal stiffness and concurrent trunk muscle co-contraction during indentation, which helps explain the temporal relation between spinal stiffness and low back pain observed in some clinical studies. Our results substantiate the role of spinal stiffness assessments in monitoring back pain progression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Spinal Stiffness in Prone and Upright Postures During 0-1.8 g Induced by Parabolic Flight.

    Science.gov (United States)

    Swanenburg, Jaap; Meier, Michael L; Langenfeld, Anke; Schweinhardt, Petra; Humphreys, B Kim

    2018-06-01

    The purpose of this study was to analyze posterior-to-anterior spinal stiffness in Earth, hyper-, and microgravity conditions during both prone and upright postures. During parabolic flight, the spinal stiffness of the L3 vertebra of a healthy 37-yr-old man was measured in normal Earth gravity (1.0 g), hypergravity (1.8 g), and microgravity (0.0 g) conditions induced in the prone and upright positions. Differences in spinal stiffness were significant across all three gravity conditions in the prone and upright positions. Most effect sizes were large; however, in the upright posture, the effect size between Earth gravity and microgravity was medium. Significant differences in spinal stiffness between the prone and upright positions were found during Earth gravity and hypergravity conditions. No difference was found between the two postures during microgravity conditions. Based on repeated measurements of a single individual, our results showed detectable changes in posterior-to-anterior spinal stiffness. Spinal stiffness increased during microgravity and decreased during hypergravity conditions. In microgravity conditions, posture did not impact spinal stiffness. More data on spinal stiffness in variable gravitational conditions is needed to confirm these results.Swanenburg J, Meier ML, Langenfeld A, Schweinhardt P, Humphreys BK. Spinal stiffness in prone and upright postures during 0-1.8 g induced by parabolic flight. Aerosp Med Hum Perform. 2018; 89(6):563-567.

  13. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    OpenAIRE

    Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of patholo...

  14. Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

    Science.gov (United States)

    Streeter, K.A.; Baker-Herman, T.L.

    2014-01-01

    Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30 min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. PMID:24681155

  15. Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation.

    Science.gov (United States)

    Streeter, K A; Baker-Herman, T L

    2014-06-01

    Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Alterações vesicais na lesão medular experimental em ratos Urinary bladder changes in experimental spinal cord injury

    Directory of Open Access Journals (Sweden)

    Fernando Meyer

    2003-06-01

    Full Text Available O trauma raquemedular é uma das lesões traumáticas com maior impacto sobre a sociedade, o que faz com que enormes investimentos sejam feitos em estudos visando sua cura. Para a realização de pesquisas sobre lesão medular, é necessário que se utilize um modelo reprodutível desta lesão. A padronização de um sistema de lesão medular experimental provoca alterações não só no sistema nervoso mas também sistêmicas. OBJETIVO: O presente estudo visa avaliar as alterações vesicais na fase aguda da lesão medular experimental. MÉTODOS Foram utilizados 34 ratos Wistar machos divididos em grupo controle (A e grupo experimento (B. Enquanto os animais do grupo B foram submetidos à laminectomia no nível T9-T10 seguida de lesão medular, os do grupo A (n=4 foram submetidos somente à laminectomia. Os animais do grupo B foram dividos em 6 grupos distintos (n=5 e foram submetidos à eutanásia após 2, 4, 8, 24, 48 horas e 4 dias. RESULTADOS: Verificou-se redução da camada urotelial em todos animais do grupo B, presença de células inflamatórias e congestão vascular principalmente após 8 horas, entre outros achados. CONCLUSÃO: As alterações histológicas na fase aguda da lesão medular evidenciaram importante comprometimento vesical, sendo essa uma alteração sistêmica de relevância em lesados medulares.Spinal cord trauma is one of the lesions with highest socioeconomical impact. To develop research on spinal cord field it is mandatory to use a reproductible model for inducing lesions. Standardized spinal cord injury (SCI promotes changes not only in the nervous system but also systemic changes. PURPOSE: The aim of this study was to evaluate urinary bladder changes during the acute phase of experimental spinal cord injury. METHODS: Thirty four Wistar male rats were allocated in 2 groups: controll (A and experiment (B. While animals from group B underwent laminectomy at T9-T10 level followed by SCI, group A underwent only

  17. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Directory of Open Access Journals (Sweden)

    Aya Nakae

    2011-01-01

    Full Text Available Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

  18. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Science.gov (United States)

    Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

  19. Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states.

    Science.gov (United States)

    Boroujerdi, Amin; Zeng, Jun; Sharp, Kelli; Kim, Donghyun; Steward, Oswald; Luo, Z David

    2011-03-01

    Spinal cord injury (SCI) commonly results in the development of neuropathic pain, which can dramatically impair the quality of life for SCI patients. SCI-induced neuropathic pain can be manifested as both tactile allodynia (a painful sensation to a non-noxious stimulus) and hyperalgesia (an enhanced sensation to a painful stimulus). The mechanisms underlying these pain states are poorly understood. Clinical studies have shown that gabapentin, a drug that binds to the voltage-gated calcium channel alpha-2-delta-1 subunit (Ca(v)α2δ-1) proteins is effective in the management of SCI-induced neuropathic pain. Accordingly, we hypothesized that tactile allodynia post SCI is mediated by an upregulation of Ca(v)α2δ-1 in dorsal spinal cord. To test this hypothesis, we examined whether SCI-induced dysregulation of spinal Ca(v)α2δ-1 plays a contributory role in below-level allodynia development in a rat spinal T9 contusion injury model. We found that Ca(v)α2δ-1 expression levels were significantly increased in L4-6 dorsal, but not ventral, spinal cord of SCI rats that correlated with tactile allodynia development in the hind paw plantar surface. Furthermore, both intrathecal gabapentin treatment and blocking SCI-induced Ca(v)α2δ-1 protein upregulation by intrathecal Ca(v)α2δ-1 antisense oligodeoxynucleotides could reverse tactile allodynia in SCI rats. These findings support that SCI-induced Ca(v)α2δ-1 upregulation in spinal dorsal horn is a key component in mediating below-level neuropathic pain states, and selectively targeting this pathway may provide effective pain relief for SCI patients. Spinal cord contusion injury caused increased calcium channel Ca(v)α2δ-1 subunit expression in dorsal spinal cord that contributes to neuropathic pain states. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  20. Spinal atypical protein kinase C activity is necessary to stabilize inactivity-induced phrenic motor facilitation

    Science.gov (United States)

    Strey, K.A.; Nichols, N.L.; Baertsch, N.A.; Broytman, O.; Baker-Herman, T.L.

    2012-01-01

    The neural network controlling breathing must establish rhythmic motor output at a level adequate to sustain life. Reduced respiratory neural activity elicits a novel form of plasticity in circuits driving the diaphragm known as inactivity-induced phrenic motor facilitation (iPMF), a rebound increase in phrenic inspiratory output observed once respiratory neural drive is restored. The mechanisms underlying iPMF are unknown. Here, we demonstrate in anesthetized rats that spinal mechanisms give rise to iPMF, and that iPMF consists of at least two mechanistically distinct phases: 1) an early, labile phase that requires atypical PKC (PKCζ and/or PKCΙ/λ) activity to transition to a 2) late, stable phase. Early (but not late) iPMF is associated with increased interactions between PKCζ/Ι and the scaffolding protein ZIP/p62 in spinal regions associated with the phrenic motor pool. Although PKCζ/Ι activity is necessary for iPMF, spinal aPKC activity is not necessary for phrenic long-term facilitation (pLTF) following acute intermittent hypoxia, an activity-independent form of spinal respiratory plasticity. Thus, while iPMF and pLTF both manifest as prolonged increases in phrenic burst amplitude, they arise from distinct spinal cellular pathways. Our data are consistent with the hypotheses that: 1) local mechanisms sense and respond to reduced respiratory-related activity in the phrenic motor pool, and 2) inactivity-induced increases in phrenic inspiratory output require local PKCζ/Ι activity to stabilize into a long-lasting iPMF. Although the physiological role of iPMF is unknown, we suspect that iPMF represents a compensatory mechanism, assuring adequate motor output in a physiological system where prolonged inactivity ends life. PMID:23152633

  1. Using visuo-kinetic virtual reality to induce illusory spinal movement: the MoOVi Illusion

    OpenAIRE

    Harvie, Daniel S.; Smith, Ross T.; Hunter, Estin V.; Davis, Miles G.; Sterling, Michele; Moseley, G. Lorimer

    2017-01-01

    Background Illusions that alter perception of the body provide novel opportunities to target brain-based contributions to problems such as persistent pain. One example of this, mirror therapy, uses vision to augment perceived movement of a painful limb to treat pain. Since mirrors can’t be used to induce augmented neck or other spinal movement, we aimed to test whether such an illusion could be achieved using virtual reality, in advance of testing its potential therapeutic benefit. We hypothe...

  2. Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture

    OpenAIRE

    Li, Wen-Wu; Guo, Tian-Zhi; Shi, Xiaoyou; Sun, Yuan; Wei, Tzuping; Clark, David J; Kingery, Wade S

    2015-01-01

    Tibia fracture in rodents induces substance P (SP)-dependent keratinocyte activation and inflammatory changes in the hindlimb, similar to those seen in complex regional pain syndrome (CRPS). In animal pain models spinal glial cell activation results in nociceptive sensitization. This study tested the hypothesis that limb fracture triggers afferent C-fiber SP release in the dorsal horn, resulting in chronic glia activation and central sensitization. At 4 weeks after tibia fracture and casting ...

  3. 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...

  4. Effect of Aspirin on Spinal Cord Injury: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Hamed Reihani Kermani

    2016-05-01

    Full Text Available Aspirin is an anti-inflammatory drug, peroxyl radical scavenger, and antioxidant agent that inhibits phospholipases, nitric oxide synthetases, and cyclooxygenase enzymes. The existing literature contains no studies on the effects of various doses of aspirin on spinal cord injury (SCI. Therefore, we sought to investigate the putative effects of aspirin on experimental SCI. The weight-drop injury model was used to produce SCI in 100 albino Wistar rats. The animals were allocated to five groups: a control group, where the rats did not undergo any surgical or medical intervention except for anesthesia; a sham-treated group, where laminectomy was performed without SCI and no further therapy was administered; and three other groups, where the rats with SCI received low-dose aspirin [20 mg/kg], high-dose aspirin [80 mg/kg], and a vehicle, respectively. Half of the rats were sacrificed 24 hours later, and their spinal cords were excised for biochemical studies. The other rats were subjected to Basso, Beattie, and Bresnahan (BBB locomotor rating scale scoring once a week for 6 consecutive weeks. Aspirin decreased lipid peroxidation following SCI as the mean (± standard error catalase level was significantly higher in the high-dose aspirin group (46.10±12.01 than in the sham-treated group (16.07±2.42 and the vehicle-treated group (15.31±3.20 (P<0.05; P<0.05, respectively. Both of the groups treated with high-dose and low-dose aspirin demonstrated a higher mean BBB score than did the control group (P<0.001 and the sham-treated group (P<0.001. Our data provide evidence in support of the potential effects of aspirin in biochemical and neurobehavioral recovery after SCI.

  5. Spinal cord injury: overview of experimental approaches used to restore locomotor activity.

    Science.gov (United States)

    Fakhoury, Marc

    2015-01-01

    Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord's normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

  6. Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice.

    Science.gov (United States)

    Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P; Shields, Christopher B

    2013-04-01

    Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice. A focal demyelination model was created by stereotaxically injecting lysolecithin into the bilateral ventrolateral funiculus (VLF) of T8 and T9 mouse spinal cords. Immediately after lysolecithin injection mice were treated with COG112, prefix peptide control or vehicle control for 21 days. The locomotor function of the mice was measured by the beam walking test and Basso Mouse Scale (BMS) assessment. The nerve transmission of the VLF of mice was assessed in vivo by transcranial magnetic motor evoked potentials (tcMMEPs). The histological changes were also examined by by eriochrome cyanine staining, immunohistochemistry staining and electron microscopy (EM) method. The area of demyelination in the spinal cord was significantly reduced in the COG112 group. EM examination showed that treatment with COG112 increased the thickness of myelin sheaths and the numbers of surviving axons in the lesion epicenter. Locomotor function was improved in COG112 treated animals when measured by the beam walking test and BMS assessment compared to controls. TcMMEPs also demonstrated the COG112-mediated enhancement of amplitude of evoked responses. The apoE-mimetic COG112 demonstrates a favorable combination of activities in suppressing inflammatory response, mitigating demyelination and in promoting remyelination and associated functional recovery in animal model

  7. Rivaroxaban-Induced Nontraumatic Spinal Subdural Hematoma: An Uncommon Yet Life-Threatening Complication

    Directory of Open Access Journals (Sweden)

    Mazen Zaarour

    2015-01-01

    Full Text Available In the last decade, the desire for safer oral anticoagulants (OACs led to the emergence of newer drugs. Available clinical trials demonstrated a lower risk of OACs-associated life-threatening bleeding events, including intracranial hemorrhage, compared to warfarin. Nontraumatic spinal hematoma is an uncommon yet life-threatening neurosurgical emergency that can be associated with the use of these agents. Rivaroxaban, one of the newly approved OACs, is a direct factor Xa inhibitor. To the best of our knowledge, to date, only two published cases report the incidence of rivaroxaban-induced nontraumatic spinal subdural hematoma (SSDH. Our case is the third one described and the first one to involve the cervicothoracic spine.

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

    Directory of Open Access Journals (Sweden)

    Steffen Franz

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

  9. Altered expression of IGF-I system in neurons of the inflamed spinal cord during acute experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Parvaneh Tafreshi, Azita; Talebi, Farideh; Ghorbani, Samira; Bernard, Claude; Noorbakhsh, Farshid

    2017-10-01

    There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling. Although neurons in the non EAE spinal cords did not show the IGF-I immunoreactivity, they were numerously positive for the IGFBP-1. In the inflamed EAE spinal cord however, the patterns of expressions were reversed, that is, a significant increased number of IGF-I expressing neurons versus a reduced number of IGFBP-1 positive neurons. Moreover, while nearly all IGF-I-ir neurons expressed GSK3β, some expressed it more intensely. Considering our previous finding where we showed a significant reduced number of the inactive (phosphorylated) but not that of the total GSK3β expressing neurons in the EAE spinal cord, it is conceivable that the intense total GSK3β expression in the IGF-I-ir neurons belongs to the active form of GSK3β known to exert neuroinflammatory effects. We therefore suggest that the altered expression of the IGF-I system including GSK3β in spinal cord neurons might involve in pathophysiological events during the EAE. © 2017 Wiley Periodicals, Inc.

  10. Spinal cord transection-induced allodynia in rats--behavioral, physiopathological and pharmacological characterization.

    Directory of Open Access Journals (Sweden)

    Saïd M'Dahoma

    Full Text Available In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us to thoroughly investigate (i mechanical and thermal sensory alterations, (ii responses to acute treatments with drugs having patent or potential anti-allodynic properties and (iii the spinal/ganglion expression of transcripts encoding markers of neuronal injury, microglia and astrocyte activation in rats that underwent complete spinal cord transection (SCT. SCT was performed at thoracic T8-T9 level under deep isoflurane anaesthesia, and SCT rats were examined for up to two months post surgery. SCT induced a marked hyper-reflexia at hindpaws and strong mechanical and cold allodynia in a limited (6 cm2 cutaneous territory just rostral to the lesion site. At this level, pressure threshold value to trigger nocifensive reactions to locally applied von Frey filaments was 100-fold lower in SCT- versus sham-operated rats. A marked up-regulation of mRNAs encoding ATF3 (neuronal injury and glial activation markers (OX-42, GFAP, P2×4, P2×7, TLR4 was observed in spinal cord and/or dorsal root ganglia at T6-T11 levels from day 2 up to day 60 post surgery. Transcripts encoding the proinflammatory cytokines IL-1β, IL-6 and TNF-α were also markedly but differentially up-regulated at T6-T11 levels in SCT rats. Acute treatment with ketamine (50 mg/kg i.p., morphine (3-10 mg/kg s.c. and tapentadol (10-20 mg/kg i.p. significantly increased pressure threshold to trigger nocifensive reaction in the von Frey filaments test, whereas amitriptyline, pregabalin, gabapentin and clonazepam were ineffective. Because all SCT rats developed long lasting, reproducible and stable allodynia, which could be alleviated by drugs effective in humans, thoracic cord transection might be a

  11. Experimentally-induced dissociation impairs visual memory.

    Science.gov (United States)

    Brewin, Chris R; Mersaditabari, Niloufar

    2013-12-01

    Dissociation is a phenomenon common in a number of psychological disorders and has been frequently suggested to impair memory for traumatic events. In this study we explored the effects of dissociation on visual memory. A dissociative state was induced experimentally using a mirror-gazing task and its short-term effects on memory performance were investigated. Sixty healthy individuals took part in the experiment. Induced dissociation impaired visual memory performance relative to a control condition; however, the degree of dissociation was not associated with lower memory scores in the experimental group. The results have theoretical and practical implications for individuals who experience frequent dissociative states such as patients with posttraumatic stress disorder (PTSD). Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Radiation induced microvascular damage in the rat spinal cord: cellular and secretory factors

    International Nuclear Information System (INIS)

    Pfeffer, M. Raphael; Siegal, Tali; Meltzer, A; Shezen, E; Ovadia, Haim

    1996-01-01

    Purpose/Objective: To investigate the short and long-term effect of radiation on micro vessel permeability, endothelin and nitric oxide production, and cellular profile in the spinal cord of rats and to evaluate the influence of recombinant human manganese superoxide dismutase (r-hMnSOD) on these effects. Materials and Methods: The thoracolumbar spinal cord of Fischer rats was irradiated to a dose of 15 Gy. At various times afterwards the rats were killed and the spinal cord was excised. Endothelin and nitric oxide synthase (NOS) activity and microvascular permeability were assayed quantitatively. Astrocytes, microglia, vascular basal membrane and neuro filaments were immunohistochemically evaluated. Results: None of the rats developed signs of neurological dysfunction. Endothelin concentrations in the spinal cord were significantly reduced 18 hours after irradiation and continued to decrease until after 10 days (p=<0.007). After 56 days endothelin concentration returned to normal and then rose to markedly elevated levels at 120 and 180 days (p=<0.002). NOS activity was reduced soon after irradiation and remained very low throughout the period of observation despite the changes in endothelin. Vascular permeability was markedly increased after 18 hours and again after 120 and 180 days. Treatment with r-hMnSOD had no effect on normal vascular permeability but abolished the increase in vascular permeability seen after irradiation. Standard microscopic examination revealed no changes in the irradiated spinal cord. Immunohistochemical stains showed a progressive increase in the number of microglial cells per field after 120 and 180 days (p=<0.0003). An increase in astrocytic cells was seen after 180 days with an earlier short lasting peak after 14 days. No abnormalities were found in blood vessel configuration, density and diameter. Vascular basal membrane and neuro filaments were unchanged throughout the study. Conclusions: Following radiation to the spinal cord there

  13. Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

    Directory of Open Access Journals (Sweden)

    Ouyang Handong

    2011-05-01

    Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

  14. Role of prophylactic ondansetron for prevention of spinal anaesthesia induced hypotension in lower segment caesarean section

    International Nuclear Information System (INIS)

    Abbas, N.

    2016-01-01

    Objective: To determine the efficacy of prophylactic administration of intravenous Ondansetron for prevention of spinal anaesthesia induced hypotension in lower segment caesarean section. Study Design: Double blinded randomized controlled trial. Place and Duration of Study: It was conducted in Anesthesiology department, CMH Rawalakot; from 3 Mar to 4 Jun 2014. Material and Methods: One hundred patients were selected for this study, and randomly divided in two groups of 50 each, using random numbers table. Both groups were preloaded with Ringer's lactate at dose of 10ml/kg. Group A received 04 mg of IV ondansetron 5 min prior to spinal anaesthesia, whereas Group B received normal saline 05 minutes before administration of Spinal Anaesthesia. Results: Average age of Group A was 28.62 +- 4.64 years, whereas that of Group B was 27.88 +- 3.98 (p-value= 0.394). Average weight of Group A was 70.30 +- 6.25 kg, whereas that of Group B was 70.74 +- 6.17 kg (p-value= 0.724). Hypotension was noted in 21 patients in group A (42 percent), whereas it was observed in 34 Patients in Group B (68 percent) (p-value= 0.009). Bradycardia was noted in 9 patients in Group A (18 percent) and 19 patients in Group B (p=0.026). Conclusion: Intravenous administration of 04 mg of intravenous ondansetron, 05 minutes prior to subarachnoid block, is effective in decreasing frequency of hypotension. (author)

  15. Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

    Science.gov (United States)

    Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

    2012-06-01

    Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

  16. Immobilisation-induced hypercalcemia following spinal cord injury affecting the kidney function in two young native Greenlanders

    DEFF Research Database (Denmark)

    Linstow, Michael V; Biering-Sørensen, Fin

    2017-01-01

    INTRODUCTION: Immobilisation-induced hypercalcemia following SCI affecting the kidney function, is a rare but potentially serious condition. We report immobilisation-induced hypercalcemia affecting the kidney function in two young native Greenlanders with spinal cord injury (SCI). CASE...... PRESENTATIONS: Two 15- and 24-year-old male native Greenlanders, both with traumatic C5 SCI were admitted to our spinal cord unit. They were non-smokers without history of daily alcohol intake pre- or immediately post-injury. No physical demanding activities pre-injury. Due to complaints of nausea/vomiting 10...... the last 20 years our spinal cord unit has only experienced immobilisation-induced hypercalcemia following SCI affecting the kidney function in two young male native Greenlanders. This finding of immobilisation-induced hypercalcemia following SCI affecting the kidney function in two young native...

  17. Vestibular lesion-induced developmental plasticity in spinal locomotor networks during Xenopus laevis metamorphosis.

    Science.gov (United States)

    Beyeler, Anna; Rao, Guillaume; Ladepeche, Laurent; Jacques, André; Simmers, John; Le Ray, Didier

    2013-01-01

    During frog metamorphosis, the vestibular sensory system remains unchanged, while spinal motor networks undergo a massive restructuring associated with the transition from the larval to adult biomechanical system. We investigated in Xenopus laevis the impact of a pre- (tadpole stage) or post-metamorphosis (juvenile stage) unilateral labyrinthectomy (UL) on young adult swimming performance and underlying spinal locomotor circuitry. The acute disruptive effects on locomotion were similar in both tadpoles and juvenile frogs. However, animals that had metamorphosed with a preceding UL expressed restored swimming behavior at the juvenile stage, whereas animals lesioned after metamorphosis never recovered. Whilst kinematic and electrophysiological analyses of the propulsive system showed no significant differences in either juvenile group, a 3D biomechanical simulation suggested that an asymmetry in the dynamic control of posture during swimming could account for the behavioral restoration observed in animals that had been labyrinthectomized before metamorphosis. This hypothesis was subsequently supported by in vivo electromyography during free swimming and in vitro recordings from isolated brainstem/spinal cord preparations. Specifically, animals lesioned prior to metamorphosis at the larval stage exhibited an asymmetrical propulsion/posture coupling as a post-metamorphic young adult. This developmental alteration was accompanied by an ipsilesional decrease in propriospinal coordination that is normally established in strict left-right symmetry during metamorphosis in order to synchronize dorsal trunk muscle contractions with bilateral hindlimb extensions in the swimming adult. Our data thus suggest that a disequilibrium in descending vestibulospinal information during Xenopus metamorphosis leads to an altered assembly of adult spinal locomotor circuitry. This in turn enables an adaptive compensation for the dynamic postural asymmetry induced by the vestibular imbalance

  18. Diabetes-induced microvascular complications at the level of the spinal cord; a contributing factor in diabetic neuropathic pain.

    Science.gov (United States)

    Ved, N; Da Vitoria Lobo, M E; Bestall, S M; L Vidueira, C; Beazley-Long, N; Ballmer-Hofer, K; Hirashima, M; Bates, D O; Donaldson, L F; Hulse, R P

    2018-05-17

    Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain. Nociceptive pain behaviour was investigated in a chemically induced model of type 1 diabetes (streptozotocin induced, insulin supplemented; either vehicle or VEGF-A 165 b treated) and an inducible endothelial knockdown of VEGFR2 (tamoxifen induced). Diabetic animals developed mechanical allodynia and heat hyperalgesia. This was associated with a reduction in the number of blood vessels and reduction in Evans blue extravasation in the lumbar spinal cord of diabetic animals versus age-matched controls. Endothelial markers occludin, CD31 and VE-cadherin were downregulated in the spinal cord of the diabetic group versus controls, as well as a concurrent reduction of VEGF-A 165 b expression. In diabetic animals, VEGF-A 165 b treatment (biweekly intraperitoneal, 20 ng g -1 ) restored normal Evans blue extravasation and prevented vascular degeneration, diabetes-induced central neuron activation and neuropathic pain. Inducible knockdown of VEGFR2 (tamoxifen treated Tie2CreER T2 -vegfr2 flfl mice) led to a reduction in blood vessel network volume in the lumbar spinal cord and development of heat hyperalgesia. These findings indicate that hyperglycaemia leads to a reduction in the VEGF-A/VEGFR2 signalling cascade resulting in endothelial dysfunction in the spinal cord, which could be an undiscovered contributing factor to diabetic neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All

  19. Modulation of formalin-induced Fos-like immunoreactivity in the spinal cord by swim stress-induced analgesia, morphine and ketamine

    Directory of Open Access Journals (Sweden)

    Asma Hayati, Ahmad

    2008-06-01

    Full Text Available Induction of c-fos in the spinal cord due to pain is well established. This study aims to look at the effects of acute swim stress on Fos-like immunoreactivity (FLI induced by formalin and how it is modulated by ketamine and morphine. Acutely-stressed and non-stressed adult male Sprague Dawley rats were pretreated with intraperitoneal injection of ketamine 5 mg/kg (Ketava, Atlantic Lab, morphine 10 mg/kg (Rhotard, Custom Pharmaceutical, or saline, 5 minutes prior to experimentation. Rats were acutely stressed by swimming for 3 min in 20°C water. Dilute formalin (Formaldehyde, Merck was injected to the hindpaw and the formalin score recorded. Rats were then sacrificed and spinal cords (L4-L5 removed for immunohistochemical analysis of FLI. Two-way ANOVA showed significant effects of stress, drug and stress-drug interactions in formalin test and FLI. Both morphine and ketamine produced analgesia in the formalin test. In the saline stressed group, FLI was suppressed on the ipsilateral side (p<0.01 but increased on the contralateral side (p<0.01 compared with non-stressed saline. In morphine and ketamine stressed groups, FLI was increased on both ipsilateral and contralateral sides for morphine (ipsilateral: p<0.05; contralateral: p<0.001 and ketamine (ipsilateral: p<0.05, contralateral: p<0.05 compared with their corresponding non-stressed groups. In conclusion, presence of stress may lead to discrepancy between behavioural manifestation of pain and c-fos induction in the spinal cord.

  20. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα

    Science.gov (United States)

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena; Tian, Xuebi; Liu, Ying; Wang, Zaijie Jim

    2016-01-01

    Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin’s mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling. PMID:26744842

  1. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.

    Directory of Open Access Journals (Sweden)

    Xiaoyu Hu

    Full Text Available Opioid-induced hyperalgesia (OIH is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.

  2. Experimental study of capacity of the blood blow of spinal cord using radiolabelling microspbere technique

    International Nuclear Information System (INIS)

    Hu Xuan; Li Rui

    2007-01-01

    Objective In order to study the relation ship between local blood flow and neurofunction at the later stage of spinal injury. Method: Measured the capacity of the local blood flow in the spinal cord injury by the radiolabelling microsphere technique and scored the nervus function grade. Result: There are no correlation between the local blood flow and the nervus function. Conclusion: It is obvious that the increase of the local blood supply can't reflect the nervus function. (authors)

  3. Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury

    Science.gov (United States)

    Feng, Linjie; Gan, Hongquan; Zhao, Wenguo; Liu, Yingjie

    2017-01-01

    Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium-induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium-treated group; group B, normal BMSC-treated group; group C, OEC conditioned medium-induced BMSC-treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein-43 and neuron-specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results. PMID:28656221

  4. Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

    Science.gov (United States)

    Zhang, Jin; Wu, Dan; Xie, Cheng; Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

    2013-01-01

    Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.

  5. Borax partially prevents neurologic disability and oxidative stress in experimental spinal cord ischemia/reperfusion injury.

    Science.gov (United States)

    Koc, Emine Rabia; Gökce, Emre Cemal; Sönmez, Mehmet Akif; Namuslu, Mehmet; Gökce, Aysun; Bodur, A Said

    2015-01-01

    The aim of this study is to investigate the potential effects of borax on ischemia/reperfusion injury of the rat spinal cord. Twenty-one Wistar albino rats were divided into 3 groups: sham (no ischemia/reperfusion), ischemia/reperfusion, and borax (ischemia/reperfusion + borax); each group was consist of 7 animals. Infrarenal aortic cross clamp was applied for 30 minutes to generate spinal cord ischemia. Animals were evaluated functionally with the Basso, Beattie, and Bresnahan scoring system and inclined-plane test. The spinal cord tissue samples were harvested to analyze tissue concentrations of nitric oxide, nitric oxide synthase activity, xanthine oxidase activity, total antioxidant capacity, and total oxidant status and to perform histopathological examination. At the 72nd hour after ischemia, the borax group had significantly higher Basso, Beattie, and Bresnahan and inclined-plane scores than those of ischemia/reperfusion group. Histopathological examination of spinal cord tissues in borax group showed that treatment with borax significantly reduced the degree of spinal cord edema, inflammation, and tissue injury disclosed by light microscopy. Xanthine oxidase activity and total oxidant status levels of the ischemia/reperfusion group were significantly higher than those of the sham and borax groups (P borax group were significantly higher than those of the ischemia/reperfusion group (P borax groups in terms of total antioxidant capacity levels (P > .05). The nitric oxide levels and nitric oxide synthase activity of all groups were similar (P > .05). Borax treatment seems to protect the spinal cord against injury in a rat ischemia/reperfusion model and improve neurological outcome. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. Therapy induces widespread reorganization of motor cortex after complete spinal transection that supports motor recovery.

    Science.gov (United States)

    Ganzer, Patrick D; Manohar, Anitha; Shumsky, Jed S; Moxon, Karen A

    2016-05-01

    Reorganization of the somatosensory system and its relationship to functional recovery after spinal cord injury (SCI) has been well studied. However, little is known about the impact of SCI on organization of the motor system. Recent studies suggest that step-training paradigms in combination with spinal stimulation, either electrically or through pharmacology, are more effective than step training alone at inducing recovery and that reorganization of descending corticospinal circuits is necessary. However, simpler, passive exercise combined with pharmacotherapy has also shown functional improvement after SCI and reorganization of, at least, the sensory cortex. In this study we assessed the effect of passive exercise and serotonergic (5-HT) pharmacological therapies on behavioral recovery and organization of the motor cortex. We compared the effects of passive hindlimb bike exercise to bike exercise combined with daily injections of 5-HT agonists in a rat model of complete mid-thoracic transection. 5-HT pharmacotherapy combined with bike exercise allowed the animals to achieve unassisted weight support in the open field. This combination of therapies also produced extensive expansion of the axial trunk motor cortex into the deafferented hindlimb motor cortex and, surprisingly, reorganization within the caudal and even the rostral forelimb motor cortex areas. The extent of the axial trunk expansion was correlated to improvement in behavioral recovery of hindlimbs during open field locomotion, including weight support. From a translational perspective, these data suggest a rationale for developing and optimizing cost-effective, non-invasive, pharmacological and passive exercise regimes to promote plasticity that supports restoration of movement after spinal cord injury. Copyright © 2016. Published by Elsevier Inc.

  7. Signaling proteins in spinal parenchyma and dorsal root ganglion in rat with spinal injury-induced spasticity

    Czech Academy of Sciences Publication Activity Database

    Kupcová Skalníková, Helena; Navarro, R.; Marsala, S.; Hrabáková, Rita; Vodička, Petr; Gadher, S. J.; Kovářová, Hana; Marsala, M.

    2013-01-01

    Roč. 91, č. 1 (2013), s. 41-57 ISSN 1874-3919 R&D Projects: GA MŠk(CZ) ME10044; GA TA ČR TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : spinal cord trauma * spasticity * hyper-reflexia Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.929, year: 2013

  8. Effects of melatonin on spinal cord injury-induced oxidative damage in mice testis.

    Science.gov (United States)

    Yuan, X-C; Wang, P; Li, H-W; Wu, Q-B; Zhang, X-Y; Li, B-W; Xiu, R-J

    2017-09-01

    This study evaluated the effects of melatonin on spinal cord injury (SCI)-induced oxidative damage in testes. Adult male C57BL/6 mice were randomly divided into sham-, SCI- or melatonin (10 mg/kg, i.p.)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a contusion injury at T10 was used. After 1 week, testicular blood flow velocity was measured using the Laser Doppler Line Scanner. Malondialdehyde (MDA), glutathione (GSH), oxidised glutathione (GSSG) and myeloperoxidase (MPO) were measured in testis homogenates. Microvascular permeability of the testes to Evan's Blue was examined by spectrophotometric and fluorescence microscopic quantitation. The tight junction protein zonula occludens-1 (ZO-1) and occludin in testes were assessed by immunoblot analysis. Melatonin increased the reduced blood flow and decreased SCI-induced permeability of capillaries. MDA levels and MPO activity were elevated in the SCI group compared with shams, which was reversed by melatonin. In contrast, SCI-induced reductions in GSH/GSSG ratio were restored by melatonin. Decreased expression of ZO-1 and occludin was observed, which was attenuated by melatonin. Overall, melatonin treatment protects the testes against oxidative stress damage caused by SCI. © 2016 Blackwell Verlag GmbH.

  9. Cervical spinal erythropoietin induces phrenic motor facilitation via ERK and Akt signaling

    Science.gov (United States)

    Dale, Erica A.; Satriotomo, Irawan; Mitchell, Gordon S.

    2012-01-01

    Erythropoietin (EPO) is typically known for its role in erythropoiesis, but is also a potent neurotrophic/neuroprotective factor for spinal motor neurons. Another trophic factor regulated by Hypoxia-Inducible Factor-1, vascular endothelial growth factor (VEGF), signals via ERK and Akt activation to elicit long-lasting phrenic motor facilitation (pMF). Since EPO also signals via ERK and Akt activation, we tested the hypothesis that EPO elicits similar pMF. Using retrograde labeling and immunohistochemical techniques, we demonstrate in adult, male, Sprague-Dawley rats that EPO and its receptor, EPO-R, are expressed in identified phrenic motor neurons. Intrathecal EPO at C4 elicits long-lasting pMF; integrated phrenic nerve burst amplitude increased >90 min post-injection (63±12% baseline 90 min post-injection; pphrenic motor neurons; EPO also increased pAkt (1.6 fold vs controls; pphrenic motor neurons (p<0.05), indicating a complex interaction between these kinases. We conclude that EPO elicits spinal plasticity in respiratory motor control. Since EPO expression is hypoxia-sensitive, it may play a role in respiratory plasticity in conditions of prolonged or recurrent low oxygen. PMID:22539857

  10. Granulocyte Colony-Stimulating Factor Combined with Methylprednisolone Improves Functional Outcomes in Rats with Experimental Acute Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    William Gemio Jacobsen Teixeira

    2018-02-01

    Full Text Available OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment; G-CSF (G-CSF at the time of injury and daily over the next five days; methylprednisolone (methylprednisolone for 24 h; and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days. Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001. This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001. The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75. CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.

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

    Science.gov (United States)

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

    2018-05-01

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

  12. Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons

    NARCIS (Netherlands)

    Southerland, E. M.; Milhorn, D. M.; Foreman, R. D.; Linderoth, B.; DeJongste, M. J. L.; Armour, J. A.; Subramanian, V.; Singh, M.; Singh, K.; Ardell, J. L.

    2007-01-01

    Our objective was to determine whether electrical neuromodulation using spinal cord stimulation ( SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of

  13. Electrical stimulation-induced Gluteal and Hamstring muscle activation can reduce sitting pressure in individuals with a spinal cord injury

    NARCIS (Netherlands)

    Janssen, T. W J; De Koning, A.; Legemate, K. J A; Smit, C. A J

    2010-01-01

    Individuals with spinal cord injury (SCI) are at high risk of developing pressure sores, in part due to high sitting pressures under the buttocks. PURPOSE: To evaluate the effect of ES-induced activation of the gluteal and hamstring muscles on the sitting pressure in individuals with SCI. METHODS:

  14. [Mechanism of disorders of inhibition of electrogenesis in spinal alpha-motor neurons in experimental local botulin poisoning].

    Science.gov (United States)

    Mikhaĭlov, V V; Barashkov, G N

    1977-06-01

    Disorders of postsynaptic inhibition and of the spinal cord alpha-motoneurons were studied in cats with experimental local botulinum intoxication. A significant decrease of the reciprocal, and, to a lesser extent, of polysynaptic inhibitory postsynaptic potential (IPSP) was noted. With the appearance of total paralysis of the muscles in the poisoned extremity there proved to be an even greater depression of the reciprocal and polysynaptic IPSP; however, they never disappeared or turned into depolarization potentials. Synaptic permeability of motor neurons as a rule decreased during the IPSP development, this indirectly indicating a reduction of ion transport.

  15. Modelo experimental de trauma medular agudo produzido por aparelho estereotáxico modificado Experimental model of acute spinal cord injury produced by modified steriotaxic equipment

    Directory of Open Access Journals (Sweden)

    B.B.J. Torres

    2010-02-01

    Full Text Available Foram utilizados 55 ratos machos da espécie Rattus novergicus, variedade Wistar, com o objetivo de propor um modelo experimental de trauma medular produzido por aparelho estereotáxico modificado, capaz de reproduzir clinicamente lesões medulares padronizadas. Após realização de laminectomia dorsal de T13, utilizou-se peso compressivo de 50,5g (25 animais - grupo I ou 70,5g (30 animais - grupo II, durante cinco minutos, comprimindo a medula espinhal. Os animais foram assistidos durante oito dias, por meio de testes comportamentais para avaliar a sensibilidade dolorosa, a capacidade motora, o posicionamento tátil e proprioceptivo e a capacidade de manter-se em plano inclinado. No grupo I, observaram-se déficits neurológicos moderados e transitórios, que variaram entre os animais. No grupo II, foi possível obter um trauma padronizado, caracterizado por paraplegia bilateral e simétrica dos membros posteriores, perda de propriocepção e da sensibilidade dolorosa de todos os animais. A utilização do aparelho estereotáxico desenvolvido permite reproduzir clinicamente trauma medular padronizado em ratos, de maneira simples, econômica e satisfatória, o que poderá proporcionar avanços nas investigações terapêuticas, abrangendo doenças neurodegenerativas, como é o caso do trauma medular agudo.Fifty-five male rats (Rattus novergicus, Wistar variety, were used with the purpose of suggesting an experimental model of spinal cord trauma performed by using a modified stereotaxic equipment capable to reproduce clinically (standardized pattern spinal cord injury. After dorsal laminectomy of T13, a compression was performed with 50.5g (25 animals - group I or 70.5g (30 animals - group II during five minutes on spinal cord. The animals were assisted during eight days by behavioral tests to evaluate painful sensibility, motor capacity, proprioceptive and tactil placing, and stability on inclined plan. In the group I, moderate and transitory

  16. Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs.

    Science.gov (United States)

    Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Bouchard, Caroline; Ardell, Jeffrey L; Foreman, Robert D; Armour, J Andrew

    2006-11-01

    Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

  17. Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB phosphorylation in spinal cord of mice.

    Directory of Open Access Journals (Sweden)

    Junzo Kamei

    Full Text Available Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB in the spinal dorsal horn. Rikkunshito (RKT, a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.

  18. Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability

    International Nuclear Information System (INIS)

    Siegal, Tali; Pfeffer, M. Raphael

    1995-01-01

    Purpose: To investigate the profile of biochemical and physiological changes induced in the rat spinal cord by radiation, over a period of 8 months. Methods and Materials: The thoraco-lumbar spinal cords of Fisher rats were irradiated to a dose of 15 Gy. The rats were then followed and killed at various times afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. Results: None of the rats developed neurologic dysfunction, and histologic examination revealed only occasional gliosis in the ventral white matter at 240 days after irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thoracic and cervical segments (p 2 (PGE 2 ), thromboxane (TXB 2 ), and prostacyclin [6 keto-PGF1α (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglandins. Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane followed, while prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radiation the calculated (TXB 2 (6KPGF)) ratio remained balanced, regardless of the observed abrupt early fluctuations in their rate of synthesis. Later, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was observed which returned to normal by 3 days. Normal permeability was maintained at 14 and 28 days, but at 120 and 240 days a persistent and significant increase of 98% and 73% respectively above control level was noted. Conclusions: Radiation induces severe impairment in

  19. Tail nerve electrical stimulation induces body weight-supported stepping in rats with spinal cord injury.

    Science.gov (United States)

    Zhang, Shu-Xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

    2010-03-30

    Walking or stepping has been considered the result from the activation of the central pattern generator (CPG). In most patients with spinal cord injury (SCI) the CPG is undamaged. To date, there are no noninvasive approaches for activating the CPG. Recently we developed a noninvasive technique, tail nerve electrical stimulation (TANES), which can induce positive hind limb movement of SCI rats. The purpose of this study is to introduce the novel technique and examine the effect of TANES on CPG activation. A 25 mm contusion injury was produced at spinal cord T10 of female, adult Long-Evans rats by using the NYU impactor device. Rats received TANES ( approximately 40 mA at 4 kHz) 7 weeks after injury. During TANES all injured rats demonstrated active body weight-supported stepping of hind limbs with left-right alternation and occasional front-hind coordination, resulting in significant, temporary increase in BBB scores (p<0.01). However, there is no response to TANES from rats with L2 transection, consistent with other reports that the CPG may be located at L1-2. S1 transection negatively implies the key role of TANES in CPG activation. The TANES not only renders paralyzed rats with a technique-induced ability to walk via activating CPG, but also is likely to be used for locomotor training. It has more beneficial effects for physical training over other training paradigms including treadmill training and invasive functional electrical stimulation. Therefore the TANES may have considerable potential for achieving improvement of functional recovery in animal models and a similar method may be suggested for human study. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  20. Ameliorating Role of Caffeic Acid Phenethyl Ester (CAPE Against Methotrexate-Induced Oxidative Stress in the Sciatic Nerve, Spinal Cord and Brain Stem Tissues of Rats

    Directory of Open Access Journals (Sweden)

    Ertuğrul Uzar

    2010-03-01

    Full Text Available OBJECTIVE: Methotrexate (MTX-associated neurotoxicity is an important clinical problem in cancer patients, but the mechanisms of MTX-induced neurotoxicity are not yet known exactly. The aims of this study were (1 to investigate the possible role of malondialdehyde (MDA, superoxide dismutase (SOD enzyme, glutathione peroxidase (GSH-Px and catalase (CAT in the pathogenesis of MTX-induced neurotoxicity and (2 to determine whether there is a putative protective effect of caffeic acid phenethyl ester (CAPE on MTX-induced neurotoxicity in the spinal cord, brainstem and sciatic nerve of rats. METHODS: A total of 19 adult Wistar male rats were divided into three experimental groups. Group I, control group; Group II, MTX-treated group; and Group III, MTX + CAPE-treated group. MTX was administered to the MTX and MTX + CAPE groups intraperitoneally (IP with a single dose of 20 mg/kg on the second day of the experiment. CAPE was administered to the MTX + CAPE group IP with a dose of 10 μmol/kg for 7 days. RESULTS: In the sciatic nerve and spinal cord tissue, CAT and GSH-Px activities were increased in the MTX group in comparison with the control group. CAPE treatment with MTX significantly decreased CAT and GSH-Px activities in the neuronal tissues of rats in comparison with the MTX group. In the spinal cord and brainstem tissues, SOD activity in the MTX group was decreased in comparison with the control group, but in the sciatic nerve, there was no significant difference. In the spinal cord and brainstem of rats, SOD activity was increased in the CAPE + MTX group when compared with the MTX group. The level of MDA was higher in the MTX group than in the control group. CAPE administration with MTX injection caused a significant decrease in MDA level when compared with the MTX group. CONCLUSION: These results reveal that MTX increases oxidative stress in the sciatic nerve, spinal cord and brainstem of rats and that CAPE has a preventive effect on the

  1. Evidence that spinal astrocytes but not microglia contribute to the pathogenesis of paclitaxel-induced painful neuropathy

    OpenAIRE

    Zhang, Haijun; Yoon, Seo-Yeon; Zhang, Hongmei; Dougherty, Patrick M.

