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Sample records for adult rat spinal

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

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

    2016-01-01

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

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

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

    2017-01-01

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

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

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    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

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

    Science.gov (United States)

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

    2003-01-01

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

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

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

    2013-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Atsushi Miyanohara

    2016-01-01

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

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

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

    2015-07-01

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

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

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    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.

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

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

    1997-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

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

    2016-08-10

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

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

    International Nuclear Information System (INIS)

    Kaneko, Ai; Matsushita, Akira; Sankai, Yoshiyuki

    2015-01-01

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

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

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

    2001-06-01

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

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

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

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

    1994-08-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Changxing Wang

    2017-03-01

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

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

    Science.gov (United States)

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

    2001-12-01

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

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

    Science.gov (United States)

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

    2011-07-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    NARCIS (Netherlands)

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

    2001-01-01

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

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

    Science.gov (United States)

    Bambakidis, Nicholas C; Miller, Robert H

    2004-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

    Miyanohara, A.; Kamizato, K.; Juhás, Štefan; Juhásová, Jana; Navarro, M.; Maršala, S.; Lukáčová, N.; Hruška-Plocháň, M.; Curtis, E.; Gabel, B.; Ciacci, J. D.; Ahrens, E. T.; Kaspar, B. K.; Cleveland, D.; Maršala, M.

    2016-01-01

    Roč. 3, č. 1 (2016), č. článku 16046. ISSN 2329-0501 R&D Projects: GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : AAV9 * rat * pig Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.610, year: 2016

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

    Science.gov (United States)

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

    2015-01-01

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

  7. Adeno-associated viral vector-mediated neurotrophin gene transfer in the injured adult rat spinal cord improves hind-limb function

    NARCIS (Netherlands)

    Blits, B; Oudega, M.; Boer, G J; Bartlett Bunge, M; Verhaagen, J

    2003-01-01

    To foster axonal growth from a Schwann cell bridge into the caudal spinal cord, spinal cells caudal to the implant were transduced with adeno-associated viral (AAV) vectors encoding for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (AAV-NT-3). Control rats received AAV vectors encoding

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

    OpenAIRE

    Bhatoe H

    2000-01-01

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

  9. Stimulation of 5-HT2A receptors recovers sensory responsiveness in acute spinal neonatal rats.

    Science.gov (United States)

    Swann, Hillary E; Kauer, Sierra D; Allmond, Jacob T; Brumley, Michele R

    2017-02-01

    Quipazine is a 5-HT 2A -receptor agonist that has been used to induce motor activity and promote recovery of function after spinal cord injury in neonatal and adult rodents. Sensory stimulation also activates sensory and motor circuits and promotes recovery after spinal cord injury. In rats, tail pinching is an effective and robust method of sacrocaudal sensory afferent stimulation that induces motor activity, including alternating stepping. In this study, responsiveness to a tail pinch following treatment with quipazine (or saline vehicle control) was examined in spinal cord transected (at midthoracic level) and intact neonatal rats. Rat pups were secured in the supine posture with limbs unrestricted. Quipazine or saline was administered intraperitoneally and after a 10-min period, a tail pinch was administered. A 1-min baseline period prior to tail-pinch administration and a 1-min response period postpinch was observed and hind-limb motor activity, including locomotor-like stepping behavior, was recorded and analyzed. Neonatal rats showed an immediate and robust response to sensory stimulation induced by the tail pinch. Quipazine recovered hind-limb movement and step frequency in spinal rats back to intact levels, suggesting a synergistic, additive effect of 5-HT-receptor and sensory stimulation in spinal rats. Although levels of activity in spinal rats were restored with quipazine, movement quality (high vs. low amplitude) was only partially restored. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. 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....

  11. Neuroprotective effect corilagin in spinal cord injury rat model by ...

    African Journals Online (AJOL)

    Background: Neurological functions get altered in a patient suffering from spinal cord injury (SCI). Present study evaluates the neuroprotective effect of corilagin in spinal cord injury rats by inhibiting nuclear factor-kappa B (NF-κB), inflammatory mediators and apoptosis. Materials and method: Spinal cord injury was ...

  12. Effects of long-term theophylline exposure on recovery of respiratory function and expression of adenosine A1 mRNA in cervical spinal cord hemisected adult rats.

    Science.gov (United States)

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

    2003-07-01

    Our lab has previously shown that when administered acutely, the methylxanthine theophylline can activate a latent respiratory motor pathway to restore function to the hemidiaphragm paralyzed by an ipsilateral C2 spinal cord hemisection. The recovery is mediated by the antagonism of CNS adenosine A1 receptors. The objective of the present study was to assess quantitatively recovery after chronic theophylline administration, the effects of weaning from the drug, and the effects of the drug on adenosine A1 receptor mRNA expression in adult rats subjected to a C2 hemisection. Rats subjected to a left C2 hemisection received theophylline orally for 3, 7, 12, or 30 days and were classified as 3D, 7D, 12D, or 30D respectively. Separate groups of 3D animals were weaned from drug administration for 7, 12, and 30 days before assessment of respiratory recovery. Additional groups of 7D and 12D animals were also weaned from drug administration for 7 and 12 days prior to assessment. Sham-operated controls received theophylline vehicle for similar periods. Quantitative assessment of recovered respiratory activity was conducted under standardized electrophysiologic recording conditions approximately 18 h after each drug application period. Serum theophylline analysis was conducted at the end of electrophysiologic recordings. Adenosine A1 receptor mRNA expression in the phrenic nucleus was assessed with in situ hybridization and immunohistochemistry. Chronic theophylline induced a dose-dependent effect on respiratory recovery over a serum theophylline range of 1.2-1.9 microg/ml. Recovery was characterized as respiratory-related activity in the left phrenic nerve and expressed as a percentage of activity in the homolateral nerve in noninjured animals under similar recording conditions. Recovered activity was 34.13 +/- 2.07, 55.89 +/- 2.96, 74.78 +/- 1.93, and 79.12 +/- 1.75% respectively in the 3D, 7D, 12D, and 30D groups. Theophylline-induced recovered activity persisted for as

  13. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury

    DEFF Research Database (Denmark)

    Lee, I. Hui; Lindqvist, Eva; Kiehn, Ole

    2005-01-01

    Spinal cord injury induces a complex cascade of degenerative and remodeling events evolving over time. The possible roles of changed intercellular communication via gap junctions after spinal cord injury (SCI) have remained relatively unexplored. We investigated the temporospatial expression...... patterns of gap junctional genes and proteins, connexin 43 (Cx43), Cx36, and Cx32, by in situ hybridization and immunohistochemistry in the rat neonatal, adult normal, and adult injured spinal cord. Cx36 was strongly expressed in immature neurons, and levels declined markedly during development, whereas Cx...

  14. 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.

  15. Brain protection by methylprednisolone in rats with spinal cord injury.

    Science.gov (United States)

    Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

    2009-07-01

    Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

  16. Spinal Cord Studies in the African Giant Rat (Cricetomys gambianus ...

    African Journals Online (AJOL)

    olayemitoyin

    J. Physiol. Sci. 30 (2015) 025 – 032 www.njps.com.ng. Spinal Cord Studies in the African Giant Rat (Cricetomys gambianus .... Body and Spinal Cord measurements of the AGR (C. gambianus), Mean ±SEM ... the eighth cervical segment appeared circular in shape. ... other lumbar segments, sacral and coccygeal segments.

  17. Activation of Akt/FKHR in the medulla oblongata contributes to spontaneous respiratory recovery after incomplete spinal cord injury in adult rats.

    Science.gov (United States)

    Felix, M S; Bauer, S; Darlot, F; Muscatelli, F; Kastner, A; Gauthier, P; Matarazzo, V

    2014-09-01

    After incomplete spinal cord injury (SCI), patients and animals may exhibit some spontaneous functional recovery which can be partly attributed to remodeling of injured neural circuitry. This post-lesion plasticity implies spinal remodeling but increasing evidences suggest that supraspinal structures contribute also to the functional recovery. Here we tested the hypothesis that partial SCI may activate cell-signaling pathway(s) at the supraspinal level and that this molecular response may contribute to spontaneous recovery. With this aim, we used a rat model of partial cervical hemisection which injures the bulbospinal respiratory tract originating from the medulla oblongata of the brainstem but leads to a time-dependent spontaneous functional recovery of the paralyzed hemidiaphragm. We first demonstrate that after SCI the PI3K/Akt signaling pathway is activated in the medulla oblongata of the brainstem, resulting in an inactivation of its pro-apoptotic downstream target, forkhead transcription factor (FKHR/FOXO1A). Retrograde labeling of medullary premotoneurons including respiratory ones which project to phrenic motoneurons reveals an increased FKHR phosphorylation in their cell bodies together with an unchanged cell number. Medulla infusion of the PI3K inhibitor, LY294002, prevents the SCI-induced Akt and FKHR phosphorylations and activates one of its death-promoting downstream targets, Fas ligand. Quantitative EMG analyses of diaphragmatic contractility demonstrate that the inhibition of medulla PI3K/Akt signaling prevents spontaneous respiratory recovery normally observed after partial cervical SCI. Such inhibition does not however affect either baseline contractile frequency or the ventilatory reactivity under acute respiratory challenge. Together, these findings provide novel evidence of supraspinal cellular contribution to the spontaneous respiratory recovery after partial SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Changes in the neuroglial cell populations of the rat spinal cord after local X-irradiation

    International Nuclear Information System (INIS)

    Hubbard, B.M.; Hopewell, J.W.

    1979-01-01

    A 16 mm length of cervical spinal cord of young adult female rats was irradiated with 4000 rad of 250 kV X-rays. Counts of astrocyte and oligodendrocyte nuclei were made in the dorsal columns of both irradiated and control cervical cords during the latent period before the onset of radionecrosis. The numbers of both astrocyte and oligodendrocyte nuclei were reduced one month after exposure to radiation. Both cell populations showed an apparent recovery but this was subsequently followed by a rapid loss of cells prior to the development of white-matter necrosis. The oligodendrocyte population in unirradiated spinal cords increased with age, and mitotic figures were observed among the neuroglia of both irradiated and control cervical spinal cords. A slow, natural turnover of neuroglial cells in the cervical spinal cord is proposed and the relevance of this to the manifestation of delayed white matter necrosis is discussed. (author)

  19. Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats.

    Science.gov (United States)

    Song, Y Y; Peng, C G; Ye, X B

    2015-12-29

    This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P edaravone can enhance the survival and differentiation of NSCs in injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

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

    Science.gov (United States)

    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.

  1. Serotonin receptor and dendritic plasticity in the spinal cord mediated by chronic serotonergic pharmacotherapy combined with exercise following complete SCI in the adult rat.

    Science.gov (United States)

    Ganzer, Patrick D; Beringer, Carl R; Shumsky, Jed S; Nwaobasi, Chiemela; Moxon, Karen A

    2018-06-01

    Severe spinal cord injury (SCI) damages descending motor and serotonin (5-HT) fiber projections leading to paralysis and serotonin depletion. 5-HT receptors (5-HTRs) subsequently upregulate following 5-HT fiber degeneration, and dendritic density decreases indicative of atrophy. 5-HT pharmacotherapy or exercise can improve locomotor behavior after SCI. One might expect that 5-HT pharmacotherapy acts on upregulated spinal 5-HTRs to enhance function, and that exercise alone can influence dendritic atrophy. In the current study, we assessed locomotor recovery and spinal proteins influenced by SCI and therapy. 5-HT, 5-HT 2A R, 5-HT 1A R, and dendritic densities were quantified both early (1 week) and late (9 weeks) after SCI, and also following therapeutic interventions (5-HT pharmacotherapy, bike therapy, or a combination). Interestingly, chronic 5-HT pharmacotherapy largely normalized spinal 5-HTR upregulation following injury. Improvement in locomotor behavior was not correlated to 5-HTR density. These results support the hypothesis that chronic 5-HT pharmacotherapy can mediate recovery following SCI, despite acting on largely normal spinal 5-HTR levels. We next assessed spinal dendritic plasticity and its potential role in locomotor recovery. Single therapies did not normalize the loss of dendritic density after SCI. Groups displaying significantly atrophied dendritic processes were rarely able to achieve weight supported open-field locomotion. Only a combination of 5-HT pharmacotherapy and bike therapy enabled significant open-field weigh-supported stepping, mediated in part by restoring spinal dendritic density. These results support the use of combined therapies to synergistically impact multiple markers of spinal plasticity and improve motor recovery. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2001-05-15

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

  3. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    Directory of Open Access Journals (Sweden)

    Essam M Abdelalim

    2016-12-01

    Full Text Available Brain natriuretic peptide (BNP exerts its functions through natriuretic peptide receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using RT-PCR and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and DRG. BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the dorsal horn of the spinal cord and in the neurons of the intermediate column and ventral horn. Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I-II labeled with calcitonin gene-related peptide (CGRP, suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase in the motor neurons of the ventral horn. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NPR-A and/or NPR-B in the DRG and spinal cord.