    2012-01-01

    Paclitaxel often induces persistent painful neuropathy as its most common treatment limiting side effect. Little is known concerning the underlying mechanisms. Given the prominent role of glial cells in many types of neuropathic pain, we investigated here the morphological and functional changes of spinal astrocytes and microglia in a rat model of paclitaxel-induced neuropathy. Immunohistochemistry, western blotting and real-time polymerase chain reaction (rt-PCR) were performed with samples ...

  2. Experimental Model of Spinal Cord Injury (SCI) in rats: management guidelines

    OpenAIRE

    Falavigna, Asdrubal; Cechetti, Fernanda; Finger, Guilherme; Ruschel, Leonardo Gilmone; Marcon, Grasiela; Silva, Pedro Guarise da

    2013-01-01

    Surgical experiments with laboratory animals are necessary for medical research. These studies aim to clarify the mechanism of disease, investigate the action and efficacy of new drugs or biological markers, as well as develop and enhance new therapies and apply new techniques. Regarding the models of spinal cord injury (SCI), there are several different methods that address the handling of the animals, especially concerning the use of analgesics, antibiotics and pre- and postoperative manage...

  3. Tribology of flexible and sliding spinal implants: Development of experimental and numerical models.

    Science.gov (United States)

    Le Cann, Sophie; Chaves-Jacob, Julien; Rossi, Jean-Marie; Linares, Jean-Marc; Chabrand, Patrick

    2018-01-01

    New fusionless devices are being developed to get over the limits of actual spinal surgical treatment, based on arthrodesis. However, due to their recentness, no standards exist to test and validate those devices, especially concerning the wear. A new tribological first approach to the definition of an in vitro wear protocol to study wear of flexible and sliding spinal devices is presented in this article, and was applied to a new concept. A simplified synthetic spine portion (polyethylene) was developed to reproduce a simple supra-physiological spinal flexion (10° between two vertebrae). The device studied with this protocol was tested in wet environment until 1 million cycles (Mc). We obtained an encouraging estimated wear volume of same order of magnitude compared to similar devices. An associated finite element (FE) numerical model has permitted to access contact information and study the effect of misalignment of one screw. First results could point out how to improve the design and suggest that a vertical misalignment of a screw (under or over-screwing) has more impact than a horizontal one. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 104-111, 2018. © 2016 Wiley Periodicals, Inc.

  4. Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yun Kyung; Kim, Gunha; Park, Serah; Sim, Ju Hee; Won, You Jin [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hwang, Chang Ho [Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714 (Korea, Republic of); Yoo, Jong Yoon, E-mail: jyyoo@amc.seoul.kr [Department of Rehabilitation Medicine, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hong, Hea Nam, E-mail: hnhong@amc.seoul.kr [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Lysolecithin-induced demyelination elevated EpoR expression in OPCs. Black-Right-Pointing-Pointer In association with elevated EpoR, EPO increased OPCs proliferation. Black-Right-Pointing-Pointer EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. Black-Right-Pointing-Pointer EPO promoted myelin repair following lysolecithin-induced demyelination. -- Abstract: Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to a limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.

  5. Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

    Science.gov (United States)

    Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

    2017-03-01

    Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

  6. Protective effects of gallic acid against spinal cord injury-induced oxidative stress.

    Science.gov (United States)

    Yang, Yong Hong; Wang, Zao; Zheng, Jie; Wang, Ran

    2015-08-01

    The present study aimed to investigate the role of gallic acid in oxidative stress induced during spinal cord injury (SCI). In order to measure oxidative stress, the levels of lipid peroxide, protein carbonyl, reactive oxygen species and nitrates/nitrites were determined. In addition, the antioxidant status during SCI injury and the protective role of gallic acid were investigated by determining glutathione levels as well as the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. Adenosine triphophatase (ATPase) enzyme activities were determined to evaluate the role of gallic acid in SCI-induced deregulation of the activity of enzymes involved in ion homeostasis. The levels of inflammatory markers such as nuclear factor (NF)-κB and cycloxygenase (COX)-2 were determined by western blot analysis. Treatment with gallic acid was observed to significantly mitigate SCI-induced oxidative stress and the inflammatory response by reducing the oxidative stress, decreasing the expression of NF-κB and COX-2 as well as increasing the antioxidant status of cells. In addition, gallic acid modulated the activity of ATPase enzymes. Thus the present study indicated that gallic acid may have a role as a potent antioxidant and anti-inflammatory agent against SCI.

  7. Combined approaches for the relief of spinal cord injury-induced neuropathic pain.

    Science.gov (United States)

    Gwak, Young S; Kim, Hee Young; Lee, Bong Hyo; Yang, Chae Ha

    2016-04-01

    The adequate treatment of spinal cord injury (SCI)-induced neuropathic pain still remains an unresolved problem. The current medications predominantly used in the SCI-induced neuropathic pain therapy are morphine, anticonvulsants, antidepressants, and antiepileptics, which suggests that psychiatric aspects might be important factors in the treatment of neuropathic pain. It is well documented that the modulation of the sensory events is not a unique way for achieving pain relief. In addition, pain patients still express dissatisfaction and complain of unwanted effects of the medications, suggesting that alternative approaches for the treatment of neuropathic pain are essential. In psychiatry, pain relief represents relaxation and a feeling of comfort and satisfaction, which suggests that cognitive and emotional motivations are important factors in the treatment of neuropathic pain. The comorbidity of chronic pain and psychiatric disorders, which is well recognized, suggests that the effective therapeutic relief for neuropathic pain induced by SCI can be achieved in conjunction with the management of the sensory and psychiatric aspects of patient. In this review, we address the feasibility of a combined acupuncture and pharmacotherapy treatment for the relief of neuropathic pain behavior following SCI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Intrathecal volume changes in lumbar spinal canal stenosis following extension and flexion: An experimental cadaver study.

    Science.gov (United States)

    Teske, Wolfram; Schwert, Martin; Zirke, Sonja; von Schulze Pellengahr, Christoph; Wiese, Matthias; Lahner, Matthias

    2015-01-01

    The spinal canal stenosis is a common disease in elderly. The thecal sac narrowing is considered as the anatomical cause for the disease. There is evidence that the anatomical proportions of the lumbar spinal canal are influenced by postural changes. The liquor volume shift during these postural changes is a valuable parameter to estimate the dynamic qualities of this disease. The aim of this human cadaver study was the determination of intrathecal fluid volume changes during the lumbar flexion and the extension. A special measuring device was designed and built for the study to investigate this issue under controlled conditions. The measuring apparatus fixed the lumbar spine firmly and allowed only flexion and extension. The dural sac was closed water tight. The in vitro changes of the intrathecal volumes during the motion cycle were determined according to the principle of communicating vessels. Thirteen human cadaver spines from the Institute of Anatomy were examined in a test setting with a continuous adjustment of motion. The diagnosis of the lumbar spinal stenosis was confirmed by a positive computer tomography prior testing. The volume changes during flexion and extension cycles were measured stepwise in a 2 degree distance between 18° flexion and 18° extension. Three complete series of measurements were performed for each cadaver. Two specimens were excluded because of fluid leaks from further investigation. The flexion of the lumbar spine resulted in an intrathecal volume increase. The maximum volume effects were seen in the early flexion positions of 2° and 4°. The spine reclination resulted in a volume reduction. The maximum extension effect was seen between 14° and 16°. According to our results, remarkable volume effects were seen in the early movements of the lumbar spine especially for the flexion. The results support the concept of the spinal stenosis as a dynamic disease and allow a better understanding of the pathophysiology of this

  9. Effects of Danggui Sini decoction on neuropathic pain: experimental studies and clinical pharmacological significance of inhibiting glial activation and proinflammatory cytokines in the spinal cord
.

    Science.gov (United States)

    Liu, Ming; Qiang, Qiu Hong; Ling, Qian; Yu, Chang Xi; Li, Xuejun; Liu, Suhuan; Yang, Shuyu

    2017-05-01

    Neuropathic pain responds poorly to drug treatments. Partial relief is achieved in only about half of the patients. Danggui Sini decoction (DSD), an aqueous extract of Angelica sinensis, Ramulus Cinnamomi, and Radix Puerariae, has been used extensively in China to treat inflammatory and ischemic diseases. The current study examined the putative effects of DSD on neuropathic pain. We used two commonly-used animal models: chronic constriction injury (CCI) and diabetic neuropathy for the study. And we examined effects of DSD on pain response, activation of microglia and astroglia in spinal dorsal horn, and expression of proinflammatory cytokines in the spinal cord. Consecutive intragastric administration of DSD (25 - 100 mg/kg) for 10 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models, DSD inhibited the over-expression of specific markers for microglia (Iba-1) and astroglia (GFAP) activation in the spinal dorsal horn. DSD also reduced the elevated nuclear NF-κB level and inhibited the up-regulation of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. DSD can alleviate CCI and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of DSD may be related to the suppression of spinal NF-κB activation and/or cytokines expression.
.

  10. Experimental investigation of cavitation induced air release

    Directory of Open Access Journals (Sweden)

    Kowalski Karoline

    2017-01-01

    Full Text Available Variations in cross-sectional areas may lead to pressure drops below a critical value, such that cavitation and air release are provoked in hydraulic systems. Due to a relatively slow dissolution of gas bubbles, the performance of hydraulic systems will be affected on long time scales by the gas phase. Therefore predictions of air production rates are desirable to describe the system characteristics. Existing investigations on generic geometries such as micro-orifice flows show an outgassing process due to hydrodynamic cavitation which takes place on time scales far shorter than diffusion processes. The aim of the present investigation is to find a correlation between global, hydrodynamic flow characteristics and cavitation induced undissolved gas fractions generated behind generic flow constrictions such as an orifice or venturi tube. Experimental investigations are realised in a cavitation channel that enables an independent adjustment of the pressure level upstream and downstream of the orifice. Released air fractions are determined by means of shadowgraphy imaging. First results indicate that an increased cavitation activity leads to a rapid increase in undissolved gas volume only in the choking regime. The frequency distribution of generated gas bubble size seems to depend only indirectly on the cavitation intensity driven by an increase of downstream coalescence events due to a more densely populated bubbly flow.

  11. Experimental investigation of cavitation induced air release

    Science.gov (United States)

    Kowalski, Karoline; Pollak, Stefan; Hussong, Jeanette

    Variations in cross-sectional areas may lead to pressure drops below a critical value, such that cavitation and air release are provoked in hydraulic systems. Due to a relatively slow dissolution of gas bubbles, the performance of hydraulic systems will be affected on long time scales by the gas phase. Therefore predictions of air production rates are desirable to describe the system characteristics. Existing investigations on generic geometries such as micro-orifice flows show an outgassing process due to hydrodynamic cavitation which takes place on time scales far shorter than diffusion processes. The aim of the present investigation is to find a correlation between global, hydrodynamic flow characteristics and cavitation induced undissolved gas fractions generated behind generic flow constrictions such as an orifice or venturi tube. Experimental investigations are realised in a cavitation channel that enables an independent adjustment of the pressure level upstream and downstream of the orifice. Released air fractions are determined by means of shadowgraphy imaging. First results indicate that an increased cavitation activity leads to a rapid increase in undissolved gas volume only in the choking regime. The frequency distribution of generated gas bubble size seems to depend only indirectly on the cavitation intensity driven by an increase of downstream coalescence events due to a more densely populated bubbly flow.

  12. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

    Science.gov (United States)

    Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

    2017-12-01

    Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

  13. Using visuo-kinetic virtual reality to induce illusory spinal movement: the MoOVi Illusion.

    Science.gov (United States)

    Harvie, Daniel S; Smith, Ross T; Hunter, Estin V; Davis, Miles G; Sterling, Michele; Moseley, G Lorimer

    2017-01-01

    Illusions that alter perception of the body provide novel opportunities to target brain-based contributions to problems such as persistent pain. One example of this, mirror therapy, uses vision to augment perceived movement of a painful limb to treat pain. Since mirrors can't be used to induce augmented neck or other spinal movement, we aimed to test whether such an illusion could be achieved using virtual reality, in advance of testing its potential therapeutic benefit. We hypothesised that perceived head rotation would depend on visually suggested movement. In a within-subjects repeated measures experiment, 24 healthy volunteers performed neck movements to 50 o of rotation, while a virtual reality system delivered corresponding visual feedback that was offset by a factor of 50%-200%-the Motor Offset Visual Illusion (MoOVi)-thus simulating more or less movement than that actually occurring. At 50 o of real-world head rotation, participants pointed in the direction that they perceived they were facing. The discrepancy between actual and perceived direction was measured and compared between conditions. The impact of including multisensory (auditory and visual) feedback, the presence of a virtual body reference, and the use of 360 o immersive virtual reality with and without three-dimensional properties, was also investigated. Perception of head movement was dependent on visual-kinaesthetic feedback ( p  = 0.001, partial eta squared = 0.17). That is, altered visual feedback caused a kinaesthetic drift in the direction of the visually suggested movement. The magnitude of the drift was not moderated by secondary variables such as the addition of illusory auditory feedback, the presence of a virtual body reference, or three-dimensionality of the scene. Virtual reality can be used to augment perceived movement and body position, such that one can perform a small movement, yet perceive a large one. The MoOVi technique tested here has clear potential for assessment and

  14. Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability

    International Nuclear Information System (INIS)

    Siegal, T.; Pfeffer, M.R.

    1995-01-01

    To investigate the profile of biochemical and physiological changes induced in the rat spinal cord by radiation, over a period of 8 months. The thoraco-lumbar spinal cords of Fisher rats were irradiated to a dose of 15 Gy. The rats were then followed and killed at various times afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. None of the rats developed neurologic dysfunction, and histologic examination revealed only occasional gliosis in the ventral white matter at 240 days after irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thoracic and cervical segments (p 2 (PGE 2 ), thromboxane (TXB 2 ), and prostacyclin [6 keto-PGF1α (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglandins. Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane followed, white prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radiation the calculated TXB 2 /6KPGF ratio remained balanced, regardless of the observed abrupt early fluctuations in their rate of synthesis. Later, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was observed which returned to normal by 3 days. 57 refs., 3 figs

  15. Imaging micro-glial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by Positron Emission Tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714

    International Nuclear Information System (INIS)

    Abourbeh, Galith; Theze, Benoit; Dubois, Albertine; Tavitian, Bertrand; Boisgard, Raphael; Maroy, Renaud; Brulon, Vincent; Fontyn, Yoann; Dolle, Frederic

    2012-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated micro-glia/macrophages play a key role in the immuno-pathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Micro-glia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of micro-glial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuro-inflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [ 18 F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5- a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [ 18 F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [ 18 F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl) - isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [ 18 F]DPA-714, neuro-inflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuro-inflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuro-inflammation for detection, monitoring, and research in MS. (authors)

  16. Development of an Animal Model of Thoracolumbar Burst Fracture-Induced Acute Spinal Cord Injury

    Science.gov (United States)

    2016-07-01

    seven days after injury. Magnetic resonance imaging (MRI) and histology were performed on postoperative day one and seven respectively. Results: The...custom spinal cord impactor delivered consistent, predictable, impacts to the spinal cord. MRI and histology showed a positive correlation between...Accomplishments Specific Aim 1 – Develop and complete proof of concept for a novel animal model of anterior (ventral) spinal cord injury following simulated

  17. Antinociception induced by chronic glucocorticoid treatment is correlated to local modulation of spinal neurotransmitter content

    Directory of Open Access Journals (Sweden)

    Almeida Armando

    2009-07-01

    Full Text Available Abstract Background While acute effects of stress on pain are well described, those produced by chronic stress are still a matter of dispute. Previously we demonstrated that chronic unpredictable stress results in antinociception in the tail-flick test, an effect that is mediated by increased levels of corticosteroids. In the present study, we evaluated nociception in rats after chronic treatment with corticosterone (CORT and dexamethasone (DEX in order to discriminate the role of each type of corticosteroid receptors in antinociception. Results Both experimental groups exhibited a pronounced antinociceptive effect after three weeks of treatment when compared to controls (CONT; however, at four weeks the pain threshold in CORT-treated animals returned to basal levels whereas in DEX-treated rats antinociception was maintained. In order to assess if these differences are associated with altered expression of neuropeptides involved in nociceptive transmission we evaluated the density of substance P (SP, calcitonin gene-related peptide (CGRP, somatostatin (SS and B2-γ-aminobutiric acid receptors (GABAB2 expression in the spinal dorsal horn using light density measurements and stereological techniques. After three weeks of treatment the expression of CGRP in the superficial dorsal horn was significantly decreased in both CORT and DEX groups, while GABAB2 was significantly increased; the levels of SP for both experimental groups remained unchanged at this point. At 4 weeks, CGRP and SP are reduced in DEX-treated animals and GABAB2 unchanged, but all changes were restored to CONT levels in CORT-treated animals. The expression of SS remained unaltered throughout the experimental period. Conclusion These data indicate that corticosteroids modulate nociception since chronic corticosteroid treatment alters the expression of neuropeptides involved in nociceptive transmission at the spinal cord level. As previously observed in some supraspinal areas, the

  18. Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons

    International Nuclear Information System (INIS)

    Ticku, M.K.; Lowrimore, P.; Lehoullier, P.

    1986-01-01

    Ethanol has a pharmacological profile similar to other centrally acting drugs, which facilitate GABAergic transmission. GABA is known to produce its effects by increasing the conductance to Cl- ions. In this study, we have examined the effect of ethanol on GABA-induced 36Cl-influx in primary spinal cord cultured neurons. GABA produces a concentration-dependent, and saturable effect on 36Cl-influx in these neurons. Ethanol potentiates the effect of GABA on 36Cl-influx in these neurons. GABA (20 microM) increased the 36Cl-influx by 75% over the basal value, and in the presence of 50 mM ethanol, the observed increase was 142%. Eadie-Hoffstee analysis of the saturation curves indicated that ethanol decreases the Km value of GABA (10.6 microM to 4.2 microM), and also increases the Vmax. Besides potentiating the effect of GABA, ethanol also appears to have a direct effect in the absence of added GABA. These results suggest that ethanol enhances GABA-induced 36Cl-influx and indicate a role of GABAergic system in the actions of ethanol. These results also support the behavioral and electrophysiological studies, which have implicated GABA systems in the actions of ethanol. The potential mechanism(s) and the role of direct effect of ethanol is not clear at this time, but is currently being investigated

  19. Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Yu-ping Mo

    2016-01-01

    Full Text Available In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI, this study investigated the effects of electroacupuncture (EA for SCI rat models. SCI was induced by a modified Allen’s weight-drop method. We investigated the response of EA at Dazhui (GV 14 and Mingmen (GV 4 acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats’ hind limbs among groups, and EA was shown to promote the recovery of SCI rats’ motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3 in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3.

  20. High-cervical spinal cord electrical stimulation in brain low perfusion syndromes: experimental basis and preliminary clinical report.

    Science.gov (United States)

    Broseta, J; García-March, G; Sánchez-Ledesma, M J; Gonçalves, J; Silva, I; Barcia, J A; Llácer, J L; Barcia-Salorio, J L

    1994-01-01

    Previous studies of our group showed that C1-C2 spinal cord stimulation increases carotid and brain blood flow in normal conditions in the goat and dog and it has a beneficial vasomotor effect in a model of vasospasm in the rat. For further clinical application it seemed rational to investigate the possible vascular changes mediated by this technique in experimental brain infarction. To this aim, 45 New Zealand rabbits were used. Brain infarction was produced by bilateral carotid ligation in 15, unilateral microcoagulation of the middle cerebral artery in 15 and by microcoagulation of the vertebral artery at the craniocervical junction in the other 15. One week later, following daily clinical scoring and cortical and posterior fossa blood flow readings by laser Doppler, a period of 120 min of right C1-C2 spinal cord electric stimulation was performed. A mean of 27% increase in previous blood flow recordings was obtained at the right hemisphere and a mean of 32% in the posterior fossa. This procedure was used in 10 patients presenting with various cerebral low perfusion syndromes. Though not constant, an increase in alertness, retention, speech, emotional lability and performance in skilled acts was achieved. No MR changes were observed, though SPECT readings showed an increase in blood flow in the penumbral perilesional area.

  1. Preload versus coload and vasopressor requirement for the prevention of spinal anesthesia induced hypotension in non-obstetric patients

    International Nuclear Information System (INIS)

    Khan, M.U.; Aqil, M.

    2015-01-01

    To compare the effectiveness of preload and coload for the prevention of Spinal Induced Hypotension (SIH) and vasopressor requirements. Study Design: Randomized trial. Place and Duration of Study: Department of Anesthesia, The Aga Khan University Hospital, Karachi, Pakistan, from June 2007 - June 2010. Methodology: Sixty patients were randomly divided into preload and coload group of 30 each. Patients with ASA1 - 3, aged 20 - 60 years were included. Patients with history of IHD, COPD, BMI > 30 and surgical procedure TURP were excluded. All patients received crystalloid 10 ml/kg before induction of spinal anesthesia in preload group and at the time of spinal anesthesia in coload group. Blood pressure and heart rate were recorded at different time intervals till 45 minutes. Patients received ephedrine 5 mg when systolic blood pressure dropped below 90 mmHg and heart rate was less than 60 beats/minute and/or phenylephrine 50 micrograms when systolic blood pressure dropped below 90 mmHg and heart rate was more than 60 beats/minute. Results: There was no statistically significant difference at different time intervals in heart rate, systolic and mean arterial pressure between the groups. Diastolic blood pressure was significantly different in both groups at 6 - 15 minutes after spinal anesthesia. SIH occurred (21) 70% and (15) 50% in preload and coload groups, respectively (p=0.187). Ephedrine requirement for SIH was significantly high in preload group (p=0.017). Phenylephrine requirement for SIH was high in preload group which was statistically non-significant (p=0.285). Conclusion: Coload group has lower incidence of spinal induced hypotension and significantly less vasopressor requirement than the preload group. (author)

  2. Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.

    Science.gov (United States)

    Ando, Shiori; Funato, Michinori; Ohuchi, Kazuki; Kameyama, Tsubasa; Inagaki, Satoshi; Seki, Junko; Kawase, Chizuru; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kaneko, Hideo; Hara, Hideaki

    2017-11-05

    Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons. We first found that edaravone could improve impaired neural development of SMA-iPSCs-derived spinal motor neurons with limited effect on nuclear SMN protein expression. Furthermore, edaravone inhibited the generation of reactive oxygen species and mitochondrial reactive oxygen species upregulated in SMA-iPSCs-derived spinal motor neurons, and reversed oxidative-stress induced apoptosis. In this study, we suggest that oxidative stress might be partly the reason for selective apoptosis in spinal motor neurons in SMA pathology, and that oxidative stress-induced apoptosis might be the therapeutic target of SMA. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Plateau properties in mammalian spinal interneurons during transmitter-induced locomotor activity

    DEFF Research Database (Denmark)

    Kiehn, O.; Johnson, B. R.; Raastad, M.

    1996-01-01

    We examined the organization of spinal networks controlling locomotion in the isolated spinal cord of the neonatal rat, and in this study we provide the first demonstration of plateau and bursting mechanisms in mammalian interneurons that show locomotor-related activity. Using tight-seal whole...

  4. Trauma: Spinal Cord Injury.

    Science.gov (United States)

    Eckert, Matthew J; Martin, Matthew J

    2017-10-01

    Injuries to the spinal column and spinal cord frequently occur after high-energy mechanisms of injury, or with lower-energy mechanisms, in select patient populations like the elderly. A focused yet complete neurologic examination during the initial evaluation will guide subsequent diagnostic procedures and early supportive measures to help prevent further injury. For patients with injury to bone and/or ligaments, the initial focus should be spinal immobilization and prevention of inducing injury to the spinal cord. Spinal cord injury is associated with numerous life-threatening complications during the acute and long-term phases of care that all acute care surgeons must recognize. Published by Elsevier Inc.

  5. Estrogen alleviates neuropathic pain induced after spinal cord injury by inhibiting microglia and astrocyte activation.

    Science.gov (United States)

    Lee, Jee Youn; Choi, Hae Young; Ju, Bong-Gun; Yune, Tae Young

    2018-04-16

    Neuropathic pain after spinal cord injury (SCI) is developed in about 80% of SCI patients and there is no efficient therapeutic drug to alleviate SCI-induced neuropathic pain. Here we examined the effect of estrogen on SCI-induced neuropathic pain at below-level and its effect on neuroinflammation as underlying mechanisms. Neuropathic pain is developed at late phase after SCI and a single dose of 17β-estradiol (100, 300 μg/kg) were administered to rats with neuropathic pain after SCI through intravenous injection. As results, both mechanical allodynia and thermal hyperalgesia were significantly reduced by 17β-estradiol compared to vehicle control. Both microglia and astrocyte activation in the lamina I and II of L4-5 dorsal horn was also inhibited by 17β-estradiol. In addition, the levels of p-p38MAPK and p-ERK known to be activated in microglia and p-JNK known to be activated in astrocyte were significantly decreased by 17β-estradiol. Furthermore, the mRNA expression of inflammatory mediators such as Il-1β, Il-6, iNos, and Cox-2 was more attenuated in 17β-estradiol-treated group than in vehicle-treated group. Particularly, we found that the analgesic effect by 17β-estradiol was mediated via estrogen receptors, which are expressed in dorsal horn neurons. These results suggest that 17β-estradiol may attenuate SCI-induced neuropathic pain by inhibiting microglia and astrocyte activation followed inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

    International Nuclear Information System (INIS)

    Hao, J.X.; Xu, X.J.; Aldskogius, H.; Seiger, A.; Wiesenfeld-Hallin, Z.

    1991-01-01

    Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord

  7. Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel Dysfunction in DRG Neurons.

    Science.gov (United States)

    Zemel, Benjamin M; Muqeem, Tanziyah; Brown, Eric V; Goulão, Miguel; Urban, Mark W; Tymanskyj, Stephen R; Lepore, Angelo C; Covarrubias, Manuel

    2017-08-23

    Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3.4 current. Attenuated Kv3.4 currents also exhibited slowed inactivation. We observed similar effects on the recombinant Kv3.4 channel heterologously expressed in Chinese hamster ovary cells, supporting our findings in DRG neurons. Elucidating the molecular basis of these effects, mutation of four previously characterized serines within the Kv3.4 N-terminal inactivation domain eliminated the effects of CaN inhibition on the Kv3.4 current. SCI similarly induced concurrent Kv3.4 current attenuation and slowing of inactivation. Although there was little change in CaN expression and localization after injury, SCI induced upregulation of the native regulator of CaN 1 (RCAN1) in the DRG at the transcript and protein levels. Consistent with CaN inhibition resulting from RCAN1 upregulation, overexpression of RCAN1 in naive DRG neurons recapitulated the effects of pharmacological CaN inhibition on the Kv3.4 current and the AP. Overall, these results demonstrate a novel regulatory pathway that links CaN, RCAN1, and Kv3.4 in DRG neurons. Dysregulation of this pathway might underlie a peripheral mechanism of pain sensitization induced by SCI. SIGNIFICANCE STATEMENT Pain sensitization associated with spinal cord injury (SCI) involves poorly understood maladaptive modulation of neuronal excitability. Although central mechanisms have

  8. RAE-1 expression is induced during experimental autoimmune encephalomyelitis and is correlated with microglia cell proliferation.

    Science.gov (United States)

    Djelloul, Mehdi; Popa, Natalia; Pelletier, Florence; Raguénez, Gilda; Boucraut, José

    2016-11-01

    Retinoic acid early induced transcript-1 (RAE-1) glycoproteins are ligands of the activating immune receptor NKG2D. They are known as stress molecules induced in pathological conditions. We previously reported that progenitor cells express RAE-1 in physiological conditions and we described a correlation between RAE-1 expression and cell proliferation. In addition, we showed that Raet1 transcripts are induced in the spinal cord of experimental autoimmune encephalomyelitis (EAE) mice. EAE is a model for multiple sclerosis which is accompanied by microglia proliferation and activation, recruitment of immune cells and neurogenesis. We herein studied the time course expression of the two members of the Raet1 gene family present in C57BL/6 mice, namely Raet1d and Raet1e, in the spinal cord during EAE. We report that Raet1d and Raet1e genes are induced early upon EAE onset and reach a maximal expression at the peak of the pathology. We show that myeloid cells, i.e. macrophages as well as microglia, are cellular sources of Raet1 transcripts. We also demonstrate that only Raet1d expression is induced in microglia, whereas macrophages expressed both Raet1d and Raet1e. Furthermore, we investigated the dynamics of RAE-1 expression in microglia cultures. RAE-1 induction correlated with cell proliferation but not with M1/M2 phenotypic orientation. We finally demonstrate that macrophage colony-stimulating factor (M-CSF) is a major factor controlling RAE-1 expression in microglia. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Using visuo-kinetic virtual reality to induce illusory spinal movement: the MoOVi Illusion

    Directory of Open Access Journals (Sweden)

    Daniel S. Harvie

    2017-02-01

    Full Text Available Background Illusions that alter perception of the body provide novel opportunities to target brain-based contributions to problems such as persistent pain. One example of this, mirror therapy, uses vision to augment perceived movement of a painful limb to treat pain. Since mirrors can’t be used to induce augmented neck or other spinal movement, we aimed to test whether such an illusion could be achieved using virtual reality, in advance of testing its potential therapeutic benefit. We hypothesised that perceived head rotation would depend on visually suggested movement. Method In a within-subjects repeated measures experiment, 24 healthy volunteers performed neck movements to 50o of rotation, while a virtual reality system delivered corresponding visual feedback that was offset by a factor of 50%–200%—the Motor Offset Visual Illusion (MoOVi—thus simulating more or less movement than that actually occurring. At 50o of real-world head rotation, participants pointed in the direction that they perceived they were facing. The discrepancy between actual and perceived direction was measured and compared between conditions. The impact of including multisensory (auditory and visual feedback, the presence of a virtual body reference, and the use of 360o immersive virtual reality with and without three-dimensional properties, was also investigated. Results Perception of head movement was dependent on visual-kinaesthetic feedback (p = 0.001, partial eta squared = 0.17. That is, altered visual feedback caused a kinaesthetic drift in the direction of the visually suggested movement. The magnitude of the drift was not moderated by secondary variables such as the addition of illusory auditory feedback, the presence of a virtual body reference, or three-dimensionality of the scene. Discussion Virtual reality can be used to augment perceived movement and body position, such that one can perform a small movement, yet perceive a large one. The Mo

  10. Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Zanon Renata G

    2010-05-01

    Full Text Available Abstract Background Astrocytes play a major role in preserving and restoring structural and physiological integrity following injury to the nervous system. After peripheral axotomy, reactive gliosis propagates within adjacent spinal segments, influenced by the local synthesis of nitric oxide (NO. The present work investigated the importance of inducible nitric oxide synthase (iNOS activity in acute and late glial responses after injury and in major histocompatibility complex class I (MHC I expression and synaptic plasticity of inputs to lesioned alpha motoneurons. Methods In vivo analyses were carried out using C57BL/6J-iNOS knockout (iNOS-/- and C57BL/6J mice. Glial response after axotomy, glial MHC I expression, and the effects of axotomy on synaptic contacts were measured using immunohistochemistry and transmission electron microscopy. For this purpose, 2-month-old animals were sacrificed and fixed one or two weeks after unilateral sciatic nerve transection, and spinal cord sections were incubated with antibodies against classical MHC I, GFAP (glial fibrillary acidic protein - an astroglial marker, Iba-1 (an ionized calcium binding adaptor protein and a microglial marker or synaptophysin (a presynaptic terminal marker. Western blotting analysis of MHC I and nNOS expression one week after lesion were also performed. The data were analyzed using a two-tailed Student's t test for parametric data or a two-tailed Mann-Whitney U test for nonparametric data. Results A statistical difference was shown with respect to astrogliosis between strains at the different time points studied. Also, MHC I expression by iNOS-/- microglial cells did not increase at one or two weeks after unilateral axotomy. There was a difference in synaptophysin expression reflecting synaptic elimination, in which iNOS-/- mice displayed a decreased number of the inputs to alpha motoneurons, in comparison to that of C57BL/6J. Conclusion The findings herein indicate that i

  11. Spinal 5-HT7 Receptors and Protein Kinase A Constrain Intermittent Hypoxia-Induced Phrenic Long-term Facilitation

    Science.gov (United States)

    Hoffman, M.S.; Mitchell, G.S.

    2013-01-01

    Phrenic long-term facilitation (pLTF) is a form of serotonin-dependent respiratory plasticity induced by acute intermittent hypoxia (AIH). pLTF requires spinal Gq protein-coupled serotonin-2 receptor (5-HT2) activation, new synthesis of brain-derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, TrkB. Intrathecal injections of selective agonists for Gs protein-coupled receptors (adenosine 2A and serotonin-7; 5-HT7) also induce long-lasting phrenic motor facilitation via TrkB “trans-activation.” Since serotonin release near phrenic motor neurons may activate multiple serotonin receptor subtypes, we tested the hypothesis that 5-HT7 receptor activation contributes to AIH-induced pLTF. A selective 5-HT7 receptor antagonist (SB-269970, 5mM, 12μl) was administered intrathecally at C4 to anesthetized, vagotomized and ventilated rats prior to AIH (3, 5-min episodes, 11% O2). Contrary to predictions, pLTF was greater in SB-269970 treated versus control rats (80±11% vs 45±6% 60 min post-AIH; p<0.05). Hypoglossal LTF was unaffected by spinal 5-HT7 receptor inhibition, suggesting that drug effects were localized to the spinal cord. Since 5-HT7 receptors are coupled to protein kinase A (PKA), we tested the hypothesis that PKA inhibits AIH-induced pLTF. Similar to 5-HT7 receptor inhibition, spinal PKA inhibition (KT-5720, 100μM, 15μl) enhanced pLTF (99±15% 60 min post-AIH; p<0.05). Conversely, PKA activation (8-br-cAMP, 100μM, 15μl) blunted pLTF versus control rats (16±5% vs 45±6% 60 min post-AIH; p<0.05). These findings suggest a novel mechanism whereby spinal Gs protein-coupled 5-HT7 receptors constrain AIH-induced pLTF via PKA activity. PMID:23850591

  12. Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation.

    Science.gov (United States)

    Chow, Lok-Hi; Chen, Yuan-Hao; Wu, Wan-Chuan; Chang, En-Pei; Huang, Eagle Yi-Kung

    2016-01-01

    Previously, we demonstrated intrathecal administration of oxytocin strongly induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist (atosiban), the descending oxytocinergic pathway was found to regulate inflammatory hyperalgesia in our previous study using male rats. The activity of this neural pathway is elevated during hyperalgesia, but whether this effect differs in a sex-dependent manner remains unknown. We conducted plantar tests on adult male and female virgin rats in which paw inflammation was induced using carrageenan. Exogenous (i.t.) application of oxytocin exerted no anti-hyperalgesic effect in female rats, except at an extremely high dose. Female rats exhibited similar extent of hyperalgesia to male rats did when the animals received the same dose of carrageenan. When atosiban was administered alone, the severity of hyperalgesia was not increased in female rats. Moreover, insulin-regulated aminopeptidase (IRAP) was expressed at higher levels in the spinal cords of female rats compared with those of male rats. Oxytocin-induced anti-hyperalgesia exhibits a sex-dependent difference in rats. This difference can partially result from the higher expression of IRAP in the spinal cords of female rats, because IRAP functions as an enzyme that degrades oxytocin. Our study confirms the existence of a sex difference in oxytocin-induced anti-hyperalgesia at the spinal level in rats.

  13. In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury.

    Science.gov (United States)

    Sundberg, Laura M; Herrera, Juan J; Narayana, Ponnada A

    2010-10-01

    Comprehensive in vivo longitudinal studies that include multi-modal magnetic resonance imaging (MRI) and a battery of behavioral assays to assess functional outcome were performed at multiple time points up to 56 days post-traumatic spinal cord injury (SCI) in rodents. The MRI studies included high-resolution structural imaging for lesion volumetry, and diffusion tensor imaging (DTI) for probing the white matter integrity. The behavioral assays included open-field locomotion, grid walking, inclined plane, computerized activity box performance, and von Frey filament tests. Additionally, end-point histology was assessed for correlation with both the MRI and behavioral data. The temporal patterns of the lesions were documented on structural MRI. DTI studies showed significant changes in white matter that is proximal to the injury epicenter and persisted to day 56. White matter in regions up to 1 cm away from the injury epicenter that appeared normal on conventional MRI also exhibited changes that were indicative of tissue damage, suggesting that DTI is a more sensitive measure of the evolving injury. Correlations between DTI and histology after SCI could not be firmly established, suggesting that injury causes complex pathological changes in multiple tissue components that affect the DTI measures. Histological evidence confirmed a significant decrease in myelin and oligodendrocyte presence 56 days post-SCI. Multiple assays to evaluate aspects of functional recovery correlated with histology and DTI measures, suggesting that damage to specific white matter tracts can be assessed and tracked longitudinally after SCI.

  14. A novel approach for automatic visualization and activation detection of evoked potentials induced by epidural spinal cord stimulation in individuals with spinal cord injury.

    Science.gov (United States)

    Mesbah, Samineh; Angeli, Claudia A; Keynton, Robert S; El-Baz, Ayman; Harkema, Susan J

    2017-01-01

    Voluntary movements and the standing of spinal cord injured patients have been facilitated using lumbosacral spinal cord epidural stimulation (scES). Identifying the appropriate stimulation parameters (intensity, frequency and anode/cathode assignment) is an arduous task and requires extensive mapping of the spinal cord using evoked potentials. Effective visualization and detection of muscle evoked potentials induced by scES from the recorded electromyography (EMG) signals is critical to identify the optimal configurations and the effects of specific scES parameters on muscle activation. The purpose of this work was to develop a novel approach to automatically detect the occurrence of evoked potentials, quantify the attributes of the signal and visualize the effects across a high number of scES parameters. This new method is designed to automate the current process for performing this task, which has been accomplished manually by data analysts through observation of raw EMG signals, a process that is laborious and time-consuming as well as prone to human errors. The proposed method provides a fast and accurate five-step algorithms framework for activation detection and visualization of the results including: conversion of the EMG signal into its 2-D representation by overlaying the located signal building blocks; de-noising the 2-D image by applying the Generalized Gaussian Markov Random Field technique; detection of the occurrence of evoked potentials using a statistically optimal decision method through the comparison of the probability density functions of each segment to the background noise utilizing log-likelihood ratio; feature extraction of detected motor units such as peak-to-peak amplitude, latency, integrated EMG and Min-max time intervals; and finally visualization of the outputs as Colormap images. In comparing the automatic method vs. manual detection on 700 EMG signals from five individuals, the new approach decreased the processing time from several

  15. Spinal NMDA receptor activation constrains inactivity-induced phrenic motor facilitation in Charles River Sprague-Dawley rats.

    Science.gov (United States)

    Streeter, K A; Baker-Herman, T L

    2014-10-01

    Reduced spinal synaptic inputs to phrenic motor neurons elicit a unique form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). iPMF requires tumor necrosis factor-α (TNF-α) and atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize early, transient increases in phrenic burst amplitude into long-lasting iPMF. Here we tested the hypothesis that spinal N-methyl-d-aspartate receptor (NMDAR) activation constrains long-lasting iPMF in some rat substrains. Phrenic motor output was recorded in anesthetized, ventilated Harlan (HSD) and Charles River (CRSD) Sprague-Dawley rats exposed to a 30-min central neural apnea. HSD rats expressed a robust, long-lasting (>60 min) increase in phrenic burst amplitude (i.e., long-lasting iPMF) when respiratory neural activity was restored. By contrast, CRSD rats expressed an attenuated, transient (∼15 min) iPMF. Spinal NMDAR inhibition with DL-2-amino-5-phosphonopentanoic acid (APV) before neural apnea or shortly (4 min) prior to the resumption of respiratory neural activity revealed long-lasting iPMF in CRSD rats that was phenotypically similar to that in HSD rats. By contrast, APV did not alter iPMF expression in HSD rats. Spinal TNF-α or aPKC inhibition impaired long-lasting iPMF enabled by NMDAR inhibition in CRSD rats, suggesting that similar mechanisms give rise to long-lasting iPMF in CRSD rats with NMDAR inhibition as those giving rise to long-lasting iPMF in HSD rats. These results suggest that NMDAR activation can impose constraints on TNF-α-induced aPKC activation after neural apnea, impairing stabilization of transient iPMF into long-lasting iPMF. These data may have important implications for understanding differential responses to reduced respiratory neural activity in a heterogeneous human population. Copyright © 2014 the American Physiological Society.

  16. Ischemic Tolerance of the Brain and Spinal Cord: A Review.

    Science.gov (United States)

    Yunoki, Masatoshi; Kanda, Takahiro; Suzuki, Kenta; Uneda, Atsuhito; Hirashita, Koji; Yoshino, Kimihiro

    2017-11-15

    Ischemic tolerance is an endogenous neuroprotective phenomenon induced by sublethal ischemia. Ischemic preconditioning (IPC), the first discovered form of ischemic tolerance, is widely seen in many species and in various organs including the brain and the spinal cord. Ischemic tolerance of the spinal cord is less familiar among neurosurgeons, although it has been reported from the viewpoint of preventing ischemic spinal cord injury during aortic surgery. It is important for neurosurgeons to have opportunities to see patients with spinal cord ischemia, and to understand ischemic tolerance of the spinal cord as well as the brain. IPC has a strong neuroprotective effect in animal models of ischemia; however, clinical application of IPC for ischemic brain and spinal diseases is difficult because they cannot be predicted. In addition, one drawback of preconditioning stimuli is that they are also capable of producing injury with only minor changes to their intensity or duration. Numerous methods to induce ischemic tolerance have been discovered that vary in their timing and the site at which short-term ischemia occurs. These methods include ischemic postconditioning (IPoC), remote ischemic preconditioning (RIPC), remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPoC), which has had a great impact on clinical approaches to treatment of ischemic brain and spinal cord injury. Especially RIPerC and RIPoC to induce spinal cord tolerance are considered clinically useful, however the evidence supporting these methods is currently insufficient; further experimental or clinical research in this area is thus necessary.

  17. Experimental evaluation of earthquake induced relay chattering

    International Nuclear Information System (INIS)

    Bandyopadhyay, K.; Hofmayer, C.; Shteyngart, S.

    1990-01-01

    An experimental evaluation of relay performance under vibratory environments is discussed in this paper. Single frequency excitation was used for most tests. Limited tests were performed with random multifrequency inputs. The capacity of each relay was established based on a two-millisecond chatter criterion. The experimental techniques are described and the effects of parameters in controlling the relay capacity levels are illustrated with test data. A wide variation of the capacity levels was observed due to the influence of parameters related to the design of the relay and nature of the input motion. 3 refs., 15 figs

  18. Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats

    Directory of Open Access Journals (Sweden)

    Yano Takahisa

    2011-01-01

    Full Text Available Abstract Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol and memantine (1 μmol, NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t. and ifenprodil (50 mg/kg, p.o. significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase but not on Day 5 (early phase. Moreover, we examined the involvement of nitric oxide synthase (NOS as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

  19. Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

    Science.gov (United States)

    Zhang, S-X; Huang, F; Gates, M; Shen, X; Holmberg, E G

    2016-11-01

    This is a randomized controlled prospective trial with two parallel groups. The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. This study was conducted in SCS Research Center in Colorado, USA. A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

  20. Experimental study of dynamic diffusion tensor imaging in spinal cord of goats under persistent compression

    International Nuclear Information System (INIS)

    Liu Jicun; Liu Huaijun; He Dan; Huang Boyuan; Cui Caixia; Wang Zhihong; Xu Yingjin

    2009-01-01

    Objective: To explore the dynamic changes of diffusion tensor imaging (DTI) in spinal cord of goats with persistent compression injury. Methods: Eighteen goats weighted 20-25 kg were divided into three groups with completely random design: A, B and C. A balloon catheter was inserted into the epidural space at C3-4 level via intervertabral foramen for each goat. The balloon was inflated by injection of variable volumes of saline in group A and B 10 days following operation. The volume of saline was 0.3 ml in group A and 0.2 ml in group B, respectively. The compression sustained for 40 days. Group C served as uncompressed control without injection of saline. The locomotor rating score was applied to each group. Conventional MRI and DTI were performed. The apparent diffusion coefficient (ADC)and fractional anisotropy(FA) values were measured. Histopathological assessments of the compressed spinal cord were performed 50 days following operation with light microscope and transmission electron microscopy. Results: Before operation, the locomotor rating score was 5, the ADC value was (1.23 ± 0.05) x 10 -3 mm 2 /s and the FA value was (0.72 ± 0.05) each group. Of six goats in Group A, the locomotor rating score severely decreased and reached (1.5 ± 0.4)on the 40 th day after compression. The ADC value at compression site decreased soon and reached the minimum (0.75 ± 0.04) x 10 -3 mm 2 /s on the 5 th day after compression. Then the ADC value increased gradually, restored normal on the 10 th day or so, then became markedly higher than normal and reached (1.61±0.05) x 10 -3 mm 2 /s on the 40 th day. The FA value at compression site decreased soon, reached (0.54±0.04)on the 1st day, then decreased gradually and reached (0.43± 0.05) on the 40 th day. It appeared high signal intensity on T 2 WI on the 10 th day. In Group B, the locomotor rating score was moderately decreased and reached (3.4 ± 0.5) on the 40 th day. The ADC value at compression site decreased slightly

  1. Experimental Contact Lens to Prevent Glaucoma-Induced Blindness

    Science.gov (United States)

    ... An Experimental Contact Lens to Prevent Glaucoma-Induced Blindness By Sharon Reynolds Posted January 23, 2014 An ... group of conditions that can result in irreversible blindness. This vision loss can be reduced if glaucoma ...

  2. Intra- and interpersonal consequences of experimentally induced concealment

    NARCIS (Netherlands)

    Bouman, T.K.

    2003-01-01

    Secrecy, concealment, and thought supression are assumed to be important aspects of psychopathology. However, most studies address these from an intrapersonal perspective. This study investigates both the intra- as well as the interpersonal consequences of experimentally induced concealment. Two

  3. Time-dependent, bidirectional, anti- and pro-spinal hyper-reflexia and muscle spasticity effect after chronic spinal glycine transporter 2 (GlyT2) oligonucleotide-induced downregulation.

    Science.gov (United States)

    Kamizato, Kota; Marsala, Silvia; Navarro, Michael; Kakinohana, Manabu; Platoshyn, Oleksandr; Yoshizumi, Tetsuya; Lukacova, Nadezda; Wancewicz, Ed; Powers, Berit; Mazur, Curt; Marsala, Martin

    2018-07-01

    The loss of local spinal glycine-ergic tone has been postulated as one of the mechanisms contributing to the development of spinal injury-induced spasticity. In our present study using a model of spinal transection-induced muscle spasticity, we characterize the effect of spinally-targeted GlyT2 downregulation once initiated at chronic stages after induction of spasticity in rats. In animals with identified hyper-reflexia, the anti-spasticity effect was studied after intrathecal treatment with: i) glycine, ii) GlyT2 inhibitor (ALX 1393), and iii) GlyT2 antisense oligonucleotide (GlyT2-ASO). Administration of glycine and GlyT2 inhibitor led to significant suppression of spasticity lasting for a minimum of 45-60 min. Treatment with GlyT2-ASO led to progressive suppression of muscle spasticity seen at 2-3 weeks after treatment. Over the subsequent 4-12 weeks, however, the gradual appearance of profound spinal hyper-reflexia was seen. This was presented as spontaneous or slight-tactile stimulus-evoked muscle oscillations in the hind limbs (but not in upper limbs) with individual hyper-reflexive episodes lasting between 3 and 5 min. Chronic hyper-reflexia induced by GlyT2-ASO treatment was effectively blocked by intrathecal glycine. Immunofluorescence staining and Q-PCR analysis of the lumbar spinal cord region showed a significant (>90%) decrease in GlyT2 mRNA and GlyT2 protein. These data demonstrate that spinal GlyT2 downregulation provides only a time-limited therapeutic benefit and that subsequent loss of glycine vesicular synthesis resulting from chronic GlyT2 downregulation near completely eliminates the tonic glycine-ergic activity and is functionally expressed as profound spinal hyper-reflexia. These characteristics also suggest that chronic spinal GlyT2 silencing may be associated with pro-nociceptive activity. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. The effect of milrinone on induced hypotension in elderly patients during spinal surgery: a randomized controlled trial.

    Science.gov (United States)

    Hwang, Wonjung; Kim, Eunsung

    2014-08-01

    Induced hypotension is widely used intraoperatively to reduce blood loss and to improve the surgical field during spinal surgery. To determine the effect of milrinone on induced hypotension during spinal surgery in elderly patients. Prospective randomized clinical trial. Forty patients, 60 to 70 years old, ASA I-II, who underwent elective lumbar fusion surgery. Intraoperative hemodynamics, blood loss, hourly urine output, and grade of surgical field. All patients were randomized to group M or N. The study drug was infused after perivertebral muscle retraction until complete interbody fusion. In group M, 50 μg/kg/min of milrinone was infused over 10 minutes as a loading dose followed by 0.6 μg/kg/min of milrinone as a continuous dose. In group N, an identical volume of normal saline was infused in the same fashion. This study was not funded by commercial or other sponsorship and the authors confirm no conflicts of interest, financial or otherwise. During infusion of the study drug, the systolic and mean blood pressures were maintained within adequate limits of induced hypotension in group M. Intraoperative blood loss was 445.0±226.5 mL in group M and 765.0±339.2 mL in group N (p=.001). Hourly urine output was 1.4±0.6 mL in group M and 0.8±0.2 mL in group N (pmilrinone is useful for induced hypotension in elderly patients during spinal surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Perineural pretreatment of bee venom attenuated the development of allodynia in the spinal nerve ligation injured neuropathic pain model; an experimental study.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong Soo; Lee, Jong Hyuk; Lee, So Hee; Lee, Sun Kyung; Lee, Yoon Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2014-11-04

    Diluted bee venom (BV) is known to have anti-nociceptive and anti-inflammatory effects. We therefore assessed whether perineural bee venom pretreatment could attenuate the development of neuropathic pain in the spinal nerve ligation injured animal model. Neuropathic pain was surgically induced in 30 male Sprague Dawley rats by ligation of the L5 and L6 spinal nerves, with 10 rats each treated with saline and 0.05 and 0.1 mg BV. Behavioral testing for mechanical, cold, and thermal allodynia was conducted on postoperative days 3 to 29. Three rats in each group and 9 sham operated rats were sacrificed on day 9, and the expression of transient receptor potential vanilloid type 1 (TRPV1), ankyrin type 1 (TRPA1), and melastatin type 8 (TRPM8) receptors in the ipsilateral L5 dorsal root ganglion was analyzed. The perineural administration of BV to the spinal nerves attenuated the development of mechanical, thermal, and cold allodynia, and the BV pretreatment reduced the expression of TRPV1, TRPA1, TRPM8 and c - Fos in the ipsilateral dorsal root ganglion. The current study demonstrates that the perineural pretreatment with diluted bee venom before the induction of spinal nerve ligation significantly suppresses the development of neuropathic pain. Furthermore, this bee venom induced suppression was strongly related with the involvement of transient receptor potential family members.

  6. The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report

    Science.gov (United States)

    Ozturk, Cengiz; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yolas, Coskun; Kabalar, Mehmet Esref; Gundogdu, Betul; Duman, Aslihan; Kanat, Ilyas Ferit; Gundogdu, Cemal

    2015-01-01

    Context: Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. Aims: The goal of this study was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar subarachnoid hemorrhage (SAH) on bowel dilatation severity. Settings and Design: An experimental rabbit study. Materials and Methods: The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13), serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. Results: The mean volume of imaginary descending colons was estimated as 93 ± 12 cm3 in the control group and 121 ± 26 cm3 in the SS group and 176 ± 49 cm3 in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05). Conclusion: An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies. PMID:25972712

  7. The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report

    Directory of Open Access Journals (Sweden)

    Cengiz Ozturk

    2015-01-01

    Full Text Available Context: Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. Aims: The goal of this study was to study the effects Adamkiewicz artery (AKA vasospasm in lumbar subarachnoid hemorrhage (SAH on bowel dilatation severity. Settings and Design: An experimental rabbit study. Materials and Methods: The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13, serum saline (SS (SS; N = 7 and control (N = 5 groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois. Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. Results: The mean volume of imaginary descending colons was estimated as 93 ± 12 cm 3 in the control group and 121 ± 26 cm 3 in the SS group and 176 ± 49 cm 3 in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05. Conclusion: An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

  8. The impact of L5 dorsal root ganglion degeneration and Adamkiewicz artery vasospasm on descending colon dilatation following spinal subarachnoid hemorrhage: An experimental study; first report.

    Science.gov (United States)

    Ozturk, Cengiz; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yolas, Coskun; Kabalar, Mehmet Esref; Gundogdu, Betul; Duman, Aslihan; Kanat, Ilyas Ferit; Gundogdu, Cemal

    2015-01-01

    Somato-sensitive innervation of bowels are maintained by lower segments of spinal cord and the blood supply of the lower spinal cord is heavily dependent on Adamkiewicz artery. Although bowel problems are sometimes seen in subarachnoid hemorrhage neither Adamkiewicz artery spasm nor spinal cord ischemia has not been elucidated as a cause of bowel dilatation so far. The goal of this study was to study the effects Adamkiewicz artery (AKA) vasospasm in lumbar subarachnoid hemorrhage (SAH) on bowel dilatation severity. An experimental rabbit study. The study was conducted on 25 rabbits, which were randomly divided into three groups: Spinal SAH (N = 13), serum saline (SS) (SS; N = 7) and control (N = 5) groups. Experimental spinal SAH was performed. After 21 days, volume values of descending parts of large bowels and degenerated neuron density of L5DRG were analyzed. Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois). Two-tailed t-test and Mann-Whitney U-tests were used. The statistical significance was set at P < 0.05. The mean volume of imaginary descending colons was estimated as 93 ± 12 cm(3) in the control group and 121 ± 26 cm(3) in the SS group and 176 ± 49 cm(3) in SAH group. Volume augmentations of the descending colons and degenerated neuron density L5DRG were significantly different between the SAH and other two groups (P < 0.05). An inverse relationship between the living neuronal density of the L5DRG and the volume of imaginary descending colon values was occurred. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

  9. Status of experimental data for neutron induced reactions

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Mamoru [Tohoku Univ., Sendai (Japan)

    1998-11-01

    A short review is presented on the status of experimental data for neutron induced reactions above 20 MeV based on the EXFOR data base and journals. Experimental data which were obtained in a systematic manner and/or by plural authors are surveyed and tabulated for the nuclear data evaluation and the benchmark test of the evaluated data. (author). 61 refs.

  10. Systematic review of induced pluripotent stem cell technology as a potential clinical therapy for spinal cord injury.

    Science.gov (United States)

    Kramer, Anne S; Harvey, Alan R; Plant, Giles W; Hodgetts, Stuart I

    2013-01-01

    Transplantation therapies aimed at repairing neurodegenerative and neuropathological conditions of the central nervous system (CNS) have utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages. The use and popularity of each cell type is guided by a number of factors including the nature of the experimental model, neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cells' myelination capability. The promise of stem cells, with their reported ability to give rise to neuronal lineages to replace lost endogenous cells and myelin, integrate into host tissue, restore functional connectivity, and provide trophic support to enhance and direct intrinsic regenerative ability, has been seen as a most encouraging step forward. The advent of the induced pluripotent stem cell (iPSC), which represents the ability to "reprogram" somatic cells into a pluripotent state, hails the arrival of a new cell transplantation candidate for potential clinical application in therapies designed to promote repair and/or regeneration of the CNS. Since the initial development of iPSC technology, these cells have been extensively characterized in vitro and in a number of pathological conditions and were originally reported to be equivalent to embryonic stem cells (ESCs). This review highlights emerging evidence that suggests iPSCs are not necessarily indistinguishable from ESCs and may occupy a different "state" of pluripotency with differences in gene expression, methylation patterns, and genomic aberrations, which may reflect incomplete reprogramming and may therefore impact on the regenerative potential of these donor cells in therapies. It also highlights the limitations of current technologies used to generate these cells. Moreover, we provide a systematic review of the state of play with regard to the use of iPSCs in the treatment of neurodegenerative and neuropathological conditions. The

  11. Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.

    Science.gov (United States)

    Illien-Jünger, Svenja; Lu, Young; Qureshi, Sheeraz A; Hecht, Andrew C; Cai, Weijing; Vlassara, Helen; Striker, Gary E; Iatridis, James C

    2015-01-01

    Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.

  12. Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.

    Directory of Open Access Journals (Sweden)

    Svenja Illien-Jünger

    Full Text Available Intervertebral disc (IVD degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs, cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+ or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG. dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.

  13. Pulmonary emphysema induced by methylphenidate: experimental study.

    Science.gov (United States)

    Rapello, Gabriel Victor Guimarães; Antoniolli, Andréia; Pereira, Daniel Martins; Facco, Gilberto; Pêgo-Fernandes, Paulo Manuel; Pazetti, Rogério

    2015-01-01

    Methylphenidate is the most widely used drug for treating attention deficit hyperactivity disorder. However, it has important side effects, such as abdominal pain, insomnia, anorexia and loss of appetite, and also some cases of early severe emphysema after drug abuse have been reported. Our aim was to investigate the development of pulmonary emphysema in rats that were subjected to different doses of methylphenidate. Experimental study carried out at the laboratory of a public university. Eighteen male Wistar rats were divided into three groups: control (0.9% saline solution); MP 0.8 (methylphenidate, 0.8 mg/kg); MP 1.2 (methylphenidate, 1.2 mg/kg). After 90 days of daily gavage, the animals were sacrificed and lung tissue samples were prepared for analysis on the mean alveolar diameter (Lm). The Lm was greater in MP 0.8 (47.91 ± 3.13; P pulmonary emphysema.

  14. Experimental induced avian E. coli salpingitis

    DEFF Research Database (Denmark)

    Olsen, Rikke Heidemann; Thøfner, Ida; Pors, Susanne Elisabeth

    2016-01-01

    Several types of Escherichia coli have been associated with extra-intestinal infections in poultry, however, they may vary significantly in their virulence potential. The aim of the present study was to investigate the virulence of five strains of E. coli obtained from different disease......) had a distinct ability to cause disease. Results of the study shows major differences in virulence of different strains of E. coli in ascending infections; however, there was no indication of tissue-specific adaptation, since strains obtained from lesions unrelated to the reproductive system were...... fully capable of causing experimental infection. In conclusion, the study provides evidence for the clinical outcome of infection with E. coli in poultry is largely influenced by the specific strain as well as individual host factors....

  15. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

    Science.gov (United States)

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  16. Bortezomib induces neuropathic pain through protein kinase C-mediated activation of presynaptic NMDA receptors in the spinal cord.

    Science.gov (United States)

    Xie, Jing-Dun; Chen, Shao-Rui; Chen, Hong; Pan, Hui-Lin

    2017-09-01

    Chemotherapeutic drugs, including bortezomib, often cause painful peripheral neuropathy, which is a severe dose-limiting adverse effect experienced by many cancer patients. The glutamate N-methyl-d-aspartate receptors (NMDARs) at the spinal cord level are critically involved in the synaptic plasticity associated with neuropathic pain. In this study, we determined whether treatment with bortezomib, a proteasome inhibitor, affects the NMDAR activity of spinal dorsal horn neurons. Systemic treatment with bortezomib in rats did not significantly affect postsynaptic NMDAR currents elicited by puff application of NMDA directly to dorsal horn neurons. Bortezomib treatment markedly increased the baseline frequency of miniature excitatory postsynaptic currents (EPSCs), which was completely normalized by the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5). AP5 also reduced the amplitude of monosynaptic EPSCs evoked by dorsal root stimulation in bortezomib-treated, but not vehicle-treated, rats. Furthermore, inhibition of protein kinase C (PKC) with chelerythrine fully reversed the increased frequency of miniature EPSCs and the amplitude of evoked EPSCs in bortezomib-treated rats. Intrathecal injection of AP5 and chelerythrine both profoundly attenuated mechanical allodynia and hyperalgesia induced by systemic treatment with bortezomib. In addition, treatment with bortezomib induced striking membrane translocation of PKC-βII, PKC-δ, and PKC-ε in the dorsal root ganglion. Our findings indicate that bortezomib treatment potentiates nociceptive input from primary afferent nerves via PKC-mediated tonic activation of presynaptic NMDARs. Targeting presynaptic NMDARs and PKC at the spinal cord level may be an effective strategy for treating chemotherapy-induced neuropathic pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

    Science.gov (United States)

    Chen, Wenling; Marvizón, Juan Carlos G.

    2009-01-01

    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

  18. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

    Science.gov (United States)

    Chen, W; Marvizón, J C G

    2009-06-16

    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

  19. Beneficial effect of human induced pluripotent stem cell-derived neural precursors in spinal cord injury repair

    Czech Academy of Sciences Publication Activity Database

    Romanyuk, Nataliya; Amemori, Takashi; Turnovcová, Karolína; Procházka, Pavel; Onteniente, B.; Syková, Eva; Jendelová, Pavla

    2015-01-01

    Roč. 24, č. 9 (2015), s. 1781-1797 ISSN 0963-6897 R&D Projects: GA MŠk LH12024; GA ČR(CZ) GA13-00939S; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : human induced pluripotent stem cells * neural precursors * spinal cord injury Subject RIV: FH - Neurology Impact factor: 3.427, year: 2015

  20. Experimental carcinogenesis induced by incorporated plutonium

    International Nuclear Information System (INIS)

    Oghiso, Yoichi

    1999-01-01

    The carcinogenic effects of an alpha-emitter, 239 Pu, were investigated by animal experiments as focused on both pulmonary tumors after inhalation exposures to insoluble oxide aerosols and tumor spectra induced by injection of soluble citrate. The life-span study using Wistar strain rats exposed to Pu dioxide aerosols has shown differential dose-related responses of malignancies and histopathological phenotypes of lung tumors, suggesting a threshold dose around 1.0 Gy of the lung dose. As abnormality of tumor-related genes could be supposed for the background of pulmonary carcinogenesis, the mutations of p53 tumor suppressor gene were examined by PCR-SSCP analysis using DNA fragments extracted from lung tumors. While mutations were detected in 23 cases (about 28%) among 82 lung tumors, their relations to either malignancies, histological phenotypes, dose, or oncogenesis are not yet to be elucidated. The life-span study using C3H strain mice injected with Pu citrate has shown contrast dose responses between osteosarcomas and lymphoid tumors around 10 Gy of the skeletal dose, and further indicated specific tumor spectra differed from low LET radiation exposures as shown by much more frequency of B cell type leukemic lymphomas and none of myeloid leukemias. (author)

  1. Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model

    Directory of Open Access Journals (Sweden)

    Zhi-Hong Wen

    2012-08-01

    Full Text Available Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the analgesic properties of sinularin based on in vivo experiments. In the present study, we found that sinularin significantly inhibits the upregulation of proinflammatory proteins, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2 and upregulates the production of transforming growth factor-β (TGF-β in lipopolysaccharide (LPS-stimulated murine macrophage RAW 264.7 cells according to western blot analysis. We found that subcutaneous (s.c. administration of sinularin (80 mg/kg 1 h before carrageenan injection significantly inhibited carrageenan-induced nociceptive behaviors, including thermal hyperalgesia, mechanical allodynia, cold allodynia, and hindpaw weight-bearing deficits. Further, s.c. sinularin (80 mg/kg significantly inhibited carrageenan-induced microglial and astrocyte activation as well as upregulation of iNOS in the dorsal horn of the lumbar spinal cord. Moreover, s.c. sinularin (80 mg/kg inhibited carrageenan-induced tissue inflammatory responses, redness and edema of the paw, and leukocyte infiltration. The results of immunohistochemical studies indicate that s.c. sinularin (80 mg/kg could upregulate production of TGF-β1 in carrageenan-induced inflamed paw tissue. The present results demonstrate that systemic sinularin exerts analgesic effects at the behavioral and spinal levels, which are associated with both inhibition of leukocyte infiltration and upregulation of TGF-β1.Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the

  2. Theophylline-induced respiratory recovery following cervical spinal cord hemisection is augmented by serotonin 2 receptor stimulation.

    Science.gov (United States)

    Basura, Gregory J; Nantwi, Kwaku D; Goshgarian, Harry G

    2002-11-22

    Cervical spinal cord hemisection leads to a disruption of bulbospinal innervation of phrenic motoneurons resulting in paralysis of the ipsilateral hemidiaphragm. We have previously demonstrated separate therapeutic roles for theophylline, and more recently serotonin (5-HT) as modulators to phrenic nerve motor recovery; mechanisms that likely occur via adenosine A1 and 5-HT2 receptors, respectively. The present study was designed to specifically determine if concurrent stimulation of 5-HT2 receptors may enhance motor recovery induced by theophylline alone. Adult female rats (250-350 g; n=7 per group) received a left cervical (C2) hemisection that resulted in paralysis of the ipsilateral hemidiaphragm. Twenty-four hours later rats were given systemic theophylline (15 mg/kg, i.v.), resulting in burst recovery in the ipsilateral phrenic nerve. Theophylline-induced recovery was enhanced with the 5-HT2A/2C receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI; 1.0 mg/kg). DOI-evoked augmentation of theophylline-induced recovery was attenuated following subsequent injection of the 5-HT2 receptor antagonist, ketanserin (2.0 mg/kg). In a separate group, rats were pretreated with ketanserin, which did not prevent subsequent theophylline-induced respiratory recovery. However, pretreatment with ketanserin did prevent DOI-induced augmentation of the theophylline-evoked phrenic nerve burst recovery. Lastly, using immunocytochemistry and in situ hybridization, we showed for the first time a positive co-localization of adenosine A1 receptor mRNA and immunoreactivity with phrenic motoneurons of the cervical ventral horns. Taken together, the results of the present study suggest that theophylline may induce motor recovery likely at adenosine A1 receptors located at the level of the spinal cord, and the concurrent stimulation of converging 5-HT2 receptors may augment the response.

  3. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α₂-Adrenergic Receptor.

    Science.gov (United States)

    Choi, Jiho; Jeon, Changhoon; Lee, Ji Hwan; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin; Kim, Sun Kwang

    2017-10-31

    Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α₂-adrenergic receptor antagonist (idazoxan, 50 µg), but not α₁-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α₂-adrenergic receptor.

  4. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

    Directory of Open Access Journals (Sweden)

    Jiho Choi

    2017-10-01

    Full Text Available Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal on four alternate days (days 0, 2, 4, and 6 induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36 relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36 and phospholipase A2 (0.12 mg/kg, ST36 were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg, but not α1-adrenergic receptor antagonist (prazosin, 30 µg, blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor.

  5. Quadri-Pulse Theta Burst Stimulation using Ultra-High Frequency Bursts - A New Protocol to Induce Changes in Cortico-Spinal Excitability in Human Motor Cortex

    DEFF Research Database (Denmark)

    Jung, Nikolai H; Gleich, Bernhard; Gattinger, Norbert

    2016-01-01

    Patterned transcranial magnetic stimulation (TMS) such as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS) can induce changes in cortico-spinal excitability, commonly referred to as long-term potentiation (LTP)-like and long-term depression (LTD)-like effects in human motor cortex (M...... of sinusoidal TMS pulses elicited either a posterior-anterior (PA) or anterior-posterior (AP) directed current in M1. Motor evoked potentials (MEPs) were recorded before and after qTBS to probe changes in cortico-spinal excitability. PA-qTBS at 666 Hz caused a decrease in PA-MEP amplitudes, whereas AP...... in cortico-spinal excitability. Induced current direction in the brain appears to be relevant when qTBS targets I-wave periodicity, corroborating that high-fidelity spike timing mechanisms are critical for inducing bi-directional plasticity in human M1....

  6. Electrophysiological characterization of spinal neurons in different models of diabetes type 1- and type 2-induced neuropathy in rats.

    Science.gov (United States)

    Schuelert, N; Gorodetskaya, N; Just, S; Doods, H; Corradini, L

    2015-04-16

    Diabetic polyneuropathy (DPN) is a devastating complication of diabetes. The underlying pathogenesis of DPN is still elusive and an effective treatment devoid of side effects presents a challenge. There is evidence that in type-1 and -2 diabetes, metabolic and morphological changes lead to peripheral nerve damage and altered central nociceptive transmission, which may contribute to neuropathic pain symptoms. We characterized the electrophysiological response properties of spinal wide dynamic range (WDR) neurons in three diabetic models. The streptozotocin (STZ) model was used as a drug-induced model of type-1 diabetes, and the BioBreeding/Worcester (BB/Wor) and Zucker diabetic fatty (ZDF) rat models were used for genetic DPN models. Data were compared to the respective control group (BB/Wor diabetic-resistant, Zucker lean (ZL) and saline-injected Wistar rat). Response properties of WDR neurons to mechanical stimulation and spontaneous activity were assessed. We found abnormal response properties of spinal WDR neurons in all diabetic rats but not controls. Profound differences between models were observed. In BB/Wor diabetic rats evoked responses were increased, while in ZDF rats spontaneous activity was increased and in STZ rats mainly after discharges were increased. The abnormal response properties of neurons might indicate differential pathological, diabetes-induced, changes in spinal neuronal transmission. This study shows for the first time that specific electrophysiological response properties are characteristic for certain models of DPN and that these might reflect the diverse and complex symptomatology of DPN in the clinic. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Neuroimmune processes associated with Wallerian degeneration support neurotrophin-3-induced axonal sprouting in the injured spinal cord.

    Science.gov (United States)

    Chen, Qin; Shine, H David

    2013-10-01

    Lesions of the spinal cord cause two distinctive types of neuroimmune responses, a response at the lesion site that leads to additional tissue destruction and a more subtle response, termed Wallerian degeneration (WD), that occurs distal to the lesion site. We have evidence that the neuroimmune response associated with WD may support tissue repair. Previously, we found that overexpression of neurotrophin-3 (NT-3) induced axonal growth in the spinal cord after a unilateral corticospinal tract (CST) lesion, but only if the immune system was intact and activated. We reasoned that a neuroimmune response associated with WD was involved in this neuroplasticity. To test this, we compared NT-3-induced axonal sprouting in athymic nude rats that lack functional T cells with rats with functional T cells and in nude rats grafted with CD4(+) T cells or CD8(+) T cells. There was no sprouting in nude rats and in nude rats grafted with CD8(+) T cells. However, nude rats grafted with CD4(+) T cells mounted a sprouting response. To determine which CD4(+) subtype, type 1 T helper (Th1) or type 2 T helper (Th2) cells, was responsible, we grafted Th1 and Th2 cells into nude rats and tested whether they would support sprouting. Axonal sprouting was greater in rats grafted with Th2 cells, demonstrating that the Th2 subtype was responsible for supporting axonal sprouting. These data suggest that WD activates Th2 cells that, along with the direct effects of NT-3 on CST axons, act to support axonal sprouting in the lesioned spinal cord. Copyright © 2013 Wiley Periodicals, Inc.

  8. Assessment of magnetic field interactions and radiofrequency‐radiation‐induced heating of metallic spinal implants in 7 T field

    Science.gov (United States)

    Tsukimura, Itsuko; Sasaki, Makoto; Endo, Hirooki; Yamabe, Daisuke; Oikawa, Ryosuke; Doita, Minoru

    2017-01-01

    ABSTRACT The safety of metallic spinal implants in magnetic resonance imaging (MRI) performed using ultrahigh fields has not been established. Hence, we examined whether the displacement forces caused by a static magnetic field and the heating induced by radiofrequency radiation are substantial for spinal implants in a 7 T field. We investigated spinal rods of various lengths and materials, a screw, and a cross‐linking bridge in accordance with the American Society for Testing and Materials guidelines. The displacement forces of the metallic implants in static 7 T and 3 T static magnetic fields were measured and compared. The temperature changes of the implants during 15‐min‐long fast spin‐echo and balanced gradient‐echo image acquisition sequences were measured in the 7 T field. The deflection angles of the metallic spinal materials in the 7 T field were 5.0–21.0° [median: 6.7°], significantly larger than those in the 3 T field (1.0–6.3° [2.2°]). Among the metallic rods, the cobalt–chrome rods had significantly larger deflection angles (17.8–21.0° [19.8°]) than the pure titanium and titanium alloy rods (5.0–7.7° [6.2°]). The temperature changes of the implants, including the cross‐linked rods, were 0.7–1.0°C [0.8°C] and 0.6–1.0°C [0.7°C] during the fast spin‐echo and balanced gradient‐echo sequences, respectively; these changes were slightly larger than those of the controls (0.4–1.1°C [0.5°C] and 0.3–0.9°C [0.6°C], respectively). All of the metallic spinal implants exhibited small displacement forces and minimal heating, indicating that MRI examinations using 7 T fields may be performed safely on patients with these implants. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1831–1837, 2017. PMID:27769107

  9. Assessment of magnetic field interactions and radiofrequency-radiation-induced heating of metallic spinal implants in 7 T field.

    Science.gov (United States)

    Tsukimura, Itsuko; Murakami, Hideki; Sasaki, Makoto; Endo, Hirooki; Yamabe, Daisuke; Oikawa, Ryosuke; Doita, Minoru

    2017-08-01

    The safety of metallic spinal implants in magnetic resonance imaging (MRI) performed using ultrahigh fields has not been established. Hence, we examined whether the displacement forces caused by a static magnetic field and the heating induced by radiofrequency radiation are substantial for spinal implants in a 7 T field. We investigated spinal rods of various lengths and materials, a screw, and a cross-linking bridge in accordance with the American Society for Testing and Materials guidelines. The displacement forces of the metallic implants in static 7 T and 3 T static magnetic fields were measured and compared. The temperature changes of the implants during 15-min-long fast spin-echo and balanced gradient-echo image acquisition sequences were measured in the 7 T field. The deflection angles of the metallic spinal materials in the 7 T field were 5.0-21.0° [median: 6.7°], significantly larger than those in the 3 T field (1.0-6.3° [2.2°]). Among the metallic rods, the cobalt-chrome rods had significantly larger deflection angles (17.8-21.0° [19.8°]) than the pure titanium and titanium alloy rods (5.0-7.7° [6.2°]). The temperature changes of the implants, including the cross-linked rods, were 0.7-1.0°C [0.8°C] and 0.6-1.0°C [0.7°C] during the fast spin-echo and balanced gradient-echo sequences, respectively; these changes were slightly larger than those of the controls (0.4-1.1°C [0.5°C] and 0.3-0.9°C [0.6°C], respectively). All of the metallic spinal implants exhibited small displacement forces and minimal heating, indicating that MRI examinations using 7 T fields may be performed safely on patients with these implants. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1831-1837, 2017. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

  10. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    ; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...

  11. Generation of Oligodendrogenic Spinal Neural Progenitor Cells From Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Khazaei, Mohamad; Ahuja, Christopher S; Fehlings, Michael G

    2017-08-14

    This unit describes protocols for the efficient generation of oligodendrogenic neural progenitor cells (o-NPCs) from human induced pluripotent stem cells (hiPSCs). Specifically, detailed methods are provided for the maintenance and differentiation of hiPSCs, human induced pluripotent stem cell-derived neural progenitor cells (hiPS-NPCs), and human induced pluripotent stem cell-oligodendrogenic neural progenitor cells (hiPSC-o-NPCs) with the final products being suitable for in vitro experimentation or in vivo transplantation. Throughout, cell exposure to growth factors and patterning morphogens has been optimized for both concentration and timing, based on the literature and empirical experience, resulting in a robust and highly efficient protocol. Using this derivation procedure, it is possible to obtain millions of oligodendrogenic-NPCs within 40 days of initial cell plating which is substantially shorter than other protocols for similar cell types. This protocol has also been optimized to use translationally relevant human iPSCs as the parent cell line. The resultant cells have been extensively characterized both in vitro and in vivo and express key markers of an oligodendrogenic lineage. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley and Sons, Inc.

  12. Does Spinal Block Through Tattooed Skin Cause Histological Changes in Nervous Tissue and Meninges?: An Experimental Model in Rabbits.

    Science.gov (United States)

    Ferraz, Isabela Leite; Barros, Guilherme Antônio Moreira de; Ferreira Neto, Patrícia Gomes; Solanki, Daneshivari; Marques, Mariângela Alencar; Machado, Vânia Maria de Vasconcelos; Cabral, Lucas Wynne; Lima, Rodrigo Moreira E; Vianna, Pedro Thadeu Galvão; Navarro, Lais Helena Camacho; Ganen, Eliana Marisa

    2015-01-01

    Although there is no documented evidence that tattoo pigments can cause neurological complications, the implications of performing neuraxial anesthesia through tattooed skin are unknown. In this study, we aimed to assess whether spinal puncture performed through tattooed skin of rabbits determines changes over the spinal cord and meninges. In addition, we sought to evaluate the presence of ink fragments entrapped in spinal needles. Thirty-six young male adult rabbits, each weighing between 3400 and 3900 g and having a spine length between 38.5 and 39 cm, were divided by lot into 3 groups as follows: GI, spinal puncture through tattooed skin; GII, spinal puncture through tattooed skin and saline injection; and GIII, spinal puncture through skin free of tattoo and saline injection. After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance with a 22-gauge 2½ Quincke needle. Animals in GII and GIII received 5 μL/cm of spinal length (0.2 mL) of saline intrathecally. In GI, the needle tip was placed into the yellow ligament, and no solution was injected into the intrathecal space; after tattooed skin puncture, 1 mL of saline was injected through the needle over a histological slide to prepare a smear that was dyed by the Giemsa method to enable tissue identification if present. All animals remained in captivity for 21 days under medical observation and were killed by decapitation. The lumbosacral spinal cord portion was removed for histological analysis using hematoxylin-eosin stain. None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group (GIII) showed signs of injuries to meninges. In GII, however, 4 animals presented with signs of meningeal injury. The main histological changes observed were focal areas of perivascular lymphoplasmacyte infiltration in the pia mater and arachnoid. There was no

  13. A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord

    DEFF Research Database (Denmark)

    Hoeber, Jan; Konig, Niclas; Trolle, Carl

    2017-01-01

    Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly......MIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of Meso...... their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular “bridges” in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient...

  14. Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition

    Directory of Open Access Journals (Sweden)

    Schlichter Rémy

    2008-05-01

    Full Text Available Abstract Background Recent evidence suggests that oxytocin (OT, secreted in the superficial spinal cord dorsal horn by descending axons of paraventricular hypothalamic nucleus (PVN neurons, produces antinociception and analgesia. The spinal mechanism of OT is, however, still unclear and requires further investigation. We have used patch clamp recording of lamina II neurons in spinal cord slices and immunocytochemistry in order to identify PVN-activated neurons in the superficial layers of the spinal cord and attempted to determine how this neuronal population may lead to OT-mediated antinociception. Results We show that OT released during PVN stimulation specifically activates a subpopulation of lamina II glutamatergic interneurons which are localized in the most superficial layers of the dorsal horn of the spinal cord (lamina I-II. This OT-specific stimulation of glutamatergic neurons allows the recruitment of all GABAergic interneurons in lamina II which produces a generalized elevation of local inhibition, a phenomenon which might explain the reduction of incoming Aδ and C primary afferent-mediated sensory messages. Conclusion Our results obtained in lamina II of the spinal cord provide the first clear evidence of a specific local neuronal network that is activated by OT release to induce antinociception. This OT-specific pathway might represent a novel and interesting therapeutic target for the management of neuropathic and inflammatory pain.

  15. Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

    Directory of Open Access Journals (Sweden)

    Talbot Sébastien

    2012-01-01

    Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p

  16. Patterns of x-radiation-induced Schwann cell development in spinal cords of immature rats

    International Nuclear Information System (INIS)

    Gilmore, S.A.; Heard, J.K.; Leiting, J.E.

    1983-01-01

    Schwann cells, Schwann cell myelin, and connective tissue components develop in the spinal cord of the immature rat following exposure to x-rays. For the purposes of this paper, these intraspinal peripheral nervous tissue constituents are referred to as IPNT. A series of investigations are in progress to elucidate factors related to the development of IPNT, and the present study is a light microscopic evaluation of the relationship between the amount of radiation administered (1,000-3,000R) to the lumbosacral spinal cord in 3-day-old rats and the incidence and distribution of IPNT at intervals up to 60 days postirradiation (P-I). The results showed that IPNT was present in only 33% of the rats exposed to 1,000R, whereas its presence was observed in 86% or more of those in the 2,000-, 2,500-, and 3,000R groups. The distribution of IPNT was quite limited in the 1,000R group, where it was restricted to the spinal cord-dorsal root junction and was found in only a few sections within the irradiated area. The distribution was more widespread with increasing amounts of radiation, and IPNT occupied substantial portions of the dorsal funiculi and extended into the dorsal gray matter in the 3,000R group. In all aR mals developing IPNT in the groups receiving 2,000R or more, the IPNT was present in essentially all sections from the irradiated area. Further studies will compare in detail spinal cords exposed to 1,000R in which IPNT is an infrequent, limited occurrence with those exposed to higher doses where IPNT occurs in a more widespread fashion in essentially all animals

  17. Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

    OpenAIRE

    Streeter, K.A.; Baker-Herman, T.L.

    2014-01-01

    Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30 min) block axon conduction in bulbospinal axons...

  18. Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

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    Jens O Watzlawik

    Full Text Available Neonatal white matter injury (nWMI is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2-3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life

  19. Cholescintigraphy in experimentally induced obstructive and parenchymatous jaundice

    International Nuclear Information System (INIS)

    Baehre, M.; Biersack, H.J.; Hofmann, S.; Winkler, C.

    1979-01-01

    Animal studies have been performed in 30 dogs in order to obtain information concerning typical patterns of cholescintigraphy in acute obstructive jaundice. In 14 the choledochus was ligated and in 16 galactosamine-hepatitis was induced as an experimental model for parenchymatous jaundice. The results suggest a number of diagnostic criteria in obstructive disease. (Auth.)

  20. Surfactant induced flows in thin liquid films : an experimental study

    NARCIS (Netherlands)

    Sinz, D.K.N.

    2012-01-01

    The topic of the experimental work summarized in my thesis is the flow in thin liquid films induced by non-uniformly distributed surfactants. The flow dynamics as a consequence of the deposition of a droplet of an insoluble surfactant onto a thin liquid film covering a solid substrate where

  1. Experimentally Induced Learned Helplessness: How Far Does it Generalize?

    Science.gov (United States)

    Tuffin, Keith; And Others

    1985-01-01

    Assessed whether experimentally induced learned helplessness on a cognitive training task generalized to a situationally dissimilar social interaction test task. No significant differences were observed between groups on the subsequent test task, showing that helplessness failed to generalize. (Author/ABB)

  2. Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

    Science.gov (United States)

    Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

    2014-01-01

    Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

  3. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0A degrees......Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper...

  4. Alterations in the neural circuits from peripheral afferents to the spinal cord: possible implications for diabetic polyneuropathy in streptozotocin-induced type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Zhen-Zhen eKou

    2014-01-01

    Full Text Available Diabetic polyneuropathy (DPN presents as a wide variety of sensorimotor symptoms and affects approximately 50% of diabetic patients. Changes in the neural circuits may occur in the early stages in diabetes and are implicated in the development of DPN. Therefore, we aimed to detect changes in the expression of isolectin B4 (IB4, the marker for nonpeptidergic unmyelinated fibers and their cell bodies and calcitonin gene-related peptide (CGRP, the marker for peptidergic fibers and their cell bodies in the dorsal root ganglion (DRG and spinal cord of streptozotocin (STZ-induced type 1 diabetic rats showing alterations in sensory and motor function. We also used cholera toxin B subunit (CTB to show the morphological changes of the myelinated fibers and motor neurons. STZ-induced diabetic rats exhibited hyperglycemia, decreased body weight gain, mechanical allodynia and impaired locomotor activity. In the DRG and spinal dorsal horn, IB4-labeled structures decreased, but both CGRP immunostaining and CTB labeling increased from day 14 to day 28 in diabetic rats. In spinal ventral horn, CTB labeling decreased in motor neurons in diabetic rats. Treatment with intrathecal injection of insulin at the early stages of DPN could alleviate mechanical allodynia and impaired locomotor activity in diabetic rats. The results suggest that the alterations of the neural circuits between spinal nerve and spinal cord via the DRG and ventral root might be involved in DPN.

  5. Spinal cord homogenates from SOD1 familial amyotrophic lateral sclerosis induce SOD1 aggregation in living cells.

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    Edward Pokrishevsky

    Full Text Available Mutant Cu/Zn superoxide dismutase (SOD1 can confer its misfolding on wild-type SOD1 in living cells; the propagation of misfolding can also be transmitted between cells in vitro. Recent studies identified fluorescently-tagged SOD1G85R as a promiscuous substrate that is highly prone to aggregate by a variety of templates, in vitro and in vivo. Here, we utilized several SOD1-GFP reporter proteins with G37R, G85R, or G93A mutations in SOD1. We observed that human spinal cord homogenates prepared from SOD1 familial ALS (FALS can induce significantly more intracellular reporter protein aggregation than spinal cord homogenates from sporadic ALS, Alzheimer's disease, multiple system atrophy or healthy control individuals. We also determined that the induction of reporter protein aggregation by SOD1-FALS tissue homogenates can be attenuated by incubating the cells with the SOD1 misfolding-specific antibody 3H1, or the small molecule 5-fluorouridine. Our study further implicates SOD1 as the seeding particle responsible for the spread of SOD1-FALS neurodegeneration from its initial onset site(s, and demonstrates two potential therapeutic strategies for SOD1-mediated disease. This work also comprises a medium-throughput cell-based platform of screening potential therapeutics to attenuate propagated aggregation of SOD1.

  6. Structural and molecular alterations of primary afferent fibres in the spinal dorsal horn in vincristine-induced neuropathy in rat.