  4. Zinc-enriched boutons in rat spinal cord

    DEFF Research Database (Denmark)

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

    2000-01-01

    The rat spinal cord reveals a complex pattern of zinc-enriched (ZEN) boutons. As a result of in vivo exposure to selenide ions, nanosized clusters of zinc selenide are created in places where zinc ions are present, including the zinc-containing synaptic vesicles of ZEN boutons. The clusters can...

  5. Potential of human dental stem cells in repairing the complete transection of rat spinal cord

    Science.gov (United States)

    Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

    2017-04-01

    Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

  6. Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury.

    Science.gov (United States)

    Ozturk, Anil Murat; Sozbilen, Murat Celal; Sevgili, Elvin; Dagci, Taner; Özyalcin, Halit; Armagan, Guliz

    2018-03-22

    Spinal cord injury (SCI) leads to vascular damage and disruption of blood-spinal cord barrier which participates in secondary nerve injury. Epidermal growth factor (EGF) is an endogenous protein which regulates cell proliferation, growth and differention. Previous studies reported that EGF exerts neuroprotective effect in spinal cord after SCI. However, the molecular mechanisms underlying EGF-mediated protection in different regions of nervous system have not shown yet. In this study, we aimed to examine possible anti-apoptotic and protective roles of EGF not only in spinal cord but also in brain following SCI. Twenty-eight adult rats were divided into four groups of seven animals each as follows: sham, trauma (SCI), SCI + EGF and SCI + methylprednisolone (MP) groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic protein levels and antioxidant enzyme activities were measured in spinal cord and frontal cortex. In our study, EGF promoted locomotor recovery and motor neuron survival of SCI rats. EGF treatment significantly decreased Bax and increased Bcl-2 protein expressions both in spinal cord and brain when compared to SCI group. Moreover, antioxidant enzyme activities including catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were increased following EGF treatment similar to MP treatment. Our experiment also suggests that alteration of the ratio of Bcl-2 to Bax may result from decreased apoptosis following EGF treatment. As a conclusion, these results show, for the first time, that administration of EGF exerts its protection via regulating apoptotic and oxidative pathways in response to spinal cord injury in different regions of central nervous system. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Preventive Effect of Intrathecal Paracetamol on Spinal Cord Injury in Rats

    Science.gov (United States)

    Sahin, Murat; Sayar, Ilyas; Peker, Kemal; Gullu, Huriye; Yildiz, Huseyin

    2014-01-01

    Background: Ischemic injury of the spinal cord during the surgical repair of thoracoabdominal aortic aneurysms might lead to paraplegia. Although a number of different mechanisms have been proposed, the exact cause of paraplegia has remained unknown, hampering the development of effective pharmacologic or other strategies for prevention of this condition. A number of studies suggested that cyclooxygenases (COX) contribute to neural breakdown; thus, COX inhibitors might reduce injury. Objectives: We aimed to assess the preventive effect of intrathecal (IT) pretreatment with paracetamol on spinal cord injury in a rat model. Materials and Methods: This experimental study was performed in Ataturk University Animal Research Laboratory Center, Erzurum, Turkey. Adult male Wistar rats were randomly allocated to three experimental groups (n = 6) to receive IT physiologic saline (controls), 50 µg of paracetamol, or 100 µg paracetamol one hour before induction of spinal cord ischemia. Six other rats were considered as the sham group. For the assessment of ischemic injury, motor functions of the hind limbs and histopathologic changes of the lumbar spinal cord were evaluated. Additional 20 rats were divided into two equal groups for the second part of the study where the survival rates were recorded in controls and in animals receiving 100 µg of paracetamol during the 28-day observation period. Results: Pretreatment with 100 µg of paracetamol resulted in a significant improvement in motor functions and histopathologic findings (P < 0.05). Despite a higher rate of survival in 100 µg of paracetamol group (70%) at day 28, the difference was not statistically significant in comparison with controls. Conclusions: Our results suggest a protective effect of pretreatment with IT paracetamol on ischemic spinal cord injury during thoracolumbar aortic aneurysm surgery. PMID:25763224

  8. Histochemical alternations in the Nissl bodies and ribonucleic acid (RNA) in the spinal, gangalion neurones of gamma irradiated rats

    International Nuclear Information System (INIS)

    Mousa, Tohamy A.; Roushdy, Hamed M.; Raid, Nahed A.; Al-Zahaby, Al-Ahmady S.; Sanad, Samia M.

    1984-01-01

    Four groups of adult male albino rats were subjected to whole body gamma-irradiation at the exposure levels of 200, 400, 600 and 1000 rads and the spinal ganglia were dissected out after different intervals of 3 hr., 1, 3, 5, 7, 10, 15 and 30 days. Nissl bodies and ribonucleic acid were demonstrated histochemically. Gamma irradiation may cause a decrease in RNA synthesis which was reflected in a reduced amount of Nissl substance visible in toluidine blue stained you thick sections of spinal ganglion of gamma irradiated rats and in the total amount of cytoplasmic RNA in pyronin-methyl green stained sections compared with control animals

  9. Regional differences in radiosensitivity across the rat cervical spinal cord

    International Nuclear Information System (INIS)

    Bijl, Hendrik P.; Luijk, Peter van; Coppes, Rob P.; Schippers, Jacobus M.; Konings, Antonius W.T.; Kogel, Albert J. van der

    2005-01-01

    Purpose: To study regional differences in radiosensitivity within the rat cervical spinal cord. Methods and materials: Three types of inhomogeneous dose distributions were applied to compare the radiosensitivity of the lateral and central parts of the rat cervical spinal cord. The left lateral half of the spinal cord was irradiated with two grazing proton beams, each with a different penumbra (20-80% isodoses): lateral wide (penumbra = 1.1 mm) and lateral tight (penumbra = 0.8 mm). In the third experiment, the midline of the cord was irradiated with a narrow proton beam with a penumbra of 0.8 mm. The irradiated spinal cord length (CT-2) was 20 mm in all experiments. The animals were irradiated with variable single doses of unmodulated protons (150 MeV) with the shoot-through method, whereby the plateau of the depth-dose profile is used rather than the Bragg peak. The endpoint for estimating isoeffective dose (ED 50 ) values was paralysis of fore and/or hind limbs within 210 days after irradiation. Histology of the spinal cords was performed to assess the radiation-induced tissue damage. Results: High-precision proton irradiation of the lateral or the central part of the spinal cord resulted in a shift of dose-response curves to higher dose values compared with the homogeneously irradiated cervical cord to the same 20-mm length. The ED 50 values were 28.9 Gy and 33.4 Gy for the lateral wide and lateral tight irradiations, respectively, and as high as 71.9 Gy for the central beam experiment, compared with 20.4 Gy for the homogeneously irradiated 20-mm length of cervical cord. Histologic analysis of the spinal cords showed that the paralysis was due to white matter necrosis. The radiosensitivity was inhomogeneously distributed across the spinal cord, with a much more radioresistant central white matter (ED 50 = 71.9 Gy) compared with lateral white matter (ED 50 values = 28.9 Gy and 33.4 Gy). The gray matter did not show any noticeable lesions, such as necrosis or

  10. Ileus Following Adult Spinal Deformity Surgery.

    Science.gov (United States)

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

    2018-05-23

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

  11. Mechanism of Restoration of Forelimb Motor Function after Cervical Spinal Cord Hemisection in Rats: Electrophysiological Verification

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    Takumi Takeuchi

    2017-01-01

    Full Text Available The objective of this study was to electrophysiologically assess the corticospinal tracts of adult rats and the recovery of motor function of their forelimbs after cervical cord hemisection. Of 39 adult rats used, compound muscle action potentials (CMAPs of the forelimbs of 15 rats were evaluated, before they received left C5 segmental hemisection of the spinal cord, by stimulating the pyramid of the medulla oblongata on one side using an exciting microelectrode. All 15 rats exhibited contralateral electrical activity, but their CMAPs disappeared after hemisection. The remaining 24 rats received hemisection first, and CMAPs of 12 rats were assessed over time to study their recovery time. All of them exhibited electrical activity of the forelimbs in 4 weeks after surgery. The remaining 12 rats received additional right C2 segmental hemisection, and variation of CMAPs between before and after surgery was examined. The right side of the 12 rats that received the additional hemisection exhibited no electrical activity in response to the stimulation of the pyramids on both sides. These results suggest that changes in path between the resected and healthy sides, activation of the ventral corticospinal tracts, and propriospinal neurons were involved in the recovery of motor function after cervical cord injury.

  12. Electroacupuncture improves gait locomotion, H-reflex and ventral root potentials of spinal compression injured rats.

    Science.gov (United States)

    Escobar-Corona, Carlos; Torres-Castillo, Sergio; Rodríguez-Torres, Erika Elizabeth; Segura-Alegría, Bertha; Jiménez-Estrada, Ismael; Quiroz-González, Salvador

    2017-05-01

    This study explored the effect of electroacupuncture stimulation (EA) on alterations in the Hoffman reflex (H-reflex) response and gait locomotion provoked by spinal cord injury (SCI) in the rat. A compression lesion of the spinal cord was evoked by insufflating a Fogarty balloon located in the epidural space at the T8-9 spinal level of adult Wistar male rats (200-250 gr; n=60). In different groups of SCI rats, EA (frequencies: 2, 50 and 100Hz) was applied simultaneously to Huantiao (GB30), Yinmen (BL37), Jizhong (GV6) and Zhiyang (GV9) acupoints from the third post-injury day until the experimental session. At 1, 2, 3 and 4 post-injury weeks, the BBB scores of the SCI group of rats treated with EA at 50Hz showed a gradual but greater enhancement of locomotor activity than the other groups of rats. Unrestrained gait kinematic analysis of SCI rats treated with EA-50Hz stimulation showed a significant improvement in stride duration, length and speed (p<0.05), whereas a discrete recovery of gait locomotion was observed in the other groups of animals. After four post-injury weeks, the H-reflex amplitude and H-reflex/M wave amplitude ratio obtained in SCI rats had a noticeable enhancement (217%) compared to sham rats (n=10). Meanwhile, SCI rats treated with EA at 50Hz manifested a decreased facilitation of the H-reflex amplitude and H/M amplitude ratio (154%) and a reduced frequency-dependent amplitude depression of the H-reflex (66%). In addition, 50 Hz-EA treatment induced a recovery of the presynaptic depression of the Gs-VRP evoked by PBSt conditioning stimulation in the SCI rat (63.2±8.1%; n=9). In concordance with the latter, it could be suggested that 50 Hz-EA stimulation reduced the hyper-excitability of motoneurons and provokes a partial improvement of the locomotive performance and H reflex responses by a possible recovery of presynaptic mechanisms in the spinal cord of experimentally injured rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. [RECONSTRUCTION OF LOWER EXTREMITY FUNCTION OF COMPLETE SPINAL CORD INJURY RATS BY FIRST NEURON CONNECTION].

    Science.gov (United States)

    Wang, Fangyong; Yuan, Yuan; Li, Jianjun

    2015-12-01

    To investigate the effects of the first neuron connection for the reconstruction of lower extremity function of complete spinal cord injury rats. Forty adult female Sprague Dawley rats of 300-350 g in weight were selected to prepare the models of L₁ transverse spinal cord injury. After 2 weeks of establishing model, the rats were randomly divided into control group (n = 20) and experimental group (n = 20). In the experimental group, the right hind limb function was reconstructed directly by the first neuron; in the control group, the other treatments were the same to the experimental group except that the distal tibial nerve and the proximal femoral nerve were not sutured. The recovery of motor function of lower extremity was observed by the Basso-Beattie-Bresnahan (BBB) scoring system on bilateral hind limbs at 7, 30, 50, and 70 days after operation. The changes of the spinal cord were observed by HE staining, neurofilament 200 immunohistochemistry staining, and the technique of horseradish peroxidase (HRP) tracing. After establishing models, 6 rats died. The right hind limb had no obvious recovery of the motor function, with the BBB score of 0 in 2 groups; the left hind limb motor function was recovered in different degrees, and there was no significant difference in BBB score between 2 groups (P > 0.05). In the experimental group, HE staining showed that the spinal cord was reconstructed with the sciatic nerve, which was embedded in the spinal cord, and the sciatic nerve membrane was clearly identified, and there was no obvious atrophy in the connecting part of the spinal cord. In the experimental group, the expression of nerve fiber was stained with immunohistochemistry, and the axons of the spinal cord were positively by stained and the peripheral nerve was connected with the spinal cord. HRP labelled synapses were detected by HRP retrograde tracing in the experimental group, while there was no HRP labelled synapse in the control group. Direct reconstruction

  14. Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats.

    Science.gov (United States)

    Oti, Takumi; Takanami, Keiko; Ito, Saya; Ueda, Takashi; Matsuda, Ken Ichi; Kawata, Mitsuhiro; Soh, Jintetsu; Ukimura, Osamu; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2018-04-01

    The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord controls male sexual function in rats. In contrast, in female rats, GRP neurons could scarcely be detected around puberty when circulating ovarian steroid hormones such as estradiol and progesterone levels are increasing. However, little information is available on feminizing or demasculinizing effects of ovarian steroids on the central nervous system in female puberty and adulthood. In this study, to visualize the spinal GRP neurons in vivo, we generated a GRP-promoter-Venus transgenic (Tg) rat line and studied the effects of the sex steroid hormones on GRP expression in the rat lumbar cord by examining the Venus fluorescence. In these Tg rats, the sexually dimorphic spinal GRP neurons controlling male sexual function were clearly labeled with Venus fluorescence. As expected, Venus fluorescence in the male lumbar cord was markedly decreased after castration and restored by chronic androgen replacement. Furthermore, androgen-induced Venus expression in the spinal cord of adult Tg males was significantly attenuated by chronic treatment with progesterone but not with estradiol. A luciferase assay using a human GRP-promoter construct showed that androgens enhance the spinal GRP system, and more strikingly, that progesterone acts to inhibit the GRP system via an androgen receptor-mediated mechanism. These results demonstrate that circulating androgens may play an important role in the spinal GRP system controlling male sexual function not only in rats but also in humans and that progesterone could be an important feminizing factor in the spinal GRP system in females during pubertal development.

  15. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

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    Yesim Cokay Abut

    2015-02-01

    Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

  16. Substance P release from rat hypothalamus and spinal cord

    International Nuclear Information System (INIS)

    Kronheim, S.; Sheppard, M.C.; Pimstone, B.L.

    1980-01-01

    A specific and sensitive radioimmunoassay for substance P has been developed to study the release of immunoreactive substance P from incubated rat hypothalamus and rat spinal cord in vitro. Release was significantly increased in the presence of two depolarizing stimuli (56 mM KCl and 75 μM veratrine) and was calcium-dependent. The released immunoreactive material diluted in parallel with synthetic substance P and showed close identity on Sephadex chromatography. A neuromodulator role for the peptide in the central nervous system is suggested

  17. Baicalin ameliorates neuropathic pain by suppressing HDAC1 expression in the spinal cord of spinal nerve ligation rats

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    Chen-Hwan Cherng

    2014-08-01

    Conclusion: The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.

  18. The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

    Science.gov (United States)

    Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

    2006-04-01

    Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

  19. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord.

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    Sharyn L Rossi

    2010-07-01

    Full Text Available Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit.In order to investigate the amenability of the injured adult spinal cord to motor neuron differentiation, we transplanted spinal cord injured animals with a high purity population of human motor neuron progenitors (hMNP derived from human embryonic stem cells (hESCs. In vitro, hMNPs displayed characteristic motor neuron-specific markers, a typical electrophysiological profile, functionally innervated human or rodent muscle, and secreted physiologically active growth factors that caused neurite branching and neuronal survival. hMNP transplantation into cervical SCI sites in adult rats resulted in suppression of intracellular signaling pathways associated with SCI pathogenesis, which correlated with greater endogenous neuronal survival and neurite branching. These neurotrophic effects were accompanied by significantly enhanced performance on all parameters of the balance beam task, as compared to controls. Interestingly, hMNP transplantation resulted in survival, differentiation, and site-specific integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near the SCI site reverted to a neuronal progenitor state, suggesting an environmental deficiency for neuronal maturation associated with SCI.These findings underscore the barriers imposed on neuronal differentiation of transplanted cells by the gliogenic nature of the injured spinal cord, and the physiological relevance of transplant-derived neurotrophic support to functional recovery.

  20. Diffusion tensor imaging of spinal cord parenchyma lesion in rat with chronic spinal cord injury.

    Science.gov (United States)

    Zhao, Can; Rao, Jia-Sheng; Pei, Xiao-Jiao; Lei, Jian-Feng; Wang, Zhan-Jing; Zhao, Wen; Wei, Rui-Han; Yang, Zhao-Yang; Li, Xiao-Guang

    2018-04-01

    Adequate evaluation of spinal cord parenchyma and accurate identification of injury range are considered two premises for the research and treatment of chronic spinal cord injury (SCI). Diffusion tensor imaging (DTI) provides information about water diffusion in spinal cord, and thus makes it possible to realize these premises. In this study, we conducted magnetic resonance imaging (MRI) for Wistar rats 84days after spinal cord contusion. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) from different positions of the injured cord were collected, analyzed, and compared with the histological results and locomotor outcomes. Moreover, we performed fiber tractography, and examined the difference in cavity percentage obtained respectively via conventional MRI, DTI and histology. Results showed that the chronic SCI rats had the largest changes of all DTI metrics at the epicenter; the farther away from the epicenter, the smaller the variation. FA, AD and RD were all influenced by SCI in a greater space range than MD. The good consistency of FA values and histological results in specific regions evidenced FA's capability of reflecting Wallerian degeneration after SCI. DTI metrics at the epicenter in ventral funiculus also showed a close correlation with the BBB scores. Additionally, supported by the histological results, DTI enables a more accurate measurement of cavity percentage compared to the conventional MRI. DTI parameters might comprehensively reflect the post-SCI pathological status of spinal cord parenchyma at the epicenter and distal parts during the chronic stage, while showing good consistency with locomotor performance. DTI combined with tractography could intuitively display the distribution of spared fibers after SCI and accurately provide information such as cavity area. This may shed light on the research and treatment of chronic SCI. Copyright © 2017 Elsevier Inc. All rights

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

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    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.

  3. The Long Term Effects of Chronic Spinal Cord Injury on Sperm Parameters in Rats

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    MA Khalili

    2004-07-01

    Full Text Available Introduction: Spinal cord injury (SCI is a serious public health problem which seriously affects the victim, family, and even the society. Research studies have shown that 80% of SCI victims are men. In recent years, there have been extensive research works on the effect of SCI (acute and/or chronic on fertility potential of sperm and spermatogenesis in laboratory animals. SCI may disturb the spermatogenic cell lines in laboratory animals. The objective of this experimental study was to investigate the effect of chronic spinal cord injury (CSCI on sperm parameters in adult rats. Materials & Methods: Adult Wistar rats weighing between 225-275g were divided into 3groups of control (n=5, sham (n=10, and experimental CSCI (n=10. No surgery was done on control animals. Only laminectomy was done in the sham animals at T10. CSCI was developed in experimental rats using 10g weight dropped 5cm above the exposed T10 level. All animals were sacrificed 50 days post experiment to extract epididymal samples. Sperm parameters of count, motility, morphology, as well as number of round cells were evaluated with the aid of Makler chamber and Geimsa staining. Results: Progressive motility was significantly reduced in CSCI group (P<0.05. The percentage of normal morphology of spermatozoa was 99.0±1.0 in control rats which was significantly reduced to 74.90±37.64 in CSCI animals In addition, sperm counts in control and CSCI rats were 69.20±12.43 and 25.0±13.68, respectively (P<0.01. Round cell concentration was increased in CSCI group as compared to controls. Conclusion: The results suggest that reduction in parameters of progressive motility, morphology, as well as sperm count following CSCI in rats may disturb the fertility potential of spermatozoa.

  4. Spinal anesthesia with diphenhydramine and pheniramine in rats.

    Science.gov (United States)

    Hung, Ching-Hsia; Chu, Chin-Chen; Chen, Yu-Chung; Chen, Yu-Wen; Li, Zong-Ying; Wang, Jhi-Joung

    2011-12-30

    The aim of this study was to evaluate the local anesthetic effects of pheniramine and diphenhydramine, two histamine H₁ receptor antagonists, on spinal anesthesia and their comparison with lidocaine, a commonly used local anesthetic. After rats were injected intrathecally with diphenhydramine and pheniramine, the dose-response curves were obtained. The potency and duration of diphenhydramine and pheniramine on spinal anesthesia were compared with lidocaine. We showed that diphenhydramine and pheniramine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED₅₀) basis, the rank of potency of drugs was diphenhydramine=pheniramine>lidocaine (ppheniramine or lidocaine (ppheniramine or lidocaine, elicited longer duration of sensory block than that of motor block at the same dose of 1.75 μmol. These preclinical data reported that diphenhydramine with a more sensory-selective action over motor blockade demonstrated more potent and longer-lasting spinal blockades, compared with pheniramine or lidocaine. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Radiation therapy for primary spinal cord tumors in adults

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  6. 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.

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

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    Inacia Sátiro Xavier de França

    2014-07-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  9. Spinal cord stimulation of dorsal columns in a rat model of neuropathic pain: evidence for a segmental spinal mechanism of pain relief.

    Science.gov (United States)

    Smits, H; van Kleef, M; Joosten, E A

    2012-01-01

    Although spinal cord stimulation (SCS) of the dorsal columns is an established method for treating chronic neuropathic pain, patients still suffer from a substantial level of pain. From a clinical perspective it is known that the location of the SCS is of pivotal importance, thereby suggesting a segmental spinal mode of action. However, experimental studies suggest that SCS acts also through the modulation of supraspinal mechanisms, which might suggest that the location is unimportant. Here we investigated the effect of the rostrocaudal location of SCS stimulation and the effectiveness of pain relief in a rat model of chronic neuropathic pain. Adult male rats (n=45) were submitted to a partial ligation of the sciatic nerve. The majority of animals developed tactile hypersensitivity in the nerve lesioned paw. All allodynic rats were submitted to SCS (n=33) for 30 minutes (f=50 Hz; pulse width 0.2 ms). In one group (n=16) the electrodes were located at the level where the injured sciatic nerve afferents enter the spinal cord (T13), and in a second group (n=17) the electrodes were positioned at more rostral levels (T11) as verified by X-ray. A repositioning experiment of electrodes from T12 to T13 was performed in 2 animals. Our data demonstrate that SCS of the dorsal columns at the level where the injured fibers enter the spinal cord dorsal horn result in a much better pain-relieving effect than SCS at more rostral levels. From this we conclude that SCS in treatment of neuropathic pain acts through a segmental spinal site of action. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  10. 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.

  11. 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.