    Science.gov (United States)

    Thibault, Karine; Rivals, Isabelle; M'Dahoma, Saïd; Dubacq, Sophie; Pezet, Sophie; Calvino, Bernard

    2013-11-01

    Vincristine is one of the most common anti-cancer drug therapies administered for the treatment of many types of cancer. Its dose-limiting side effect is the emergence of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. This study sought to understand the mechanisms underlying the development of neuropathic pain by vincristine-induced neurotoxicity. We focused on signs of functional changes and revealed that deep layers of the spinal cord (III-IV) experience increased neuronal activity both in the absence of peripheral stimulation and, as a result of tactile mechanical stimulations. These laminae and superficial laminae I-II were also subject to structural changes as evidenced by an increase in immunoreactivity of Piccolo, a marker of active presynaptic elements. Further investigations performed, using DNA microarray technology, describe a large number of genes differentially expressed in dorsal root ganglions and in the spinal dorsal horn after vincristine treatment. Our study describes an important list of genes differentially regulated by vincristine treatment that will be useful for future studies and brings forward evidence for molecular and anatomical modifications of large diameter sensory neurons terminating in deep dorsal horn laminae, which could participate in the development of tactile allodynia.

  7. Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats

    Czech Academy of Sciences Publication Activity Database

    Amemori, Takashi; Růžička, Jiří; Romanyuk, Nataliya; Jhanwar-Uniyal, M.; Syková, Eva; Jendelová, Pavla

    2015-01-01

    Roč. 6, Dec (2015), s. 257 ISSN 1757-6512 R&D Projects: GA MŠk(CZ) LH12024 Institutional support: RVO:68378041 Keywords : spinal cord injury * human induced pluripotent stem cells * cell therapy * cell application route Subject RIV: FH - Neurology Impact factor: 4.504, year: 2015

  8. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury: Effect of duty cycle

    NARCIS (Netherlands)

    MSc Karin J.A. Legemate; MD Christof A. J. Smit; MSc Anja de Koning; PhD Sonja de Groot; MD, PhD Janneke M. Stolwijk-Swuste; PhD Thomas W.H. Janssen

    2013-01-01

    Abstract—Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation

  9. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury : Effect of duty cycle

    NARCIS (Netherlands)

    Smit, Christof A. J.; Legemate, Karin J. A.; de Koning, Anja; de Groot, Sonja; Stolwijk-Swuste, Janneke M.; Janssen, Thomas W. J.

    2013-01-01

    Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation on

  10. Protective effect of nicotinamide adenine dinucleotide (NAD+) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis.

    Science.gov (United States)

    Xie, Lei; Wang, Zhenfei; Li, Changwei; Yang, Kai; Liang, Yu

    2017-02-01

    As previous studies demonstrate that oxidative stress and apoptosis play crucial roles in ischemic pathogenesis and nicotinamide adenine dinucleotide (NAD + ) treatment attenuates oxidative stress-induced cell death among primary neurons and astrocytes as well as significantly reduce cerebral ischemic injury in rats. We used a spinal cord ischemia injury (SCII) model in rats to verify our hypothesis that NAD + could ameliorate oxidative stress-induced neuronal apoptosis. Adult male rats were subjected to transient spinal cord ischemia for 60min, and different doses of NAD + were administered intraperitoneally immediately after the start of reperfusion. Neurological function was determined by Basso, Beattie, Bresnahan (BBB) scores. The oxidative stress level was assessed by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The degree of apoptosis was analyzed by deoxyuridinetriphosphate nick-end labeling (TUNEL) staining and protein levels of cleaved caspase-3 and AIF (apoptosis inducing factor). The results showed that NAD + at 50 or 100mg/kg significantly decreased the oxidative stress level and neuronal apoptosis in the spinal cord of ischemia-reperfusion rats compared with saline, as accompanied with the decreased oxidative stress, NAD + administration significantly restrained the neuronal apoptosis after ischemia injury while improved the neurological and motor function. These findings suggested that NAD + might protect against spinal cord ischemia-reperfusion via reducing oxidative stress-induced neuronal apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Gluteal blood flow and oxygenation during electrical stimulation-induced muscle activation versus pressure relief movements in wheelchair users with a spinal cord injury

    NARCIS (Netherlands)

    Smit, C. A. J.; Zwinkels, M.; van Dijk, T.; de Groot, S.; Stolwijk-Swuste, J. M.; Janssen, T. W. J.

    Background: Prolonged high ischial tuberosities pressure (IT pressure), decreased regional blood flow (BF) and oxygenation (%SO2) are risk factors for developing pressure ulcers (PUs) in patients with spinal cord injury (SCI). Electrical stimulation (ES)-induced gluteal and hamstring muscle

  12. Allopregnanolone suppresses diabetes-induced neuropathic pain and motor deficit through inhibition of GABAA receptor down-regulation in the spinal cord of diabetic rats

    Directory of Open Access Journals (Sweden)

    Samira Afrazi

    2014-05-01

    Full Text Available Objective(s:Painful diabetic neuropathy is associated with hyperexcitability and hyperactivity of spinal cord neurons. However, its underlying pathophysiological mechanisms have not been fully clarified. Induction of excitatory/inhibitory neurotransmission imbalance at the spinal cord seems to account for the abnormal neuronal activity in diabetes. Protective properties of neurosteroids have been demonstrated in numerous cellular and animal models of neurodegeneration. Materials and Methods: Here, the protective effects of allopregnanolone, a neurosteroid were investigated in an in vivo model of diabetic neuropathy. The tail-flick test was used to assess the nociceptive threshold. Diabetes was induced by injection of 50 mg/kg (IP streptozotocin. Seven weeks after the induction of diabetes, the dorsal half of the lumbar spinal cord was assayed for the expression of γ2 subunit of GABAA receptor using semiquantitative RT-PCR. Results: The data shows that allopregnanolone (5 and 20 mg/kg markedly ameliorated diabetes-induced thermal hyperalgesia and motor deficit. The weights of diabetic rats that received 5 and 20 mg/kg allopregnanolone did not significantly reduce during the time course of study. Furthermore, this neurosteroid could inhibit GABAA receptor down-regulation induced by diabetes in the rat spinal cord. Conclusion: The data revealed that allopregnanolone has preventive effects against hyperglycemic-induced neuropathic pain and motor deficit which are related to the inhibition of GABAA receptor down-regulation.

  13. 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.

  14. Brown-Séquard syndrome following intracranial subarachnoid hemorrhage-induced spinal arachnoid cyst

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    Yew-Weng Fong

    2017-12-01

    Full Text Available Objective: Arachnoid cyst associated with spinal arachnoiditis following subarachnoid hemorrhage (SAH is a rare complication. Correctly diagnosing this condition and providing an effective treatment are extremely important. Case report: A 60-year-old women had a history of SAH due to an intradural vertebral artery dissecting aneurysm post-coil embolization, without neurologic deficits on discharge from our institution. She experienced left hemiparesis with muscle power graded at 4/5 eight months later due to a right middle cerebral artery territory infarct. Nine months after stroke rehabilitation, there was a progression of left-side weakness and right-side numbness down below the nipple level. On neurological examination, there were right sensory deficits below T6, and left hemiparesis with muscle power of the left upper extremity graded at 4/5 and that of the left lower extremity graded at 3/5. Deep tendon reflex was symmetrically increased at the bilateral lower extremities. Spinal magnetic resonance imaging (MRI revealed a cervicothoracic multiseptated arachnoid cyst with a major compression effect at T6. Eight months after T5–6 hemilaminectomy and fenestration of the cyst wall, the neurologic deficits had not improved. The patient then underwent a cysto-peritoneal shunt. A follow-up MRI documented a complete resolution of the arachnoid cyst. The patient's Brown-Séquard syndrome showed clinical improvement. Conclusion: Prompt investigation revealed a spinal arachnoid cyst in a patient with a history of intracranial SAH presenting with unexplained progressive Brown-Séquard syndrome. For cases of multiseptated and long arachnoid cyst, as in our patient, a shunting procedure is a better choice than fenestration alone.

  15. Transcutaneous spinal direct current stimulation induces lasting fatigue resistance and enhances explosive vertical jump performance

    Science.gov (United States)

    Tate, Rothwelle J.; Conway, Bernard A.

    2017-01-01

    Transcutaneous spinal direct current stimulation (tsDCS) is a non-invasive neuromodulatory intervention that has been shown to modify excitability in spinal and supraspinal circuits in animals and humans. Our objective in this study was to explore the functional neuromodulatory potential of tsDCS by examining its immediate and lasting effects over the repeated performance of a whole body maximal exercise in healthy volunteers. Using a double-blind, randomized, crossover, sham-controlled design we investigated the effects of 15 min of anodal tsDCS on repeated vertical countermovement jump (VCJ) performance at 0, 20, 60, and 180 minutes post-stimulation. Measurements of peak and take-off velocity, vertical displacement, peak power and work done during countermovement and push-off VCJ phases were derived from changes in vertical ground reaction force (12 performance parameters) in 12 healthy participants. The magnitude and direction of change in VCJ performance from pre- to post-stimulation differed significantly between sham and active tsDCS for 7 of the 12 VCJ performance measures (P 0.05). Our original findings demonstrate that one single session of anodal tsDCS in healthy subjects can prevent fatigue and maintain or enhance different aspects of whole body explosive motor power over repeated sets of VCJs performed over a period of three hours. The observed effects are discussed in relation to alterations in central fatigue mechanisms, muscle contraction mode during jump execution and changes in spinal cord excitability. These findings have important implications for power endurance sport performance and for neuromotor rehabilitation. PMID:28379980

  16. Transcutaneous spinal direct current stimulation induces lasting fatigue resistance and enhances explosive vertical jump performance.

    Directory of Open Access Journals (Sweden)

    Helen R Berry

    Full Text Available Transcutaneous spinal direct current stimulation (tsDCS is a non-invasive neuromodulatory intervention that has been shown to modify excitability in spinal and supraspinal circuits in animals and humans. Our objective in this study was to explore the functional neuromodulatory potential of tsDCS by examining its immediate and lasting effects over the repeated performance of a whole body maximal exercise in healthy volunteers. Using a double-blind, randomized, crossover, sham-controlled design we investigated the effects of 15 min of anodal tsDCS on repeated vertical countermovement jump (VCJ performance at 0, 20, 60, and 180 minutes post-stimulation. Measurements of peak and take-off velocity, vertical displacement, peak power and work done during countermovement and push-off VCJ phases were derived from changes in vertical ground reaction force (12 performance parameters in 12 healthy participants. The magnitude and direction of change in VCJ performance from pre- to post-stimulation differed significantly between sham and active tsDCS for 7 of the 12 VCJ performance measures (P 0.05. Our original findings demonstrate that one single session of anodal tsDCS in healthy subjects can prevent fatigue and maintain or enhance different aspects of whole body explosive motor power over repeated sets of VCJs performed over a period of three hours. The observed effects are discussed in relation to alterations in central fatigue mechanisms, muscle contraction mode during jump execution and changes in spinal cord excitability. These findings have important implications for power endurance sport performance and for neuromotor rehabilitation.

  17. Prolonged drug-induced hypothermia in experimental stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Jørgensen, Henrik Stig; Reith, Jakob

    2007-01-01

    In experimental and human stroke, hypothermia is strongly related to a favorable outcome. Previous attempts to manipulate the core temperature in focal cerebral ischemia have been based on mechanical cooling. The purpose of the study is to establish a model for long-term drug-induced hypothermia...... in focal ischemia by pharmacological alteration of the central thermoregulatory set-point. We tested the hypothesis that the dopaminergic agonist Talipexole, which induces hypothermia, reduces infarct size. Body temperature was monitored by a radio-pill-implant. Rats had reversible occlusion of the middle...... that the core body temperature was reduced by 1.7 degrees C for 24 hours after MCAO in rats treated with Talipexole. This treatment induced a significant reduction of infarct volume at 7 days after focal ischemia by 47%. We suggest that the reduction in infarct volume is related to drug-induced hypothermia...

  18. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

    Science.gov (United States)

    Schwab, Andrew J; Ebert, Allison D

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

  19. The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong-Soo; Kim, Ji Hyun; Yoon, Hye Joo; Ahn, Ho-Soo; Lee, Sun Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2016-06-21

    Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.

  20. Functional recovery in rat spinal cord injury induced by hyperbaric oxygen preconditioning.

    Science.gov (United States)

    Lu, Pei-Gang; Hu, Sheng-Li; Hu, Rong; Wu, Nan; Chen, Zhi; Meng, Hui; Lin, Jiang-Kai; Feng, Hua

    2012-12-01

    It is a common belief that neurosurgical interventions can cause inevitable damage resulting from the procedure itself in surgery especially for intramedullary spinal cord tumors. The present study was designed to examine if hyperbaric oxygen preconditioning (HBO-PC) was neuroprotective against surgical injuries using a rat model of spinal cord injury (SCI). Sprague-Dawley rats were randomly divided into three groups: HBO-PC group, hypobaric hypoxic preconditioning (HH-PC) control group, and normobaric control group. All groups were subjected to SCI by weight drop device. Rats from each group were examined for neurological behavior and electrophysiological function. Tissue sections were analyzed by using immunohistochemistry, TdT-mediated dUTP-biotin nick end labeling, and axonal tract tracing. Significant neurological deficits were observed after SCI and HBO-PC and HH-PC improved neurological deficits 1 week post-injury. The latencies of motor-evoked potential and somatosensory-evoked potential were significantly delayed after SCI, which was attenuated by HBO-PC and HH-PC. Compared with normobaric control group, pretreatment with HBO and hypobaric hypoxia significantly reduced the number of TdT-mediated dUTP-biotin nick end labeling-positive cells, and increased nestin-positive cells. HBO-PC and HH-PC enhanced axonal growth after SCI. In conclusion, preconditioning with HBO and hypobaric hypoxia can facilitate functional recovery and suppress cell apoptosis after SCI and may prove to be a useful preventive strategy to neurosurgical SCI.

  1. Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.

    Science.gov (United States)

    Reznikov, A G; Sinitsyn, P V; Tarasenko, L V; Polyakova, L I

    2003-10-01

    An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.

  2. Experimental identification of pedestrian-induced lateral forces on footbridges

    DEFF Research Database (Denmark)

    Ingólfsson, Einar Thór; Georgakis, Christos; Ricciardelli, Francesco

    2011-01-01

    combinations of frequencies (0.33-1.07 Hz) and amplitudes 4.5-48 mm). The experimental campaign involved seventy-one male and female human adults and covered approximately 55 km of walking distributed between 4954 individual tests. When walking on a laterally moving surface, motion-induced forces develop also......This paper presents a comprehensive experimental analysis of lateral forces generated by single pedestrians during continuous walking on a treadmill. Two different conditions are investigated; initially the treadmill is fixed and then it is laterally driven in a sinusoidal motion at varying...... and inter-subject variability. It is shown that the motion induced portion of the pedestrian load (on average) inputs energy into the structure in the frequency range (normalised by the average walking frequency) between approximately 0.6 and 1.2. Furthermore, it is shown that the load component in phase...

  3. Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

    Science.gov (United States)

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

  4. Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

    Science.gov (United States)

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

  5. Transformation induced plasticity in maraging steel: an experimental study

    International Nuclear Information System (INIS)

    Nagayama, K.; Kitajima, Y.; Kigami, S.; Tanaka, K.

    2000-01-01

    The deformation behavior of a maraging TRIP (transformation induced plasticity) steel (MAVAL X12) is studied experimentally under a constant load. The existence of the back stress in the axial direction is directly proved by investigating the dilatation curves. Martensite-start lines are given under tensile, compressive and shear stresses. The evolution of TRIP strain and the maximum TRIP strain are determined. The alloy response during isothermal tensile test is explained in terms of influences both by the composite and transformation. (orig.)

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

    Science.gov (United States)

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

    2012-01-01

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

  7. Hemodynamic parameters and neurogenic pulmonary edema following spinal cord injury: an experimental model Parâmetros hemodinâmicos e edema pulmonar neurogênico após traumatismo raquimedular: modelo experimental

    Directory of Open Access Journals (Sweden)

    Manoel Baldoino Leal Filho

    2005-12-01

    Full Text Available Neurogenic pulmonary edema is a serious and always life-threatening complication following several lesions of the central nervous system. We report an experiment with 58 Wistar-Hanover adult male rats. Two groups were formed: control (n=4 and experimental (n=54. The experimental group sustained acute midthoracic spinal cord injury by Fogarty’s balloon-compression technique containing 20µL of saline for 5, 15, 30 or 60 seconds. The rats were anesthetized by intraperitoneal (i.p. sodium pentobarbital (s.p. 60 mg/Kg. The quantitative neurological outcome was presented at 4, 24 and 48 hours from compression to characterize the injury graduation in different groups. Poor outcome occurred with 60 seconds of compression. Six animals died suddenly with pulmonary edema. Using the procedure to investigate the pulmonary edema during 60 seconds of compression, followed by decompression and time-course of 60 seconds, 20 rats were randomly asigned to one of the following groups: control (1, n=4, anesthetized by i.p. s.p., 60 mg/Kg but without compression and experimental (2, n=7, anesthetized by i.p. xylazine 10 mg/Kg and ketamine 75 mg/Kg and (3, n=9, anesthetized by i.p. s.p., 60 mg/Kg. The pulmonary index (100 x wet lung weight / body weight was 0.395 ± 0.018 in control group, rose to 0.499 ± 0.060 in group 2, and was 0.639 ± 0.14 in group 3. Histologic examination of the spinal cord showed parenchymal ruptures and acute hemorrhage. Comparison of the pulmonary index with morphometric evaluation of edema fluid-filled alveoli by light microscopy showed that relevant intra-alveolar edema occurred only for index values above 0.55. The results suggest that the pulmonary edema induced by spinal compression is of neurogenic nature and that the type of anesthesia used might be important for the genesis of lung edema.Edema pulmonar neurogênico é complicação séria e aumenta o risco de vida em pacientes com várias lesões do sistema nervoso central

  8. Histopathological and Follicular Atresia Assessment of Rat’s Ovarian Tissue Following Experimental Chronic Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Sam Zarbakhsh

    2017-06-01

    Full Text Available Background One of the important side effects in spinal cord injuries in both genders is sexual dysfunction. This study aimed at investigating histopathological changes of ovaries in the chronic phase after spinal cord injury. Methods Animals (adult female rats were divided to the following groups, Control (Co, Sham (Sh, and Spinal Cord Injury (SCI; each group contained 18 rats. The spinal cord of SCI animals was transected by the bilateral laminectomy method on level T9, while the rats of the sham group were incised in the same location without any spinal cord injury. Animals were sacrified at 7th, 14th and 21st day postsurgical intervention, then the body weight, and the weight and volume of ovaries were measured. The slices were stained by hematoxylin and eosin and periodic acid Schiff methods. The histomorphometric changes of the diameter of the follicle and ovum, and the thickness of granulosa layer were measured in different kinds of follicles including, Unilaminar Primary Follicle (UPF, Multilaminar Primary Follicle (MPF, Secondary Follicle (SF, and Tertiary Follicle (TF. Results The results showed that the animal weights were decreased in three SCI groups (P = 0.018. In the SCI groups, the diameter of follicle and ovum and the thickness of granulosa layer were significantly decreased in different kinds of follicles (P = 0.012. Also the thickness of zona pellucida and theca interna were significantly decreased in UPF, SF, and TF in the SCI groups on 14th and 21st day (P = 0.024. The histopathologic examination revealed widespread ovarian follicle atresia in the SCI groups on the 14th and 21st day, including numerous cell debris and inflammatory cells in the antrum atretic follicles. The ovarian stroma showed edema, fibrosis, hypercellularity, and vasodilation in the SCI group, compared to the sham or control groups. Conclusions The histopathlogic data indicated that after spinal cord injury many histologic parameter changes occurred and

  9. Glucocorticoid-induced diabetes in patients with metastatic spinal cord compression

    DEFF Research Database (Denmark)

    Schultz, Helga; Engelholm, Svend Aage; Harder, Eva

    2018-01-01

    in a prospective, observational cohort study. The primary endpoint was development of DM defined by two or more plasma glucose values ≥11.1 mmol/L. Plasma glucose was monitored on a daily basis for 12 days during radiotherapy. RESULTS: Fifty-six of the patients (43%; 95% CI 35-52%) were diagnosed with DM based...... spinal cord compression (MSCC) in patients referred to radiotherapy. Furthermore, to describe the time course of development of DM. SUBJECTS AND METHODS: 140 patients were recruited (131 were included in the analysis) with MSCC receiving high-dose glucocorticoid ≥100 mg prednisolone per day were included...... on plasma glucose measurements during the study period. Sixteen patients, 12% (95% CI 6-18%), were treated with insulin. At multivariate analysis, only high baseline HbA1c predicted the development of insulin-treated DM. An HbA1c-value value of 96...

  10. Pathogenesis of spinal cord involvement induced by lower cervical instability in rheumatoid spondylitis

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Hironobu; Kuwabara, Shigeru; Fukuda, Kenji; Kuroki, Tatsuji; Tajima, Naoya (Miyazaki Medical Coll., Kiyotake (Japan))

    1994-07-01

    To examine prognostic factors in rheumatoid arthritis (RA), plain radiography findings and magnetic resonance imaging (MRI) findings were compared with histopathological findings in 129 RA patients who had local or neurologic symptoms due to the cervical spine. All patients underwent plain radiography, and subdislocation more than 2 mm towards the anterior and posterior directions on plain radiographs was defined as instability. In predicting induction of instability of the inferior cervical spine and risk for spinal compression, erosion of the vertebral rim, as seen on plain X-rays, and irregular findings of the end-plate of the vertebral body and Gd-enhanced nodules around the intervertebral disk, as seen on MRI, seemed to be important. (N.K.).

  11. Spinal Cord Injury 101

    Medline Plus

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

  12. Spinal Cord Injury 101

    Medline Plus

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

  13. First report of important causal relationship between the Adamkiewicz artery vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid hemorrhage: An experimental study using a rabbit model.

    Science.gov (United States)

    Turkmenoglu, Osman N; Kanat, Ayhan; Yolas, Coskun; Aydin, Mehmet Dumlu; Ezirmik, Naci; Gundogdu, Cemal

    2017-01-01

    The blood supply of the lower spinal cord is heavily dependent on the artery of Adamkiewicz. The goal of this study was to elucidate the effects of lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG) cells secondary to Adamkiewicz artery (AKA) vasospasm. This study was conducted on 20 rabbits, which were randomly divided into three groups: Spinal SAH ( n = 8), serum saline (SS) (SS; n = 6) and control ( n = 6) groups. Experimental spinal SAH was performed. After 20 days, volume values of AKA and neuron density of L4DRG were analyzed. The mean alive neuron density of the L4DRG was 15420 ± 1240/mm 3 and degenerated neuron density was 1045 ± 260/mm 3 in the control group. Whereas, the density of living and degenerated neurons density were 12930 ± 1060/mm 3 and 1365 ± 480/mm 3 in serum saline (SS), 9845 ± 1028/mm 3 and 4560 ± 1340/mm 3 in the SAH group. The mean volume of imaginary AKAs was estimated as 1,250 ± 0,310 mm 3 in the control group and 1,030 ± 0,240 mm 3 in the SF group and 0,910 ± 0,170 mm 3 in SAH group. Volume reduction of the AKAs and neuron density L4DRG were significantly different between the SAH and other two groups ( P < 0.05). Decreased volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH compared with controls. Increased degeneration the L4 dorsal root ganglion in animals with SAH was also noted. Our findings will aid in the planning of future experimental studies and determining the clinical relevance on such studies.

  14. Transcutaneous Spinal Direct Current Stimulation (tsDCS

    Directory of Open Access Journals (Sweden)

    Filippo eCogiamanian

    2012-07-01

    Full Text Available In the past ten years renewed interest has centered on non-invasive transcutaneous weak direct currents applied over the scalp to modulate cortical excitability (brain polarization or transcranial direct current stimulation, tDCS. Extensive literature shows that tDCS induces marked changes in cortical excitability that outlast stimulation.Aiming at developing a new, non invasive, approach to spinal cord neuromodulation we assessed the after-effects of thoracic transcutaneous spinal DC stimulation (tsDCS on somatosensory potentials (SEPs evoked in healthy subjects by posterior tibial nerve (PTN stimulation. Our findings showed that thoracic anodal tsDCS depresses the cervico-medullary PTN-SEP component (P30 without eliciting adverse effects. tsDCS also modulates post-activation H-reflex dynamics. Later works further confirmed that transcutaneous electric fields modulate spinal cord function. Subsequent studies in our laboratory showed that tsDCS modulates the flexion reflex in the human lower limb. Besides influencing the laser evoked potentials, tsDCS increases pain tolerance in healthy subjects. Hence, though the underlying mechanisms remain speculative, tsDCS modulates activity in lemniscal, spinothalamic and segmental motor systems.Here we review currently available experimental evidence that non-invasive spinal cord stimulation influences spinal function in humans and argue that, by focally modulating spinal excitability, tsDCS could provide a novel therapeutic tool complementary to drugs and invasive spinal cord stimulation in managing various pathologic conditions, including pain.

  15. Creatine kinase activity in dogs with experimentally induced acute inflammation

    Directory of Open Access Journals (Sweden)

    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  16. Microcirculation alterations in experimentally induced gingivitis in dogs.

    Science.gov (United States)

    Matsuo, Masato; Okudera, Toshimitsu; Takahashi, Shun-Suke; Wada-Takahashi, Satoko; Maeda, Shingo; Iimura, Akira

    2017-01-01

    The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.

  17. The Protective Effect of Spinal Cord Stimulation Postconditioning Against Spinal Cord Ischemia/Reperfusion Injury in Rabbits.

    Science.gov (United States)

    Li, Huixian; Dong, Xiuhua; Jin, Mu; Cheng, Weiping

    2018-01-18

    Delayed paraplegia due to spinal cord ischemia/reperfusion injury (IRI) remains one of the most severe complications of thoracoabdominal aneurysm surgery, for which effective prevention and treatment is still lacking. The current study investigates whether spinal cord stimulation (SCS) postconditioning has neuroprotective effects against spinal cord IRI. Ninety-six New Zealand white male rabbits were randomly divided into four groups as follows: a sham group and three experimental groups (C group, 2 Hz group, and 50 Hz group) n = 24/group. Spinal cord ischemia was induced by transient infrarenal aortic balloon occlusion for 28 min, after which rabbits in group C underwent no additional intervention, while rabbits in the other two experimental groups underwent 2 Hz or 50 Hz epidural SCS for 30 min at the onset of reperfusion and then daily until sacrifice. Hind limb neurologic function of rabbits was assessed using Jacob scale. Lumbar spinal cords were harvested immediately after sacrifice for histological examination and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The number of viable α-motor neurons in ventral horn was counted and TUNEL-positive rate of α-motor neurons was calculated. Spinal cord IRI was caused by transient infrarenal aorta occlusion for 28 min. Both 2 Hz and 50 Hz SCS postconditioning had neuroprotective effects, particularly the 2 Hz SCS postconditioning. Comparing to C group and 50 Hz group, rabbits in the 2 Hz group demonstrated better hind limb motor function and a lower rate of TUNEL-positive α-motor neuron after eight hours, one day, three days, and seven days of spinal cord reperfusion. More viable α-motor neurons were preserved after one and three days of spinal cord reperfusion in 2 Hz group rabbits than in C group and 50 Hz group rabbits. SCS postconditioning at 2 Hz protected the spinal cord from IRI. © 2018 International Neuromodulation Society.

  18. Traumatic injury induces changes in the expression of the serotonin 1A receptor in the spinal cord of lampreys.

    Science.gov (United States)

    Cornide-Petronio, María Eugenia; Fernández-López, Blanca; Barreiro-Iglesias, Antón; Rodicio, María Celina

    2014-02-01

    After spinal cord injury (SCI) in mammals, the loss of serotonin coming from the brainstem reduces the excitability of motor neurons and leads to a compensatory overexpression of serotonin receptors. Despite the key role of the serotonin receptor 1a in the control of locomotion, little attention has been put in the study of this receptor after SCI. In contrast to mammals, lampreys recover locomotion after a complete SCI, so, studies in this specie could help to understand events that lead to recovery of function. Here, we showed that in lampreys there is an acute increase in the expression of the serotonin 1A receptor transcript (5-ht1a) after SCI and a few weeks later expression levels go back to normal rostrally and caudally to the lesion. Overexpression of the 5-ht1a in rostral levels after SCI has not been reported in mammals, suggesting that this could be part of the plastic events that lead to the recovery of function in lampreys. The analysis of changes in 5-ht1a expression by zones (periventricular region and horizontally extended grey matter) showed that they followed the same pattern of changes detected in the spinal cord as a whole, with the exception of the caudal periventricular layer, where no significant differences were observed between control and experimental animals at any time post lesion. This suggests that different molecular signals act on the periventricular cells of the rostral and caudal regions to injury site and thus affecting their response to the injury in terms of expression of the 5-ht1a.

  19. Experimental study of effectiveness of local application of electroneurostimulation, cortexin and methylprednisolone in acute spinal cord injury

    Directory of Open Access Journals (Sweden)

    Tsymbaliuk V.I.

    2014-09-01

    Full Text Available The tasks were to investigate the effect of topical electroneurostimulation, cortexin and methy¬lprednisolone in acute spinal cord injury in electrophysiological experiments on laboratory rats. The animals un¬derwent half transection of the spinal cord in the lower-thoracic area to simulate Brown-Sequard’s syndrome. Drugs were administered subdurally once daily in the dose of 0.03 mg for cortexin and 0.7 mg for methylprednisolone during 72 hours. Electrophysiological studies were carried out using standard electrophysiological apparatus. Reliable changes of bioelectric indicators in neuromuscular complex during topical application of electrical stimulation, as well as in administered methylprednisolone, failed to be found. However, local application of cortexin in terms of traumatic spinal cord injury due the antioxidant and neurotrophic effect results in improvement of bioelectrical indicators; this is manifested in reliable (p<0.05 increase of amplitude of the background electromyogram impulses at rest by 33% and increase of spontaneous oscillations frequency by 29.82%.

  20. Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors.

    Science.gov (United States)

    Wessells, H; Hruby, V J; Hackett, J; Han, G; Balse-Srinivasan, P; Vanderah, T W

    2003-01-01

    Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracavernous pressure nor augmented neurostimulated erectile responses. We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.

  1. Experimental study of ion-induced nucleation by radon decay

    International Nuclear Information System (INIS)

    He, F.; Hopke, P.K.

    1993-01-01

    In the environment, the presence of ions from natural radioactivity may increase the rate of new particle formation through ion-induced nucleation. A thermal diffusion cloud chamber (TDCC) has been built to experimentally study ion-induced nucleation where the ions are produced by gaseous radioactive sources. The critical supersaturation values and nucleation rates for methanol, ethanol, 1-propanol, and 1-butanol vapors on ions produced within the volume of the chamber by alpha decay of 222 Rn have been measured quantitatively at various radioactivity concentrations and supersaturations. The presence of ion tracks and the effect of an external electric field were also investigated. The alpha tracks and ion-induced nucleation formed by 222 Rn decay become visible at the critical supersaturation that is below the value needed for homogeneous nucleation. At this supersaturation, the nucleation rates increase substantially with increasing 222 Rn at low activity concentrations, but attain limiting values at higher concentrations. The experimental results indicate that the ionization by radon decay will promote ion-cluster formation and lower the free energy barriers. The formation of visible droplets is strongly dependent on the supersaturation. This study also confirms that the external electric field has a significant effect on the observed rates of nucleation

  2. Machine Induced Experimental Background Conditions in the LHC

    CERN Document Server

    Levinsen, Yngve Inntjore; Stapnes, Steinar

    2012-09-19

    The Large Hadron Collider set a new energy record for particle accelerators in late 2009, breaking the previous record held by Tevatron of 2 TeV collision energy. The LHC today operates at a collision energy of 7 TeV. With higher beam energy and intensity, measures have to be taken to ensure optimal experimental conditions and safety of the machine and detectors. Machine induced experimental background can severely reduce the quality of experimental triggers and track reconstruction. In a worst case, the radiation levels can be damaging for some of the subdetectors. The LHC is a particular challenge in this regard due to the vastly different operating conditions of the different experiments. The nominal luminosity varies by four orders of magnitude. The unprecedented stored beam energy and the amount of superconducting elements can make it challenging to protect the accelerator itself as well. In this work we have simulated and measured the machine induced background originating from various sources: the beam...

  3. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

    Science.gov (United States)

    Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  4. Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

    Science.gov (United States)

    Kras, J V; Kartha, S; Winkelstein, B A

    2015-11-01

    The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  5. Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.

    Science.gov (United States)

    Pinho-Ribeiro, Felipe A; Fattori, Victor; Zarpelon, Ana C; Borghi, Sergio M; Staurengo-Ferrari, Larissa; Carvalho, Thacyana T; Alves-Filho, Jose C; Cunha, Fernando Q; Cunha, Thiago M; Casagrande, Rubia; Verri, Waldiceu A

    2016-06-01

    We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-κB and increased cytokine production (IL-1β, TNF-α and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-κB activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

  6. Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

    Directory of Open Access Journals (Sweden)

    Veronica Ghiglieri

    2012-01-01

    Full Text Available In Parkinson’s disease (PD, alteration of dopamine- (DA- dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID. Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

  7. A pneumatic phantom for mimicking respiration-induced artifacts in spinal MRI.

    Science.gov (United States)

    De Tillieux, Philippe; Topfer, Ryan; Foias, Alexandru; Leroux, Iris; El Maâchi, Imanne; Leblond, Hugues; Stikov, Nikola; Cohen-Adad, Julien

    2018-01-01

    To design a phantom capable of mimicking human respiration to serve as a testing platform for correction of the static and time-evolving magnetic field distortions typically encountered in MRI of the spinal cord. An inflation system to mimic the air variation of the human lungs was constructed. The inflation system was linked to a phantom containing synthetic lungs and an ex vivo human spine. The relationship between air pressure and phantom lung volume was evaluated via imaging experiment. The geometric distortion (pseudo-displacement) caused by the B0 inhomogeneities was measured on echo planar imaging slices for different air volumes. Linear and quadratic relations linking air pressure to phantom lung volume were observed with a Pearson correlation coefficient of 0.99. Air distribution was uneven across the synthetic lungs, exhibiting a left-to-right lung volume ratio of up to 5/4. The pseudo-displacement artifact of the spine caused by the air-filled lungs was observed. The proposed phantom can reproduce the lung volume variation of human respiration and thus can serve as a reliable testing platform for the correction of the associated time-varying B 0 field distortions. Details of the construction and code for the inflation system microcontroller are available for download as open source. Magn Reson Med 79:600-605, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  8. Discrimination of Motor Imagery-Induced EEG Patterns in Patients with Complete Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    G. Pfurtscheller

    2009-01-01

    Full Text Available EEG-based discrimination between different motor imagery states has been subject of a number of studies in healthy subjects. We investigated the EEG of 15 patients with complete spinal cord injury during imagined right hand, left hand, and feet movements. In detail we studied pair-wise discrimination functions between the 3 types of motor imagery. The following classification accuracies (mean ± SD were obtained: left versus right hand 65.03% ± 8.52, left hand versus feet 68.19% ± 11.08, and right hand versus feet 65.05% ± 9.25. In 5 out of 8 paralegic patients, the discrimination accuracy was greater than 70% but in only 1 out of 7 tetraplagic patients. The present findings provide evidence that in the majority of paraplegic patients an EEG-based BCI could achieve satisfied results. In tetraplegic patients, however, it is expected that extensive training-sessions are necessary to achieve a good BCI performance at least in some subjects.

  9. Effect of oxidative stress induced by intracranial iron overload on central pain after spinal cord injury.

    Science.gov (United States)

    Meng, Fan Xing; Hou, Jing Ming; Sun, Tian Sheng

    2017-02-08

    Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model. Rats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors. SCI may cause intracranial iron overload through the NOS-iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain.

  10. Immediate effects of chocolate on experimentally induced mood states.

    Science.gov (United States)

    Macht, Michael; Mueller, Jochen

    2007-11-01

    In this work two hypotheses were tested: (1) that eating a piece of chocolate immediately affects negative, but not positive or neutral mood, and (2) that this effect is due to palatability. Experiment 1 (48 normal-weight and healthy women and men) examined the effects of eating a piece of chocolate and drinking water on negative, positive and neutral mood states induced by film clips. Eating chocolate reduced negative mood compared to drinking water, whereas no or only marginal effects were found on neutral and positive moods. Experiment 2 (113 normal-weight and healthy women and men) compared effects of eating palatable and unpalatable chocolate on negative mood, and examined the duration of chocolate-induced mood change. Negative mood was improved after eating palatable chocolate as compared to unpalatable chocolate or nothing. This effect was short lived, i.e., it disappeared after 3 min. In both experiments, chocolate-induced mood improvement was associated with emotional eating. The present studies demonstrate that eating a small amount of sweet food improves an experimentally induced negative mood state immediately and selectively and that this effect of chocolate is due to palatability. It is hypothesized that immediate mood effects of palatable food contribute to the habit of eating to cope with stress.

  11. Oxidative stress in immature brain following experimentally-induced seizures

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava

    2013-01-01

    Roč. 62, Suppl.1 (2013), S39-S48 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR(CZ) GA309/08/0292; GA ČR(CZ) GAP303/10/0999; GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) LL1204 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : immature rats * experimentally-induced seizures * oxidative stress * mitochondrial dysfunction * antioxidant defense Subject RIV: FH - Neurology Impact factor: 1.487, year: 2013

  12. Patterns of experimentally induced pain in pericranial muscles

    DEFF Research Database (Denmark)

    Schmidt-Hansen, Peter Thede; Svensson, Peter; Jensen, Troels Staehelin

    2006-01-01

    into the masseter muscle (anova: P pain areas (anova: P cervically innervated muscles had significantly different patterns of spread and referral of pain according to trigeminally vs....... cervically innervated dermatomes (P pain patterns and pain sensitivity in different craniofacial muscles in healthy volunteers, which may be of importance for further research on different craniofacial pain conditions.......Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter...

  13. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    Science.gov (United States)

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

  14. An experimental model of hemolysis-induced acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Saruc M.

    2003-01-01

    Full Text Available The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH in 20% (v/v ethanol on the first experimental day (day 0. One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha and platelet-activating factor (PAF contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70% of 50 rats, moderate hemolysis in seven (14%, and no hemolysis in eight (16%. Thirty-three of 35 (94.2% rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8% had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

  15. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells

    Science.gov (United States)

    Rezende, Rafael M.; Oliveira, Rafael P.; Medeiros, Samara R.; Gomes-Santos, Ana C.; Alves, Andrea C.; Loli, Flávia G.; Guimarães, Mauro A.F.; Amaral, Sylvia S.; da Cunha, André P.; Weiner, Howard L.; Azevedo, Vasco; Miyoshi, Anderson; Faria, Ana M.C.

    2013-01-01

    Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-β - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice. PMID:22939403

  16. Effects of the Post-Spinal Cord Injury Microenvironment on the Differentiation Capacity of Human Neural Stem Cells Derived from Induced Pluripotent Stem Cells.

    Science.gov (United States)

    López-Serrano, Clara; Torres-Espín, Abel; Hernández, Joaquim; Alvarez-Palomo, Ana B; Requena, Jordi; Gasull, Xavier; Edel, Michael J; Navarro, Xavier

    2016-10-01

    Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.

  17. Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain

    Directory of Open Access Journals (Sweden)

    Shih Ming-Hung

    2008-12-01

    Full Text Available Abstract Spinal cord α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs mediate acute spinal processing of nociceptive and non-nociceptive information, but whether and how their activation contributes to the central sensitization that underlies persistent inflammatory pain are still unclear. Here, we examined the role of spinal AMPARs in the development and maintenance of complete Freund's adjuvant (CFA-induced persistent inflammatory pain. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 μg and GYKI 52466 (50 μg, significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli. Locomotor activity was not altered in any of the drug-treated animals. CFA-induced inflammation did not change total expression or distribution of AMPAR subunits GluR1 and GluR2 in dorsal horn but did alter their subcellular distribution. The amount of GluR2 was markedly increased in the crude cytosolic fraction and decreased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h post-CFA injection. Conversely, the level of GluR1 was significantly decreased in the crude cytosolic fraction and increased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h post-CFA injection. These findings suggest that spinal AMPARs might participate in the central spinal mechanism of persistent inflammatory pain.

  18. Acute electromyographic responses of deep thoracic paraspinal muscles to spinal manual therapy interventions. An experimental, randomized cross-over study.

    Science.gov (United States)

    Fryer, Gary; Bird, Michael; Robbins, Barry; Johnson, Jane C

    2017-07-01

    This single group, randomized, cross-over study explored whether manual therapy alters motor tone of deep thoracic back muscles by examining resting electromyographic activity (EMG) after 2 types of manual therapy and a sham control intervention. Twenty-two participants with thoracic spinal pain (15 females, 7 males, mean age 28.1 ± 6.4 years) had dual fine-wire, intramuscular electrodes inserted into deep transversospinalis muscles at a thoracic level where tissues appeared abnormal to palpation (AbP) and at 2 sites above and below normal and non-tender to palpation (NT). A surface electrode was on the contralateral paraspinal mass at the level of AbP. EMG signals were recorded for resting prone, two 3-s free neck extension efforts, two 3-s resisted maximal voluntary isometric contractions (MVIC), and resting prone before the intervention. Randomized spinal manipulation, counterstrain, or sham manipulation was delivered and EMG re-measured. Participants returned 1 and 2 weeks later for the remaining 2 treatments. Reductions in resting EMG followed counterstrain in AbP (median decrease 3.3%, P = 0.01) and NT sites (median decrease 1.0%, P = 0.05) and for the surface electrode site (median decrease 2.0%, P = 0.009). Reduction in EMG following counterstrain during free neck extension was found for the surface electrode site (median decrease 2.7%, P < 0.01). Spinal manipulation produced no change in EMG, whereas counterstrain technique produced small significant reductions in paraspinal muscle activity during prone resting and free neck extension conditions. The clinical relevance of these changes is unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Age-Related Features of Reactive Catecholamine Shifts in the Spinal Cord in Acute Somatic Pain: Experimental Study

    Directory of Open Access Journals (Sweden)

    V. G. Ovsyannikov

    2007-01-01

    Full Text Available Objective: to study the age-related features of an adrenergic response of the central nervous system to acute somatic pain (ASP.Subjects and methods: The spinal cord (SC levels of adrenaline (A, noradrenaline (NA, and dopamine (DA were studied in albino male rats of five age groups: 1 neonatal (2—4-day rats; 2 17—18-day rats that began to see; 3 monthly rats; 4 sexually mature (3—4 month ones; and 5 old ones aged over 2 years. ASP was reproduced by electrodermal stimulation of the rat tail; the levels of catecholamines (CA were measured by spectrofluorimetric microassay.Results. During postnatal ontogenesis, the rats were found to have a phase pattern of physiological changes in the spinal concentrations of CA: a decrease in their high neonatal levels (due to DA by the time the animals began to see; their progressive increase by prepuberty (due to NA and in sexually maturity (due to A and DA, and a reduction in all CA fractions in old rats. ASP was attended by a rise in the SC concentration of CA in the neonatal animals and by clearly-cut reactive shifts in all fractions in the old ones. With A and DA increases, the SC concentrations of NA halved in the rats that began to see and had ASP; the amount of CA remained unchanged as compared with the controls. In prepubertal and sexually mature male rats, there was a reduction in the spinal CA pool, but due to different components: to A and NA in 35-day rats and to A and DA in 3-month ones.Conclusion. Age-related changes in the pattern of a spinal CA response in rats with ASP show a ontogenetic trend in the development of adrenal responsiveness from the immature generalized forms of an early postnatal period to the definitive differentiated economic reactions of the hypo-to-normergic type and then to the hyperergic destructive reactions of old age. 