  12. Edaravone combined with Schwann cell transplantation may repair spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    Shu-quan Zhang

    2015-01-01

    Full Text Available Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for the treatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T 9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-labeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-labeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined withSchwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.

  13. Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

    International Nuclear Information System (INIS)

    Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Morris, G.M.

    2000-01-01

    In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED 50 ) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

  14. Persistent polyuria in a rat spinal contusion model.

    Science.gov (United States)

    Ward, Patricia J; Hubscher, Charles H

    2012-10-10

    Polyuria contributes to bladder overdistention, which confounds both lower and upper urinary tract management in individuals having a spinal cord injury (SCI). Bladder overdistention post-SCI is one of the most common triggers for autonomic dysreflexia, a potentially life-threatening condition. Post-SCI polyuria is thought to result from loss of vascular tone in the lower extremities, leading to edema and subsequent excess fluid, resulting in polyuria. Mild SCIs that have near complete recovery would therefore be expected to have little to no polyuria, while severe injuries resulting in flaccid limbs and lower extremity edema would be expected to exhibit severe polyuria. Since interventions that may decrease lower extremity edema are recommended to lessen the severity of polyuria, step training (which promotes vascular circulation) was evaluated as a therapy to reduce post-SCI polyuria. In the present study, polyuria was evaluated in mild, moderate, and severe contusive SCI in adult male rats. The animals were housed in metabolic cages for 24-hour periods pre- and post-SCI (to 6 weeks). Urine, feces, food, water, and body weights were collected. Other assessments included residual expressed urine volumes, locomotor scoring, in-cage activity, and lesion histology. SCI produced an immediate increase in 24-hour urine collection, as early as 3 days post-SCI. Approximately 2.6-fold increases in urine collection occurred from weeks 1-6 post-SCI for all injury severities. Even with substantial gains in locomotor and bladder function following a mild SCI, polyuria remained severe. Step training (30 min/day, 6 days/week) did not alleviate polyuria in the moderate SCI contusion group. These results indicate that (1) mild injuries retaining weight-bearing locomotion that should have mild, if any, edema/loss of vascular tone still exhibit severe polyuria, and (2) step training was unable to reduce post-SCI polyuria. Taken together, these results indicate that the current

  15. Development of serotonergic and adrenergic receptors in the rat spinal cord: effects of neonatal chemical lesions and hyperthyroidism.

    Science.gov (United States)

    Lau, C; Pylypiw, A; Ross, L L

    1985-03-01

    The sympathetic preganglionic neurons in the spinal cord receive dense serotonergic (5-HT) and catecholaminergic (CA) afferent inputs from the descending supraspinal pathways. In the rat spinal cord, the levels of these biogenic amines and their receptors are low at birth, but undergo rapid ontogenetic increases in the ensuing 2-3 postnatal weeks until the adult levels are reached. In many systems it has been shown that denervation of presynaptic neurons leads to an up-regulation of the number of postsynaptic receptors. To determine whether the 5-HT and CA receptors in the developing spinal cord are also subject to such transsynaptic regulation, we examined the ontogeny of serotonergic receptors and alpha- and beta-adrenergic receptors in thoracolumbar spinal cord of rats given neurotoxins which destroy serotonergic (5,7-dihydroxytryptamine (5,7-DHT)) or noradrenergic (6-hydroxydopamine (6-OHDA)) nerve terminals. Intracisternal administration of 5,7-DHT or 6-OHDA at 1 and 6 days of age prevented, respectively, the development of 5-HT and CA levels in the spinal cord. Rats lesioned with 5,7-DHT displayed a marked elevation of 5-HT receptors with a binding of 50% greater than controls at 1 week and a continuing increase to twice normal by 4 weeks. A similar pattern of up-regulation was also detected with the alpha-adrenergic receptor, as rats lesioned with 6-OHDA exhibited persistent increases in receptor concentration. However, in these same animals ontogeny of the beta-adrenergic receptor in the spinal cord remained virtually unaffected by the chemical lesion. In several other parts of the nervous system, it has been demonstrated that the beta-adrenergic sensitivity can be modulated by hormonal signals, particularly that of the thyroid hormones. This phenomenon was examined in the spinal cord and in confirmation with previous studies neonatal treatment of triiodothyronine (0.1 mg/kg, s.c. daily) was capable of evoking persistent increases in beta

  16. Distribution of glycinergic neuronal somata in the rat spinal cord.

    Science.gov (United States)

    Hossaini, Mehdi; French, Pim J; Holstege, Jan C

    2007-04-20

    Glycine transporter 2 (GlyT2) mRNA is exclusively expressed in glycinergic neurons, and is presently considered a reliable marker for glycinergic neuronal somata. In this study, we have performed non-radioactive in situ hybridization to localize GlyT2 mRNA in fixed free-floating sections of cervical (C2 and C6), thoracic (T5), lumbar (L2 and L5) and sacral (S1) segments of the rat spinal cord. The results showed that in all segments the majority of the GlyT2 mRNA labeled (glycinergic) neuronal somata was present in the deep dorsal horn and the intermediate zone (laminae III-VIII), with around 50% (range 43.7-70.9%) in laminae VII&VIII. In contrast, the superficial dorsal horn, the motoneuronal cell groups and the area around the central canal contained only few glycinergic neuronal somata. The density (number of glycinergic neuronal somata per mm(2)) was also low in these areas, while the highest densities were found in laminae V to VIII. The lateral spinal nucleus and the lateral cervical nucleus also contained a limited number of glycinergic neurons. Our findings showed that the distribution pattern of the glycinergic neuronal somata is similar in all the examined segments. The few differences that were found in the relative laminar distribution between some of the segments, are most likely due to technical reasons. We therefore conclude that the observed distribution pattern of glycinergic neuronal somata is present throughout the spinal cord. Our findings further showed that the non-radioactive in situ hybridization technique for identifying GlyT2 mRNA in fixed free-floating sections is a highly efficient tool for identifying glycinergic neurons in the spinal cord.

  17. Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

    Science.gov (United States)

    Asante, Curtis O.; Dickenson, Anthony H.

    2010-01-01

    We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

  18. Tolerance of rat spinal cord to continuous interstitial irradiation

    International Nuclear Information System (INIS)

    Pop, Lucas A.M.; Plas, Mirjam van der; Ruifrok, Arnout C.C.; Schalkwijk, Lia J.M.; Hanssen, Alex E.J.; Kogel, Albert J. van der

    1998-01-01

    Purpose: To study the kinetics of repair in rat spinal cord during continuous interstitial irradiation at different dose rates and to investigate the impact of a rapid dose fall off over the spinal cord thickness. Material and Methods: Two parallel catheters were inserted on each side of the vertebral bodies from the level of T 10 to L 4 . These catheters were afterloaded with two 192 Ir- wires of 4 cm length each (activity 1 - 10 mCi/cm) or connected to the HDR- microSelectron. Experiments have been carried out to obtain complete dose response curves at 7 different dose rates: 0.53, 0.90, 1.64, 2.56, 4.4, 9.9 and 120 Gy/h. Paralysis of the hindlegs after 5 - 6 months and histopathological examination of the spinal cord of each animal were used as experimental endpoints. Results: The distribution of the histological damage was a good reflection of the rapid dose fall - off over the spinal cord, with white matter necrosis or demyelination predominantly seen in the dorsal tracts of the spinal cord or dorsal roots. With each reduction of the dose rate, spinal cord tolerance was significantly increased, with a maximum dose rate factor of 4.3 if the dose rate was reduced from 120 Gy/h to 0.53 Gy/h (ED 50 of 17.3 Gy and 75.0 Gy, respectively). Estimates of the repair parameters using different types of analysis are presented. For the direct analysis the best fit of the data was obtained if a biexponential function for repair was used. For the 100% dose prescribed at the ventral side of the spinal cord the (α(β)) ratio is 1.8 Gy (0.8 - 2.8) and two components of repair are observed: a slow component of repair of 2.44 h (1.18 - ∞) and a fast component of 0.15 h (0.02 - ∞). The proportion of the damage repaired with the slow component is 0.59 (0.18 - 1). For the maximum of 150% of the prescribed dose at the dorsal side of the spinal cord the (α(β)) ratio is 2.7 Gy (1.5 - 4.4); the two components for the kinetics of repair remain the same. Conclusions: Spinal cord

  19. Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Dasa Cizkova

    2018-03-01

    Full Text Available It was recently shown that the conditioned medium (CM of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM applied intrathecally (IT for spinal cord injury (SCI recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth. Afterwards, rats underwent SCI and were treated with IT delivery of MScCM or vehicle at postsurgical Days 1, 5, 9, and 13, and left to survive 10 weeks. Rats that received MScCM showed significantly higher motor function recovery, increase in spared spinal cord tissue, enhanced GAP-43 expression and attenuated inflammation in comparison with vehicle-treated rats. Spared tissue around the lesion site was infiltrated with GAP-43-labeled axons at four weeks that gradually decreased at 10 weeks. Finally, a cytokine array performed on spinal cord extracts after MScCM treatment revealed decreased levels of IL-2, IL-6 and TNFα when compared to vehicle group. In conclusion, our results suggest that molecular cocktail found in MScCM is favorable for final neuroregeneration after SCI.

  20. Histomorphology of the Olfactory Mucosa and Spinal Tissue Sparing Following Transplantation in the Partial Spinal Cord Injury in Rats

    Directory of Open Access Journals (Sweden)

    H Delaviz

    2011-01-01

    Full Text Available Introduction & Objective: Nowadays, cellular and tissues transplant has become the focus of attention for spinal cord injury. It has been shown olfactory nerve cells or olfactory mucosa whi have more efficient on nervous tissue repair and they have been more studied in experimental study. Furthermore, they were used in a few clinical centers for spinal defect. But mucosa tissue and spinal tissue have different structure and there is doubt about the integration of mucosa tissue in nervous tissue. Thus, in this research the morphology and the effect of the fetal olfactory mucosa (FOM on spinal tissue sparing were studied after transplanted into the spinal cord hemisection in rats. Materials & Methods: This experimental study was conducted at Iran University of Medical Sciences in 2008. Of thirty eight female Sprague-Dawley (200-250g rats twenty- eight were spinally hemisected at the L1 spinal level and were randomized into two groups of 14 animals. Treatment group received FOM graft and the control group received fetal respiratory mucosa graft (FRM. The other animals received surgical procedure without spinal cord injury as a sham group. The morphology of the transplant region and spinal tissue sparing was examined histological eight weeks after transplantation. The collected data was analyzed by the SPSS software using ANOVA and the morphology of the transplant region were studied by light microscope. Results: Histological study showed that the both mucosa tissues could not integrate with the parenchyma of the spinal tissue. Although the FOM were fused more than the FRM with the host tissue but clear boundary was seen at the graft–host interface. The mean spinal tissue sparing of the treatment group increased a little compare to the control but a significant difference was not apparent whereas, the spinal tissue sparing in treatment and control groups compare to the sham group decreased significantly (P < 0.05. Conclusion: Transplantation of

  1. Re-irradiation tolerance in the rat spinal cord

    International Nuclear Information System (INIS)

    Shun Wong, C.; Poon, J.K.; Hill, R.P.

    1993-01-01

    The influence of the level of initial radiation damage on the long term recovery and re-irradiation tolerance in the rat spinal cord was investigated. Rats were irradiated with 0, 10, 20, 30 and 36 daily fractions of 2.15 Gy initially representing 0, 25, 50, 75 and 90% of cord tolerance. After an interval of 20 weeks, retreatments were given using graded single doses of X-ray. The end-point was paralysis of the forelimbs due to white matter necrosis. Latent times to paralysis were inversely proportional to the level of initial injury and retreatment doses. The retreatment ED 50 s were 19.0, 17.0, 15.7, 14.0 and 11.8 Gy for the control animals and animals irradiated initially with 10. 20, 30 and 36 fractions of 2.15 Gy respectively. Using the extrapolated response dose (ERD) concept, α/β of 3.0 Gy, the retreatment of ED 50 s in % ERD were 81, 70, 58 and 42% after initial doses of 25, 50, 75 and 90% ERD respectively. The level of initial injury appeared to influence the proportion of residual injury. For an initial injury of 25 and 90% of ERD, the respective residual injury was 74 and 65% of the initial damage; for an initial injury of 50 and 75% ERD, the residual injury decreased to 59 and 57% respectively. It is concluded that there was significant long-term recovery in the rat spinal cord, and that the level of initial radiation damage influenced both the treatment tolerance and the time expression of injury. (author). tabs

  2. Characterization of upper thoracic spinal neurons responding to esophageal distension in diabetic rats

    DEFF Research Database (Denmark)

    Qin, Chao; Ghorbani, Marie L M; Wu, Mingyuan

    2008-01-01

    The aim of this study was to examine spinal neuronal processing of innocuous and noxious mechanical inputs from the esophagus in diabetic rats. Streptozotocin (50 mg/kg, ip) was used to induce diabetes in 15 male Sprague-Dawley rats, and vehicle (10 mM citrate buffer) was injected into 15 rats...

  3. Spinal mechanism of micturition reflex inhibition by naftopidil in rats.

    Science.gov (United States)

    Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki

    2014-10-29

    We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Bone blood flow after spinal paralysis in the rat

    International Nuclear Information System (INIS)

    Takahashi, H.; Yamamuro, T.; Okumura, H.; Kasai, R.; Tada, K.

    1990-01-01

    The goal of this study was to investigate the acute and chronic effects of paralysis induced by spinal cord section or sciatic neurotomy on bone blood flow in the rat. Regional bone blood flow was measured in the early stage with the hydrogen washout technique and the change of whole bone blood flow was measured in the early and the late stages with the radioactive microsphere technique. Four to 6 h after cordotomy at the level of the 13th thoracic vertebra, the regional bone blood flow in the denervated tibia increased significantly (p less than 0.01). After hemicordotomy with rhizotomy at the same level, the regional bone blood flow in the denervated tibia increased significantly (p less than 0.05) 6 h postoperatively. The whole bone blood flow in the denervated tibia had also increased significantly (p less than 0.05) at 6 h and at 4 and 12 weeks postoperatively. After sciatic neurotomy, the regional and the whole bone blood flow in the paralytic tibia did not change significantly. The present study demonstrated that monoplegic paralysis caused an increase in bone blood flow in the denervated hind limb from a very early stage. It was suggested that the spinal nervous system contributed to the control of bone blood flow

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

    Directory of Open Access Journals (Sweden)

    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.

  6. SPINAL ANTINOCICEPTION BY MORPHINE IN RATS IS ANTAGONIZED BY GALANIN RECEPTOR ANTAGONISTS

    NARCIS (Netherlands)

    REIMANN, W; ENGLBERGER, W; FRIDERICHS, E; SELVE, N; WILFFERT, B

    1994-01-01

    Galanin, a 29 amino acid peptide, has been reported to possess antinociceptive properties at the spinal site and to potentiate opioid-induced antinociception. Our aim was to investigate whether also endogenous galanin interacts with an exogenously administered opioid, morphine, in the rat spinal

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

    Science.gov (United States)

    2016-01-01

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

  8. Neural progenitor cells but not astrocytes respond distally to thoracic spinal cord injury in rat models

    Directory of Open Access Journals (Sweden)

    Tara Nguyen

    2017-01-01

    Full Text Available Traumatic spinal cord injury (SCI is a detrimental condition that causes loss of sensory and motor function in an individual. Many complex secondary injury cascades occur after SCI and they offer great potential for therapeutic targeting. In this study, we investigated the response of endogenous neural progenitor cells, astrocytes, and microglia to a localized thoracic SCI throughout the neuroaxis. Twenty-five adult female Sprague-Dawley rats underwent mild-contusion thoracic SCI (n = 9, sham surgery (n = 8, or no surgery (n = 8. Spinal cord and brain tissues were fixed and cut at six regions of the neuroaxis. Immunohistochemistry showed increased reactivity of neural progenitor cell marker nestin in the central canal at all levels of the spinal cord. Increased reactivity of astrocyte-specific marker glial fibrillary acidic protein was found only at the lesion epicenter. The number of activated microglia was significantly increased at the lesion site, and activated microglia extended to the lumbar enlargement. Phagocytic microglia and macrophages were significantly increased only at the lesion site. There were no changes in nestin, glial fibrillary acidic protein, microglia and macrophage response in the third ventricle of rats subjected to mild-contusion thoracic SCI compared to the sham surgery or no surgery. These findings indicate that neural progenitor cells, astrocytes and microglia respond differently to a localized SCI, presumably due to differences in inflammatory signaling. These different cellular responses may have implications in the way that neural progenitor cells can be manipulated for neuroregeneration after SCI. This needs to be further investigated.

  9. Neurologic Outcomes of Complex Adult Spinal Deformity Surgery

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  10. Imaging of infectious spinal disorders in children and adults

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-04-15

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

  11. Local injection of Lenti-Olig2 at lesion site promotes functional recovery of spinal cord injury in rats.

    Science.gov (United States)

    Tan, Bo-Tao; Jiang, Long; Liu, Li; Yin, Ying; Luo, Ze-Ru-Xin; Long, Zai-Yun; Li, Sen; Yu, Le-Hua; Wu, Ya-Min; Liu, Yuan

    2017-06-01

    Olig2 is one of the most critical factors during CNS development, which belongs to b-HLH transcription factor family. Previous reports have shown that Olig2 regulates the remyelination processes in CNS demyelination diseases models. However, the role of Olig2 in contusion spinal cord injury (SCI) and the possible therapeutic effects remain obscure. This study aims to investigate the effects of overexpression Olig2 by lentivirus on adult spinal cord injury rats. Lenti-Olig2 expression and control Lenti-eGFP vectors were prepared, and virus in a total of 5 μL (10 8 TU/mL) was locally injected into the injured spinal cord 1.5 mm rostral and caudal near the epicenter. Immunostaining, Western blot, electron microscopy, and CatWalk analyzes were employed to investigate the effects of Olig2 on spinal cord tissue repair and functional recovery. Injection of Lenti-Olig2 significantly increased the number of oligodendrocytes lineage cells and enhanced myelination after SCI. More importantly, the introduction of Olig2 greatly improved hindlimb locomotor performances. Other oligodendrocyte-related transcription factors, which were downregulated or upregulated after injury, were reversed by Olig2 induction. Our findings provided the evidence that overexpression Olig2 promotes myelination and locomotor recovery of contusion SCI, which gives us more understanding of Olig2 on spinal cord injury treatment. © 2017 John Wiley & Sons Ltd.

  12. A cell population that strongly expresses the CB1 cannabinoid receptor in the ependyma of the rat spinal cord.

    Science.gov (United States)

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Sierra-Palomares, Yolanda; Molina-Holgado, Eduardo

    2013-01-01

    The cells surrounding the central canal of the spinal cord are a source of stem/precursor cells that may give rise to neurons, astrocytes, or oligodendrocytes. However, they are a heterogeneous population that remains poorly understood. Here we describe a subpopulation characterized by their strong expression of the CB(1) cannabinoid receptor, oval/round soma, apical nucleus, a variable number of cilia (0, 1, or 2), and the presence of a single short and occasionally ramified basal process. These cells are mainly located in the lateral and dorsal central canal throughout the spinal cord. These CB(1)(HIGH) cells are closely related to the basal lamina labyrinths or fractones derived from subependymal microglia. In addition, CB(1)(HIGH) cells express some stem/precursor cell markers, including vimentin, nestin, Sox2, Sox9, and GLAST, but not others such as CD15 or GFAP. In addition, this cell population does not proliferate in the intact adult spinal cord, although up to 50% of these cells express the proliferation marker Ki67 in newly born rats or after a spinal cord contusion. The present findings contribute to our understanding of the spinal cord central canal structure and reveal the targets for endocannabinoids inside this neurogenic niche. Copyright © 2012 Wiley Periodicals, Inc.

  13. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats

    Science.gov (United States)

    Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-01-01

    Objective The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Methods Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (pkefir group were significantly higher than ischemia group (pkefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (pkefir group compared with ischemia group (pkefir group were significantly higher than ischemia group at 24 h (pkefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future. PMID:26113960

  14. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

    Science.gov (United States)

    Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-05-01

    The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (pkefir group were significantly higher than ischemia group (pkefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (pkefir group compared with ischemia group (pkefir group were significantly higher than ischemia group at 24 h (pkefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

  15. Different Astrocytic Activation between Adult Gekko japonicus and Rats during Wound Healing In Vitro.

    Directory of Open Access Journals (Sweden)

    Yun Gu

    Full Text Available Glial scar formation is a major obstacle to regeneration after spinal cord injury. Moreover, it has been shown that the astrocytic response to injury differs between species. Gekko japonicas is a type of reptile and it shows differential glial activation compared to that of rats. The purpose of the present study was to compare the proliferation and migration of astrocytes in the spinal cords of geckos and rats after injury in vitro. Spinal cord homogenate stimulation and scratch wound models were used to induce astrocytic activation in adult and embryonic rats, as well as in adult geckos. Our results indicated that astrocytes from the adult rat were likely activated by mechanical stimulation, even though they showed lower proliferation abilities than the astrocytes from the gecko under normal conditions. Furthermore, a transcriptome analysis revealed that the differentially expressed genes in astrocytes from adult rats and those from geckos were enriched in pathways involved in proliferation and the response to stimuli. This implies that intrinsic discrepancies in gene expression patterns might contribute to the differential activation of astrocytes between species.

  16. Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats.

    Science.gov (United States)

    Kaegi, Sibille; Schwab, Martin E; Dietz, Volker; Fouad, Karim

    2002-07-01

    This investigation was designed to study the spontaneous functional recovery of adult rats with incomplete spinal cord injury (SCI) at thoracic level during a time course of 2 weeks. Daily testing sessions included open field locomotor examination and electromyographic (EMG) recordings from a knee extensor (vastus lateralis, VL) and an ankle flexor muscle (tibialis anterior, TA) in the hindlimbs of treadmill walking rats. The BBB score (a locomotor score named after Basso et al., 1995, J. Neurotrauma, 12, 1-21) and various measures from EMG recordings were analysed (i.e. step cycle duration, rhythmicity of limb movements, flexor and extensor burst duration, EMG amplitude, root-mean-square, activity overlap between flexor and extensor muscles and hindlimb coupling). Directly after SCI, a marked drop in locomotor ability occurred in all rats with subsequent partial recovery over 14 days. The recovery was most pronounced during the first week. Significant changes were noted in the recovery of almost all analysed EMG measures. Within the 14 days of recovery, many of these measures approached control levels. Persistent abnormalities included a prolonged flexor burst and increased activity overlap between flexor and extensor muscles. Activity overlap between flexor and extensor muscles might be directly caused by altered descending input or by maladaptation of central pattern generating networks and/or sensory feedback.

  17. Pretreatment with AQP4 and NKCC1 Inhibitors Concurrently Attenuated Spinal Cord Edema and Tissue Damage after Spinal Cord Injury in Rats.

    Science.gov (United States)

    Yan, Xiaodong; Liu, Juanfang; Wang, Xiji; Li, Wenhao; Chen, Jingyuan; Sun, Honghui

    2018-01-01

    Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na + -K + -Cl - cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored. Additionally, aforementioned parameters in rats treated with AQP4 and/or NKCC1 inhibitors were assessed 2 days after SCI. Spinal cord water content was significantly increased 1 h after SCI while AQP4 and NKCC1 expression and spinal fluid LDH activity elevated 6 h after SCI. Spinal cord edema and spinal cord destruction peaked around 24 h after SCI and maintained at high levels thereafter. Treating rats with AQP4 inhibitor TGN-020 and NKCC1 antagonist bumetanide significantly reduced spinal cord edema, tissue destruction, and AQP4 and NKCC1 expression after SCI in an additive manner. These results demonstrated the benefits of simultaneously inhibiting both AQP4 and NKCC1 after SCI.