  20. Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury

    Directory of Open Access Journals (Sweden)

    Alexander G. Rabchevsky

    2012-08-01

    Full Text Available We recently reported that the neuropathic pain medication, gabapentin (GBP; Neurontin, significantly attenuated both noxious colorectal distension (CRD-induced autonomic dysreflexia (AD and tail pinch-induced spasticity compared to saline-treated cohorts 2-3 weeks after complete high thoracic (T4 spinal cord injury (SCI. Here we employed long-term blood pressure telemetry to test, firstly, the efficacy of daily versus acute GBP treatment in modulating AD and tail spasticity in response to noxious stimuli at 2 and 3 weeks post-injury. Secondly, we determined whether daily GBP alters baseline cardiovascular parameters, as well as spontaneous AD events detected using a novel algorithm based on blood pressure telemetry data. At both 14 and 21 days after SCI, irrespective of daily treatment, acute GBP given 1 hr prior to stimulus significantly attenuated CRD-induced AD and pinch-evoked tail spasticity; conversely, acute saline had no such effects. Moreover, daily GBP did not alter 24 hr mean arterial pressure (MAP or heart rate values compared to saline treatment, nor did it reduce the incidence of spontaneous AD events compared to saline over the three week assessment period. Power spectral density analysis of the MAP signals demonstrated relative power losses in mid frequency ranges (0.2-0.8 Hz for all injured animals relative to low frequency MAP power (0.02-0.08 Hz. However, there was no significant difference between groups over time post-injury; hence, GBP had no effect on the persistent loss of MAP fluctuations in the mid frequency range after injury. In summary, the mechanism(s by which acute GBP treatment mitigate aberrant somatosensory and cardiophysiological responses to noxious stimuli after SCI remain unclear. Nevertheless, with further refinements in defining the dynamics associated with AD events, such as eliminating requisite concomitant bradycardia, the objective repeatability of automatic detection of hypertensive crises provides a

  1. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury: Effect of duty cycle

    OpenAIRE

    Christof A. J. Smit, MD; Karin J. A. Legemate, MSc; Anja de Koning, MSc; Sonja de Groot, PhD; Janneke M. Stolwijk-Swuste, MD, PhD; Thomas W. J. Janssen, PhD

    2013-01-01

    Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation on interface pressure distribution in sitting individuals with SCI and study the usability of a newly developed electrode garment (ES shorts). Ten individuals with SCI participated in this study, in which t...

  2. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

    OpenAIRE

    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-01-01

    Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund?s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extr...

  3. Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia

    OpenAIRE

    Ochi-ishi, Ryutaro; Nagata, Kenichiro; Inoue, Tomoyuki; Tozaki-Saitoh, Hidetoshi; Tsuda, Makoto; Inoue, Kazuhide

    2014-01-01

    Background Paclitaxel is an effective chemotherapeutic agent widely used for the treatment of solid tumors. The major dose-limiting toxicity of paclitaxel is peripheral neuropathy. The mechanisms underlying the development and maintenance of paclitaxel-induced peripheral neuropathy are still unclear, and there are no currently established effective treatments. Accumulating evidence in models of neuropathic pain in which peripheral nerves are lesioned has implicated spinal microglia and chemok...

  4. Experimentally induced cam impingement in the sheep hip.

    Science.gov (United States)

    Siebenrock, Klaus A; Fiechter, Ruth; Tannast, Moritz; Mamisch, Tallal C; von Rechenberg, Brigitte

    2013-04-01

    Sheep hips have a natural non-spherical femoral head similar to a cam-type deformity in human beings. By performing an intertrochanteric varus osteotomy, cam-type femoro-acetabular impingement (FAI) during flexion can be created. We tested the hypotheses that macroscopic lesions of the articular cartilage and an increased Mankin score (MS) can be reproduced by an experimentally induced cam-type FAI in this ovine in vivo model. Furthermore, we hypothesized that the MS increases with longer ambulatory periods. Sixteen sheep underwent unilateral intertrochanteric varus osteotomy of the hip with the non-operated hip as a control. Four sheep were sacrificed after 14, 22, 30, and 38-weeks postoperatively. We evaluated macroscopic chondrolabral alterations, and recorded the MS, based on histochemical staining, for each ambulatory period. A significantly higher prevalence of macroscopic chondrolabral lesions was found in the impingement zone of the operated hips. The MS was significantly higher in the acetabular/femoral cartilage of the operated hips. Furthermore, these scores increased as the length of the ambulatory period increased. Cam-type FAI can be induced in an ovine in vivo model. Localized chondrolabral degeneration of the hip, similar to that seen in humans (Tannast et al., Clin Orthop Relat Res 2008; 466: 273-280; Beck et al., J Bone Joint Surg Br 2005; 87: 1012-1018), can be reproduced. This experimental sheep model can be used to study cam-type FAI. Copyright © 2012 Orthopaedic Research Society.

  5. Spinal Cord Injury-Induced Dysautonomia via Plasticity in Paravertebral Sympathetic Postganglionic

    Science.gov (United States)

    2017-10-01

    previous annual report (2016) provided details of our recordings of spontaneous and optogenetically evoked synaptic responses. This past year was associated...studies to examine network and cellular plasticity induced by SCI to answer the following two questions : (a) Does SCI lead to plasticity in synaptic...network and cellular plasticity induced by SCI to answer the following two questions : (a) Does SCI lead to plasticity in synaptic interactions between

  6. Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

    Science.gov (United States)

    Yang, Hai-Yu; Wu, Zhi-Yuan; Bian, Jin-Song

    2014-09-01

    Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a μ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

  7. PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes.

    Science.gov (United States)

    Liu, Jinbo; Du, Lijian

    2015-11-13

    Mitochondrial dysfunction is a direct target of hypoxic/ischemic stress in astrocytes, which results in the increased production of reactive oxygen species (ROS). Previous reports showed that ROS can activate NF-kB in spinal cord astrocytes, which occurs as a secondary injury during the pathological process of spinal cord injury (SCI). Protein kinase RNA (PKR)-like ER kinase (PERK) plays an important role in mitochondrial dysfunction. To elucidate the specific role of PERK in hypoxic/ischemic-induced NF-kB activation in spinal astrocytes, we utilized an in vitro oxygen-glucose deprivation (OGD) model, which showed an enhanced formation of ROS and NF-kB activation. Knockdown of PERK resulted in reduced activation of PERK and ROS generation in astrocytes under OGD conditions. Notably, the knockdown of PERK also induced NF-kB activation in astrocytes. These data suggest that PERK is required for the hypoxic/ischemic-induced-dependent regulation of ROS and that it is involved in NF-kB activation in the astrocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. A Fully Implantable Stimulator With Wireless Power and Data Transmission for Experimental Investigation of Epidural Spinal Cord Stimulation.

    Science.gov (United States)

    Xu, Qi; Hu, Dingyin; Duan, Bingyu; He, Jiping

    2015-07-01

    Epidural spinal cord stimulation (ESCS) combined with partial weight-bearing therapy (PWBT) has been shown to facilitate recovery of functional walking for individuals after spinal cord injury (SCI). The investigation of neural mechanisms of recovery from SCI under this treatment has been conducted broadly in rodent models, yet a suitable ESCS system is still unavailable. This paper describes a practical, programmable, and fully implantable stimulator for laboratory research on rats to explore fundamental neurophysiological principles for functional recovery after SCI. The ESCS system is composed of a personal digital assistant (PDA), an external controller, an implantable pulse generator (IPG), lead extension, and stimulating electrodes. The stimulation parameters can be programmed and adjusted through a graphical user interface on the PDA. The external controller is placed on the rat back and communicates with the PDA via radio-frequency (RF) telemetry. An RF carrier from the class-E power amplifier in the external controller provides both data and power for the IPG through an inductive link. The IPG is built around a microcontroller unit to generate voltage-regulated pulses delivered to the bipolar electrode for ESCS in rats. The encapsulated IPG measures 22 mm × 23 mm × 7 mm with a mass of  ∼  3.78 g. This fully implantable batteryless stimulator provided a simplified and efficient method to carry out chronic experiments in untethered animals for medical electro-neurological research.

  9. Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the α5β1 integrin

    Science.gov (United States)

    Boroujerdi, Amin; Welser-Alves, Jennifer V.; Milner, Richard

    2013-01-01

    Alterations in vascular structure and function are a central component of demyelinating disease. In addition to blood-brain barrier (BBB) breakdown, which occurs early in the course of disease, recent studies have described angiogenic remodeling, both in multiple sclerosis tissue and in the mouse demyelinating model, experimental autoimmune encephalomyelitis (EAE). As the precise timing of vascular remodeling in demyelinating disease has yet to be fully defined, the purpose of the current study was to define the time-course of these events in the MOG35-55 EAE model. Quantification of endothelial cell proliferation and vessel density revealed that a large part of angiogenic remodeling in cervical spinal cord white matter occurs during the pre-symptomatic phase of EAE. At the height of vascular remodeling, blood vessels in the cervical spinal cord showed strong transient upregulation of fibronectin and the α5β1 integrin. In vitro experiments revealed that α5 integrin inhibition reduced brain endothelial cell proliferation under inflammatory conditions. Interestingly, loss of vascular integrity was evident in all vessels during the first 4–7 days post-immunization, but after 14 days, was localized predominantly to venules. Taken together, our data demonstrate that extensive vascular remodeling occurs during the pre-symptomatic phase of EAE and point to a potential role for the fibronectin-α5β1 integrin interaction in promoting vascular remodeling during demyelinating disease. PMID:24056042

  10. Bee Venom Acupuncture Reduces Interleukin-6, Increases Interleukin-10, and Induces Locomotor Recovery in a Model of Spinal Cord Compression.

    Science.gov (United States)

    Nascimento de Souza, Raquel; Silva, Fernanda Kohn; Alves de Medeiros, Magda

    2017-06-01

    Spinal cord injuries (SCIs) initiate a series of molecular and cellular events in which inflammatory responses can lead to major neurological dysfunctions. The present study aims to investigate whether bee venom (BV) acupuncture applied at acupoints ST36 (Zusanli) and GV3 (Yaoyangquan) could minimize locomotor deficits and the magnitude of neural tissue losses, and change the balance between pro- and anti-inflammatory cytokines after an SCI by compression. Wistar rats were subjected to an SCI model by compression in which a 2-French Fogarty embolectomy catheter was inflated in the extradural space. The effects of BV acupuncture, in which 20 μL of BV diluted in saline (0.08 mg/kg) was injected at acupoints GV3 and ST36 [BV(ST36+GV3)-SCI] was compared with BV injected at nonacupoints [BV(NP)-SCI] and with no treatment [group subjected only to SCI (CTL-SCI)]. The BV(ST36+GV3)-SCI group showed a significant improvement in the locomotor performance and a decrease of lesion size compared with the controls. BV acupuncture at the ST36 + GV3 increased the expression of interleukin-10 (anti-inflammatory) at 6 hours and reduced the expression of interleukin-6 (proinflammatory) at 24 hours after SCI compared with the controls. Our results suggest that BV acupuncture can reduce neuroinflammation and induce recovery in the SCI compression model. Copyright © 2017. Published by Elsevier B.V.

  11. Signal-inducing bone cements for MRI-guided spinal cementoplasty: evaluation of contrast-agent-based polymethylmethacrylate cements

    International Nuclear Information System (INIS)

    Bail, Hermann Josef; Tsitsilonis, Serafim; Wichlas, Florian; Sattig, Christoph; Papanikolaou, Ioannis; Teichgraeber, Ulf Karl Mart

    2012-01-01

    The purpose of this work is to evaluate two signal-inducing bone cements for MRI-guided spinal cementoplasty. The bone cements were made of polymethylmethacrylate (PMMA, 5 ml monomeric, 12 g polymeric) and gadoterate meglumine as a contrast agent (CA, 0-40 μl) with either saline solution (NaCl, 2-4 ml) or hydroxyapatite bone substitute (HA, 2-4 ml). The cement's signal was assessed in an open 1-Tesla MR scanner, with T1W TSE and fast interventional T1W TSE pulse sequences, and the ideal amount of each component was determined. The compressive and bending strength for different amounts of NaCl and HA were evaluated. The cement's MRI signal depended on the concentration of CA, the amount of NaCl or HA, and the pulse sequence. The signal peaks were recorded between 1 and 10 μl CA per ml NaCl or HA, and were higher in fast T1W TSE than in T1W TSE images. The NaCl-PMMA-CA cements had a greater MRI signal intensity and compressive strength; the HA-PMMA-CA cements had a superior bending strength. Concerning the MR signal and biomechanical properties, these cements would permit MRI-guided cementoplasty. Due to its higher signal and greater compressive strength, the NaCl-PMMA-CA compound appears to be superior to the HA-PMMA-CA compound. (orig.)

  12. Morphine Protects Spinal Cord Astrocytes from Glutamate-Induced Apoptosis via Reducing Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2016-10-01

    Full Text Available Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS. Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

  13. Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

    Directory of Open Access Journals (Sweden)

    Giono Silvia

    2002-06-01

    Full Text Available Abstract Background Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints. Methods P-140 and PG-18 strains were each injected in the knee joints of 14 rabbits in order to evaluate and compare their arthritogenicity. P-140 was also injected in the trachea of 14 rabbits in order to test the ability of the bacteria to reach the joints and induce arthritis. Results M. fermentans produced an acute arthritis in rabbits. Joint swelling appeared first in rabbits injected with P-140, which caused a more severe arthritis than PG-18. Both strains were able to migrate to the uninoculated knee joints and they were detected viable in the joints all along the duration of the experiment. Changes in the synovial tissue were more severe by the end of the experiment and characterized by the infiltration of neutrophils and substitution of adipose tissue by connective tissue. Rabbits intracheally injected with P-140 showed induced arthritis and the bacteria could be isolated from lungs, blood, heart, kidney, spleen, brain and joints. Conclusion M. fermentans induced arthritis regardless of the inoculation route. These findings may help explain why mycoplasmas are commonly isolated from the joints of rheumatic patients.

  14. Spinal Cord Injury 101

    Medline Plus

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

  15. The influence of experimentally induced pain on shoulder muscle activity

    DEFF Research Database (Denmark)

    Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

    2009-01-01

    muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper......-105A degrees) at a speed of approximately 120A degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder...... trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows...

  16. Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response

    Directory of Open Access Journals (Sweden)

    Bin Dai

    2017-01-01

    Full Text Available We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK, eukaryotic initiation factor 2-alpha (eIF2α and activating transcription factor 4 (ATF4. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

  17. Radiation-induced osteochondroma of the T4 vertebra causing spinal cord compression

    Energy Technology Data Exchange (ETDEWEB)

    Gorospe, Luis; Madrid-Muniz, Carmen; Royo, Aranzazu; Garcia-Raya, Pilar [Department of Radiology, La Paz University Hospital, Madrid (Spain); Alvarez-Ruiz, Fernando [Department of Neurosurgery, La Paz University Hospital, Madrid (Spain); Lopez-Barea, Fernando [Department of Pathology, La Paz University Hospital, Madrid (Spain)

    2002-04-01

    A case of a radiation-induced osteochondroma arising from the vertebral body of T4 in an 18-year-old man is reported. The patient presented with a history of progressive left lower extremity weakness. At 7 years of age, he had undergone resection of a cerebellar medulloblastoma and received adjunctive craniospinal irradiation and systemic chemotherapy. Both CT and MR imaging revealed an extradural mass contiguous with the posteroinferior endplate of the T4 vertebral body. This case indicates that radiation-induced osteochondroma should be considered in the differential diagnosis of patients with symptoms of myelopathy or nerve root compression and a history of radiation therapy involving the spine in childhood. (orig.)

  18. Glial-glial and glial-neuronal interfaces in radiation-induced, glia-depleted spinal cord

    International Nuclear Information System (INIS)

    Gilmore, S.A.; Sims, T.J.

    1997-01-01

    This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomylinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2-3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. (author)

  19. Foraminiferal survival after long term experimentally induced anoxia

    Science.gov (United States)

    Langlet, D.; Geslin, E.; Baal, C.; Metzger, E.; Lejzerowicz, F.; Riedel, B.; Zuschin, M.; Pawlowski, J.; Stachowitsch, M.; Jorissen, F. J.

    2013-06-01

    Anoxia has been successfully induced in four benthic chambers installed on the Northern Adriatic seafloor from 1 week to 10 months. To accurately determine whether benthic foraminifera can survive experimentally induced prolonged anoxia, the CellTrackerGreen method has been applied. Numerous individuals have been found living at all sampling times and at all sampling depths, showing that benthic foraminifera can survive up to 10 months of anoxia with co-occurring hydrogen sulphides. However, foraminiferal standing stocks decrease with sampling time in an irregular way. A large difference in standing stock between two cores samples in initial conditions indicates the presence of a large spatial heterogeneity of the foraminiferal faunas. An unexpected increase in standing stocks after 1 month is tentatively interpreted as a reaction to increased food availability due to the massive mortality of infaunal macrofaunal organisms. After this, standing stocks decrease again in a core sampled after 2 months of anoxia, to attain a minimum in the cores sampled after 10 months. We speculate that the trend of overall decrease of standing stocks is not due to the adverse effects of anoxia and hydrogen sulphides, but rather due to a continuous diminution of labile organic matter.

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

    Directory of Open Access Journals (Sweden)

    Kouichi Isami

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

  1. Ionizing radiation-induced cancers. Experimental and clinical data

    International Nuclear Information System (INIS)

    Joveniaux, Alain.

    1978-03-01

    This work attempts to give an idea of radiocarcinogenesis, both experimental and clinical. Experimentally the possibility of radio-induced cancer formation has considerable doctrinal importance since it proves without question the carcinogenetic effect of radiations, and also yields basis information on the essential constants implicated in its occurrence: need for a latency time varying with the animal species and technique used, but quite long in relation to the specific lifetime of each species; importance of a massive irradiation, more conducive to cancerisation as long as it produces no necroses liable to stop the formation of any subsequent neoplasia; finally, rarity of is occurrence. Clinically although the cause and effect relationship between treatment and cancer is sometimes difficult to establish categorically, the fact is that hundreds of particularly disturbing observations remain and from their number often emerges under well-defined circumstances, an undeniable clinical certainty. Most importantly these observation fix the criteria necessary for the possibility of a radioinduced cancer to arise, i.e: the notion of a prior irradiation; the appearance of a cancer in the irradiation area; serious tissue damage in relation with an excessive radiation dose; a long latency period between irradition and appearance of the cancer [fr

  2. Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

    International Nuclear Information System (INIS)

    Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

    2017-01-01

    Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

  3. Inflammation-induced preterm lung maturation: lessons from animal experimentation.

    Science.gov (United States)

    Moss, Timothy J M; Westover, Alana J

    2017-06-01

    Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

  4. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

    Science.gov (United States)

    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-06-15

    Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1

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

    Science.gov (United States)

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

    2009-02-01

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

  6. A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

    Science.gov (United States)

    Janes, Kali; Esposito, Emanuela; Doyle, Timothy; Cuzzocrea, Salvatore; Tosh, Dillip K; Jacobson, Kenneth A; Salvemini, Daniela

    2014-12-01

    Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy. Copyright © 2014

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

    Science.gov (United States)

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

    2011-12-01

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

  8. Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice.

    Science.gov (United States)

    Piccinelli, Ana Claudia; Morato, Priscila Neder; Dos Santos Barbosa, Marcelo; Croda, Julio; Sampson, Jared; Kong, Xiangpeng; Konkiewitz, Elisabete Castelon; Ziff, Edward B; Amaya-Farfan, Jaime; Kassuya, Cândida Aparecida Leite

    2017-04-01

    We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection. These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences. Copyright © 2016. Published by Elsevier Inc.

  9. Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis.

    Science.gov (United States)

    Ranganathan, Vidya; Ciccia, Francesco; Zeng, Fanxing; Sari, Ismail; Guggino, Guiliana; Muralitharan, Janogini; Gracey, Eric; Haroon, Nigil

    2017-09-01

    To investigate the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of ankylosing spondylitis (AS). Patients who met the modified New York criteria for AS were recruited for the study. Healthy volunteers, rheumatoid arthritis patients, and osteoarthritis patients were included as controls. Based on the annual rate of increase in modified Stoke AS Spine Score (mSASSS), AS patients were classified as progressors or nonprogressors. MIF levels in serum and synovial fluid were quantitated by enzyme-linked immunosorbent assay. Predictors of AS progression were evaluated using logistic regression analysis. Immunohistochemical analysis of ileal tissue was performed to identify MIF-producing cells. Flow cytometry was used to identify MIF-producing subsets, expression patterns of the MIF receptor (CD74), and MIF-induced tumor necrosis factor (TNF) production in the peripheral blood. MIF-induced mineralization of osteoblast cells (SaOS-2) was analyzed by alizarin red S staining, and Western blotting was used to quantify active β-catenin levels. Baseline serum MIF levels were significantly elevated in AS patients compared to healthy controls and were found to independently predict AS progression. MIF levels were higher in the synovial fluid of AS patients, and MIF-producing macrophages and Paneth cells were enriched in their gut. MIF induced TNF production in monocytes, activated β-catenin in osteoblasts, and promoted the mineralization of osteoblasts. Our findings indicate an unexplored pathogenic role of MIF in AS and a link between inflammation and new bone formation. © 2017, American College of Rheumatology.

  10. Spinal stenosis

    Science.gov (United States)

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

  11. Intermittent reductions in respiratory neural activity elicit spinal TNF-α-independent, atypical PKC-dependent inactivity-induced phrenic motor facilitation.

    Science.gov (United States)

    Baertsch, Nathan A; Baker-Herman, Tracy L

    2015-04-15

    In many neural networks, mechanisms of compensatory plasticity respond to prolonged reductions in neural activity by increasing cellular excitability or synaptic strength. In the respiratory control system, a prolonged reduction in synaptic inputs to the phrenic motor pool elicits a TNF-α- and atypical PKC-dependent form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although iPMF may be elicited by a prolonged reduction in respiratory neural activity, iPMF is more efficiently induced when reduced respiratory neural activity (neural apnea) occurs intermittently. Mechanisms giving rise to iPMF following intermittent neural apnea are unknown. The purpose of this study was to test the hypothesis that iPMF following intermittent reductions in respiratory neural activity requires spinal TNF-α and aPKC. Phrenic motor output was recorded in anesthetized and ventilated rats exposed to brief intermittent (5, ∼1.25 min), brief sustained (∼6.25 min), or prolonged sustained (30 min) neural apnea. iPMF was elicited following brief intermittent and prolonged sustained neural apnea, but not following brief sustained neural apnea. Unlike iPMF following prolonged neural apnea, spinal TNF-α was not required to initiate iPMF during intermittent neural apnea; however, aPKC was still required for its stabilization. These results suggest that different patterns of respiratory neural activity induce iPMF through distinct cellular mechanisms but ultimately converge on a similar downstream pathway. Understanding the diverse cellular mechanisms that give rise to inactivity-induced respiratory plasticity may lead to development of novel therapeutic strategies to treat devastating respiratory control disorders when endogenous compensatory mechanisms fail. Copyright © 2015 the American Physiological Society.

  12. Experimental chaotic quantification in bistable vortex induced vibration systems

    Science.gov (United States)

    Huynh, B. H.; Tjahjowidodo, T.

    2017-02-01

    The study of energy harvesting by means of vortex induced vibration systems has been initiated a few years ago and it is considered to be potential as a low water current energy source. The energy harvester is realized by exposing an elastically supported blunt structure under water flow. However, it is realized that the system will only perform at a limited operating range (water flow) that is attributed to the resonance phenomenon that occurs only at a frequency that corresponds to the fluid flow. An introduction of nonlinear elements seems to be a prominent solution to overcome the problem. Among many nonlinear elements, a bistable spring is known to be able to improve the harvested power by a vortex induced vibrations (VIV) based energy converter at the low velocity water flows. However, it is also observed that chaotic vibrations will occur at different operating ranges that will erratically diminish the harvested power and cause a difficulty in controlling the system that is due to the unpredictability in motions of the VIV structure. In order to design a bistable VIV energy converter with improved harvested power and minimum negative effect of chaotic vibrations, the bifurcation map of the system for varying governing parameters is highly on demand. In this study, chaotic vibrations of a VIV energy converter enhanced by a bistable stiffness element are quantified in a wide range of the governing parameters, i.e. damping and bistable gap. Chaotic vibrations of the bistable VIV energy converter are simulated by utilization of a wake oscillator model and quantified based on the calculation of the Lyapunov exponent. Ultimately, a series of experiments of the system in a water tunnel, facilitated by a computer-based force-feedback testing platform, is carried out to validate the existence of chaotic responses. The main challenge in dealing with experimental data is in distinguishing chaotic response from noise-contaminated periodic responses as noise will smear

  13. Upregulation of calcium channel alpha-2-delta-1 subunit in dorsal horn contributes to spinal cord injury-induced tactile allodynia.

    Science.gov (United States)

    Kusuyama, Kazuki; Tachibana, Toshiya; Yamanaka, Hiroki; Okubo, Masamichi; Yoshiya, Shinichi; Noguchi, Koichi

    2018-01-31

    Spinal cord injury (SCI) commonly results not only in motor paralysis but also in the emergence of neuropathic pain (NeuP), both of which can impair the quality of life for patients with SCI. In the clinical field, it is well known that pregabalin, which binds to the voltage-gated calcium channel alpha-2-delta-1 (α 2 δ-1) subunit has therapeutic effects on NeuP after SCI. A previous study has demonstrated that SCI increased α 2 δ-1 in the L4-L6 dorsal spinal cord of SCI rats by Western blot analysis and that the increase of α 2 δ-1 was correlated with tactile allodynia of the hind paw. However, the detailed feature of an increase in α 2 δ-1 protein in the spinal dorsal horn and the mechanism of pregabalin effect on SCI-induced NeuP have not been fully examined. This study aimed to examine the detailed distribution of α 2 δ-1 expression in the lumbar spinal cord after thoracic SCI in rats and the correlation of the therapeutic effect of pregabalin in SCI rats. Male Sprague-Dawley rats underwent thoracic (T10) spinal cord contusion injury using the IH impactor device. Spinal cord injury rats received pregabalin (30 mg/kg) once a day for 2 weeks over a 4-week period after SCI. The mechanical threshold in the rat hind paw was measured over 4 weeks. Alpha-2-delta-1 expression in the lumbar spinal cord and in the dorsal root ganglion (DRG) was analyzed using immunohistochemistry and in situ hybridization histochemistry. A significant reduction of the withdrawal threshold of mechanical stimuli to the hind paw was observed for 2 weeks and continued at least 4 weeks after SCI. In the control rats, expression of α 2 δ-1 immunoreactivity was detected mainly in laminae I and II in the lumbar dorsal horn. Thoracic SCI significantly increased α 2 δ-1 immunoreactivity in laminae I and II in the lumbar dorsal horn 4 weeks after SCI; however, thoracic SCI did not affect the expression of α 2 δ-1 mRNA in the L4 and L5 DRGs. Meanwhile, the signal intensity of α 2

  14. Trans-spinal direct current stimulation for the modulation of the lumbar spinal motor networks

    NARCIS (Netherlands)

    Kuck, Alexander

    2018-01-01

    Trans-spinal Direct Current Stimulation (tsDCS) is a noninvasive neuromodulatory tool for the modulation of the spinal neurocircuitry. Initial studies have shown that tsDCS is able to induce a significant and lasting change in spinal-reflex- and corticospinal information processing. It is therefore

  15. Elastase-induced pulmonary emphysema: insights from experimental models

    Directory of Open Access Journals (Sweden)

    Mariana A. Antunes

    2011-12-01

    Full Text Available Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema.Diversos estímulos podem ser utilizados para reproduzir características histológicas e funcionais do enfisema humano, uma das principais causas de incapacidade e morte. Uma vez que a fumaça de cigarro é a principal causa de enfisema em humanos, estudos experimentais têm tentado reproduzir esta situação. No entanto, esse é um método dispendioso e complicado para a indução do enfisema e, alternativas mais simples e eficazes, têm sido pesquisadas. Entre essas abordagens, enzimas elastolíticas vêm sendo amplamente utilizadas para reproduzir algumas das características do enfisema humano, tais como: aumento dos espaços a

  16. Confabulation versus experimentally induced false memories in Korsakoff patients.

    Science.gov (United States)

    Van Damme, Ilse; d'Ydewalle, Géry

    2010-09-01

    The present study focuses on both the clinical symptom of confabulation and experimentally induced false memories in patients suffering from Korsakoff's syndrome. Despite the vast amount of case studies of confabulating patients and studies investigating false memories in the Deese-Roediger-McDermott (DRM) paradigm, the nature of Korsakoff patients' confabulatory behaviour and its association with DRM false memories have been rarely examined. Hence, the first aim of the present study was to evaluate confabulatory responses in a large sample of chronic Korsakoff patients and matched controls by means of the Dalla Barba Confabulation Battery. Second, the association between (provoked) confabulation and the patients' DRM false recognition performance was investigated. Korsakoff patients mainly confabulated in response to questions about episodic memory and questions to which the answer was unknown. A positive association was obtained between confabulation and the tendency to accept unstudied distractor words as being old in the DRM paradigm. On the other hand, there was a negative association between confabulation and false recognition of critical lures. The latter could be attributed to the importance of strategic retrieval at delayed memory testing.

  17. The effect of robo-horseback riding therapy on spinal alignment and associated muscle size in MRI for a child with neuromuscular scoliosis: an experimenter-blind study.

    Science.gov (United States)

    Lee, Dong Ryul; Lee, Nam Gi; Cha, Hyun Jung; Yun Sung, O; You, Sung Joshua Hyun; Oh, Jin Hwan; Bang, Hyo Seong

    2011-01-01

    This case study was conducted to highlight the clinical and radiological features of a patient with progressive neuromuscular scoliosis before and after robo-horseback riding therapy (HBRT). A clinical, laboratory, and radiological analysis of a single case. An 11-year-old child, dignosed right thoracolumbar neuromuscular scoliosis secondary to cerebral palsy. The child received a 5-week course of robo-HBRT, comprising of 60-minute periods a day, five times a week. Postural alignment was determined by Cobb's method. A real-time magnetic resonance imaging (MRI) was performed to determine the robo-HBRT-induced changes in cross-sectional area (CSA) of bilateral thoracic (T2) and lumbar (L2) paraspinalis. Clinical tests including the standard Gross Motor Function Measure (GMFM) and manual muscle testing (MMT) with the Lafayette Manual Muscle Tester were used to compare the intervention-related changes in motor performance and power. The surface EMG was also used to examine therapy-induced changes in muscle activity amplitude for bilateral T2 and L2 paraspinalis and rectus abdominis muscles. Clinical motor and strength scores increased after the intervention. Radiographic Cobb's angle, MRI, and electromyographic amplitude data demonstrated notably enhanced spinal alignment and muscle fiber CSA and symmetry, respectively. This is the first study to provide evidence of the therapeutic efficacy of a novel form of robo-HBRT on motor function and associated structural and motor control improvements, thus suggesting a method of augmenting therapy in neuromuscular scoliosis.

  18. Pathogenesis of spinal cord injury induced edema and neuropathic pain: expression of multiple isoforms of wnk1.

    Science.gov (United States)

    Ahmed, Mostafa M; Lee, HyunKyung; Clark, Zach; Miranpuri, Gurwattan S; Nacht, Carrie; Patel, Kush; Liu, Lisa; Joslin, Jiliian; Kintner, Douglus; Resnick, Daniel K

    2014-07-01

    Neuropathic pain (NP) is a common occurrence following spinal cord injury (SCI). Identification of specific molecular pathways that are involved in pain syndromes has become a major priority in current SCI research. We have investigated the role of a cation-dependent chloride transporter, Cl-regulatory protein Na(+)-K(+)-Cl(-) 1 (NKCC1), phosphorylation profile of NKCC1 and its specific involvement in neuropathic pain following contusion SCI (cSCI) using a rat model. Administration of the NKCC1 inhibitor bumetanide (BU) increases the mean hindpaw withdrawal latency time (WLT), thermal hyperalgesia (TH) following cSCI. These results demonstrate implication of NKCC1 co-transporter and BUin SCI-induced neuropathic pain. The with-no-lysine (K)-1 (WNK1) kinase has been shown to be an important regulator of NKCC1 phosphorylation in many systems, including nocioception. Mutations in a neuronal-specific exon of WNK1 (HSN2) was identified in patients that have hereditary sensory neuropathy type II (HSANII) also implicates WNK1 in nocioception, such that these patients have loss of perception to pain, touch and heat. In our ongoing research we proposed two studies utilizing our contusion SCI (cSCI) NP model of rat. Study 1 aimed at NKCC1 expression and activity is up-regulated following cSCI in the early edema and chronic neuropathic pain phases. Study 2 aimed at identifying the expression profile of alternatively spliced WNK1 isoforms in animals exhibiting thermal hyperalgesia (TH) following cSCI. Adult male Sprague Dawley rats (275-300 g) following laminectomy received cSCI at T9 with the NYU impactor-device II by dropping 10 g weight from the height of 12.5 mm. Control rats obtained laminectomy but no impaction. Following injury, functional recovery was assessed by BBB locomotor scores on day 1, 7, 14, 21, 35, and 42 and development of thermal hyperalgesia on day 21, 28, 35, and 42 day of injury by monitoring hind paw withdraw latency time (WLT) in seconds compared with

  19. Salmon and human thrombin differentially regulate radicular pain, glial-induced inflammation and spinal neuronal excitability through protease-activated receptor-1.

    Directory of Open Access Journals (Sweden)

    Jenell R Smith

    Full Text Available Chronic neck pain is a major problem with common causes including disc herniation and spondylosis that compress the spinal nerve roots. Cervical nerve root compression in the rat produces sustained behavioral hypersensitivity, due in part to the early upregulation of pro-inflammatory cytokines, the sustained hyperexcitability of neurons in the spinal cord and degeneration in the injured nerve root. Through its activation of the protease-activated receptor-1 (PAR1, mammalian thrombin can enhance pain and inflammation; yet at lower concentrations it is also capable of transiently attenuating pain which suggests that PAR1 activation rate may affect pain maintenance. Interestingly, salmon-derived fibrin, which contains salmon thrombin, attenuates nerve root-induced pain and inflammation, but the mechanisms of action leading to its analgesia are unknown. This study evaluates the effects of salmon thrombin on nerve root-mediated pain, axonal degeneration in the root, spinal neuronal hyperexcitability and inflammation compared to its human counterpart in the context of their enzymatic capabilities towards coagulation substrates and PAR1. Salmon thrombin significantly reduces behavioral sensitivity, preserves neuronal myelination, reduces macrophage infiltration in the injured nerve root and significantly decreases spinal neuronal hyperexcitability after painful root compression in the rat; whereas human thrombin has no effect. Unlike salmon thrombin, human thrombin upregulates the transcription of IL-1β and TNF-α and the secretion of IL-6 by cortical cultures. Salmon and human thrombins cleave human fibrinogen-derived peptides and form clots with fibrinogen with similar enzymatic activities, but salmon thrombin retains a higher enzymatic activity towards coagulation substrates in the presence of antithrombin III and hirudin compared to human thrombin. Conversely, salmon thrombin activates a PAR1-derived peptide more weakly than human thrombin. These

  20. ZL006 protects spinal cord neurons against ischemia-induced oxidative stress through AMPK-PGC-1α-Sirt3 pathway.

    Science.gov (United States)

    Liu, Shu-Guang; Wang, Yun-Mei; Zhang, Yan-Jun; He, Xi-Jing; Ma, Tao; Song, Wei; Zhang, Yu-Min

    2017-09-01

    Spinal cord ischemia (SCI) induces a range of cellular and molecular cascades, including activation of glutamate receptors and downstream signaling. Post-synaptic density protein 95 (PSD-95) links neuronal nitric oxide synthase (nNOS) with the N-methyl-d-aspartic acid (NMDA) receptors to form a ternary complex in the CNS. This molecular complex-mediated cytotoxicity has been implicated in brain ischemia, but its role in SCI has not been determined. The goal of the study was to investigate the potential protective effects of ZL006, a small-molecule inhibitor of the PSD-95/nNOS interaction, in an in vitro SCI model induced by oxygen and glucose deprivation (OGD) in cultured spinal cord neurons. We found that ZL006 reduced OGD-induced lactate dehydrogenase (LDH) release, neuronal apoptosis and loss of cell viability. This protection was accompanied by the preservation of mitochondrial function, as evidenced by reduced mitochondrial oxidative stress, attenuated mitochondrial membrane potential (MMP) loss, and enhanced ATP generation. In addition, ZL006 stimulated mitochondrial enzyme activities and SOD2 deacetylation in a Sirt3-dependent manner. The results of western blot analysis showed that ZL006 increased the activation of AMPK-PGC-1α-Sirt3 pathway, and the beneficial effects of ZL006 was partially abolished by AMPK inhibitor and PGC-1α knockdown. Therefore, our present data showed that, by the AMPK-PGC-1α-Sirt3 pathway, ZL006 protects spinal cord neurons against ischemia through reducing mitochondrial oxidative stress to prevent apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Spinal fusion limits upper body range of motion during gait without inducing compensatory mechanisms in adolescent idiopathic scoliosis patients.

    Science.gov (United States)

    Holewijn, R M; Kingma, I; de Kleuver, M; Schimmel, J J P; Keijsers, N L W

    2017-09-01

    Previous studies show a limited alteration of gait at normal walking speed after spinal fusion surgery for adolescent idiopathic scoliosis (AIS), despite the presumed essential role of spinal mobility during gait. This study analyses how spinal fusion affects gait at more challenging walking speeds. More specifically, we investigated whether thoracic-pelvic rotations are reduced to a larger extent at higher gait speeds and whether compensatory mechanisms above and below the stiffened spine are present. 18 AIS patients underwent gait analysis at increasing walking speeds (0.45 to 2.22m/s) before and after spinal fusion. The range of motion (ROM) of the upper (thorax, thoracic-pelvic and pelvis) and lower body (hip, knee and ankle) was determined in all three planes. Spatiotemporal parameters of interest were stride length and cadence. Spinal fusion diminished transverse plane thoracic-pelvic ROM and this difference was more explicit at higher walking speeds. Transversal pelvis ROM was also decreased but this effect was not affected by speed. Lower body ROM, step length and cadence remained unaffected. Despite the reduction of upper body ROM after spine surgery during high speed gait, no altered spatiotemporal parameters or increased compensatory ROM above or below the fusion (i.e. in the shoulder girdle or lower extremities) was identified. Thus, it remains unclear how patients can cope so well with such major surgery. Future studies should focus on analyzing the kinematics of individual spinal levels above and below the fusion during gait to investigate possible compensatory mechanisms within the spine. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Plateau potentials in alpha‐motoneurones induced by intravenous injection of L‐dopa and clonidine in the spinal cat

    DEFF Research Database (Denmark)

    Conway, B. A.; Hultborn, H.; Kiehn, O.

    1988-01-01

    1. Intracellular recordings were made from lumbar alpha‐motoneurones in unanaesthetized decerebrate acute spinal cats. The response of motoneurones to direct current pulse injection or synaptic excitation was investigated following intravenous injection of L‐beta‐3,4‐dihydroxyphenylalanine (L....... It is demonstrated that plateau potentials in the motoneurones contribute to the late long‐lasting reflexes observed in L‐DOPA‐treated spinal cats. 7. It is concluded that L‐DOPA (and clonidine) change the response properties of the motoneurones in an analogous way to 5‐hydroxy‐DL‐tryptophan (5‐HTP...

  3. Low Frequency Electroacupuncture Alleviated Spinal Nerve Ligation Induced Mechanical Allodynia by Inhibiting TRPV1 Upregulation in Ipsilateral Undamaged Dorsal Root Ganglia in Rats

    Directory of Open Access Journals (Sweden)

    Yong-Liang Jiang

    2013-01-01

    Full Text Available Neuropathic pain is an intractable problem in clinical practice. Accumulating evidence shows that electroacupuncture (EA with low frequency can effectively relieve neuropathic pain. Transient receptor potential vanilloid type 1 (TRPV1 plays a key role in neuropathic pain. The study aimed to investigate whether neuropathic pain relieved by EA administration correlates with TRPV1 inhibition. Neuropathic pain was induced by right L5 spinal nerve ligation (SNL in rats. 2 Hz EA stimulation was administered. SNL induced mechanical allodynia in ipsilateral hind paw. SNL caused a significant reduction of TRPV1 expression in ipsilateral L5 dorsal root ganglia (DRG, but a significant up-regulation in ipsilateral L4 and L6 DRGs. Calcitonin gene-related peptide (CGRP change was consistent with that of TRPV1. EA alleviated mechanical allodynia, and inhibited TRPV1 and CGRP overexpressions in ipsilateral L4 and L6 DRGs. SNL did not decrease pain threshold of contralateral hind paw, and TRPV1 expression was not changed in contralateral L5 DRG. 0.001, 0.01 mg/kg TRPV1 agonist 6′-IRTX fully blocked EA analgesia in ipsilateral hind paw. 0.01 mg/kg 6′-IRTX also significantly decreased pain threshold of contralateral paw. These results indicated that inhibition of TRPV1 up-regulation in ipsilateral adjacent undamaged DRGs contributed to low frequency EA analgesia for mechanical allodynia induced by spinal nerve ligation.

  4. 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

    The present investigation aimed to study two methodological concerns of an experimental model, where a spinal loop dialysis probe is used for administration of substances to the spinal cord and sampling of neurotransmitters by microdialysis from the same area of anaesthetized rats. [(3)H]Epibatid......The present investigation aimed to study two methodological concerns of an experimental model, where a spinal loop dialysis probe is used for administration of substances to the spinal cord and sampling of neurotransmitters by microdialysis from the same area of anaesthetized rats. [(3)H...... intraspinal administration of substances through the spinal loop dialysis probe....

  5. Subdural Thoracolumbar Spine Hematoma after Spinal Anesthesia: A Rare Occurrence and Literature Review of Spinal Hematomas after Spinal Anesthesia.

    Science.gov (United States)

    Maddali, Prasanthi; Walker, Blake; Fisahn, Christian; Page, Jeni; Diaz, Vicki; Zwillman, Michael E; Oskouian, Rod J; Tubbs, R Shane; Moisi, Marc

    2017-02-16

    Spinal hematomas are a rare but serious complication of spinal epidural anesthesia and are typically seen in the epidural space; however, they have been documented in the subdural space. Spinal subdural hematomas likely exist within a traumatically induced space within the dural border cell layer, rather than an anatomical subdural space. Spinal subdural hematomas present a dangerous clinical situation as they have the potential to cause significant compression of neural elements and can be easily mistaken for spinal epidural hematomas. Ultrasound can be an effective modality to diagnose subdural hematoma when no epidural blood is visualized. We have reviewed the literature and present a full literature review and a case presentation of an 82-year-old male who developed a thoracolumbar spinal subdural hematoma after spinal epidural anesthesia. Anticoagulant therapy is an important predisposing risk factor for spinal epidural hematomas and likely also predispose to spinal subdural hematomas. It is important to consider spinal subdural hematomas in addition to spinal epidural hematomas in patients who develop weakness after spinal epidural anesthesia, especially in patients who have received anticoagulation.