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

    Science.gov (United States)

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

    2014-12-01

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

  19. Age-related changes of neurochemically different subpopulations of cardiac spinal afferent neurons in rats.

    Science.gov (United States)

    Guić, Maja Marinović; Runtić, Branka; Košta, Vana; Aljinović, Jure; Grković, Ivica

    2013-08-01

    This study investigated the effect of aging on cardiac spinal afferent neurons in the rat. A patch loaded with retrograde tracer Fast Blue (FB) was applied to all chambers of the rat heart. Morphological and neurochemical characteristics of labeled cardiac spinal afferent neurons were assessed in young (2 months) and old (2 years) rats using markers for likely unmyelinated (isolectin B4; IB4) and myelinated (neurofilament 200; N52) neurons. The number of cardiac spinal afferent neurons decreased in senescence to 15% of that found in young rats (1604 vs. 248). The size of neuronal soma as well as proportion of IB4+ neurons increased significantly, whereas the proportion of N52+ neurons decreased significantly in senescence. Unlike somatic spinal afferents, neurochemically different populations of cardiac spinal afferent neurons experience morphological and neurochemical changes related to aging. A major decrease in total number of cardiac spinal afferent neurons occurs in senescence. The proportion of N52+ neurons decreased in senescence, but it seems that nociceptive innervation is preserved due to increased proportion and size of IB4+ unmyelinated neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Spinal cord blood flow measured by 14C-iodoantipyrine autoradiography during and after graded spinal cord compression in rats

    International Nuclear Information System (INIS)

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

    1989-01-01

    The relations between degree of thoracic spinal cord compression causing myelographic block, reversible paraparesis, and extinction of the sensory evoked potential on one hand, and spinal cord blood flow on the other, were investigated. This was done in rats using the blocking weight-technique and 14 C-iodoantipyrine autoradiography. A load of 9 g caused myelographic block. Five minutes of compression with that load caused a reduction of spinal cord blood flow to about 25%, but 5 and 60 minutes after the compression spinal cord blood flow was restored to 60% of the pretrauma value. A load of 35 g for 5 minutes caused transient paraparesis. Recovery to about 30% was observed 5 and 60 minutes thereafter. During compression at a load of 55 g, which caused almost total extinction of sensory evoked potential and irreversible paraplegia, spinal cord blood flow under the load ceased. The results indicate that myelographic block occurs at a load which does not cause irreversible paraparesis and that a load which permits sensory evoked potential to be elicited results in potentially salvageable damage

  1. Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

    Science.gov (United States)

    Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

    2016-06-01

    To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

  2. The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

    Science.gov (United States)

    Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

    2009-09-01

    Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

  3. Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    Jian Hao

    2017-01-01

    Full Text Available Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of NeuN-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.

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

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2014-01-01

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

  5. Bone marrow stem cells delivered into the subarachnoid space via cisterna magna improve repair of injured rat spinal cord white matter

    Science.gov (United States)

    Marcol, Wiesław; Slusarczyk, Wojciech; Sieroń, Aleksander L; Koryciak-Komarska, Halina; Lewin-Kowalik, Joanna

    2015-01-01

    The influence of bone marrow stem cells on regeneration of spinal cord in rats was investigated. Young adult male Wistar rats were used (n=22). Focal injury of spinal cord white matter at Th10 level was produced using our original non-laminectomy method by means of high-pressured air stream. Cells from tibial and femoral bone marrow of 1-month old rats (n=3) were cultured, labeled with BrdU/Hoechst and injected into cisterna magna (experimental group) three times: immediately after spinal cord injury and 3 as well as 7 days later. Neurons in brain stem and motor cortex were labeled with FluoroGold (FG) delivered caudally from the injury site a week before the end of experiment. Functional outcome and morphological features of regeneration were analyzed during 12-week follow-up. The lesions were characterized by means of MRI. Maximal distance of expansion of implanted cells in the spinal cord was measured and the number of FG-positive neurons in the brain was counted. Rats treated with stem cells presented significant improvement of locomotor performance and spinal cord morphology when compared to the control group. Distance covered by stem cells was 7 mm from the epicenter of the injury. Number of brain stem and motor cortex FG-positive neurons in experimental group was significantly higher than in control. Obtained data showed that bone marrow stem cells are able to induce the repair of injured spinal cord white matter. The route of cells application via cisterna magna appeared to be useful for their delivery in spinal cord injury therapy. PMID:26628950

  6. Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

    Science.gov (United States)

    Song, Zhaojun; Wang, Zhigang; Shen, Jieliang; Xu, Shengxi; Hu, Zhenming

    2017-01-01

    Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases. PMID:28280337

  7. Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

    Science.gov (United States)

    Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

    2006-07-01

    Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

  8. Retrograde tracing of fluorescent gold after autogenous nerve transplantation on spinal cord injured in rats

    DEFF Research Database (Denmark)

    Lin, X; Liu, W; Ding, Ming

    2016-01-01

    , the transplantation group using autologous sural nerve graft to repair spinal cord injury period and non-transplantation group was only exposed incision without treatment. In the 4, 6 and 8 weeks after operation, the retrograde tracing of FG Fluoro-Gold was performed to discover the recovery of the axial plasma......Objective To investigate the changes of the fluorescent gold retrograde tracing autogenous nerve transplantation on spinal cord injured in rats. Methods The animals were divided into two groups, with modified Allen impact method to establish model of spinal cord injury. After 4 weeks.......01). Conclusion After spinal cord injury, autologous nerve graft was repaired and survived well and promote the recovery of spinal cord injury segment shaft pulp transportation function....

  9. 5-HT modulation of multiple inward rectifiers in motoneurons in intact preparations of the neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Kjaerulff, Ole; Kiehn, Ole

    2001-01-01

    This study introduces novel aspects of inward rectification in neonatal rat spinal motoneurons (MNs) and its modulation by serotonin (5-HT). Whole cell tight-seal recordings were made from MNs in an isolated lumbar spinal cord preparation from rats 1-2 days of age. In voltage clamp, hyperpolarizi...

  10. The role of spinal pathways in dopamine mediated alteration in the tail-flick reflex in rats

    DEFF Research Database (Denmark)

    Jensen, T S; Schrøder, H D; Smith, D F

    1984-01-01

    The latency of the tail-flick, following intrathecal infusion of the dopamine (DA) agonist, R-apomorphine was measured in rats with intact spinal cord or with spinal cord lesions. Apomorphine failed to influence the tail-flick response in intact rats, whereas it elevated the latency of the tail-f...

  11. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons

    Directory of Open Access Journals (Sweden)

    Urszula eSlawinska

    2014-08-01

    Full Text Available There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-OHDPAT (acting on 5-HT1A/7 receptors and quipazine (acting on 5-HT2 receptors, to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor CPG. Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the locomotor activation.

  12. 5-HT₂ and 5-HT₇ receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons.

    Science.gov (United States)

    Sławińska, Urszula; Miazga, Krzysztof; Jordan, Larry M

    2014-01-01

    There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT) (acting on 5-HT1A/7 receptors) and quipazine (acting on 5-HT2 receptors), to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor central pattern generator (CPG). Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the

  13. Protective Effects of Two Constituents of Chinese Herbs on Spinal Motor Neurons from Embryonic Rats with Hypoxia Injury

    OpenAIRE

    Chen, Jian-feng; Fan, Jian; Tian, Xiao-wu; Tang, Tian-si

    2011-01-01

    Neuroprotective agents are becoming significant tools in the repair of central nervous system injuries. In this study, we determined whether ginkgolides (Gin, extract of GinkgoBiloba) and Acanthopanax senticosus saponins (ASS, flavonoids extracted from Acanthopanax herbal preparations) have protective effects on rat spinal cords exposed to anoxia and we explored the mechanisms that underlie the protective effects. Spinal motor neurons (SMNs) from rat spinal cords were obtained and divided int...

  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. A novel device for studying weight supported, quadrupedal overground locomotion in spinal cord injured rats.

    Science.gov (United States)

    Hamlin, Marvin; Traughber, Terence; Reinkensmeyer, David J; de Leon, Ray D

    2015-05-15

    Providing weight support facilitates locomotion in spinal cord injured animals. To control weight support, robotic systems have been developed for treadmill stepping and more recently for overground walking. We developed a novel device, the body weight supported ambulatory rodent trainer (i.e. BART). It has a small pneumatic cylinder that moves along a linear track above the rat. When air is supplied to the cylinder, the rats are lifted as they perform overground walking. We tested the BART device in rats that received a moderate spinal cord contusion injury and in normal rats. Locomotor training with the BART device was not performed. All of the rats learned to walk in the BART device. In the contused rats, significantly greater paw dragging and dorsal stepping occurred in the hindlimbs compared to normal. Providing weight support significantly raised hip position and significantly reduced locomotor deficits. Hindlimb stepping was tightly coupled to forelimb stepping but only when the contused rats stepped without weight support. Three weeks after the contused rats received a complete spinal cord transection, significantly fewer hindlimb steps were performed. Relative to rodent robotic systems, the BART device is a simpler system for studying overground locomotion. The BART device lacks sophisticated control and sensing capability, but it can be assembled relatively easily and cheaply. These findings suggest that the BART device is a useful tool for assessing quadrupedal, overground locomotion which is a more natural form of locomotion relative to treadmill locomotion. Published by Elsevier B.V.

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

    Science.gov (United States)

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

    2016-11-01

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

  17. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.L.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Walton, R.E.; Woodruff, K.H.; Howard, J.

    1980-01-01

    The response of rat spinal cord to irradiation with accelerated heavy ions, in particular carbon and neon ions has been studied. Two different ionization regions in the modified Bragg curve for each ion have been studied for both single and fractionated exposures. We have defined the paralytic response as a function of dose and dose per fraction, and we have determined RBE and repair values. The response of rat spinal cord is both dose and LET dependent, which allows the derivation of RBE and repair values

  18. Kappa opioid receptors in rat spinal cord vary across the estrous cycle.

    Science.gov (United States)

    Chang, P C; Aicher, S A; Drake, C T

    2000-04-07

    Kappa opioid receptors (KORs) were immunocytochemically localized in the lumbosacral spinal cord of female rats in different stages of the estrous cycle to examine the influence of hormonal status on receptor density. KOR labeling was primarily in fine processes and a few neuronal cell bodies in the superficial dorsal horn and the dorsolateral funiculus. Quantitative light microscopic densitometry of the superficial dorsal horn revealed that rats in diestrus had significantly lower KOR densities than those in proestrus or estrus. This suggests that female reproductive hormones regulate spinal KOR levels, which may contribute to variations in analgesic effectiveness of KOR agonists across the estrous cycle.

  19. Effects of polarization in low-level laser therapy of spinal cord injury in rats

    Science.gov (United States)

    Ando, Takahiro; Sato, Shunichi; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Hamblin, Michael R.; Obara, Minoru

    2012-03-01

    Low-level laser therapy (LLLT) is a promising approach to treat the spinal cord injury (SCI). Since nerve fibers have optical anisotropy, propagation of light in the spinal tissue might be affected by its polarization direction. However, the effect of polarization on the efficacy of LLLT has not been elucidated. In the present study, we investigated the effect of polarization on the efficacy of near-infrared LLLT for SCI. Rat spinal cord was injured with a weight-drop device. The lesion site was irradiated with an 808-nm diode laser beam that was transmitted through a polarizing filter immediately after injury and daily for five consecutive days. The laser power at the injured spinal cord surface was 25 mW, and the dosage per day was 9.6 J/cm2 (spot diameter, 2 cm; irradiation duration, 1200 s). Functional recovery was assessed daily by an open-field test. The results showed that the functional scores of the SCI rats that were treated with 808-nm laser irradiation were significantly higher than those of the SCI alone group (Group 1) from day 5 after injury, regardless of the polarization direction. Importantly, as compared to the locomotive function of the SCI rats that were treated with the perpendicularly-polarized laser parallel to the spinal column (Group 2), that of the SCI rats that were irradiated with the linearly aligned polarization (Group 3) was significantly improved from day 10 after injury. In addition, the ATP contents in the injured spinal tissue of Group 3, which were measured immediately after laser irradiation, were moderately higher than those of Group 2. These observations are attributable to the deeper penetration of the parallelpolarized light in the anisotropic spinal tissue, suggesting that polarization direction significantly affects the efficacy of LLLT for SCI.