  6. Spinal injury

    Science.gov (United States)

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

  7. Spinal infections

    International Nuclear Information System (INIS)

    Tali, E. Turgut; Gueltekin, Serap

    2005-01-01

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

  8. Spinal cysticercosis

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  9. Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study.

    Science.gov (United States)

    Lee, Do-Hun; Phi, Ji Hoon; Chung, You-Nam; Lee, Yun-Jin; Kim, Seung-Ki; Cho, Byung-Kyu; Kim, Dong Won; Park, Moon-Sik; Wang, Kyu-Chang

    2010-05-01

    The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes. Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group. There were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.

  10. Drug induced acute kidney injury: an experimental animal study

    International Nuclear Information System (INIS)

    Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

    2017-01-01

    Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

  11. Modulation of melanocortin- induced changes in spinal nociception by µ-opioid receptor agonist and antagonist in neuropathic rats

    NARCIS (Netherlands)

    Gispen, W.H.; Starowitcz, K.; Przewlocki, R.; Przewlocka, B.

    2002-01-01

    Co-localization of opioid and melanocortin receptor expression, especially at the spinal cord level in the dorsal horn and in the gray matter surrounding the central canal led to the suggestion that melanocortins might play a role in nociceptive processes. In the present studies, we aimed to

  12. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Science.gov (United States)

    Asante, Curtis O; Wallace, Victoria C; Dickenson, Anthony H

    2009-01-01

    Background The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR) dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via mRNA translation and thus protein

  13. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Directory of Open Access Journals (Sweden)

    Wallace Victoria C

    2009-06-01

    Full Text Available Abstract Background The mammalian target of rapamycin (mTOR is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via m

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ...

  15. Spinal Cord Injury 101

    Medline Plus

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

  16. Delayed Administration of VEGF Rescues Spinal Motor Neurons from Death with a Short Effective Time Frame in Excitotoxic Experimental Models in Vivo

    Directory of Open Access Journals (Sweden)

    Luis B Tovar-y-Romo

    2012-02-01

    Full Text Available VEGF (vascular endothelial growth factor prevents neuronal death in different models of ALS (amyotrophic lateral sclerosis, but few studies have addressed the efficacy of VEGF to protect motor neurons after the onset of symptoms, a critical point when considering VEGF as a potential therapeutic target for ALS. We studied the capability of VEGF to protect motor neurons after an excitotoxic challenge in two models of spinal neurodegeneration in rats induced by AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid administered either chronically with osmotic minipumps or acutely by microdialysis. VEGF was administered through osmotic minipumps in the chronic model or injected intracerebroventricularly in the acute model, and its effects were assessed by immunohistochemical and histological analyses and motor performance tests. In the chronic model, VEGF stopped the progression of the paralysis and protected motor neurons when administered after AMPA before the onset of the motor symptoms, whereas no protection was observed when administered after the onset. VEGF was also protective in the acute model, but with a short time window, since the protection was effective when administered 1 h but not 2 h after AMPA. Our results indicate that while VEGF has an indubitable neuroprotective effect, its therapeutic potential for halting or delaying the progression of motor neuron loss in ALS would likely have a short effective time frame.

  17. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  18. Neuroprotection and its molecular mechanism following spinal cord injury☆

    Science.gov (United States)

    Liu, Nai-Kui; Xu, Xiao-Ming

    2012-01-01

    Acute spinal cord injury initiates a complex cascade of molecular events termed ‘secondary injury’, which leads to progressive degeneration ranging from early neuronal apoptosis at the lesion site to delayed degeneration of intact white matter tracts, and, ultimately, expansion of the initial injury. These secondary injury processes include, but are not limited to, inflammation, free radical-induced cell death, glutamate excitotoxicity, phospholipase A2 activation, and induction of extrinsic and intrinsic apoptotic pathways, which are important targets in developing neuroprotective strategies for treatment of spinal cord injury. Recently, a number of studies have shown promising results on neuroprotection and recovery of function in rodent models of spinal cord injury using treatments that target secondary injury processes including inflammation, phospholipase A2 activation, and manipulation of the PTEN-Akt/mTOR signaling pathway. The present review outlines our ongoing research on the molecular mechanisms of neuroprotection in experimental spinal cord injury and briefly summarizes our earlier findings on the therapeutic potential of pharmacological treatments in spinal cord injury. PMID:25624837

  19. The Effect of Intrathecal Administration of Muscimol on Modulation of Neuropathic Pain Symptoms Resulting from Spinal Cord Injury; an Experimental Study

    Directory of Open Access Journals (Sweden)

    Marjan Hosseini

    2014-09-01

    Full Text Available Introduction: Neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. Muscimol as a new agonist of gamma-Aminobutyric acid receptor type A (GABAA have been introduced for pain management. Thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as GABAA receptor agonist in spinal cord injury (SCI model of neuropathic pain. Methods: In the present experimental study male Wistar rats were treated by muscimol 0.01, 0.1 or 1 µg/10ul, intrathecally (i.t. three weeks after induction of spinal cord injury using compression injury model. Neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. The time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively. Results: Muscimol with the dose of 0.01 µg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; F= 6.6; p<0.001, mechanical hyperalgesia (df: 24, 5; F= 7.8; p<0.001, cold allodynia (df: 24, 5; F= 6.96; p<0.001, and mechanical allodynia (df: 24, 5; F= 15.7; p<0.001. The effect of doses of 0.1 µg and 1 µg were also significant. In addition, the efficacy of different doses of muscimol didn't have difference on thermal hyperalgesia (df: 24, 5; F= 1.52; p= 0.24, mechanical hyperalgesia (df: 24, 5; F= 0.3; p= -0.75, cold allodynia (df: 24, 5; F= 0.8; p= -0.56, and mechanical allodynia (df: 24, 5; F= 1.75; p= 0.86. Conclusion: The finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg reduces the symptoms of neuropathic pain. Also the effect of GABAA agonist is short term and its effectiveness gradually decreases by time.

  20. Spinal axis irradiation with electrons: Measurements of attenuation by the spinal processes

    International Nuclear Information System (INIS)

    Muller-Runkel, R.; Vijayakumar, S.

    1986-01-01

    Electrons may be used beneficially for spinal axis irradiation in medulloblastoma children to avoid some of the long-term sequelae induced by megavoltage photons. However, the attenuation by the intervening bone ought to be considered. Three-dimensional computer treatment planning with inhomogeneity correction for electron beams is not yet generally available, and alternate methods are needed to evaluate the attenuation by the complex bony structure of the spine. Here, we present our experimental data showing the alteration in the electron isodoses due to the intervening spinous processes. Film dosimetric measurements were made in the vertebral columns obtained from autopsies of a goat, a dog, and a child. Our results show that electron beam therapy for the spinal axis is a viable option

  1. P2Y12 receptor-mediated activation of spinal microglia and p38MAPK pathway contribute to cancer-induced bone pain

    Directory of Open Access Journals (Sweden)

    Liu MJ

    2017-02-01

    Full Text Available Mingjuan Liu,1 Ming Yao,1,2 Hanqi Wang,1 Longsheng Xu,1 Ying Zheng,1 Bing Huang,1 Huadong Ni,1 Shijie Xu,1 Xuyan Zhou,1 Qingquan Lian2 1Department of Anesthesiology and Pain Medicine, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, 2Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Cancer-induced bone pain (CIBP is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent evidence has demonstrated that activation of microglial G-protein-coupled P2Y12 receptor (P2Y12R and proinflammatory cytokine production play an important role in neuropathic pain generation and maintenance. However, whether P2Y12R is involved in CIBP remains unknown.Methods: The purpose of this study was to investigate the role of P2Y12R in CIBP and its molecular mechanisms. Using the bone cancer model inoculated with Walker 256 tumor cells into the left tibia of Sprague Dawley rat, we blocked spinal P2Y12R through intrathecal administration of its selective antagonist MRS2395 (400 pmol/µL, 15 µL.Results: We found that not only the ionized calcium-binding adapter molecule 1 (Iba-1-positive microglia in the ipsilateral spinal cord but also mechanical allodynia was significantly inhibited. Furthermore, it decreased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK and the production of proinflammatory cytokines interleukin-1β (IL-1β and interleukin-6 (IL-6, whereas it increased tumor necrosis factor-α (TNF-α.Conclusion: Taken together, our present results suggest that microglial P2Y12R in the spinal cord may contribute to CIBP by the activation of spinal microglia and p38MAPK pathway, thus identifying a potential therapeutic target for the treatment of CIBP. Keywords: P2Y12 receptor, cancer-induced bone pain, p38MAPK pathway, cytokines

  2. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  3. Anatomical Recruitment of Spinal V2a Interneurons into Phrenic Motor Circuitry after High Cervical Spinal Cord Injury.

    Science.gov (United States)

    Zholudeva, Lyandysha V; Karliner, Jordyn S; Dougherty, Kimberly J; Lane, Michael A

    2017-11-01

    More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. The identity of spinal interneurons involved with respiratory plasticity post-SCI, however, has remained largely unknown. Using a transgenic Chx10-eGFP mouse line (Strain 011391-UCD), the present study is the first to demonstrate the recruitment of excitatory interneurons into injured phrenic circuitry after a high cervical SCI. Diaphragm electromyography and anatomical analysis were used to confirm lesion-induced functional deficits and document extent of the lesion, respectively. Transneuronal tracing with pseudorabies virus (PRV) was used to identify interneurons within the phrenic circuitry. There was a robust increase in the number of PRV-labeled V2a interneurons ipsilateral to the C2 hemisection, demonstrating that significant numbers of these excitatory spinal interneurons were anatomically recruited into the phrenic motor pathway two weeks after injury, a time known to correspond with functional phrenic plasticity. Understanding this anatomical spinal plasticity and the neural substrates associated with functional compensation or recovery post-SCI in a controlled, experimental setting may help shed light onto possible cellular therapeutic candidates that can be targeted to enhance spontaneous recovery.

  4. TRPV1 receptors contribute to mediate paclitaxel-induced c-Fos expression in spinal cord dorsal horn neurons

    Czech Academy of Sciences Publication Activity Database

    Kalynovska, Nataliia; Adámek, Pavel; Paleček, Jiří

    2017-01-01

    Roč. 66, č. 3 (2017), s. 549-532 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA15-11138S; GA MŠk(CZ) LH15279; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : c-Fos * paclitaxel * TRPV1 * neuropathy * spinal cord Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

  5. Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat.

    Science.gov (United States)

    Martin, Mario; Béjar, Javier; Esposito, Gennaro; Chávez, Diógenes; Contreras-Hernández, Enrique; Glusman, Silvio; Cortés, Ulises; Rudomín, Pablo

    2017-01-01

    In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials ( CDPs ). This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random) patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure to identify portions of signals as belonging to a specific functional state of connectivity among the neuronal networks involved in the generation of the CDPs . We have tested this procedure during acute nociceptive stimulation produced by the intradermic injection of capsaicin in intact as well as spinalized preparations. Altogether, our results indicate that CDP sequences cannot be generated by a renewal stochastic process. Moreover, it is possible to describe some functional features of activity in the cord dorsum by modeling the CDP sequences as generated by a Markov order one stochastic process. Finally, these Markov models make possible to determine the functional state which produced a CDP sequence. The proposed identification procedures appear to be useful for the analysis of the sequential behavior of the ongoing CDPs recorded from different spinal segments in response to a variety of experimental procedures including the changes produced by acute nociceptive stimulation. They

  6. Spinal tuberculosis.

    Science.gov (United States)

    Dunn, R N; Ben Husien, M

    2018-04-01

    Tuberculosis (TB) remains endemic in many parts of the developing world and is increasingly seen in the developed world due to migration. A total of 1.3 million people die annually from the disease. Spinal TB is the most common musculoskeletal manifestation, affecting about 1 to 2% of all cases of TB. The coexistence of HIV, which is endemic in some regions, adds to the burden and the complexity of management. This review discusses the epidemiology, clinical presentation, diagnosis, impact of HIV and both the medical and surgical options in the management of spinal TB. Cite this article: Bone Joint J 2018;100-B:425-31.

  7. Experimental and theoretical studies of bombardment induced surface morphology changes

    International Nuclear Information System (INIS)

    Carter, G.; Nobes, M.J.; Williams, J.S.

    1980-01-01

    In this review results of experimental and theoretical studies of solid surface morphology changes due to ion bombardment are discussed. An attempt is undertaken to classify the observed specific features of a structure, generated by ion bombardment [ru

  8. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  9. Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

    Directory of Open Access Journals (Sweden)

    M. Chacur

    2010-04-01

    Full Text Available Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO. In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT. Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test and allodynia (von Frey hair test. Control animals did not present any alteration (sham-animals. The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 µg in 50 µL, blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48% by day 30 in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed’s lamina X and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469%. Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20%, reaching the greatest increase (60% 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.

  10. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

    Science.gov (United States)

    Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

    2011-01-01

    Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

  11. Upregulation of adrenomedullin in the spinal cord and dorsal root ganglia in the early phase of CFA-induced inflammation in rats.

    Science.gov (United States)

    Hong, Yanguo; Liu, Yushan; Chabot, Jean-Guy; Fournier, Alain; Quirion, Rémi

    2009-11-01

    Adrenomedullin (AM), a member of calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pronociceptive mediator [28]. This study was undertaken to investigate the role of AM in a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Injection of CFA, but not of saline, in the unilateral hindpaw produced an increase in the expression of AM-like immunoreactivity (AM-IR) in laminae I-II of the spinal cord as well as in small- and medium-sized dorsal root ganglion (DRG) neurons at 48 h. The content of AM in DRG on the side ipsilateral to CFA injection started to increase at 4 h and remained at high levels at 24 and 48 h. The selective antagonist of AM receptors, AM(22-52), administered intrathecally (i.t.) 24 h after CFA injection inhibited inflammation-associated hyperalgesia in a dose-dependent manner (2, 5 and 10 nmol). Impressively, this anti-hyperalgesic effect lasted for at least 24 h. I.t. administration of AM(22-52) (10 nmol) also reversed CFA-induced increase in AM-IR in the spinal dorsal horn and DRG. Furthermore, blockade of AM receptors abolished CFA-induced changes in the expression and content of CGRP-like immunoreactivity in these regions. Taken together, our results suggest that the upregulation of AM in DRG neurons contributes to the development of inflammatory pain, and this effect is mediated, at least in part, by enhancing the expression and release of CGRP. Blocking AM receptor downstream signaling effects using antagonists has the potential of relieving pain following the induction of inflammation.

  12. Experimental and analytical studies on pedestrian induced footbridge vibrations

    DEFF Research Database (Denmark)

    Gudmundsson, Gudmundur Valur; Ingólfsson, Einar Thór; Einarsson, Baldvin

    2007-01-01

    characteristics and to measure the response of the bridges to human induced excitation such as walking, running and jumping. Two of the bridges were a part of a design competition related to the realignment of an existing highway in the city centre of Reykjavik in 2005. The bridges have similar cross sections...... modes corresponding to the measured values. The models were subsequently used to calculate the predicted acceleration according to the preliminary version of the Eurocode (ENV 1992-2: Concrete bridges) using time-history analysis with a moving load as representative for a single pedestrian. The load...... models describing human-induced vibrations on structures in current literature and standards are explained, both for a single person walking or running and crowd loading. The measured vertical acceleration induced by single pedestrians was compared against the predictions and it was found that all...

  13. Degeneration of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits following Mid-Cervical Spinal Contusion in Mice

    Science.gov (United States)

    Nicaise, Charles; Putatunda, Rajarshi; Hala, Tamara J.; Regan, Kathleen A.; Frank, David M.; Brion, Jean-Pierre; Leroy, Karelle; Pochet, Roland; Wright, Megan C.

    2012-01-01

    Abstract A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron–diaphragm circuitry. We have generated a mouse model of cervical contusion SCI that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and have examined histological and functional outcomes for up to 6 weeks post-injury. We report that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and denervation at diaphragm neuromuscular junctions (NMJ) resulted in compromised ipsilateral diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation and abnormalities in spontaneous diaphragm electromyography (EMG) recordings. This injury paradigm is reproducible, does not require ventilatory assistance, and provides proof-of-principle that generation of unilateral cervical contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This study and its accompanying analyses pave the way for using transgenic mouse technology to explore the function of specific genes in the pathophysiology of phrenic motor neuron degeneration and respiratory dysfunction following cervical SCI. PMID:23176637

  14. Repair of experimental plaque-induced periodontal disease in dogs.

    Science.gov (United States)

    Shoukry, M; Ben Ali, L; Abdel Naby, M; Soliman, A

    2007-09-01

    Forty mongrel dogs were used in this study for induction of periodontal disease by placing subgingival silk ligatures affecting maxillary and mandibular premolar teeth during a 12-month period. Experimental premolar teeth received monthly clinical, radiographic, and histometric/pathologic assessments. The results demonstrated significant increases in scores and values of periodontal disease parameters associated with variable degrees of alveolar bone loss. The experimental maxillary premolar teeth exhibited more severe and rapid rates of periodontal disease compared with mandibular premolar teeth. Histometric analysis showed significant reduction in free and attached gingiva of the experimental teeth. Histopathological examination of buccolingual sections from experimental premolar teeth showed the presence of rete pegs within the sulcular epithelium with acanthosis and erosive changes, widening of the periodontal ligament, and alveolar bone resorption. Various methods for periodontal repair were studied in 194 experimental premolar teeth exhibiting different degrees of periodontal disease. The treatment plan comprised non-surgical (teeth scaling, root planing, and oral hygiene) and surgical methods (closed gingival curettage, modified Widman flap, and reconstructive surgery using autogenous bone marrow graft and canine amniotic membrane). The initial non-surgical treatment resulted in a periodontal recovery rate of 37.6% and was found effective for treatment of early periodontal disease based on resolution of gingivitis and reduction of periodontal probing depths. Surgical treatment by closed gingival curettage to eliminate the diseased pocket lining resulted in a recovery rate of 48.8% and proved effective in substantially reducing deep periodontal pockets. Open root planing following flap elevation resulted in a recovery rate of 85.4% and was effective for deep and refractory periodontal pockets. Autogenous bone graft implantation combined with canine amniotic

  15. The NA(v)1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing

    Czech Academy of Sciences Publication Activity Database

    Torres-Pérez, J. V.; Adámek, Pavel; Paleček, Jiří; Vizcaychipi, M.; Nagy, I.; Varga, A.

    2018-01-01

    Roč. 96, č. 1 (2018), s. 75-84 ISSN 0946-2716 R&D Projects: GA ČR(CZ) GA15-11138S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) LH15279; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : pain * p-ERK1/2 * primary sensory neuron * p-S10H3 * spinal cord Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.686, year: 2016

  16. Hypersensitivity Induced by Activation of Spinal Cord PAR2 Receptors Is Partially Mediated by TRPV1 Receptors

    Czech Academy of Sciences Publication Activity Database

    Mrózková, Petra; Špicarová, Diana; Paleček, Jiří

    2016-01-01

    Roč. 11, č. 10 (2016), č. článku e0163991. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA15-11138S; GA MŠk(CZ) LH15279; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : PAR2 * TRP * neuropathy * spinal cord Subject RIV: FH - Neurology Impact factor: 2.806, year: 2016

  17. Prevention of spinal anaesthesia-induced hypotension in the elderly: i.m. methoxamine or combined hetastarch and crystalloid.

    LENUS (Irish Health Repository)

    Buggy, D J

    2012-02-03

    We have compared two methods of reducing hypotension during spinal anaesthesia in elderly patients, 6% hetastarch and crystalloid or methoxamine 10 mg i.m., in terms of haemodynamic stability and requirements for additional vasopressors. Sixty-two patients (aged 60-97 yr) undergoing surgical fixation of fractured neck of femur were allocated randomly to receive 6% hetastarch (Hespan) 500 ml followed by Hartmann\\'s solution 500 ml (group HS, n = 32) or a bolus injection of methoxamine 10 mg i.m. (group MX, n = 30), 10 min before induction of spinal anaesthesia with 0.5% hyperbaric bupivacaine 2.25-3.0 ml. Arterial pressure was measured non-invasively by an oscillotonometer at 2-min intervals from 0 to 40 min and at 5-min intervals thereafter. Methoxamine 2 mg i.v. was given if systolic arterial pressure (SAP) decreased to < 100 mm Hg. Hypotension was defined as a 25% decrease from baseline SAP or mean arterial pressure (MAP). Patient data, sensory level and blood loss were similar in the two groups. SAP and MAP increased initially from baseline until induction of spinal anaesthesia and then decreased for 30 min in both groups, but remained higher in group MX (P < 0.05). Heart rate (HR) decreased from baseline in group MX (P < 0.05) and was less than in group HS at all times from 2 to 60 min (P < 0.01). The incidence of SAP hypotension (47% vs 75%; P = 0.03, odds ratio (OR) = 3.43) and MAP hypotension (47% vs 67%; P = 0.09, OR = 2.51) was less in group MX than in group HS. Requirements for rescue methoxamine i.v. (27% vs 53%, P = 0.04, OR = 3.11) was less in group MX than in group HS but the dose of rescue methoxamine given (mean 6.3 (95% confidence intervals 3.0-9.6) vs 8.9 (5.6-12.2) mg) and time to onset of hypotension (20.7 (14.5-26.7) vs 17.3 (11.4-23.1) min) were similar in groups MX and HS, respectively. We conclude that methoxamine 10 mg i.m., given 10 min before induction of spinal anaesthesia in normovolaemic elderly patients, reduced subsequent SAP and

  18. Studying respiratory rhythm generation in a developing bird: Hatching a new experimental model using the classic in vitro brainstem-spinal cord preparation.

    Science.gov (United States)

    Vincen-Brown, Michael A; Whitesitt, Kaitlyn C; Quick, Forrest G; Pilarski, Jason Q

    2016-04-01

    It has been more than thirty years since the in vitro brainstem-spinal cord preparation was first presented as a method to study automatic breathing behaviors in the neonatal rat. This straightforward preparation has led to an incredible burst of information about the location and coordination of several spontaneously active microcircuits that form the ventrolateral respiratory network of the brainstem. Despite these advances, our knowledge of the mechanisms that regulate central breathing behaviors is still incomplete. Investigations into the nature of spontaneous breathing rhythmicity have almost exclusively focused on mammals, and there is a need for comparative experimental models to evaluate several unresolved issues from a different perspective. With this in mind, we sought to develop a new avian in vitro model with the long term goal to better understand questions associated with the ontogeny of respiratory rhythm generation, neuroplasticity, and whether multiple, independent oscillators drive the major phases of breathing. The fact that birds develop in ovo provides unparalleled access to central neuronal networks throughout the prenatal period - from embryo to hatchling - that are free from confounding interactions with mother. Previous studies using in vitro avian models have been strictly limited to the early embryonic period. Consequently, the details and even the presence of brainstem derived breathing-related rhythmogenesis in birds have never been described. In the present study, we used the altricial zebra finch (Taeniopygia guttata) and show robust spontaneous motor outflow through cranial motor nerve IX, which is first detectable on embryonic day four and continues through prenatal and early postnatal development without interruption. We also show that brainstem oscillations change dramatically over the course of prenatal development, sometimes within hours, which suggests rapid maturational modifications in growth and connectivity. We propose

  19. Radiographic evaluation of experimentally induced nephrosis in goats

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, R.; Pandey, N. N.; Singh, G. R.; Setia, H. C. [Indian Veterinary Research Institute, Izatnagar (India)

    1995-06-15

    Intravenous pyelography (IVP) with pneumoperitoneum (PP) was undertaken in normal and induced nephrotic goats. In normal goats, the technique provided visualization of both the kidneys, renal pelvis, ureter and urinary bladder at 10 min post-administration of sodium iothalamate (70%). In mercuric chloride- and oxytetracycline-induced nephrosis in goats, the urinary tract could not be visualized even 60 min post-administration of dye indicating sever failure of renal excretory function. However, in gentamicin-abused goats, renal excretory function was not significantly altered owing to a very mild renal damage. It was concluded that IVP with PP could be a dependable diagnostic test for varied degree of renal insufficiency in ruminants.

  20. Radiographic evaluation of experimentally induced nephrosis in goats

    International Nuclear Information System (INIS)

    Kumar, R.; Pandey, N.N.; Singh, G.R.; Setia, H.C.

    1995-01-01

    Intravenous pyelography (IVP) with pneumoperitoneum (PP) was undertaken in normal and induced nephrotic goats. In normal goats, the technique provided visualization of both the kidneys, renal pelvis, ureter and urinary bladder at 10 min post-administration of sodium iothalamate (70%). In mercuric chloride- and oxytetracycline-induced nephrosis in goats, the urinary tract could not be visualized even 60 min post-administration of dye indicating sever failure of renal excretory function. However, in gentamicin-abused goats, renal excretory function was not significantly altered owing to a very mild renal damage. It was concluded that IVP with PP could be a dependable diagnostic test for varied degree of renal insufficiency in ruminants

  1. An experimental facility for microwave induced plasma processing of materials

    International Nuclear Information System (INIS)

    Patil, D.S.; Ramachandran, K.; Bhide, A.L.; Venkatramani, N.

    1997-01-01

    Microwave induced plasma processing offers many advantages over conventional processes. However this technology is in the development stage. This report gives a detailed information about a microwave plasma processing facility (2.45 GHz, 700 W) set up in the Laser and Plasma Technology Division. The equipment details and the results obtained on deposition of diamond like carbon (DLC) thin films and surface modification of polymer PET (polyethylene terephthalate) using this facility are given in this report. (author)

  2. Experimental study of microwave-induced thermoacoustic imaging

    Science.gov (United States)

    Jacobs, Ryan T.

    Microwave-Induced Thermoacoustic Imaging (TAI) is a noninvasive hybrid modality which improves contrast by using thermoelastic wave generation induced by microwave absorption. Ultrasonography is widely used in medical practice as a low-cost alternative and supplement to magnetic resonance imaging (MRI). Although ultrasonography has relatively high image resolution (depending on the ultrasonic wavelength at diagnostic frequencies), it suffers from low image contrast of soft tissues. In this work samples are irradiated with sub-microsecond electromagnetic pulses inducing acoustic waves in the sample that are then detected with an unfocused transducer. The advantage of this hybrid modality is the ability to take advantage of the microwave absorption coefficients which provide high contrast in tissue samples. This in combination with the superior spatial resolution of ultrasound waves is important to providing a low-cost alternative to MRI and early breast cancer detection methods. This work describes the implementation of a thermoacoustic experiment using a 5 kW peak power microwave source.

  3. Host response in bovine mastitis experimentally induced with Staphylococcus chromogenes.

    Science.gov (United States)

    Simojoki, H; Orro, T; Taponen, S; Pyörälä, S

    2009-02-16

    An experimental infection model was developed to study host response to intramammary infection in cows caused by Staphylococcus chromogenes. CNS intramammary infections have become very common in modern dairy herds, and they can remain persistent in the mammary gland. More information would be needed about the pathophysiology of CNS mastitis, and an experimental mastitis model is a means for this research. Six primiparous Holstein-Friesian cows were challenged with S. chromogenes 4 weeks after calving. One udder quarter of each cow was inoculated with 2.1 x 10(6)cfu of S. chromogenes. All cows became infected and clinical signs were mild. Milk production of the challenged quarter decreased on average by 16.3% during 7 days post-challenge. Cows eliminated bacteria in a few days, except for one cow which developed persistent mastitis. Milk indicators of inflammation, SCC and N-acetyl-beta-D-glucosaminidase (NAGase) returned to normal within a week. Milk NAGase activity increased moderately, which reflects minor tissue damage in the udder. Concentrations of serum amyloid A (SAA) and milk amyloid A (MAA) were both elevated at 12h PC. MAA was affected by the milking times, and was at its highest before the morning milking. In our experimental model, systemic acute phase protein response with SAA occurred as an on-off type reaction. In conclusion, this experimental model could be used to study host response in CNS mastitis caused by the main CNS species and also for comparison of the host response in a mild intramammary infection and in more severe mastitis models.

  4. Ectopic expression of Ptf1a induces spinal defects, urogenital defects, and anorectal malformations in Danforth's short tail mice.

    Directory of Open Access Journals (Sweden)

    Kei Semba

    Full Text Available Danforth's short tail (Sd is a semidominant mutation on mouse chromosome 2, characterized by spinal defects, urogenital defects, and anorectal malformations. However, the gene responsible for the Sd phenotype was unknown. In this study, we identified the molecular basis of the Sd mutation. By positional cloning, we identified the insertion of an early transposon in the Sd candidate locus approximately 12-kb upstream of Ptf1a. We found that insertion of the transposon caused overexpression of three neighboring genes, Gm13344, Gm13336, and Ptf1a, in Sd mutant embryos and that the Sd phenotype was not caused by disruption of an as-yet-unknown gene in the candidate locus. Using multiple knockout and knock-in mouse models, we demonstrated that misexpression of Ptf1a, but not of Gm13344 or Gm13336, in the notochord, hindgut, cloaca, and mesonephros was sufficient to replicate the Sd phenotype. The ectopic expression of Ptf1a in the caudal embryo resulted in attenuated expression of Cdx2 and its downstream target genes T, Wnt3a, and Cyp26a1; we conclude that this is the molecular basis of the Sd phenotype. Analysis of Sd mutant mice will provide insight into the development of the spinal column, anus, and kidney.

  5. Experimental tests of induced spatial incoherence using short laser wavelength

    International Nuclear Information System (INIS)

    Obenschain, S.P.; Grun, J.; Herbst, M.J.

    1986-01-01

    The authors have developed a laser beam smoothing technique called induced spatial incoherence (ISI), which can produce the highly uniform focal profiles required for direct-drive laser fusion. Uniform well-controlled focal profiles are required to obtain the highly symmetric pellet implosions needed for high-energy gain. In recent experiments, the authors' tested the effects of ISI on high-power laser-target interaction. With short laser wavelength, the coupling physics dramatically improved over that obtained with an ordinary laser beam

  6. Shock induced response of structural systems analytical and experimental investigations

    International Nuclear Information System (INIS)

    Stangenberg, F.

    1984-01-01

    This contribution refers to the behaviour of reinforced concrete structures impacted by deformable missiles. The difference with hard missile impact problems, about which generally more knowledge exists, are point out. Structural response effects beyond the immediate contact face vicinity, beyond the local load introduction zone - i.e. effects of punching shear, of bending, of vibration transmission etc. - are emphasized. Two- and three-dimensional analytical approaches verified by experimental evaluations are discussed, and typical phenomena of the behaviour of reinforced concrete structures subjected to impact loads are demonstrated. (Author) [pt

  7. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    Directory of Open Access Journals (Sweden)

    Liu Xian-Guo

    2011-03-01

    Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

  8. Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia

    Directory of Open Access Journals (Sweden)

    Kobayashi Kimiko

    2008-04-01

    Full Text Available Abstract Background Honeybee's sting on human skin can induce ongoing pain, hyperalgesia and inflammation. Injection of bee venom (BV into the intraplantar surface of the rat hindpaw induces an early onset of spontaneous pain followed by a lasting thermal and mechanical hypersensitivity in the affected paw. The underlying mechanisms of BV-induced thermal and mechanical hypersensitivity are, however, poorly understood. In the present study, we investigated the role of mitogen-activated protein kinase (MAPK in the generation of BV-induced pain hypersensitivity. Results We found that BV injection resulted in a quick activation of p38, predominantly in the L4/L5 spinal dorsal horn ipsilateral to the inflammation from 1 hr to 7 d post-injection. Phosphorylated p38 (p-p38 was expressed in both neurons and microglia, but not in astrocytes. Intrathecal administration of the p38 inhibitor, SB203580, prevented BV-induced thermal hypersensitivity from 1 hr to 3 d, but had no effect on mechanical hypersensitivity. Activated ERK1/2 was observed exclusively in neurons in the L4/L5 dorsal horn from 2 min to 1 d, peaking at 2 min after BV injection. Intrathecal administration of the MEK inhibitor, U0126, prevented both mechanical and thermal hypersensitivity from 1 hr to 2 d. p-ERK1/2 and p-p38 were expressed in neurons in distinct regions of the L4/L5 dorsal horn; p-ERK1/2 was mainly in lamina I, while p-p38 was mainly in lamina II of the dorsal horn. Conclusion The results indicate that differential activation of p38 and ERK1/2 in the dorsal horn may contribute to the generation and development of BV-induced pain hypersensitivity by different mechanisms.

  9. Cardioprotective effect of mumie (shilajit) on experimentally induced myocardial injury.

    Science.gov (United States)

    Joukar, Siyavash; Najafipour, Hamid; Dabiri, Shahriar; Sheibani, Mohammad; Sharokhi, Nader

    2014-09-01

    This study assessed the effects of mumie (shilajit) pre-treatment, a traditional drug which is well known in the ancient medicine of both east and west, on cardiac performance of rats subjected to myocardial injury. Animals were divided into control, M250, and M500 (received mumie at dosages of 250 and 500 mg/kg/day, orally for 7 days, respectively) main groups each consisting of two subgroups-with and without heart injury. On the 6th and 7th days, isoproterenol (ISO) (85 mg/kg i.p.) was injected (s.c.) to half of the animal subgroups to induce myocardial damage. On the 8th day, after hemodynamic parameter recordings, hearts were removed for further evaluation. Mumie pre-treatment had no significant effects on hemodynamic and cardiac indices of normal animals. When the cardiac injury was induced, mumie maintained the ±dp/dt maximum, attenuated the serum cardiac troponin I, and reduced the severity of cardiac lesions. Despite the mild positive effects of mumie on total antioxidant capacity and lipid proxidation index, no significant difference was observed among animal groups. The findings suggest the prominent cardioprotective effect of mumie against destructive effects of ISO. It seems that other mechanisms than reinforcements of antioxidant system are involved in this beneficial effect.

  10. An experimental investigation of proton-induced phenomena in krypton

    International Nuclear Information System (INIS)

    Mulders, J.J.L.

    1985-01-01

    In this thesis proton-induced phenomena in krypton gas are described. The considered reactions of protons on krypton are both nuclear and atomic. The nuclear conversion processes mainly result in the production of several Rb radioisotopes, such as 81 Rb that is used in 81 Rb-sup(81m)Kr generator systems for medical diagnostics. The irradiation of krypton gas (natural composition) with protons of about 26 MeV can be used for the routine production of 81 Rb from the direct production reaction 82 Kr(p,2n) 81 Rb and from the indirect reaction 82 Kr(p,2n)sup(81m)Rb → 81 Rb. To determine the scattering of protons in krypton gas targets a quantitative autoradiographic technique was developed. Proton profiles have been determined from the proton-induced activity distribution on a copper foil. For the on-line detection of produced Rb radioisotopes several optical detection techniques were investigated. (Auth.)

  11. Tobacco experimental model to induce urinary bladder neoplasms

    Directory of Open Access Journals (Sweden)

    José Alexandre Colli Neto

    2014-01-01

    Full Text Available OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin and the concentration of carbon dioxide (CO2 confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking.

  12. Numerical-experimental assessment of roughness-induced metal-polymer interface failure

    NARCIS (Netherlands)

    Beeck, van J.; Schreurs, P.J.G.; Geers, M.G.D.

    2015-01-01

    A numerical–experimental method is presented to study the initiation and growth of interface damage in polymer–steel interfaces subjected to deformation-induced steel surface roughening. The experimentally determined displacement field of an evolving steel surface is applied to a numerical model

  13. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... spinal cord injury? play_arrow What kind of surgery is common after a spinal cord injury? play_ ... How soon after a spinal cord injury should surgery be performed? play_arrow Is it common to ...

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... L Sarah Harrison, OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury ... a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? ...

  15. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury Diane M. Rowles, MS, NP How Family Life Changes After Spinal Cord Injury Nancy Rosenberg, ... Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW ...

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury ... Jennifer Piatt, PhD David Chen, MD Read Bio Medical Director, Spinal Cord Injury Rehabilitation Program, Rehabilitation Institute ...

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising ...

  18. Spinal Cord Injury 101

    Medline Plus

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

  19. Spinal Cord Injury 101

    Medline Plus

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

  20. Spinal Cord Diseases

    Science.gov (United States)

    Your spinal cord is a bundle of nerves that runs down the middle of your back. It carries signals back ... of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such ...

  1. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW Rehabilitation ...

  2. Spinal cord contusion.

    Science.gov (United States)

    Ju, Gong; Wang, Jian; Wang, Yazhou; Zhao, Xianghui

    2014-04-15

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

  3. Alleviating effects of morin against experimentally-induced diabetic osteopenia

    Directory of Open Access Journals (Sweden)

    Abuohashish Hatem M

    2013-02-01

    Full Text Available Abstract Background Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of aging diseases particularly bone metabolic disorders. Morin (3,5,7,20,40-pentahydroxyflavone, a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. The present study was designed to investigate the putative beneficial effect of morin on diabetic osteopenia in rats. Methods Streptozotocin (STZ-induced diabetic model was used by considering 300 mg/dl fasting glucose level as diabetic. Morin (15 and 30 mg/kg was treated for five consecutive weeks to diabetic rats. Serum levels of glucose, insulin, deoxypyridinoline cross links (DPD, osteocalcin (OC, bone specific alkaline phosphatase (BALP, telopeptides of collagen type I (CTX, interleukin 1 beta (IL-1β, interleukin 6 (IL-6, tumor necrosis factor alpha (TNF-α, thiobarbituric acid reactive substance (TBARS and reduced glutathione (GSH were estimated. Femoral bones were taken for micro CT scan to measure trabecular bone mineral density (BMD and other morphometric parameters. Results Significant bone loss was documented as the level of bone turnover parameters including DPD, OC, BALP and CTX were increased in serum of diabetic rats. Morin treatment significantly attenuated these elevated levels. Bone micro-CT scan of diabetic rats showed a significant impairment in trabecular bone microarchitecture, density and other morphometric parameters. These impairments were significantly ameliorated by morin administration. Serum levels of glucose, TBARS, IL-1β, IL-6 and TNF-α were significantly elevated, while the level of insulin and GSH was decreased in diabetic rats. These serum changes in diabetic rats were bring back to normal values after 5 weeks morin treatment. Conclusion These findings revealed the protective effect of morin against diabetic induced osteopenia. We believed that this effect is through its both the anti

  4. Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury.

    Science.gov (United States)

    Zhang, Shu-xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

    2010-08-30

    Intrathecal infusion has been widely used to directly deliver drugs or neurotrophins to a lesion site following spinal cord injury. Evidence shows that intrathecal infusion is efficient for 7 days but is markedly reduced after 14 days, due to time dependent occlusion. In addition, extensive fibrotic scarring is commonly observed with intrathecal infusion. These anomalies need to be clearly elucidated in histology. In the present study, all adult Long-Evans rats received a 25 mm contusion injury on spinal cord T10 produced using the NYU impactor device. Immediately after injury, catheter tubing with an outer diameter of 0.38 mm was inserted through a small dural opening at L3 into the subdural space with the tubing tip positioned near the injury site. The tubing was connected to an Alzet mini pump, which was filled with saline solution and was placed subcutaneously. Injured rats without tubing served as control. Rats were behaviorally tested for 6 weeks using the BBB locomotor rating scale and histologically assessed for tissue scarring. Six weeks later, we found that the intrathecal tubing caused extensive scarring and inflammation, related to neutrophils, macrophages and plasma cells. The tubing's tip was occluded by scar tissue and inflammatory cells. The scar tissue surrounding the tubing consists of 20-70 layers of fibroblasts and densely compacted collagen fibers, seriously compressing and damaging the cord tissue. BBB scores of rats with intrathecal tubing were significantly lower than control rats (p<0.01) from 2 weeks after injury, implying serious impairment of functional recovery caused by the scarring. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  5. Chitosan scaffolds induce human dental pulp stem cells to neural differentiation: potential roles for spinal cord injury therapy.

    Science.gov (United States)

    Zhang, Jinlong; Lu, Xiaohui; Feng, Guijuan; Gu, Zhifeng; Sun, Yuyu; Bao, Guofeng; Xu, Guanhua; Lu, Yuanzhou; Chen, Jiajia; Xu, Lingfeng; Feng, Xingmei; Cui, Zhiming

    2016-10-01

    Cell-based transplantation strategies hold great potential for spinal cord injury (SCI) repair. Chitosan scaffolds have therapeutic benefits for spinal cord regeneration. Human dental pulp stem cells (DPSCs) are abundant available stem cells with low immunological incompatibility and can be considered for cell replacement therapy. The purpose of this study is to investigate the role of chitosan scaffolds in the neural differentiation of DPSCs in vitro and to assess the supportive effects of chitosan scaffolds in an animal model of SCI. DPSCs were incubated with chitosan scaffolds. Cell viability and the secretion of neurotrophic factors were analyzed. DPSCs incubated with chitosan scaffolds were treated with neural differentiation medium for 14 days and then neural genes and protein markers were analyzed by Western blot and reverse transcription plus the polymerase chain reaction. Our study revealed a higher cell viability and neural differentiation in the DPSC/chitosan-scaffold group. Compared with the control group, the levels of BDNF, GDNF, b-NGF, and NT-3 were significantly increased in the DPSC/chitosan-scaffold group. The Wnt/β-catenin signaling pathway played a key role in the neural differentiation of DPSCs combined with chitosan scaffolds. Transplantation of DPSCs together with chitosan scaffolds into an SCI rat model resulted in the marked recovery of hind limb locomotor functions. Thus, chitosan scaffolds were non-cytotoxic and provided a conducive and favorable microenvironment for the survival and neural differentiation of DPSCs. Transplantation of DPSCs might therefore be a suitable candidate for treating SCI and other neuronal degenerative diseases.

  6. Markovian Analysis of the Sequential Behavior of the Spontaneous Spinal Cord Dorsum Potentials Induced by Acute Nociceptive Stimulation in the Anesthetized Cat

    Directory of Open Access Journals (Sweden)

    Mario Martin

    2017-05-01

    Full Text Available In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials (CDPs. This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure to identify portions of signals as belonging to a specific functional state of connectivity among the neuronal networks involved in the generation of the CDPs. We have tested this procedure during acute nociceptive stimulation produced by the intradermic injection of capsaicin in intact as well as spinalized preparations. Altogether, our results indicate that CDP sequences cannot be generated by a renewal stochastic process. Moreover, it is possible to describe some functional features of activity in the cord dorsum by modeling the CDP sequences as generated by a Markov order one stochastic process. Finally, these Markov models make possible to determine the functional state which produced a CDP sequence. The proposed identification procedures appear to be useful for the analysis of the sequential behavior of the ongoing CDPs recorded from different spinal segments in response to a variety of experimental procedures including the changes produced by acute nociceptive

  7. Dietary oregano essential oil alleviates experimentally induced coccidiosis in broilers.

    Science.gov (United States)

    Mohiti-Asli, M; Ghanaatparast-Rashti, M

    2015-06-15

    An experiment was conducted to determine the effects of oregano essential oil on growth performance and coccidiosis prevention in mild challenged broilers. A total of 250 1-d-old chicks were used in a completely randomized design with 5 treatments and 5 replicates with 10 birds in each replication. Experimental treatments included: (1) negative control (NC; unchallenged), (2) positive control (PC; challenged with sporulated oocysts of Eimeria), (3) PC fed 200 ppm Diclazuril in diet, (4) PC fed 300 ppm oregano oil in diet, and (5) PC fed 500 ppm oregano oil in diet. At 22 d of age, all the experimental groups except for NC were challenged with 50-fold dose of Livacox T as a trivalent live attenuated coccidiosis vaccine. On d 28, two birds were slaughtered and intestinal coccidiosis lesions were scored 0-4. Moreover, dropping was scored in the scale of 0-3, and oocysts per gram feces (OPG) were measured. Oregano oil at either supplementation rate increased body weight gain (P=0.039) and improved feed conversion ratio (P=0.010) from d 22 to 28, when compared with PC group. Using 500 ppm oregano oil in challenged broilers diet increased European efficiency factor than PC group (P=0.020). Moreover, challenged broilers fed 500 ppm oregano oil or Diclazuril in diets displayed lower coccidiosis lesions scores in upper (P=0.003) and middle (P=0.018) regions of intestine than PC group, with the effect being similar to unchallenged birds. In general, challenged birds fed 500 ppm oregano oil or Diclazuril in diets had lower OPG (P=0.001), dropping scores (P=0.001), litter scores (P=0.001), and pH of litter (P=0.001) than PC group. It could be concluded that supplementation of oregano oil at the dose of 500 ppm in diet may have beneficial effect on prevention of coccidiosis in broilers. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Flagella-induced immunity against experimental cholera in adult rabbits.

    Science.gov (United States)

    Yancey, R J; Willis, D L; Berry, L J

    1979-07-01

    The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone.

  9. Experimental photoimmunology: immunologic ramifications of UV-induced carcinogenesis

    International Nuclear Information System (INIS)

    Daynes, R.A.; Bernhard, E.J.; Gurish, M.F.; Lynch, D.H.

    1981-01-01

    The use of animal model systems to investigate the sequence of events which lead to the induction and progression of skin tumors following chronic ultraviolet light (UVL) exposure has clearly shown that the direct mutagenic effects of UVL is only one of the components involved in this process. In spite of the fact that overt carcinogenesis is only one of the many effects produced by UV light, most hypotheses as to the mechanism by which UVL can cause the mutations necessary to achieve the transformed phenotype have focused on the direct effects of UVL on DNA and the generation of carcinogenic compounds. Investigations during the last 5 yr, however, have clearly demonstrated that immunologic factors are also critically important in the pathogenesis of UV-induced skin cancers. A complete understanding of UV-carcinogenesis must therefore consider the mechanisms which allow the transformed cell to evade immunologic rejection by the host in addition to those aspects which deal with conversion of a normal cell to a cancer cell. It is the object of this review to provide both a historical account of the work which established the immunologic consequences of chronic UVL exposure and the results of recent experiments designed to investigate the kinetics and mechanisms by which UVL affects the immunologic apparatus. In addition, a hypothetical model is presented to explain the sequence of events which ultimately lead to the emergence of the suppressor T-cells which regulate antitumor immune responses

  10. Electrical stimulation induces propagated colonic contractions in an experimental model.

    Science.gov (United States)

    Aellen, S; Wiesel, P H; Gardaz, J-P; Schlageter, V; Bertschi, M; Virag, N; Givel, J-C

    2009-02-01

    Direct colonic electrical stimulation may prove to be a treatment option for specific motility disorders such as chronic constipation. The aim of this study was to provoke colonic contractions using electrical stimulation delivered from a battery-operated device. Electrodes were inserted into the caecal seromuscular layer of eight anaesthetized pigs. Contractions were induced by a neurostimulator (Medtronic 3625). Caecal motility was measured simultaneously by video image analysis, manometry and a technique assessing colonic transit. Caecal contractions were generated using 8-10 V amplitude, 1000 micros pulse width, 120 Hz frequency for 10-30 s, with an intensity of 7-15 mA. The maximal contraction strength was observed after 20-25 s. Electrical stimulation was followed by a relaxation phase of 1.5-2 min during which contractions propagated orally and aborally over at least 10 cm. Spontaneous and stimulated caecal motility values were significantly different for both intraluminal pressure (mean(s.d.) 332(124) and 463(187) mmHg respectively; P < 0.001, 42 experiments) and movement of contents (1.6(0.9) and 3.9(2.8) mm; P < 0.001, 40 experiments). Electrical stimulation modulated caecal motility, and provoked localized and propagated colonic contractions.

  11. Photodynamic therapy induced vascular damage: an overview of experimental PDT

    International Nuclear Information System (INIS)

    Wang, W; Moriyama, L T; Bagnato, V S

    2013-01-01

    Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed. (review)

  12. TOLERANCE TIME OF EXPERIMENTAL THERMAL PAIN (COLD INDUCED) IN VOLUNTEERS.

    Science.gov (United States)

    Vaid, V N; Wilkhoo, N S; Jain, A K

    1998-10-01

    Perception of thermal pain (cold induced) was studied in 106 volunteers from troops and civilians deployed in J & K. Thermal stimulus devised was "holding ice". Tolerance time of holding ice was taken to be a measure of thermal sensitivity, volunteers were classified based on their native areas, addiction habits and socio-economic status, out of 106 volunteers, 81 could & 25 could not hold ice over 10 min. Sixteen out of 40 from coastline States and 9 out of 66 from non-coast line States failed to hold ice over 10 min. In "below average" "average" and "high average" socio-economic groups, three out of 27, 19 out of 73 and 03 out of 6 failed to hold ice over 10 min respectively. Fifteen out of 64 from "addiction habit group" and 10 out of 42 from "no addiction habit group" failed to hold ice over 10 min. Statistically no classification used in the study revealed significant difference in "tolerance times" of volunteers except the one based on coastline and non-coastline States.

  13. Experimentally induced metamorphosis in axolotls reduces regenerative rate and fidelity

    Science.gov (United States)

    Stier, Adrian C.; Michonneau, François; Smith, Matthew D.; Pasch, Bret; Maden, Malcolm

    2014-01-01

    Abstract While most tetrapods are unable to regenerate severed body parts, amphibians display a remarkable ability to regenerate an array of structures. Frogs can regenerate appendages as larva, but they lose this ability around metamorphosis. In contrast, salamanders regenerate appendages as larva, juveniles, and adults. However, the extent to which fundamental traits (e.g., metamorphosis, body size, aging, etc.) restrict regenerative ability remains contentious. Here we utilize the ability of normally paedomorphic adult axolotls (Ambystoma mexicanum) to undergo induced metamorphosis by thyroxine exposure to test how metamorphosis and body size affects regeneration in age‐matched paedomorphic and metamorphic individuals. We show that body size does not affect regeneration in adult axolotls, but metamorphosis causes a twofold reduction in regeneration rate, and lead to carpal and digit malformations. Furthermore, we find evidence that metamorphic blastemal cells may take longer to traverse the cell cycle and display a lower proliferative rate. This study identifies the axolotl as a powerful system to study how metamorphosis restricts regeneration independently of developmental stage, body size, and age; and more broadly how metamorphosis affects tissue‐specific changes. PMID:27499857

  14. Experimental Traumatic Brain Injury Induces Bone Loss in Rats.

    Science.gov (United States)

    Brady, Rhys D; Shultz, Sandy R; Sun, Mujun; Romano, Tania; van der Poel, Chris; Wright, David K; Wark, John D; O'Brien, Terence J; Grills, Brian L; McDonald, Stuart J

    2016-12-01

    Few studies have investigated the influence of traumatic brain injury (TBI) on bone homeostasis; however, pathophysiological mechanisms involved in TBI have potential to be detrimental to bone. The current study assessed the effect of experimental TBI in rats on the quantity and quality of two different weight-bearing bones, the femur and humerus. Rats were randomly assigned into either sham or lateral fluid percussion injury (FPI) groups. Open-field testing to assess locomotion was conducted at 1, 4, and 12 weeks post-injury, with the rats killed at 1 and 12 weeks post-injury. Bones were analyzed using peripheral quantitative computed tomography (pQCT), histomorphometric analysis, and three-point bending. pQCT analysis revealed that at 1 and 12 weeks post-injury, the distal metaphyseal region of femora from FPI rats had reduced cortical content (10% decrease at 1 week, 8% decrease at 12 weeks; p in trabecular bone volume ratio at 1 week post-injury and a 27% reduction at 12 weeks post-injury in FPI rats compared to sham (p in bone quantity and mechanical properties of the femoral midshaft between sham and TBI animals. There were no differences in locomotor outcomes, which suggested that post-TBI changes in bone were not attributed to immobility. Taken together, these findings indicate that this rat model of TBI was detrimental to bone and suggests a link between TBI and altered bone remodeling.

  15. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    Science.gov (United States)

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-09-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

  16. Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats.

    Science.gov (United States)

    Fang, Jian-Qiao; Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan

    2013-03-22

    Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.

  17. Effects of articaine on [3H]noradrenaline release from cortical and spinal cord slices prepared from normal and streptozotocin-induced diabetic rats and compared to lidocaine.

    Science.gov (United States)

    Végh, D; Somogyi, A; Bányai, D; Lakatos, M; Balogh, M; Al-Khrasani, M; Fürst, S; Vizi, E S; Hermann, P

    2017-10-01

    Since a significant proportion of diabetic patients have clinical or subclinical neuropathy, there may be concerns about the use of local anaesthetics. The present study was designed to determine and compare the effects of articaine, a widely used anaesthetic in dental practice, and lidocaine on the resting and axonal stimulation-evoked release of [ 3 H]noradrenaline ([ 3 H]NA) in prefrontal cortex slices and the release of [ 3 H]NA in spinal cord slices prepared from non-diabetic and streptozocin (STZ)-induced diabetic (glucose level=22.03±2.31mmol/l) rats. The peak of allodynia was achieved 9 weeks after STZ-treatment. Articaine and lidocaine inhibited the stimulation-evoked release in a concentration-dependent manner and increased the resting release by two to six times. These effects indicate an inhibitory action of these anaesthetics on Na + - and K + -channels. There was no difference in clinically important nerve conduction between non-diabetic and diabetic rats, as measured by the release of transmitter in response to axonal stimulation. The uptake and resting release of NA was significantly higher in the brain slices prepared from diabetic rats, but there were no differences in the spinal cord. For the adverse effects, the effects of articaine on K + channels (resting release) are more pronounced compared to lidocaine. In this respect, articaine has a thiophene ring with high lipid solubility, which may present potential risks for some patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Jarvis Michael F

    2011-05-01

    Full Text Available Abstract Background Intra-articular injection of monosodium iodoacetate (MIA in the knee joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration and subsequent nociceptive behavior that has been described as a model of osteoarthritis (OA pain. Central sensitization through activation of mitogen activated protein kinases (MAPKs is recognized as a pathogenic mechanism in chronic pain. In the present studies, induction of central sensitization as indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 phosphorylation, was assessed in the MIA-OA model. Results Behaviorally, MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks post-MIA treatment. In the same animals, activation of phospho ERK1/2 was gradually increased, reaching a significant level at post injection week 3. Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection week 1 and decreased, but remained elevated, thereafter. Double labeling from 3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but not astrocytes. Additionally, there was increased ipsilateral expression of microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force and pERK1/2 induction in MIA-OA rats. Conclusion Results of these studies support the role of MAPK activation in the progression and maintenance of central sensitization in the MIA-OA experimental pain model.

  19. Experimental particle acceleration by water evaporation induced by shock waves

    Science.gov (United States)

    Scolamacchia, T.; Alatorre Ibarguengoitia, M.; Scheu, B.; Dingwell, D. B.; Cimarelli, C.

    2010-12-01

    Shock waves are commonly generated during volcanic eruptions. They induce sudden changes in pressure and temperature causing phase changes. Nevertheless, their effects on flowfield properties are not well understood. Here we investigate the role of gas expansion generated by shock wave propagation in the acceleration of ash particles. We used a shock tube facility consisting of a high-pressure (HP) steel autoclave (450 mm long, 28 mm in internal diameter), pressurized with Ar gas, and a low-pressure tank at atmospheric conditions (LP). A copper diaphragm separated the HP autoclave from a 180 mm tube (PVC or acrylic glass) at ambient P, with the same internal diameter of the HP reservoir. Around the tube, a 30 cm-high acrylic glass cylinder, with the same section of the LP tank (40 cm), allowed the observation of the processes occurring downstream from the nozzle throat, and was large enough to act as an unconfined volume in which the initial diffracting shock and gas jet expand. All experiments were performed at Pres/Pamb ratios of 150:1. Two ambient conditions were used: dry air and air saturated with steam. Carbon fibers and glass spheres in a size range between 150 and 210 μm, were placed on a metal wire at the exit of the PVC tube. The sudden decompression of the Ar gas, due to the failure of the diaphragm, generated an initial air shock wave. A high-speed camera recorded the processes between the first 100 μsec and several ms after the diaphragm failure at frame rates ranging between 30,000 and 50,000 fps. In the experiments with ambient air saturated with steam, the high-speed camera allowed to visualize the condensation front associated with the initial air shock; a maximum velocity of 788 m/s was recorded, which decreases to 524 m/s at distance of 0.5 ±0.2 cm, 1.1 ms after the diaphragm rupture. The condensation front preceded the Ar jet front exhausting from the reservoir, by 0.2-0.5 ms. In all experiments particles velocities following the initial

  20. The potential role of amlodipine on experimentally induced bacterial rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Arzu Tatar

    Full Text Available Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione and an oxidative product (malondialdehyde were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

  1. Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review.

    Science.gov (United States)

    Mazensky, David; Flesarova, Slavka; Sulla, Igor

    2017-12-01

    Animal models are used to examine the results of experimental spinal cord injury. Alterations in spinal cord blood supply caused by complex spinal cord injuries contribute significantly to the diversity and severity of the spinal cord damage, particularly ischemic changes. However, the literature has not completely clarified our knowledge of anatomy of the complex three-dimensional arterial system of the spinal cord in experimental animals, which can impede the translation of experimental results to human clinical applications. As the literary sources dealing with the spinal cord arterial blood supply in experimental animals are limited and scattered, the authors performed a review of the anatomy of the arterial blood supply to the spinal cord in several experimental animals, including pigs, dogs, cats, rabbits, guinea pigs, rats, and mice and created a coherent format discussing the interspecies differences. This provides researchers with a valuable tool for the selection of the most suitable animal model for their experiments in the study of spinal cord ischemia and provides clinicians with a basis for the appropriate translation of research work to their clinical applications. Anat Rec, 300:2091-2106, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Environmental enrichment restores cognitive deficits induced by experimental childhood meningitis

    Directory of Open Access Journals (Sweden)

    Tatiana Barichello

    2014-12-01

    Full Text Available Objective: To evaluate the influence of environmental enrichment (EE on memory, cytokines, and brain-derived neurotrophic factor (BDNF in the brain of adult rats subjected to experimental pneumococcal meningitis during infancy. Methods: On postnatal day 11, the animals received either artificial cerebrospinal fluid (CSF or Streptococcus pneumoniae suspension intracisternally at 1 × 106 CFU/mL and remained with their mothers until age 21 days. Animals were divided into the following groups: control, control + EE, meningitis, and meningitis + EE. EE began at 21 days and continued until 60 days of age (adulthood. EE consisted of a large cage with three floors, ramps, running wheels, and objects of different shapes and textures. At 60 days, animals were randomized and subjected to habituation to the open-field task and the step-down inhibitory avoidance task. After the tasks, the hippocampus and CSF were isolated for analysis. Results: The meningitis group showed no difference in performance between training and test sessions of the open-field task, suggesting habituation memory impairment; in the meningitis + EE group, performance was significantly different, showing preservation of habituation memory. In the step-down inhibitory avoidance task, there were no differences in behavior between training and test sessions in the meningitis group, showing aversive memory impairment; conversely, differences were observed in the meningitis + EE group, demonstrating aversive memory preservation. In the two meningitis groups, IL-4, IL-10, and BDNF levels were increased in the hippocampus, and BDNF levels in the CSF. Conclusions: The data presented suggest that EE, a non-invasive therapy, enables recovery from memory deficits caused by neonatal meningitis.

  3. Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.

    Science.gov (United States)

    Renard, E; Gaudin, A; Bienvenu, G; Amiaud, J; Farges, J C; Cuturi, M C; Moreau, A; Alliot-Licht, B

    2016-02-01

    Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria. © International & American

  4. Experimental model to induce obesity in rats Modelo experimental para induzir obesidade em ratos

    Directory of Open Access Journals (Sweden)

    Vinicius Von Diemen

    2006-12-01

    Full Text Available The etiology of obesity is multifactorial and is becoming a problem of public health, due to its increased prevalence and the consequent repercussion of its comorbidities on the health of the population. The great similarity and homology between the genomes of rodents and humans make these animal models a major tool to study conditions affecting humans, which can be simulated in rats. Obesity can be induced in animals by neuroendocrine, dietary or genetic changes. The most widely used models to induce obesity in rats are a lesion of the ventromedial hypothalamic nucleus (VMH by administering monosodium glutamate or a direct electrical lesion, ovariectomy, feeding on hypercaloric diets and genetic manipulation for obesity.A obesidade tem etiologia multifatorial e está se tornando um problema de saúde pública devido ao aumento da sua prevalência e a conseqüente repercusão das suas comorbidades na saúde da população. A grande similaridade e homologia entre os genomas dos roedores e dos humanos tornam esses modelos animais uma importante ferramenta para o estudo de condições que afetam os humanos e que podem ser simuladas em ratos. A obesidade pode ser induzida em animais com alterações neuroendócrinas, dietéticas ou genéticas. Os modelos mais utilizados para indução de obesidade em ratos são lesão do núcleo hipotalâmico venteromedial (VMH através da administração de glutamato monossódico ou lesão elétrica direta, ooforectomia, alimentação com dietas hipercalóricas e manipulação genética para obesidade.

  5. Sonic hedgehog signaling in spinal cord contributes to morphine-induced hyperalgesia and tolerance through upregulating brain-derived neurotrophic factor expression

    Directory of Open Access Journals (Sweden)

    Liu S

    2018-04-01

    signaling. In naïve mice, exogenous activation of Shh signaling caused a rapid increase of BDNF expression, as well as thermal hyperalgesia. Inhibiting BDNF significantly suppressed smoothened agonist-induced hyperalgesia. Conclusion: These findings suggest that Shh signaling may be a critical mediator for MIH and tolerance by regulating BDNF expression. Inhibiting Shh signaling, especially during the early phase, may effectively delay or suppress MIH and tolerance. Keywords: sonic hedgehog, tolerance, hyperalgesia, brain-derived neurotrophic factor, spinal cord

  6. Spinal cord excitability is not influenced by elevated blood lactate levels.

    Science.gov (United States)

    Coco, Marinella; Alagona, Giovanna; Perciavalle, Valentina; Cicirata, Valentina; Perciavalle, Vincenzo

    2011-01-01

    The aim of the present study was to examine the association of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, with spinal cord excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, while 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, also at the end as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the spinal α-motoneurons was evaluated by using the H reflex technique. In both experimental conditions, it has been observed that an exhaustive exercise is associated with a strong increase of blood lactate (but not of blood glucose) and with a significant reduction of spinal excitability. Since a similar augment of blood lactate induced by an intravenous infusion, in subjects not performing any exercise, is not associated with significant changes of spinal excitability, it can be concluded that the increase of blood lactate levels during a maximal exercise is not per se capable of modifying the excitability of spinal α-motoneurons.

  7. Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability

    DEFF Research Database (Denmark)

    Jimenez, Samuel; Mordillo-Mateos, Laura; Dileone, Michele

    2018-01-01

    obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short......Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS....... In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H...

  8. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Abuse and Spinal Cord Injury Allen Heinemann, PhD How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal ... What is a spinal cord injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a ...

  9. Shedding light on restoring respiratory function after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Warren J Alilain

    2009-10-01

    Full Text Available Loss of respiratory function is one of the leading causes of death following spinal cord injury. Because of this, much work has been done in studying ways to restore respiratory function following SCI - including pharmacological and regeneration strategies. With the emergence of new and powerful tools from molecular neuroscience, new therapeutically relevant alternatives to these approaches have become available, including expression of light sensitive proteins called channelrhodopsins. In this article we briefly review the history of various attempts to restore breathing after C2 hemisection, and focus on our recent work using the activation of light sensitive channels to restore respiratory function after experimental spinal cord injury. We also discuss how such light induced activity can help shed light on the inner workings of the central nervous system respiratory circuitry that controls diaphragmatic function.

  10. Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

    Directory of Open Access Journals (Sweden)

    Sudhira Begum

    2007-12-01

    Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

  11. Tramadol Induced Adrenal Insufficiency: Histological, Immunohistochemical, Ultrastructural, and Biochemical Genetic Experimental Study

    OpenAIRE

    Abdelaleem, Shereen Abdelhakim; Hassan, Osama A.; Ahmed, Rasha F.; Zenhom, Nagwa M.; Rifaai, Rehab A.; El-Tahawy, Nashwa F.

    2017-01-01

    Tramadol is a synthetic, centrally acting analgesic. It is the most consumed narcotic drug that is prescribed in the world. Tramadol abuse has dramatically increased in Egypt. Long term use of tramadol can induce endocrinopathy. So, the aim of this study was to analyze the adrenal insufficiency induced by long term use of tramadol in experimental animals and also to assess its withdrawal effects through histopathological and biochemical genetic study. Forty male albino rats were used in this ...

  12. Comparative experimental study of cancer induced by ionizing radiations or by chemical carcinogens

    International Nuclear Information System (INIS)

    Lafuma, J.

    1983-01-01

    Animal experiments have contributed to specify a number of parameters used in setting human safety limits for ionizing radiation. In the same way, comparisons have been made between cancers induced in man and in animals in well-defined conditions. In order to use the same experimental data for chemical carcinogens, the mechanisms of carcinogenesis should be the same, i.e. additivity of responses instead of synergy of effects, which requires the development of a new experimental method [fr

  13. Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression.

    Science.gov (United States)

    Fakherpour, Atousa; Ghaem, Haleh; Fattahi, Zeinabsadat; Zaree, Samaneh

    2018-01-01

    Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS. This prospective study was conducted on 511 mother-infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS. The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m 2 , 11-20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) 100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T 4 in anaesthesia-related modelling ( P < 0.05). Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS.

  14. Effects of electrical stimulation-induced gluteal versus gluteal and hamstring muscles activation on sitting pressure distribution in persons with a spinal cord injury.

    Science.gov (United States)

    Smit, C A J; Haverkamp, G L G; de Groot, S; Stolwijk-Swuste, J M; Janssen, T W J

    2012-08-01

    Ten participants underwent two electrical stimulation (ES) protocols applied using a custom-made electrode garment with built-in electrodes. Interface pressure was measured using a force-sensitive area. In one protocol, both the gluteal and hamstring (g+h) muscles were activated, in the other gluteal (g) muscles only. To study and compare the effects of electrically induced activation of g+h muscles versus g muscles only on sitting pressure distribution in individuals with a spinal cord injury (SCI). Ischial tuberosities interface pressure (ITs pressure) and pressure gradient. In all participants, both protocols of g and g+h ES-induced activation caused a significant decrease in IT pressure. IT pressure after g+h muscles activation was reduced significantly by 34.5% compared with rest pressure, whereas a significant reduction of 10.2% after activation of g muscles only was found. Pressure gradient reduced significantly only after stimulation of g+h muscles (49.3%). g+h muscles activation showed a decrease in pressure relief (Δ IT) over time compared with g muscles only. Both protocols of surface ES-induced of g and g+h activation gave pressure relief from the ITs. Activation of both g+h muscles in SCI resulted in better IT pressure reduction in sitting individuals with a SCI than activation of g muscles only. ES might be a promising method in preventing pressure ulcers (PUs) on the ITs in people with SCI. Further research needs to show which pressure reduction is sufficient in preventing PUs.

  15. Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression

    Directory of Open Access Journals (Sweden)

    Atousa Fakherpour

    2018-01-01

    Full Text Available Background and Aims: Although spinal anaesthesia (SA is nowadays the preferred anaesthesia technique for caesarean section (CS, it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques associated with the incidence of different degrees of SA-induced hypotension during elective CS. Methods: This prospective study was conducted on 511 mother–infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age and anaesthesia-related risk factors (such as block height were associated with occurance of SA-induced hypotension during elective CS. Results: The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m2, 11–20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP 100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T4in anaesthesia-related modelling (P < 0.05. Conclusion: Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS.

  16. Effects of spinal cord injury-induced changes in muscle activation on foot drag in a computational rat ankle model.

    Science.gov (United States)

    Hillen, Brian K; Jindrich, Devin L; Abbas, James J; Yamaguchi, Gary T; Jung, Ranu

    2015-04-01

    Spinal cord injury (SCI) can lead to changes in muscle activation patterns and atrophy of affected muscles. Moderate levels of SCI are typically associated with foot drag during the swing phase of locomotion. Foot drag is often used to assess locomotor recovery, but the causes remain unclear. We hypothesized that foot drag results from inappropriate muscle coordination preventing flexion at the stance-to-swing transition. To test this hypothesis and to assess the relative contributions of neural and muscular changes on foot drag, we developed a two-dimensional, one degree of freedom ankle musculoskeletal model with gastrocnemius and tibialis anterior muscles. Anatomical data collected from sham-injured and incomplete SCI (iSCI) female Long-Evans rats as well as physiological data from the literature were used to implement an open-loop muscle dynamics model. Muscle insertion point motion was calculated with imposed ankle trajectories from kinematic analysis of treadmill walking in sham-injured and iSCI animals. Relative gastrocnemius deactivation and tibialis anterior activation onset times were varied within physiologically relevant ranges based on simplified locomotor electromyogram profiles. No-atrophy and moderate muscle atrophy as well as normal and injured muscle activation profiles were also simulated. Positive moments coinciding with the transition from stance to swing phase were defined as foot swing and negative moments as foot drag. Whereas decreases in activation delay caused by delayed gastrocnemius deactivation promote foot drag, all other changes associated with iSCI facilitate foot swing. Our results suggest that even small changes in the ability to precisely deactivate the gastrocnemius could result in foot drag after iSCI. Copyright © 2015 the American Physiological Society.

  17. Dynamic Pain Phenotypes are Associated with Spinal Cord Stimulation-Induced Reduction in Pain: A Repeated Measures Observational Pilot Study.

    Science.gov (United States)

    Campbell, Claudia M; Buenaver, Luis F; Raja, Srinivasa N; Kiley, Kasey B; Swedberg, Lauren J; Wacnik, Paul W; Cohen, Steven P; Erdek, Michael A; Williams, Kayode A; Christo, Paul J

    2015-07-01

    Spinal cord stimulation (SCS) has become a widely used treatment option for a variety of pain conditions. Substantial variability exists in the degree of benefit obtained from SCS and patient selection is a topic of expanding interest and importance. However, few studies have examined the potential benefits of dynamic quantitative sensory testing (QST) to develop objective measures of SCS outcomes or as a predictive tool to help patient selection. Psychological characteristics have been shown to play an important role in shaping individual differences in the pain experience and may aid in predicting responses to SCS. Static laboratory pain-induction measures have also been examined in their capacity for predicting SCS outcomes. The current study evaluated clinical, psychological and laboratory pain measures at baseline, during trial SCS lead placement, as well as 1 month and 3 months following permanent SCS implantation in chronic pain patients who received SCS treatment. Several QST measures were conducted, with specific focus on examination of dynamic models (central sensitization and conditioned pain modulation [CPM]) and their association with pain outcomes 3 months post SCS implantation. Results suggest few changes in QST over time. However, central sensitization and CPM at baseline were significantly associated with clinical pain at 3 months following SCS implantation, controlling for psycho/behavioral factors and pain at baseline. Specifically, enhanced central sensitization and reduced CPM were associated with less self-reported pain 3 months following SCS implantation. These findings suggest a potentially important role for dynamic pain assessment in individuals undergoing SCS, and hint at potential mechanisms through which SCS may impart its benefit. Wiley Periodicals, Inc.

  18. The State of Play with iPSCs and Spinal Cord Injury Models

    Directory of Open Access Journals (Sweden)

    Stuart I. Hodgetts

    2015-01-01

    Full Text Available The application of induced pluripotent stem cell (iPSC technologies in cell based strategies, for the repair of the central nervous system (with particular focus on the spinal cord, is moving towards the potential use of clinical grade donor cells. The ability of iPSCs to generate donor neuronal, glial and astrocytic phenotypes for transplantation is highlighted here, and we review recent research using iPSCs in attempts to treat spinal cord injury in various animal models. Also discussed are issues relating to the production of clinical grade iPSCs, recent advances in transdifferentiation protocols for iPSC-derived donor cell populations, concerns about tumourogenicity, and whether iPSC technologies offer any advantages over previous donor cell candidates or tissues already in use as therapeutic tools in experimental spinal cord injury studies.

  19. Spinal pain

    International Nuclear Information System (INIS)

    Izzo, R.; Popolizio, T.; D’Aprile, P.; Muto, M.

    2015-01-01

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

  20. 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

  1. Nutrient Induced Type 2 and Chemical Induced Type 1 Experimental Diabetes Differently Modulate Gastric GLP-1 Receptor Expression

    Directory of Open Access Journals (Sweden)

    Olga Bloch

    2015-01-01

    Full Text Available T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO by high-energy (HE diet and by streptozotocin (STZ in Sprague Dawly (SD rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

  2. 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

  3. Spinal stenosis

    International Nuclear Information System (INIS)

    Beale, S.; Pathria, M.N.; Ross, J.S.; Masaryk, T.J.; Modic, M.T.

    1988-01-01

    The authors studied 50 patients who had spinal stenosis by means of MR imaging. All patients had undergone myelography and CT. Thirty patients underwent surgery. MR imaging included T1-weighted spin echo sequences with repetition time = 600 msec, echo time = 20 (600/20) sagittal and axial sections 4 mm thick with 2 mm gap. T2-weighted 2,000/60 axial images were obtained on 14 patients. Examinations were retrospectively evaluated for central stenosis, lateral recess narrowing, and foraminal encroachment. Measurements of sagittal, interpedicular, interfacet, and recess dimensions were made at L3-5. On MR images, 20 patients had single-level and 30 had multiple-level stenosis. There was excellent agreement between modalities with central canal stenosis, but a discrepancy in six patients with bony foraminal stenosis. MR imaging was an accurate method for assessment of lumbar stenosis, but CT appears marginally better for detection of bony foraminal stenosis in certain cases

  4. Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch.

    Directory of Open Access Journals (Sweden)

    Alexandru D P Papoiu

    2011-03-01

    Full Text Available Histamine is the prototypical pruritogen used in experimental itch induction. However, in most chronic pruritic diseases, itch is not predominantly mediated by histamine. Cowhage-induced itch, on the other hand, seems more characteristic of itch occurring in chronic pruritic diseases.We tested the validity of cowhage as an itch-inducing agent by contrasting it with the classical itch inducer, histamine, in healthy subjects and atopic dermatitis (AD patients. We also investigated whether there was a cumulative effect when both agents were combined.Fifteen healthy individuals and fifteen AD patients were recruited. Experimental itch induction was performed in eczema-free areas on the volar aspects of the forearm, using different itch inducers: histamine, cowhage and their combination thereof. Itch intensity was assessed continuously for 5.5 minutes after stimulus application using a computer-assisted visual analogue scale (COVAS.In both healthy and AD subjects, the mean and peak intensity of itch were higher after the application of cowhage compared to histamine, and were higher after the combined application of cowhage and histamine, compared to histamine alone (p<0.0001 in all cases. Itch intensity ratings were not significantly different between healthy and AD subjects for the same itch inducer used; however AD subjects exhibited a prolonged itch response in comparison to healthy subjects (p<0.001.Cowhage induced a more intense itch sensation compared to histamine. Cowhage was the dominant factor in itch perception when both pathways were stimulated in the same time. Cowhage-induced itch is a suitable model for the study of itch in AD and other chronic pruritic diseases, and it can serve as a new model for testing antipruritic drugs in humans.

  5. Experimental Study on Piezoelectric Energy Harvesting from Vortex-Induced Vibrations and Wake-Induced Vibrations

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    Min Zhang

    2016-01-01

    Full Text Available A rigid circular cylinder with two piezoelectric beams attached on has been tested through vortex-induced vibrations (VIV and wake-induced vibrations (WIV by installing a big cylinder fixed upstream, in order to study the influence of the different flow-induced vibrations (FIV types. The VIV test shows that the output voltage increases with the increases of load resistance; an optimal load resistance exists for the maximum output power. The WIV test shows that the vibration of the small cylinder is controlled by the vortex frequency of the large one. There is an optimal gap of the cylinders that can obtain the maximum output voltage and power. For a same energy harvesting device, WIV has higher power generation capacity; then the piezoelectric output characteristics can be effectively improved.

  6. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    Science.gov (United States)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

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

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    Dominic M. Maggio

    2017-01-01

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

  8. Hybrid equation/agent-based model of ischemia-induced hyperemia and pressure ulcer formation predicts greater propensity to ulcerate in subjects with spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Alexey Solovyev

    Full Text Available Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI. People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation.

  9. Status of experimental data of proton-induced reactions for intermediate-energy nuclear data evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Yukinobu; Kawano, Toshihiko [Kyushu Univ., Fukuoka (Japan); Yamano, Naoki; Fukahori, Tokio

    1998-11-01

    The present status of experimental data of proton-induced reactions is reviewed, with particular attention to total reaction cross section, elastic and inelastic scattering cross section, double-differential particle production cross section, isotope production cross section, and activation cross section. (author)

  10. 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.

  11. An analysis of plasticity in the rat respiratory system following cervical spinal cord injury and the application of nanotechnology to induce or enhance recovery of diaphragm function

    Science.gov (United States)

    Walker, Janelle

    Second cervical segment spinal cord hemisection (C2Hx) results in ipsilateral hemidiaphragm paralysis. However, the intact latent crossed phrenic pathway can restore function spontaneously over time or immediately following drug administration. WGA bound fluorochromes were administered to identify nuclei associated with diaphragm function in both the acute and chronic C2Hx models. WGA is unique in that it undergoes receptor mediated endocytosis and is transsynaptically transported across select physiologically active synapses. Comparison of labeling in the acutely injured to the chronically injured rat provided an anatomical map of spinal and supraspinal injury induced synaptic plasticity. The plasticity occurs over time in the chronic C2Hx model in an effort to adapt to the loss of hemidiaphragm function. Utilizing the selectivity of WGA, a nanoconjugate was developed to target drug delivery to nuclei involved in diaphragm function post C2Hx in an effort to restore lost function. Theophylline was selected due to its established history as a respiratory stimulant. Theophylline was attached to gold nanoparticles by a transient bond designed to degrade intracellularly. The gold nanoparticles were then permanently attached to WGA-HRP. Following intradiaphragmatic injection, the WGA portion was identified in the ipsilateral phrenic nuclei and bilaterally in the rVRGs. The location of WGA should reflect the location of the AuNP since the peptide bond between them is permanent. The effectiveness of the nanoconjugate was verified with EMG analysis of the diaphragm and recordings from the phrenic nerves. All doses administered in the acute C2Hx model resulted in resorted hemidiaphragm and phrenic nerve activity. A dose of 0.14mg/kg had a significantly higher percent recovery on day 3, whereas 0.03mg/kg was significantly higher on day 14. The change in most effective dose over time is likely due to the availability or concentration of the drug and location of drug release

  12. Experimental and Theoretical Investigation of Shock-Induced Reactions in Energetic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Jeffrey J. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Park, Samuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kohl, Ian Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Knepper, Robert [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Farrow, Darcie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tappan, Alexander S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-01

    In this work, shock-induced reactions in high explosives and their chemical mechanisms were investigated using state-of-the-art experimental and theoretical techniques. Experimentally, ultrafast shock interrogation (USI, an ultrafast interferometry technique) and ultrafast absorption spectroscopy were used to interrogate shock compression and initiation of reaction on the picosecond timescale. The experiments yielded important new data that appear to indicate reaction of high explosives on the timescale of tens of picoseconds in response to shock compression, potentially setting new upper limits on the timescale of reaction. Theoretically, chemical mechanisms of shock-induced reactions were investigated using density functional theory. The calculations generated important insights regarding the ability of several hypothesized mechanisms to account for shock-induced reactions in explosive materials. The results of this work constitute significant advances in our understanding of the fundamental chemical reaction mechanisms that control explosive sensitivity and initiation of detonation.

  13. Local Wavelet-Based Filtering of Electromyographic Signals to Eliminate the Electrocardiographic-Induced Artifacts in Patients with Spinal Cord Injury.

    Science.gov (United States)

    Nitzken, Matthew; Bajaj, Nihit; Aslan, Sevda; Gimel'farb, Georgy; El-Baz, Ayman; Ovechkin, Alexander

    2013-07-18

    Surface Electromyography (EMG) is a standard method used in clinical practice and research to assess motor function in order to help with the diagnosis of neuromuscular pathology in human and animal models. EMG recorded from trunk muscles involved in the activity of breathing can be used as a direct measure of respiratory motor function in patients with spinal cord injury (SCI) or other disorders associated with motor control deficits. However, EMG potentials recorded from these muscles are often contaminated with heart-induced electrocardiographic (ECG) signals. Elimination of these artifacts plays a critical role in the precise measure of the respiratory muscle electrical activity. This study was undertaken to find an optimal approach to eliminate the ECG artifacts from EMG recordings. Conventional global filtering can be used to decrease the ECG-induced artifact. However, this method can alter the EMG signal and changes physiologically relevant information. We hypothesize that, unlike global filtering, localized removal of ECG artifacts will not change the original EMG signals. We develop an approach to remove the ECG artifacts without altering the amplitude and frequency components of the EMG signal by using an externally recorded ECG signal as a mask to locate areas of the ECG spikes within EMG data. These segments containing ECG spikes were decomposed into 128 sub-wavelets by a custom-scaled Morlet Wavelet Transform. The ECG-related sub-wavelets at the ECG spike location were removed and a de-noised EMG signal was reconstructed. Validity of the proposed method was proven using mathematical simulated synthetic signals and EMG obtained from SCI patients. We compare the Root-mean Square Error and the Relative Change in Variance between this method, global, notch and adaptive filters. The results show that the localized wavelet-based filtering has the benefit of not introducing error in the native EMG signal and accurately removing ECG artifacts from EMG signals.

  14. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage

    OpenAIRE

    Venditti, Paola; Pamplona Gras, Reinald; Ayala, Victoria; Rosa, R. de; Caldarone, G.; Di Meo, S.

    2006-01-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T-3)- or thyroxine (T-4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most ex...

  15. Protective effects of ebselen on sodium-selenite-induced experimental cataract in rats.

    Science.gov (United States)

    Aydemir, Orhan; Güler, Mete; Kaya, Mehmet Kaan; Deniz, Nurettin; Üstündağ, Bilal

    2012-12-01

    To determine whether ebselen has a protective effect or antioxidative potential in a sodium-selenite-induced experimental cataract model. Fırat University, Elazığ, Turkey. Experimental study. Twenty-one Sprague-Dawley rat pups were randomly divided into a control group, a sodium-selenite-induced-cataract group, and an ebselen-treated group; each group contained 7 rat pups. Rats in the control group received dimethyl sulfoxide (DMSO) intraperitoneally only and rats in the sodium-selenite-induced-cataract group received 30 nmol/g body weight sodium selenite subcutaneously and DMSO intraperitoneally 10 days postpartum. Rats in the ebselen group received 30 nmol/g body weight sodium selenite subcutaneously 10 days postpartum and were treated with 5 mg/kg body weight ebselen once a day for 4 consecutive days. Cataract development was assessed weekly for 3 weeks by slitlamp examination and graded using a scale. Reduced glutathione (GSH), total nitrite, and malondialdehyde (MDA) levels in lens supernatants were measured at the end of 3 weeks. In the control group, all lenses were clear. In the ebselen-treated group, the mean cataract stage was significantly lower than in the sodium-selenite-induced-cataract group (P = .022). The GSH levels were significantly lower in the sodium-selenite-induced-cataract group than in the control and ebselen groups (P ebselen group than in the sodium-selenite-induced-cataract group (P ebselen group (P = .001). Ebselen had a protective effect on cataract development in a sodium-selenite-induced experimental model. The protective effect of ebselen appears to be due to inhibition of oxidative stress. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  16. The effect of preferred music genre selection versus preferred song selection on experimentally induced anxiety levels.

    Science.gov (United States)

    Walworth, Darcy DeLoach

    2003-01-01

    The purpose of this study was to investigate the differences of experimentally induced anxiety levels reached by subjects listening to no music (n = 30), subjects listening to music selected by the experimenter from the subject's preferred genre or artist listed as relaxing (n = 30), and subjects listening to a specific song they listed as relaxing (n = 30). Subjects consisted of 90 individuals, male and female, randomly assigned to one of the three groups mentioned above. Subjects in either music group filled out a questionnaire prior to participating in the study indicating their preference of music used for relaxation purposes. Subjects in Experimental Group 1 marked their preferred genres and/or artists, and Experimental Group 2 marked specific songs used for relaxation purposes. While the experimenter hypothesized subjects in Experimental Group 2 would show less anxiety than both the control group and Experimental Group 1, there were no significant differences found between the 2 music groups in anxiety levels reached. However, there was a statistically significant difference between the no music control group and both music groups in the anxiety level reached by subjects. Subjects listening to music, both songs chosen by the experimenter and subject selected songs, showed significantly less anxiety than subjects not listening to music.

  17. Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice

    OpenAIRE

    Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B.E.; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P.; Shields, Christopher B.

    2014-01-01

    Objective Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG1...

  18. Experimental research on recombinant human endostatin-induced cardiomyocyte apoptosis in rats

    Directory of Open Access Journals (Sweden)

    Jing QIN

    2014-03-01

    Full Text Available Objective To explore the recombinant human endostatin (rh-ES-induced cardiotoxicity in rats and its mechanism. Methods Twenty four female Wistar rats were randomly divided into four groups (6 each. Rats in low, moderate and high dose group received rh-ES with a dosage of 3, 6 and 12mg/(kg·d, respectively, by intraperitoneal injection, and rats in control group received the same amount of normal saline alone. Half of rats in each group were sacrificed by spinal dislocation after 4 weeks and 8 weeks of the treatment. Pathomorphologic and ultrastructural changes in rat's myocardial tissue were evaluated by light microscopy and transmission electron microscopy. Cardiomyocyte apoptosis was detected with TdT-mediated dUTP nick end labeling (TUNEL assay. Microvessel density (MVD in myocardial tissue was measured by immunohistochemically marking endothelial cell with CD34. Results No pathomorphologic and ultrastrucural changes were found under light microscope and transmission electron microscope in the low dose and moderate dose groups, but cardiomyocyte damage were found in the high dose group. TUNEL assay revealed more apoptotic cells in high and moderate (only 8 weeks dose groups than in control group (P=0.033, P=0.000, and the apoptosis index was highest in the high dose group at 8 weeks. In addition, compared with the control group, MVD significantly increased in high dose groups at 4 weeks and 8 weeks (P<0.05. Conclusions rh-ES induces the cardiotoxicity in rats, and cardiomyocyte apoptosis is involved in the pathological course of cardiac toxicity. DOI: 10.11855/j.issn.0577-7402.2014.01.02

  19. Experimental gingivitis induces systemic inflammatory markers in young healthy individuals: a single-subject interventional study.