  20. Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.

    Science.gov (United States)

    Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

    2018-01-01

    Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions ( P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.

  1. 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.

  2. Electro-acupuncture promotes survival, differentiation of the bone marrow mesenchymal stem cells as well as functional recovery in the spinal cord-transected rats

    Science.gov (United States)

    Ding, Ying; Yan, Qing; Ruan, Jing-Wen; Zhang, Yan-Qing; Li, Wen-Jie; Zhang, Yu-Jiao; Li, Yan; Dong, Hongxin; Zeng, Yuan-Shan

    2009-01-01

    Background Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools for treatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injured spinal cord still need to be improved. In the present study, we investigated whether Governor Vessel electro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs) survival and differentiation, axonal regeneration and finally, functional recovery in the transected spinal cord. Results The spinal cords of adult Sprague-Dawley (SD) rats were completely transected at T10, five experimental groups were performed: 1. sham operated control (Sham-control); 2. operated control (Op-control); 3. electro-acupuncture treatment (EA); 4. MSCs transplantation (MSCs); and 5. MSCs transplantation combined with electro-acupuncture (MSCs+EA). After 2-8 weeks of MSCs transplantation plus EA treatment, we found that the neurotrophin-3 (NT-3), cAMP level, the differentiation of MSCs, the 5-HT positive and CGRP positive nerve fibers in the lesion site and nearby tissue of injured spinal cord were significantly increased in the MSCs+EA group as compared to the group of the MSCs transplantation or the EA treated alone. Furthermore, behavioral test and spinal cord evoked potentials detection demonstrated a significantly functional recovery in the MSCs +EA group. Conclusion These results suggest that EA treatment may promote grafted MSCs survival and differentiation; MSCs transplantation combined with EA treatment could promote axonal regeneration and partial locomotor functional recovery in the transected spinal cord in rats and indicate a promising avenue of treatment of spinal cord injury. PMID:19374777

  3. 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.

  4. A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats

    Science.gov (United States)

    Borrell, Jordan A.; Frost, Shawn B.; Peterson, Jeremy; Nudo, Randolph J.

    2017-02-01

    Objective. Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach. Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and electromyographic (EMG) activity. Via fine wire EMG electrodes, stimulus-triggered averaging (StTA) was used on rectified EMG data to determine response latency. Main results. Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance. The derived motor map provides insight into the parameters needed for future neuromodulatory devices.

  5. A THREE-DIMENSIONAL MAP OF THE HINDLIMB MOTOR REPRESENTATION IN THE LUMBAR SPINAL CORD IN SPRAGUE DAWLEY RATS

    Science.gov (United States)

    Borrell, Jordan A.; Frost, Shawn; Peterson, Jeremy; Nudo, Randolph J.

    2016-01-01

    Objective Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282,000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a three-dimensional (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and EMG activity. Via fine wire electromyographic (EMG) electrodes, Stimulus-Triggered Averaging (StTA) was used on rectified EMG data to determine response latency. Main results Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance The derived motor map provides insight into the parameters needed for future neuromodulatory devices. PMID:27934789

  6. The immunoreactivity of satellite glia of the spinal ganglia of rats treated with monosodium glutamate

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    Aleksandra Ewa Krawczyk

    2016-01-01

    Full Text Available Satellite glia of the peripheral nervous system ganglia provide metabolic protection to the neurons. The aim of this study was to determine the effects of monosodium glutamate administered parenterally to rats on the expression of glial fibrillary acidic protein, S-100β protein and Ki-67 antigen in the satellite glial cells. Adult, 60-day-old male rats received monosodium glutamate at two doses of 2 g/kg b.w. (group 1 and 4 g/kg b.w. (group 2 subcutaneously for 3 consecutive days. Animals in the control group (group C were treated with corresponding doses of 0.9% sodium chloride. Immediately after euthanasia, spinal ganglia of the lumbar region were dissected. Immunohistochemical peroxidase anti-peroxidase reactions were performed on the sections containing the examined material using antibodies against glial fibrillary acidic protein, S-100β and Ki-67. Next, morphological and morphometric analyses of immunopositive and immunonegative glia were conducted. The data were presented as the mean number of cells with standard deviation. Significant differences were analysed using ANOVA (P < 0.05. In all 63-day-old rats, immunopositivity for the examined proteins glia was observed. Increased number of cells expressing glial fibrillary acidic protein was demonstrated in group 2, whereas the number of S-100β-positive glia grew in the groups with the increasing doses of monosodium glutamate. The results indicate the early stage reactivity of glia in response to increased levels of glutamate in the extracellular space. These changes may be of a neuroprotective nature under the conditions of excitotoxicity induced by the action of this excitatory neurotransmitter.

  7. Mondia whitei (Periplocaceae prevents and Guibourtia tessmannii (Caesalpiniaceae facilitates fictive ejaculation in spinal male rats

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    Watcho Pierre

    2013-01-01

    Full Text Available Abstract Background Mondia whitei and Guibourtia tessmannii are used in Cameroon traditional medicine as aphrodisiacs. The present study was undertaken to evaluate the pro-ejaculatory effects of the aqueous and organic solvent extracts of these plants in spinal male rats. Methods In spinal cord transected and urethane-anesthetized rats, two electrodes where inserted into the bulbospongiosus muscles and the ejaculatory motor pattern was recorded on a polygraph after urethral and penile stimulations, intravenous injection of saline (0.1 ml/100 g, dopamine (0.1 μM/kg, aqueous and organic solvent plant extracts (20 mg/kg. Results In all spinal rats, urethral and penile stimulations always induced the ejaculatory motor pattern. Aqueous or hexane extract of Mondia whitei (20 mg/kg prevented the expression of the ejaculatory motor pattern. The pro-ejaculatory effects of dopamine (0.1 μM/kg were not abolished in spinal rats pre-treated with Mondia whitei extracts. Aqueous and methanolic stem bark extracts of Guibourtia tessmannii (20 mg/kg induced fictive ejaculation characterized by rhythmic contractions of the bulbospongiosus muscles followed sometimes with expulsion of seminal plugs. In rats pre-treated with haloperidol (0.26 μM/kg, no ejaculatory motor pattern was recorded after intravenous injection of Guibourtia tessmannii extracts (20 mg/kg. Conclusion These results show that Mondia whitei possesses preventive effects on the expression of fictive ejaculation in spinal male rats, which is not mediated through dopaminergic pathway; on the contrary, the pro-ejaculatory activities of Guibourtia tessmannii require the integrity of dopaminergic system to exert its effects. The present findings further justify the ethno-medicinal claims of Mondia whitei and Guibourtia tessmannii.

  8. Two chronic motor training paradigms differentially influe nce acute instrume ntal learning in spinally transected rats

    Science.gov (United States)

    Bigbee, Allison J.; Crown, Eric D.; Ferguson, Adam R.; Roy, Roland R.; Tillakaratne, Niranjala J.K.; Grau, James W.; Edgerton, V. Reggie

    2008-01-01

    The effect of two chronic motor training paradigms on the ability of the lumbar spinal cord to perform an acute instrumental learning task was examined in neonatally (postnatal day 5; P5) spinal cord transected (i.e., spinal) rats. At ∼P30, rats began either unipedal hindlimb stand training (Stand-Tr; 20-25 min/day, 5 days/wk), or bipedal hindlimb step training (Step-Tr; 20 min/day; 5 days/wk) for 7 wks. Non-trained spinal rats (Non-Tr) served as controls. After 7 wks all groups were tested on the flexor-biased instrumental learning paradigm. We hypothesized that 1) Step-Tr rats would exhibit an increased capacity to learn the flexor-biased task relative to Non-Tr subjects, as locomotion involves repetitive training of the tibialis anterior (TA), the ankle flexor whose activation is important for successful instrumental learning, and 2) Stand-Tr rats would exhibit a deficit in acute motor learning, as unipedal training activates the ipsilateral ankle extensors, but not flexors. Results showed no differences in acute learning potential between Non-Tr and Step-Tr rats, while the Stand-Tr group showed a reduced capacity to learn the acute task. Further investigation of the Stand-Tr group showed that, while both the ipsilateral and contralateral hindlimbs were significantly impaired in their acute learning potential, the contralateral, untrained hindlimbs exhibited significantly greater learning deficits. These results suggest that different types of chronic peripheral input may have a significant impact on the ability to learn a novel motor task, and demonstrate the potential for experience-dependent plasticity in the spinal cord in the absence of supraspinal connectivity. PMID:17434606

  9. Effects of glycine on motor performance in rats after traumatic spinal cord injury.

    Science.gov (United States)

    Gonzalez-Piña, Rigoberto; Nuño-Licona, Alberto

    2007-01-01

    It has been reported that glycine improves some functions lost after spinal cord injury (SCI). In order to assess the effects of glycine administration on motor performance after SCI, we used fifteen male Wistar rats distributed into three groups: sham (n = 3), spinal-cord injury (n = 6,) and spinal cord injury + glycine (n = 6). Motor performance was assessed using the beam-walking paradigm and footprint analysis. Results showed that for all animals with spinal-cord injury, scores in the beam-walking increased, which is an indication of increased motor deficit. In addition, footprint analysis showed a decrease in stride length and an increase in stride angle, additional indicators of motor deficit. These effects trended towards recovery after 8 weeks of recording and trended toward improvement by glycine administration; the effect was not significant. These results suggest that glycine replacement alone is not sufficient to improve the motor deficits that occur after SCI.

  10. Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.

    Science.gov (United States)

    Jiang, Li; Ji, Yadong; Voulalas, Pamela J; Keaser, Michael; Xu, Su; Gullapalli, Rao P; Greenspan, Joel; Masri, Radi

    2014-01-01

    Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood. To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain. We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI. MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P cortex and the prefrontal cortex. These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex. Copyright © 2014. Published by Elsevier Inc.

  11. The Neuroprotective Effect of Puerarin in Acute Spinal Cord Injury Rats

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    Dapeng Zhang

    2016-08-01

    Full Text Available Background: Acute spinal cord injury (SCI leads to permanent disabilities. This study evaluated the neuroprotective effect of puerarin, a natural extract, in a rat model of SCI. Methods: Acute SCI models were established in rats using a modified Allen's method. Locomotor function was evaluated using the BBB test. The histological changes in the spinal cord were observed by H&E staining. Neuron survival and glial cells activation were evaluated by immunostaining. ELISA and realtime PCR were used to measure secretion and gene expression of cytokines. TUNEL staining was used to examine cell apoptosis and western blot analysis was used to detect protein expression. Results: Puerarin significantly increased BBB score in SCI rats, attenuated histological injury of spinal cord, decreased neuron loss, inhibited glial cells activation, alleviated inflammation, and inhibited cell apoptosis in the injured spinal cords. In addition, the downregulated PI3K and phospho-Akt protein expression were restored by puerarin. Conclusion: Puerarin accelerated locomotor function recovery and tissue repair of SCI rats, which is associated with its neuroprotection, glial cell activation suppression, anti-inflammatory and anti-apoptosis effects. These effects may be associated with the activation of PI3K/Akt signaling pathway.

  12. Heavy metals in the spinal cord of normal rats and of animals treated with chelating agents

    DEFF Research Database (Denmark)

    Schrøder, H D; Fjerdingstad, E; Danscher, G

    1978-01-01

    The amounts of zinc, copper, and lead in the rat spinal cord were determined by means of flameless atomic absorption spectrophotometry. Zinc was present in a concentration about 100 p.p.m. (dry weight), copper in a concentration about 5 p.p.m., and lead in slightly more than 1 p.p.m. Analysis of ...