    Science.gov (United States)

    Eberhard, Jörg; Grote, Karsten; Luchtefeld, Maren; Heuer, Wieland; Schuett, Harald; Divchev, Dimitar; Scherer, Ralph; Schmitz-Streit, Ruth; Langfeldt, Daniela; Stumpp, Nico; Staufenbiel, Ingmar; Schieffer, Bernhard; Stiesch, Meike

    2013-01-01

    We here investigated whether experimental gingivitis enhances systemic markers of inflammation which are also known as surrogate markers of atherosclerotic plaque development. Gingivitis is a low-level oral infection induced by bacterial deposits with a high prevalence within Western populations. A potential link between the more severe oral disease periodontitis and cardiovascular disease has already been shown. 37 non-smoking young volunteers with no inflammatory disease or any cardiovascular risk factors participated in this single-subject interventional study with an intra-individual control. Intentionally experimental oral inflammation was induced by the interruption of oral hygiene for 21 days, followed by a 21-days resolving phase after reinitiation of oral hygiene. Primary outcome measures at baseline, day 21 and 42 were concentrations of hsCRP, IL-6, and MCP-1, as well as adhesion capacity and oxLDL uptake of isolated blood monocytes. The partial cessation of oral hygiene procedures was followed by the significant increase of gingival bleeding (34.0%, Pgingivitis. Bacterial-induced gingival low-level inflammation induced a systemic increase in inflammatory markers. Dental hygiene almost completely reversed this experimental inflammatory process, suggesting that appropriate dental prophylaxis may also limit systemic markers of inflammation in subjects with natural gingivitis. International Clinical Trials Register Platform of the World Health Organization, registry number: DRKS00003366, URL: http://apps.who.int/trialsearch/Default.aspx.

  20. Microbiological profile and calprotectin expression in naturally occurring and experimentally induced gingivitis.

    Science.gov (United States)

    Farina, Roberto; Guarnelli, Maria Elena; Figuero, Elena; Herrera, David; Sanz, Mariano; Trombelli, Leonardo

    2012-10-01

    This study was performed to evaluate the microbiological profile and the calprotectin expression in gingival crevicular fluid (GCF) in spontaneous and experimentally induced gingival inflammation. Thirty-seven periodontally healthy subjects were evaluated in real life conditions (N-O gingivitis) as well as after 21 days of experimental gingivitis trial (E-I gingivitis). During the experimental gingivitis trial, in one maxillary quadrant (test quadrant), gingival inflammation was induced by oral hygiene abstention, while in the contralateral (control) quadrant, oral hygiene was routinely continued. The results of the study showed that (1) the microbiological profile of quadrants where gingival inflammation was experimentally induced (i.e., E-I test quadrants) differed significantly from that of either quadrants where gingival inflammation was controlled by proper plaque control (i.e., E-I control quadrants) or quadrants with N-O gingivitis, and (2) GCF calprotectin was significantly higher at E-I test quadrants compared to either E-I control quadrants or quadrants with N-O gingivitis. A positive intrasubject correlation was found between GCF concentration of calprotectin at sites presenting N-O and E-I gingivitis. N-O and E-I gingivitis showed a different microbiological profile of the subgingival environment. GCF calprotectin is a reliable marker of gingival inflammation, and its concentration in N-O gingivitis is correlated with its expression in E-I gingivitis. The modality of plaque accumulation seems to affect the subgingival microbiological profile associated with a gingivitis condition. Calprotectin levels in GCF may be regarded as a promising marker of the individual susceptibility to develop gingival inflammation in response to experimentally induced plaque accumulation.

  1. Spinal Cord Injury 101

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    Full Text Available ... About Media Donate Spinal Cord Injury Medical Expert Videos ... Home Kim Eberhardt Muir, MS Coping with a New Injury Robin Dorman, PsyD Sex and Fertility After Spinal Cord Injury Diane M. ...

  2. Spinal Cord Injury 101

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    Full Text Available ... of Spinal Cord Injury Rehabilitation Kristine Cichowski, MS Occupational Therapy after Spinal Cord Injury Katie Powell, OT ... does not provide medical advice, recommend or endorse health care products or services, or control the information ...

  3. 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...

  4. Spinal Cord Injury 101

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    Full Text Available ... OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury Patti Rogers, SW Marguerite ... play_arrow What are the latest developments in the use of electrical stimulation for spinal ...

  5. Spinal Cord Injury 101

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    Full Text Available ... with SCI Personal Experiences by Topic Resources Peer Counseling Blog About Media Donate close search Understanding Spinal ... with SCI Personal Experiences by Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical ...

  6. Spinal Cord Injury 101

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    Full Text Available ... Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences ...

  7. Spinal Cord Injury 101

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    Full Text Available ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ...

  8. Spinal Cord Injury 101

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    Full Text Available ... of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  9. Spinal Cord Injury 101

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    Full Text Available ... spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  10. Spinal Cord Injury 101

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    Full Text Available ... Resources Peer Counseling Blog About Media Donate close search Understanding Spinal Cord Injury What is a Spinal ... health care products or services, or control the information found on external websites. The Hill Foundation is ...

  11. Spinal Cord Injury 101

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    Full Text Available ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ...

  12. Spinal Cord Injury 101

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    Full Text Available ... play_arrow What are the chances of regaining feeling and mobility after a spinal cord injury? play_arrow How long does it usually take for feeling and movement to return after a spinal cord ...

  13. Spinal Cord Injury 101

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    Full Text Available ... RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation ... Rogers, PT Recreational Therapy after Spinal Cord Injury Jennifer Piatt, PhD David Chen, MD Read Bio Medical ...

  14. Spinal Cord Injury 101

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    Full Text Available ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About Us Expert Videos Contact Us Personal Experience Videos Blog Videos By Topic Media Resources Donate to support families facing spinal cord ...

  15. Spinal cord stimulation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

  16. Spinal Cord Injury 101

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    Full Text Available ... Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ... a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? ...

  17. Activity and milk compositional changes following experimentally induced Streptococcus uberis bovine mastitis.

    Science.gov (United States)

    Kester, H J; Sorter, D E; Hogan, J S

    2015-02-01

    Milk constituents and physical activity of cows experimentally infected with Streptococcus uberis mastitis were compared with those of uninfected cows. Twelve late-lactation Holsteins cows were paired based on milk production and parity. One cow in each pair was experimentally infected in the right front mammary gland with Strep. uberis. The remaining cow in each pair served as an uninfected control. Real-time analyses of milk constituents provided fat, protein, and lactose percentages at each milking. Pedometers were placed on the left front leg of all cows and activity was measured. Intramammary infections with Strep. uberis reduced milk yield in experimental cows by approximately 1.6kg/d in the first week after challenge compared with control cows. Lactose percentage in milk was reduced on d 3, 4, 5, and 6 after challenge in treatment cows compared with controls. Percentages of fat and protein in milk did not differ between infected and uninfected cows the week after infections were induced. Total steps per day were reduced and minutes resting per day were increased the week after experimental challenge in infected cows compared with control cows. The number of resting bouts did not differ between infected and uninfected cows. Changes in percentage of lactose in milk and animal activity caused by experimentally induced Strep. uberis mastitis were detected by the automated milk analyzer and pedometer systems. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  18. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Directory of Open Access Journals (Sweden)

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  19. Phosphorus-31 magnetic resonance spectroscopy of experimentally induced arthritis in rats

    International Nuclear Information System (INIS)

    Blatter, D.D.

    1987-01-01

    Phosphorus-31 magnetic resonance spectroscopy (MRS) of the hind paws of rats was performed at 1.5 Tesla before and during the course of an experimentally-induced inflammatory arthritis. Arthritis was induced by daily subcutaneous administration of 6-sulfanilamidoindazole, an antibacterial sulfa known to produce an acute, self-limited arthritis and periarthritis in the hind paws of rats. Phosphorus-31 spectra obtained after the development of clinical arthritis showed a significant (p 31 P MRS may permit evaluation of the severity of an inflammatory arthritis with greater accuracy than the bony changes definable by plain roentgenograms. (orig.)

  20. Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma

    OpenAIRE

    Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Owusu-Afriyie, Osei

    2015-01-01

    Background Heliotropium indicum is used as a traditional remedy for hypertension in Ghana. The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H. indicum to manage experimentally-induced glaucoma. Methods The percentage change in intraocular pressure (IOP), after inducing acute glaucoma (15 mLkg?1 of 5?% dextrose, i.v.), in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract (HIE) (30?300 mgkg?1), acetazolamide (5 mg...

  1. Functional magnetic resonances imaging of psychological functions with experimentally induced emotion

    International Nuclear Information System (INIS)

    Grodd, W.; Schneider, F.; Klose, U.; Naegele, T.

    1995-01-01

    In this study a T 2 * FLASH sequence (TR 240 ms, TE 60 ms, slice thickness 4 mm, α=40 , matrix 64x128) was used to investigate changes in signal intensity within the temporal lobe and the amygdala during experimentally induced emotions. Visual stimuli of happy [sad] facial portraits were presented to volunteers to induce changes in the subjects' mood while lying in the tomograph. In agreement with a previous PET study, a significant increase in signal intensity in the left amygdala was found during induction of a sad mood, while no comparable effect was visible during induction of a happy mood. (orig.) [de

  2. Spinal segmental dysgenesis

    Directory of Open Access Journals (Sweden)

    N Mahomed

    2009-06-01

    Full Text Available Spinal segmental dysgenesis is a rare congenital spinal abnormality , seen in neonates and infants in which a segment of the spine and spinal cord fails to develop normally . The condition is segmental with normal vertebrae above and below the malformation. This condition is commonly associated with various abnormalities that affect the heart, genitourinary, gastrointestinal tract and skeletal system. We report two cases of spinal segmental dysgenesis and the associated abnormalities.

  3. Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury.

    Science.gov (United States)

    Figueroa, Johnny D; Cordero, Kathia; Llán, Miguel S; De Leon, Marino

    2013-05-15

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome.

  4. Dietary Omega-3 Polyunsaturated Fatty Acids Improve the Neurolipidome and Restore the DHA Status while Promoting Functional Recovery after Experimental Spinal Cord Injury

    Science.gov (United States)

    Figueroa, Johnny D.; Cordero, Kathia; llán, Miguel S.

    2013-01-01

    Abstract Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome. PMID:23294084

  5. Spinal Cord Injury 101

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    Full Text Available ... the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  6. Spinal Cord Injury 101

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    Full Text Available ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising new treatments for spinal cord injuries? play_arrow What are the latest developments in the use of electrical stimulation for spinal cord injuries? play_arrow ...

  7. 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 ...

  8. Spinal Cord Injury 101

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    Full Text Available ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  9. Bilateral passive leg raising attenuates and delays tourniquet deflation-induced hypotension and tachycardia under spinal anaesthesia: a randomised controlled trial.

    Science.gov (United States)

    Huang, Go-Shine; Wang, Chih-Chien; Hu, Mei-Hua; Cherng, Chen-Hwan; Lee, Meei-Shyuan; Tsai, Chien-Sung; Chan, Wei-Hung; Hsieh, Xhang-Xian; Lin, Leou-Chyr

    2014-01-01

    The pneumatic tourniquet is frequently used in total knee arthroplasty. Tourniquet deflation may result in hypotension and tachycardia caused by the rapid shift of blood volume back to the ischaemic limb and a decrease in cardiac preload. Passive leg raising (PLR) represents a 'self-volume challenge' that can result in an increase in preload. Such a PLR-induced increase in preload was hypothesised to attenuate the decrease in preload resulting from tourniquet deflation. To evaluate the effect of PLR on hypotension and tachycardia following tourniquet deflation. A randomised controlled trial. Single medical centre. Seventy patients who underwent unilateral total knee arthroplasty were randomised into two groups: tourniquet deflation with PLR (n = 35) or without PLR (control group, n = 35). Patients in both groups were administered a single dose of plain bupivacaine for spinal anaesthesia. The pneumatic tourniquet was inflated on the thigh and the surgery was performed. The study composed of four steps: for the PLR group, step 1 - inflation of the tourniquet while the patient was supine; step 2 - the patient's legs were raised to a 45° angle; step 3 - the tourniquet was deflated while the patient's legs were still raised; and step 4 - the legs were returned to the supine position. In the control group, the same perioperative procedure was used, but PLR was not conducted. The patients' blood pressure and heart rate were measured before, during and after tourniquet deflation. After tourniquet deflation, the magnitude of the changes in blood pressure and heart rate was less in the PLR group than that in the control group. In addition, the blood pressure nadir also occurred later in the PLR group than in the controls. Bilateral PLR is a simple, reversible manoeuvre that mimics rapid fluid loading. Bilateral PLR attenuates the severity of, and delays the time to, hypotension and tachycardia following deflation of a lower limb tourniquet. ClinicalTrials.gov number

  10. Radiation-induced myelopathy in long-term surviving metastatic spinal cord compression patients after hypofractionated radiotherapy: a clinical and magnetic resonance imaging analysis

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; Bellavita, Rita; Floridi, Piero; Celani, Grazia; Righetti, Enrico; Lupattelli, Marco; Panizza, Bianca Moira; Frattegiani, Alessandro; Pelliccioli, Gian Piero; Latini, Paolo

    2001-01-01

    Background and purpose: Hypofractionated radiotherapy is often administered in metastatic spinal cord compression (MSCC), but no studies have been published on the incidence of radiation-induced myelopathy (RIM) in long-term surviving patients. Our report addresses this topic. Patients and methods: Of 465 consecutive MSCC patients submitted to radiotherapy between 1988 and 1997, 13 live patients (seven females, six males, median age 69 years, median follow-up 69 months) surviving for 2 years or more were retrospectively reviewed to evaluate RIM. All patients underwent radiotherapy. Eight patients underwent a short-course regimen of 8 Gy, with 7 days rest, and then another 8 Gy. Five patients underwent a split-course regimen of 5 Gy x3, 4 days rest, and then 3 Gy x5. Only one patient also underwent laminectomy. Full neurological examination and magnetic resonance imaging (MRI) were performed. Results: Of 12 patients submitted to radiotherapy alone, 11 were ambulant (eight without support and three with support) with good bladder function. In nine of these 11 patients, MRI was negative; in one case MRI evidenced an in-field relapse 30 months after the end of radiotherapy, and in the other, two new MSCC foci outside the irradiated spine. In the remaining patient RIM was suspected at 18 months after radiotherapy when the patient became paraplegic and cystoplegic, and magnetic resonance images evidenced an ischemic injury in the irradiated area. The only patient treated with surgery plus postoperative radiotherapy worsened and remained paraparetic. Magnetic resonance images showed cord atrophy at the surgical level, explained as an ischemic necrosis due to surgery injury. Conclusions: On the grounds of our data regarding RIM in long-term surviving MSCC patients, we believe that a hypofractionated radiotherapy regimen can be used for the majority of patients. For a minority of patients, more protracted radiation regimens could be considered

  11. Modified cytoplasmic Ca2+ sequestration contributes to spinal cord injury-induced augmentation of nerve-evoked contractions in the rat tail artery.

    Directory of Open Access Journals (Sweden)

    Hussain Al Dera

    Full Text Available In rat tail artery (RTA, spinal cord injury (SCI increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

  12. Are there endogenous stem cells in the spinal cord?

    Science.gov (United States)

    Ferrucci, Michela; Ryskalin, Larisa; Busceti, Carla L; Gaglione, Anderson; Biagioni, Francesca; Fornai, Francesco

    2017-12-01

    Neural progenitor cells (NPC) represent the stem-like niche of the central nervous system that maintains a regenerative potential also in the adult life. Despite NPC in the brain are well documented, the presence of NPC in the spinal cord has been controversial for a long time. This is due to a scarce activity of NPC within spinal cord, which also makes difficult their identification. The present review recapitulates the main experimental studies, which provided evidence for the occurrence of NPC within spinal cord, with a special emphasis on spinal cord injury and amyotrophic lateral sclerosis. By using experimental models, here we analyse the site-specificity, the phenotype and the main triggers of spinal cord NPC. Moreover, data are reported on the effect of specific neurogenic stimuli on these spinal cord NPC in an effort to comprehend the endogenous neurogenic potential of this stem cell niche.

  13. Remyelination of the injured spinal cord

    Science.gov (United States)

    Sasaki, Masanori; Li, Bingcang; Lankford, Karen L.; Radtke, Christine; Kocsis, Jeffery D.

    2008-01-01

    Contusive spinal cord injury (SCI) can result in necrosis of the spinal cord, but often long white matter tracts outside of the central necrotic core are demyelinated. One experimental strategy to improve functional outcome following SCI is to transplant myelin-forming cells to remyelinate these axons and improve conduction. This review focuses on transplantation studies using olfactory ensheathing cell (OEC) to improve functional outcome in experimental models of SCI and demyelination. The biology of the OEC, and recent experimental research and clinical studies using OECs as a potential cell therapy candidate are discussed. PMID:17618995

  14. Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway

    Directory of Open Access Journals (Sweden)

    Song Fu

    2018-02-01

    Full Text Available Resveratrol, a polyphenol found in various plants, including grapes, plums and peanuts has shown various medIRInal properties, including antioxidant, protection of cardiovascular disease and cancer risk. However, the effects of resveratrol on spinal cord reperfusion injury have not been investigated. Hence, the present study was designed to evaluate the effect of resveratrol on nitric oxide synthase (iNOS/p38MAPK signaling pathway and to elucidate its regulating effect on the protection of spinal cord injury. Spinal cord ischemia–reperfusion injury (IRI was performed by the infrarenal abdominal aorta with mini aneurysm clip model. The expressions of iNOS and p38MAPK and the levels of biochemical parameters, including nitrite/nitrate, malondialdehyde (MDA, advanced oxidation products (AOPP, reduced glutathione (GSH, superoxide dismutase (SOD and catalase (CAT were measured in control and experimental groups. IRI-induced rats treated with 10 mg/kg resveratrol protected spinal cord from ischemia injury as supported by improved biological parameters measured in spinal cord tissue homogenates. The resveratrol treatment significantly decreased the levels of plasma nitrite/nitrate, iNOS mRNA and protein expressions and phosphorylation of p38MAPK in IRI-induced rats. Further, IRI-produced free radicals were reduced by resveratrol treatment by increasing enzymatic and non-enzymatic antioxidant levels such as GSH, SOD and CAT. Taken together, administration of resveratrol protects the damage caused by spinal cord ischemia with potential mechanism of suppressing the activation of iNOS/p38MAPK pathway and subsequent reduction of oxidative stress due to IRI.

  15. Trust and Cheating in Sri Lanka: The Role of Experimentally-Induced Emotions about Tsunam

    OpenAIRE

    Pierluigi Conzo

    2014-01-01

    Through a field experiment in Sri Lanka I analyze the role of experimentally-induced memories of 2004 tsunami on behavior in a trust game in which personal notions of cheating are elicited. Microfinance borrowers were randomly assigned to a treatment (control) group consisting in watching a video about the calamity before (after) playing. Trust game participants were asked how much to receive (return) in order not to (make the counterpart) feel cheated; in a survey they selected whether the v...

  16. Changes in thermal nociceptive responses in dairy cows following experimentally induced Esherichia coli mastitis

    DEFF Research Database (Denmark)

    Rasmussen, Ditte B.; Fogsgaard, Katrine; Røntved, Christine Maria

    2011-01-01

    Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS......) in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables....

  17. Experimentally induced spermatophore production and immune responses reveal a trade-off in crickets

    OpenAIRE

    Angela M. Kerr; Susan N. Gershman; Scott K. Sakaluk

    2010-01-01

    The energetic demands of the immune system and reproduction are often high and can lead to trade-offs between these 2 life-history traits. In decorated crickets, Gryllodes sigillatus, much of a male's reproductive effort is devoted to calling, and to the synthesis of a spermatophylax, a large, gelatinous, non--sperm-containing mass forming part of the spermatophore and consumed by the female after mating. We employed a reciprocal design in which we experimentally induced an immune response in...

  18. Experimental realization of an on-chip all-optical analogue to electromagnetically induced transparency.

    Science.gov (United States)

    Xu, Qianfan; Sandhu, Sunil; Povinelli, Michelle L; Shakya, Jagat; Fan, Shanhui; Lipson, Michal

    2006-03-31

    We provide the first experimental observation of structure tuning of the electromagnetically induced transparency-like spectrum in integrated on-chip optical resonator systems. The system consists of coupled silicon ring resonators with 10 microm diameter on silicon, where the coherent interference between the two coupled resonators is tuned. We measured a transparency-resonance mode with a quality factor of 11,800.

  19. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

    Science.gov (United States)

    Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

    2006-03-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

  20. Acute pulmonary injury induced by experimental muscle trauma Lesão pulmonar aguda induzida por trauma muscular experimental

    Directory of Open Access Journals (Sweden)

    Márcia Andréa da Silva Carvalho Sombra

    2011-01-01

    Full Text Available PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6: G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0ml i.p; G-3 rats were treated with dexamethasone (DE (2 mg/kg body weight i.p.. Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97% 100 ml/kg i.p. rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung were collected for myeloperoxidase (MPO assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.OBJETIVO: Desenvolver um modelo facilmente reprodutível de lesão pulmonar aguda decorrente de trauma muscular experimental em ratos sadios. MÉTODOS: Dezoito ratos Wistar adultos foram randomizados em 3 grupos (n=6: G-1-controle, G-2 - trauma+salina e G-3 - trauma+dexametasona. Grupos G-1 e G-2 foram tratados com salina 2,0 ml ip, G-3 ratos foram tratados com dexametasona (DE (2 mg/kg peso corporal ip. Salina e DE foram aplicadas 2h antes e 12h depois do trauma. Trauma foi induzido em ratos G-2 e G-3 anestesiados (tribromoetanol 97% de 100 ml/kg, i.p. por secção da musculatura anterior da coxa logo acima da articulação do joelho, preservando os grandes vasos e nervos. Amostras de tecido (pulmão foram coletadas para avaliação da mieloperoxidase (MPO, e exames histopatológicos. RESULTADOS: Vinte e quatro horas após a indução da lesão muscular houve um aumento significativo na infiltração de neutr

  1. Does the application site of spinal manipulative therapy alter spinal tissues loading?

    Science.gov (United States)

    Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Gregory N

    2018-01-31

    Previous studies found that the intervertebral disc (IVD) experiences the greatest loads during spinal manipulation therapy (SMT). Based on that, this study aimed to determine if loads experienced by spinal tissues are significantly altered when the application site of SMT is changed. A biomechanical robotic serial dissection study. Thirteen porcine cadaveric motion segments. Forces experienced by lumbar spinal tissues. A servo-controlled linear actuator provided standardized 300 N SMT simulations to six different cutaneous locations of the porcine lumbar spine: L2-L3 and L3-L4 facet joints (FJ), L3 and L4 transverse processes (TVP), and the space between the FJs and the TVPs (BTW). Vertebral kinematics were tracked optically using indwelling bone pins; the motion segment was removed and mounted in a parallel robot equipped with a six-axis load cell. Movements of each SMT application at each site were replayed by the robot with the intact specimen and following the sequential removal of spinal ligaments, FJs and IVD. Forces induced by SMT were recorded, and specific axes were analyzed using linear mixed models. Analyses yielded a significant difference (p<.05) in spinal structures loads as a function of the application site. Spinal manipulative therapy application at the L3 vertebra caused vertebral movements and forces between L3 and L4 spinal segment in the opposite direction to when SMT was applied at L4 vertebra. Additionally, SMT applications over the soft tissue between adjacent vertebrae significantly decreased spinal structure loads. Applying SMT with a constant force at different spinal levels creates different relative kinetics of the spinal segments and load spinal tissues in significantly different magnitudes. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Extracts from rabbit skin inflamed by the vaccinia virus attenuate bupivacaine-induced spinal neurotoxicity in pregnant rats

    Institute of Scientific and Technical Information of China (English)

    Rui Cui; Shiyuan Xu; Liang Wang; Hongyi Lei; Qingxiang Cai; Hongfei Zhang; Dongmei Wang

    2013-01-01

    Extracts from rabbit skin inflamed by the vaccinia virus can relieve pain and promote repair of nerve injury. The present study intraperitoneally injected extracts from rabbit skin inflamed by the vaccinia virus for 3 and 4 days prior to and following intrathecal injection of bupivacaine into pregnant rats. The pain threshold test after bupivacaine injection showed that the maximum possible effect of tail-flick latency peaked 1 day after intrathecal injection of bupivacaine in the extract-pretreatment group, and gradually decreased, while the maximum possible effect in the bupivacaine group continued to increase after intrathecal injection of bupivacaine. Histological observation showed that after 4 days of intrathecal injection of bupivacaine, the number of shrunken, vacuolated, apoptotic and caspase-9-positive cells in the dorsal root ganglion in the extract-pretreatment group was significantly reduced compared with the bupivacaine group. These findings indicate that extracts from rabbit skin inflamed by the vaccinia virus can attenuate neurotoxicity induced by intrathecal injection of bupivacaine in pregnant rats, possibly by inhibiting caspase-9 protein expression and suppressing nerve cell apoptosis.

  3. Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

    Science.gov (United States)

    Shah, Mamta B; Goswami, S S; Santani, D D

    2004-10-01

    Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. Copyright 2004 John Wiley & Sons, Ltd.

  4. The relevance of cytokines in the radiation-induced lung reaction. Experimental basis and clinical significance

    International Nuclear Information System (INIS)

    Ruebe, C.E.; Ruebe, C.; Rodemann, H.P.

    2004-01-01

    Methods: published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. Results and conclusion: the major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-β (TGF-β) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-β-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely. (orig.)

  5. Spectroscopic evaluation of painted layer structural changes induced by gamma radiation in experimental models

    International Nuclear Information System (INIS)

    Manea, Mihaela M.; Moise, Ioan V.; Virgolici, Marian; Negut, Constantin D.; Barbu, Olimpia-Hinamatsuri; Cutrubinis, Mihalis; Fugaru, Viorel; Stanculescu, Ioana R.; Ponta, Corneliu C.

    2012-01-01

    The degradation of cultural heritage objects by insects and microorganisms is an important issue for conservators, art specialists and humankind in general. Gamma irradiation is an efficient method of polychrome wooden artifacts disinfestation. Color changes and other modifications in the physical chemical properties of materials induced by gamma irradiation are feared by cultural heritage responsible committees and they have to be evaluated objectively and precisely. In this paper FTIR and FT-Raman spectroscopy methods were used to investigate the structural changes in some experimental models of tempera paint layers on wood following 11 kGy gamma irradiation at two dose rates. Radiation chemistry depends on the particular pigment, matrix formed by protein, resin (in case of varnished samples) and water presence. For the majority of painted layer in experimental models very small spectral variations were observed. Small changes in the FTIR spectra were observed for the raw sienna experimental model: for the higher dose rate the egg yolk protein oxidation peaks and the CH stretching bands due to lipids degradation products increased. - Highlights: ► Experimental models of tempera paint layers on wood were γ-irradiated at two dose rates. ► Changes induced by γ-irradiation were evaluated by vibrational spectroscopy. ► Minor spectral variations of painted layer were observed. ► Raw sienna FTIR spectra showed little changes of egg yolk and lipids at higher dose rate. ► Gamma irradiation is recommended for disinfection of painted wooden artifacts.

  6. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  7. Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia

    Directory of Open Access Journals (Sweden)

    Eiji Masaki

    2016-03-01

    Full Text Available Background: Brain-derived neurotrophic factor (BDNF from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. Results: Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. Conclusion: These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.

  8. Experimentally induced mastitis and metritis modulate soy bean derived isoflavone biotransformation in diary cows.

    Science.gov (United States)

    Kowalczyk-Zieba, I; Woclawek-Potocka, I; Piskula, M K; Piotrowska-Tomala, K K; Boruszewska, D; Bah, M M; Siemieniuch, M J; Skarzynski, D J

    2011-12-01

    The present study compared the changes in isoflavone (daidzein and genistein) and their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma of cows with induced mastitis and metritis after feeding with soy bean. Sixteen cows were divided into four groups: control for mastitis group, cows with induced mastitis group, control for metritis group, and cows with induced metritis group. All cows were fed a single dose of 2.5 kg of soy bean and then blood samples were taken from the jugular vein for 8 h at predetermined intervals. The concentrations of soy bean-derived isoflavones and their active metabolites were measured in the blood plasma on HPLC system. β-Glucuronidase activity in the blood plasma of cows was measured by fluorometric method. In the blood plasma of cows with induced mastitis and metritis, we found considerably higher concentrations and time-dependent increase in isoflavone metabolites (equol and para-ethyl-phenol) with reference to cyclic cows (P < 0.05). Moreover, we noticed significant decrease of genistein in the blood plasma of the cows with induced metritis compared with control cows (P < 0.05). In addition, in the blood plasma of the cows with induced metritis, we found an increase in β-glucuronidase activity compared with control cows (P < 0.05). In conclusion, health status of the females influenced the concentrations of isoflavone metabolites in the blood plasma of the cows. Experimentally induced mastitis and metritis increased isoflavone absorption, biotransformation and metabolism. Therefore, we suggest that cows with induced mastitis and metritis are more exposed to active isoflavone metabolite actions than healthy cows. Copyright © 2011. Published by Elsevier Inc.

  9. Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

    Science.gov (United States)

    Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

    2016-04-01

    Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

  10. The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

    Science.gov (United States)

    Gao, Meiya; Long, Hu; Ma, Wenqiang; Liao, Lina; Yang, Xin; Zhou, Yang; Shan, Di; Huang, Renhuan; Jian, Fan; Wang, Yan; Lai, Wenli

    2016-12-01

    This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3 -/- ) mice. Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. International Spinal Cord Injury

    DEFF Research Database (Denmark)

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

    2015-01-01

    STUDY DESIGN: Survey of expert opinion, feedback and final consensus. OBJECTIVE: To describe the development and the variables included in the International Spinal Cord Injury (SCI) Spinal Interventions and Surgical Procedures Basic Data set. SETTING: International working group. METHODS......: A committee of experts was established to select and define data elements. The data set was then disseminated to the appropriate committees and organizations for comments. All suggested revisions were considered and both the International Spinal Cord Society and the American Spinal Injury Association endorsed...... spinal intervention and procedure is coded (variables 1 through 7) and the spinal segment level is described (variables 8 and 9). Sample clinical cases were developed to illustrate how to complete it. CONCLUSION: The International SCI Spinal Interventions and Surgical Procedures Basic Data Set...

  12. Experimental diabetes induces structural, inflammatory and vascular changes of Achilles tendons.

    Directory of Open Access Journals (Sweden)

    Rodrigo R de Oliveira

    Full Text Available This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS and nitrate and nitrite level. The Achilles tendon thickness (µm/100g of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98 vessels/field when compared to the control group 0.89 (1.68 vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18 vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99 vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy.

  13. Experimental parameter identification of a multi-scale musculoskeletal model controlled by electrical stimulation: application to patients with spinal cord injury.

    Science.gov (United States)

    Benoussaad, Mourad; Poignet, Philippe; Hayashibe, Mitsuhiro; Azevedo-Coste, Christine; Fattal, Charles; Guiraud, David

    2013-06-01

    We investigated the parameter identification of a multi-scale physiological model of skeletal muscle, based on Huxley's formulation. We focused particularly on the knee joint controlled by quadriceps muscles under electrical stimulation (ES) in subjects with a complete spinal cord injury. A noninvasive and in vivo identification protocol was thus applied through surface stimulation in nine subjects and through neural stimulation in one ES-implanted subject. The identification protocol included initial identification steps, which are adaptations of existing identification techniques to estimate most of the parameters of our model. Then we applied an original and safer identification protocol in dynamic conditions, which required resolution of a nonlinear programming (NLP) problem to identify the serial element stiffness of quadriceps. Each identification step and cross validation of the estimated model in dynamic condition were evaluated through a quadratic error criterion. The results highlighted good accuracy, the efficiency of the identification protocol and the ability of the estimated model to predict the subject-specific behavior of the musculoskeletal system. From the comparison of parameter values between subjects, we discussed and explored the inter-subject variability of parameters in order to select parameters that have to be identified in each patient.

  14. Electron microscopic study of spontaneous and experimentally induced leukemia in IRC mice

    International Nuclear Information System (INIS)

    Hiraki, S.; Ranadive, K.J.; Dmochowski, L.

    1974-01-01

    Spontaneous, serially transplanted, and experimentally induced leukemias of ICRC mice were studied by electron microscopy in an attempt to detect the presence of virus particles, if any, and to observe the influence of chemical and hormonal treatment on the presence of these virus particles. The first series of experiments included spontaneous, serially transplanted, and radiation-induced leukemia. The paucity of type C virus particles was quite conspicuous in spontaneous leukemia. Serially transplanted and radiation-accelerated leukemic lesions showed the presence of some type C and intracisternal type A particles. Found in two of these leukemic lesions (thymus and lymphosarcoma), in addition to type C virus particles, were budding and some mature type B virus particles, and numerous intracytoplasmic type A particles. ''Viropexis'' of type B virus particles has been observed in the lymphosarcoma and in a leukemic thymus gland. The second series of experiments included leukemia induced in ovariectomized ICRC mice with 20-methylcholanthrene (MCA), pituitary transplants, and ovarian hormones (estradiol and estradiol-progesterone). In ovariectomized ICRC mice, leukemic lesions induced by MCA or pituitary transplants, or by MCA and pituitary transplants, showed type C virus particles and, in most cases, intracisternal type A particles. In leukemia induced in ovariectomized ICRC mice by MCA and estradiol, numerous intracytoplasmic type A particles were observed but no type C virus particles

  15. Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

    Science.gov (United States)

    Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

    2017-01-01

    This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

  16. Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

    1991-04-01

    A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

  17. Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

    Science.gov (United States)

    Morimoto, A; Nakamori, T; Watanabe, T; Ono, T; Murakami, N

    1988-04-01

    To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

  18. Topiramate as a neuroprotective agent in a rat model of spinal cord injury

    Directory of Open Access Journals (Sweden)

    Firat Narin

    2017-01-01

    Full Text Available Topiramate (TPM is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury (SCI. After rat models of thoracic contusive SCI were established by free weight-drop method, TPM (40 mg/kg was given at 12-hour intervals for four times orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were significantly reduced and reduced glutathione levels were increased, while immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats. In addition, TPM treatment improved the functional recovery of SCI rats. This study suggests that administration of TPM exerts neuroprotective effects on SCI.

  19. "Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

    Science.gov (United States)

    Pieretti, Stefano; Ranjan, Amalendu P; Di Giannuario, Amalia; Mukerjee, Anindita; Marzoli, Francesca; Di Giovannandrea, Rita; Vishwanatha, Jamboor K

    2017-10-01

    Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The inhibition of subchondral bone lesions significantly reversed the weight-bearing deficit and the overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn in the monosodium iodoacetate induced model of osteoarthritis pain.

    Directory of Open Access Journals (Sweden)

    Degang Yu

    Full Text Available Chronic pain is the most prominent and disabling symptom of osteoarthritis (OA. Clinical data suggest that subchondral bone lesions contribute to the occurrence of joint pain. The present study investigated the effect of the inhibition of subchondral bone lesions on joint pain.Osteoarthritic pain was induced by an injection of monosodium iodoacetate (MIA into the rat knee joint. Zoledronic acid (ZOL, a third generation of bisphosphonate, was used to inhibit subchondral bone lesions. Joint histomorphology was evaluated using X-ray micro computed tomography scanning and hematoxylin-eosin staining. The activity of osteoclast in subchondral bone was evaluated using tartrate-resistant acid phosphatase staining. Joint pain was evaluated using weight-bearing asymmetry, the expression of calcitonin gene-related peptide (CGRP in the dorsal root ganglion (DRG, and spinal glial activation status using glial fibrillary acidic protein (GFAP and ionized calcium binding adaptor molecule-1 (Iba-1 immunofluorescence. Afferent neurons in the DRGs that innervated the joints were identified using retrograde fluorogold labeling.MIA injections induced significant histomorphological alterations and joint pain. The inhibition of subchondral bone lesions by ZOL significantly reduced the MIA-induced weight-bearing deficit and overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn at 3 and 6 weeks after MIA injection; however, joint swelling and synovial reaction were unaffected.The inhibition of subchondral bone lesions alleviated joint pain. Subchondral bone lesions should be a key target in the management of osteoarthritic joint pain.

  1. Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

    Science.gov (United States)

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

    2014-06-01

    Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  2. Spinal cord injury in rats: inability of nimodipine or anti-neutrophil serum to improve spinal cord blood flow or neurologic status

    International Nuclear Information System (INIS)

    Holtz, A.; Nystroem, B.; Gerdin, B.

    1989-01-01

    The role of a calcium-mediated increase in vascular resistance and of vascular damage caused by polymorphonuclear leukocytes (PMNLs) in the development of neurologic deficit and disturbance of spinal cord circulation following spinal cord compression was studied in the rat. Spinal cord injury was induced by 5 min of compression with a load of 35 g on a 2.2 x 5.0 mm compression plate. This caused transient paraparesis. The rats received either the calcium receptor antagonist nimodipine or an anti-rat neutrophil serum (ANS). Nimodipine was infused i.v. for 4 h in an amount of 1.5 μg/kg/min starting 60 min after trauma. The number of circulating PMNLs was depleted by intraperiotoneal injection of an ANS raised in sheep given 12 h before trauma. This caused a reduction to about 2% of the pre-ANS value. Controls received saline or normal sheep serum. The motor performance was assessed daily on the inclined plane. On day one, the day after injury, the capacity angle had decreased from about 63 deg. preoperatively to close to 32 deg. in the experimental groups. There was then a slow improvement in both the control and experimental groups and on day 4 the capacity angle was close to 43 deg. in all 3 groups. Spinal cord blood flow, as measured with the 14 C-iodoantipyrine autoradiography method, was similar in all groups on day 4. As neither the neurologic dysfunction nor the spinal cord blood flow was affected by post-trauma treatment with nimodipine or pretreatment with ANS, the possibility that calcium-mediated vasoconstriction or PMNLs play a role in the development of posttraumatic neuroligic disability was not supported by this study. (author)

  3. Ethylenediaminetetraacetic acid induces antioxidant and anti-inflammatory activities in experimental liver fibrosis.

    Science.gov (United States)

    González-Cuevas, J; Navarro-Partida, J; Marquez-Aguirre, A L; Bueno-Topete, M R; Beas-Zarate, C; Armendáriz-Borunda, J

    2011-01-01

    Experimental liver fibrosis induced by carbon tetrachloride (CCl(4)) is associated with oxidative stress, lipid peroxidation, and inflammation. This work was focused on elucidating the anti-inflammatory and antioxidant effects of ethylenediaminetetraacetic acid (EDTA) in this model of hepatotoxicity. Wistar male rats were treated with CCl(4) and EDTA (60, 120, or 240 mg/kg). Morphometric analyses were carried out in Masson's stained liver sections to determine fibrosis index. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) were also determined. Gene expression for transforming growth factor beta (TGF-beta1), alpha1(I) procollagen gene (alpha1 Col I), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) was monitored by real-time PCR. Antioxidant effect of EDTA was measured by its effects on lipid peroxidation; biological activity of ceruloplasmin (Cp), SOD, and catalase (Cat) were analyzed by zymography assays. Animals with CCl(4)-hepatic injury that received EDTA showed a decrement in fibrosis (20%) and lipid peroxidation (22%). The mRNA expression for TNF-alpha (55%), TGF-beta1 (50%), IL-6 (52%), and alpha1 Col I (60%) was also decreased. This group of animals showed increased Cp (62%) and SOD (25%) biological activities. Coagulation blood tests, Cat activity, and gene expression for SOD were not modified by EDTA treatment. This study demonstrates that EDTA treatment induces the activity of antioxidant enzymes, decreases lipid peroxidation, hepatic inflammation, and fibrosis in experimental liver fibrosis induced by CCl(4).

  4. Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis

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    Liming Liu

    2017-01-01

    Full Text Available Aims. Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD. Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21 is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT lipolysis. Methods. Mice were given 2.5% dextran sulfate sodium (DSS ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21 treatment; lipolysis was assessed. Results. DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions. Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.

  5. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

    Directory of Open Access Journals (Sweden)

    Amira M. Abo-youssef

    2016-06-01

    Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

  6. Experimental and numerical analysis for magnetically induced vibrations of conducting structure

    International Nuclear Information System (INIS)

    Nishio, Satoshi; Nakahira, Masataka; Miura, H.; Isono, A.

    1993-01-01

    The coupling effect between the electromagnetic field and mechanical response of a conducting structure is of importance in magnetic fusion devices as tokamak machine. The electromagnetically induced motion of the structure due to the Lorentz force induces additional eddy currents and further modifies the dynamic characteristics of the system. This paper is concerned with numerical modeling of the dynamic field-structure interaction and its verification by experimental tests. Here, a finite element numerical model for mechanical deformation and a wiregrid numerical model for eddy currents are employed for non-ferrous and elastic conductors. A computer code has been developed for 3-D thin shell structure. Experimental tests for the code verification were carried out by using a rectangular thin copper plate. Three kinds of the plate supporting systems, i.e., a cantilever system, a fixed both ends system and a simply supported ends system were investigated. A good agreement between the numerical and experimental results was obtained. Therefore, the computer code developed here is available for analyzing the electromagnetomechanical behavior of the plasma facing components of the tokamak device. (author)

  7. Numerical and experimental evaluation of residual strains induced by pulsed laser welding

    International Nuclear Information System (INIS)

    Touvrey, C.; Bruyere, V.; Namy, P.

    2014-01-01

    The aim of the present study is to compare the residual strains induced by different welding processes during the assembly of two Ti6Al4V thin sheets. Several welding configurations and two means (pulsed laser and continuous one) are tested. The first part of the study intends to experimentally quantify strains induced by laser-matter interaction when one of the plates can freely bend. In this configuration the residual stresses are minimum, and consequently the strains measurement constitute a good indicator of the mechanical evolution. The displacements are in-situ reported thanks to a mechanical sensor. The second part of the study is dedicated to the numerical modeling of the processes. Unfortunately, the model is not completely predictive and appears to be oversimplified to describe the measured distortion. As it appears difficult to model the laser-matter interaction (especially in the case of many impacts recovering), we have adopted an equivalent approach to simulate the thermal evolution within the work pieces. An optimization procedure has been developed to determine an equivalent thermal flux, which leads to a melted zone shape in good agreement with experimental evaluations. The thermo-mechanical problem is computed by means of the finite elements software COMSOL Multiphysics. The results are compared to experimental data (displacement measurements) throughout the complete simulation. We plan to apply the complete model for more complex geometries, involving the generation of residual stresses. (authors)

  8. GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats

    Science.gov (United States)

    Sun, Yi-Ning; Luo, Jin-Yan; Rao, Zhi-Ren; Lan, Li; Duan, Li

    2005-01-01

    AIM: To investigate the response of astrocytes and neurons in rat lumbo-sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS: Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group (n = 17), colonic inflammation was induced by intra-luminal administration of trinitrobenzenesulfonic acid (TNBS); control group (n = 16), saline was administered intra-luminally. After 3, 7, 14, and 28 d of administration, the lumbo-sacral spinal cord and medulla oblongata were removed and processed for anti-glial fibrillary acidic protein (GFAP), Fos and GFAP/Fos immunohistochemistry. RESULTS: Activated astrocytes positive for GFAP were mainly distributed in the superficial laminae (laminae I-II) of dorsal horn, intermediolateral nucleus (laminae V), posterior commissural nucleus (laminae X) and anterolateral nucleus (laminae IX). Fos-IR (Fos-immunoreactive) neurons were mainly distributed in the deeper laminae of the spinal cord (laminae III-IV, V-VI). In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were mainly distributed in the medullary visceral zone (MVZ). The density of GFAP in the spinal cord of experimental rats was significantly higher after 3, 7, and 14 d of TNBS administration compared with the controls (50.4±16.8, 29.2±6.5, 24.1±5.6, P0.05). CONCLUSION: Astrocytes in spinal cord and medulla oblongata can be activated by colonic inflammation. The activated astrocytes are closely related to Fos-IR neurons. With the recovery of colonic inflammation, the activity of astrocytes in the spinal c