  13. Locomotor recovery after spinal cord contusion injury in rats is improved by spontaneous exercise

    NARCIS (Netherlands)

    Gispen, W.H.; Meeteren, N.L. van; Eggers, L.; Lankhorst, A.J.; Hamers, F.P.

    2003-01-01

    We have recently shown that enriched environment (EE) housing significantly enhances locomotor recovery following spinal cord contusion injury (SCI) in rats. As the type and intensity of locomotor training with EE housing are rather poorly characterized, we decided to compare the effectiveness of EE

  14. Radiation nephropathy in young and adult rats

    International Nuclear Information System (INIS)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-01-01

    The effects of bilateral kidney irradiation were compared in young and adult rats. During a 1 year period after a single dose of 0, 7.5, 10, 12.5, or 15 Gy on both kidneys, renal function (glomerular filtration rate and effective renal plasma flow), urine composition, and systolic blood pressure were measured periodically. The first changes after irradiation were observed in the glomerular filtration rate and urine osmolality. One month after 10, 12.5, and 15 Gy, glomerular filtration rate (GFR) and urine osmolality had declined below control values in the young rats. After this initial decline, renal function increased at control rate or even more during the third and fourth month after irradiation but decreased progressively thereafter. In the adult rats, GFR and urine osmolality started to decrease 3 months after 10, 12.5, and 15 Gy. A rise in systolic blood pressure and proteinuria started 2-3 months after 12.5 and 15 Gy in both age groups. Early changes in the glomerular filtration rate with a drop in urine osmolality in young rats, occurring during a period of rapid renal development indicated an irradiation-induced inhibition of glomerular and tubular development. Although renal function deteriorated at a later time in adult rats, dose-response relationships obtained in young and adult rats did not show significant differences

  15. Lumbar spinal mobility changes among adults with advancing age

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    Ismaila Adamu Saidu

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  17. 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.

  18. Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

    Science.gov (United States)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

    The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

  19. Stretching After Heat But Not After Cold Decreases Contractures After Spinal Cord Injury in Rats.

    Science.gov (United States)

    Iwasawa, Hiroyuki; Nomura, Masato; Sakitani, Naoyoshi; Watanabe, Kosuke; Watanabe, Daichi; Moriyama, Hideki

    2016-12-01

    Contractures are a prevalent and potentially severe complication in patients with neurologic disorders. Although heat, cold, and stretching are commonly used for treatment of contractures and/or spasticity (the cause of many contractures), the sequential effects of these modalities remain unclear. Using an established rat model with spinal cord injury with knee flexion contracture, we sought to determine what combination of heat or cold before stretching is the most effective for treatment of contractures derived from spastic paralyses and investigated which treatment leads to the best (1) improvement in the loss of ROM; (2) restoration of deterioration in the muscular and articular factors responsible for contractures; and (3) amelioration of histopathologic features such as muscular fibrosis in biceps femoris and shortening of the joint capsule. Forty-two adolescent male Wistar rats were used. After spasticity developed at 2 weeks postinjury, each animal with spinal cord injury underwent the treatment protocol daily for 1 week. Knee extension ROM was measured with a goniometer by two examiners blinded to each other's scores. The muscular and articular factors contributing to contractures were calculated by measuring ROM before and after the myotomies. We quantitatively measured the muscular fibrosis and the synovial intima length, and observed the distribution of collagen of skeletal muscle. The results were confirmed by a blinded observer. The ROM of heat alone (34° ± 1°) and cold alone (34° ± 2°) rats were not different with the numbers available from that of rats with spinal cord injury (35° ± 2°) (p = 0.92 and 0.89, respectively). Stretching after heat (24° ± 1°) was more effective than stretching alone (27° ± 3°) at increasing ROM (p contractures. Although quantification of muscular fibrosis in the rats with spinal cord injury (11% ± 1%) was higher than that of controls (9% ± 0.4%) (p = 0.01), no difference was found between spinal cord

  20. Spinal cord thyrotropin releasing hormone receptors of morphine tolerant-dependent and abstinent rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-07-01

    The effect of chronic administration of morphine and its withdrawal on the binding of 3H-(3-MeHis2)thyrotropin releasing hormone (3H-MeTRH) to membranes of the spinal cord of the rat was determined. Male Sprague-Dawley rats were implanted with either 6 placebo or 6 morphine pellets (each containing 75-mg morphine base) during a 7-day period. Two sets of animals were used. In one, the pellets were left intact at the time of sacrificing (tolerant-dependent) and in the other, the pellets were removed 16 hours prior to sacrificing (abstinent rats). In placebo-pellet-implanted rats, 3H-MeTRH bound to the spinal cord membranes at a single high affinity binding site with a Bmax of 21.3 +/- 1.6 fmol/mg protein, and an apparent dissociation constant Kd of 4.7 +/- 0.8 nM. In morphine tolerant-dependent or abstinent rats, the binding constants of 3H-MeTRH to spinal cord membranes were unaffected. Previous studies from this laboratory indicate that TRH can inhibit morphine tolerance-dependence and abstinence processes without modifying brain TRH receptors. Together with the present results, it appears that the inhibitory effect of TRH on morphine tolerance-dependence and abstinence is probably not mediated via central TRH receptors but may be due to its interaction with other neurotransmitter systems.

  1. Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats

    DEFF Research Database (Denmark)

    Ghorbani, Marie Louise M; Qin, Chao; Wu, Mingyuan

    2011-01-01

    The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague-Dawley rats and citrate buffer was injected in 14 control rats. After 4-11weeks...

  2. 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.

  3. Time Course of Spinal Doublecortin Expression in Developing Rat and Porcine Spinal Cord: Implication in In Vivo Neural Precursor Grafting Studies

    Czech Academy of Sciences Publication Activity Database

    Juhásová, Jana; Juhás, Štefan; Hruška-Plocháň, M.; Doležalová, D.; Holubová, Monika; Strnádel, Ján; Marsala, S.; Motlík, Jan; Marsala, M.

    2015-01-01

    Roč. 35, č. 1 (2015), s. 57-70 ISSN 0272-4340 R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : doublecortin * spinal cord development * spinal neural precursor grafting * minipig * rat * GFAP Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.328, year: 2015

  4. Changes in rat spinal cord gene expression after inflammatory hyperalgesia of the joint and manual therapy.

    Science.gov (United States)

    Ruhlen, Rachel L; Singh, Vineet K; Pazdernik, Vanessa K; Towns, Lex C; Snider, Eric J; Sargentini, Neil J; Degenhardt, Brian F

    2014-10-01

    Mobilization of a joint affects local tissue directly but may also have other effects that are mediated through the central nervous system. To identify differential gene expression in the spinal cords of rats with or without inflammatory joint injury after manual therapy or no treatment. Rats were randomly assigned to 1 of 4 treatment groups: no injury and no touch (NI/NT), injury and no touch (I/NT), no injury and manual therapy (NI/MT), and injury and manual therapy (I/MT). We induced acute inflammatory joint injury in the rats by injecting carrageenan into an ankle. Rats in the no-injury groups did not receive carrageenan injection. One day after injury, rats received manual therapy to the knee of the injured limb. Rats in the no-touch groups were anesthetized without receiving manual therapy. Spinal cords were harvested 30 minutes after therapy or no touch, and spinal cord gene expression was analyzed by microarray for 3 comparisons: NI/NT vs I/NT, I/MT vs I/NT, and NI/NT vs NI/MT. Three rats were assigned to each group. Of 38,875 expressed sequence tags, 755 were differentially expressed in the NI/NT vs I/NT comparison. For the other comparisons, no expressed sequence tags were differentially expressed. Cluster analysis revealed that the differentially expressed sequence tags were over-represented in several categories, including ion homeostasis (enrichment score, 2.29), transmembrane (enrichment score, 1.55), and disulfide bond (enrichment score, 2.04). An inflammatory injury to the ankle of rats caused differential expression of genes in the spinal cord. Consistent with other studies, genes involved in ion transport were among those affected. However, manual therapy to the knees of injured limbs or to rats without injury did not alter gene expression in the spinal cord. Thus, evidence for central nervous system mediation of manual therapy was not observed. © 2014 The American Osteopathic Association.

  5. Regulation of peripheral inflammation by spinal p38 MAP kinase in rats.

    Directory of Open Access Journals (Sweden)

    David L Boyle

    2006-09-01

    Full Text Available Somatic afferent input to the spinal cord from a peripheral inflammatory site can modulate the peripheral response. However, the intracellular signaling mechanisms in the spinal cord that regulate this linkage have not been defined. Previous studies suggest spinal cord p38 mitogen-activated protein (MAP kinase and cytokines participate in nociceptive behavior. We therefore determined whether these pathways also regulate peripheral inflammation in rat adjuvant arthritis, which is a model of rheumatoid arthritis.Selective blockade of spinal cord p38 MAP kinase by administering the p38 inhibitor SB203580 via intrathecal (IT catheters in rats with adjuvant arthritis markedly suppressed paw swelling, inhibited synovial inflammation, and decreased radiographic evidence of joint destruction. The same dose of SB203580 delivered systemically had no effect, indicating that the effect was mediated by local concentrations in the neural compartment. Evaluation of articular gene expression by quantitative real-time PCR showed that spinal p38 inhibition markedly decreased synovial interleukin-1 and -6 and matrix metalloproteinase (MMP3 gene expression. Activation of p38 required tumor necrosis factor alpha (TNFalpha in the nervous system because IT etanercept (a TNF inhibitor given during adjuvant arthritis blocked spinal p38 phosphorylation and reduced clinical signs of adjuvant arthritis.These data suggest that peripheral inflammation is sensed by the central nervous system (CNS, which subsequently activates stress-induced kinases in the spinal cord via a TNFalpha-dependent mechanism. Intracellular p38 MAP kinase signaling processes this information and profoundly modulates somatic inflammatory responses. Characterization of this mechanism could have clinical and basic research implications by supporting development of new treatments for arthritis and clarifying how the CNS regulates peripheral immune responses.

  6. Radiography used to measure internal spinal cord deformation in an in vivo rat model.

    Science.gov (United States)

    Lucas, E; Whyte, T; Liu, J; Tetzlaff, W; Cripton, P A

    2018-04-11

    Little is known about the internal mechanics of the in vivo spinal cord during injury. The objective of this study was to develop a method of tracking internal and surface deformation of in vivo rat spinal cord during compression using radiography. Since neural tissue is radio-translucent, radio-opaque markers were injected into the spinal cord. Two tantalum beads (260 µm) were injected into the cord (dorsal and ventral) at C5 of nine anesthetized rats. Four beads were glued to the lateral surface of the cord, caudal and cranial to the injection site. A compression plate was displaced 0.5 mm, 2 mm, and 3 mm into the spinal cord and lateral X-ray images were taken before, during, and after each compression for measuring bead displacements. Potential bead migration was monitored for by comparing displacements of the internal and glued surface beads. Dorsal beads moved significantly more than ventral beads with a range in averages of 0.57-0.71 mm and 0.31-0.35 mm respectively. Bead displacements during 0.5 mm compressions were significantly lower than 2 mm and 3 mm compressions. There was no statistically significant migration of the internal beads. The results indicate the merit of this technique for measuring in vivo spinal cord deformation. The pattern of bead displacements illustrates the complex internal and surface deformations of the spinal cord during transverse compression. This information is needed for validating physical and finite element spinal cord surrogates and to define relationships between loading parameters, internal cord deformation, and biological and functional outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

    Science.gov (United States)

    Zeng, Xiang; Qiu, Xue-Cheng; Ma, Yuan-Huan; Duan, Jing-Jing; Chen, Yuan-Feng; Gu, Huai-Yu; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

    2015-06-01

    Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro. Intra-GS formation of MSC assemblies emulating neural network (MSC-GS) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC-GS or GS was then grafted acutely into a 2 mm-wide transection gap in the T9-T10 spinal cord segments of adult rats. Eight weeks later, hindlimb function of the MSC-GS-treated SCT rats was significantly improved relative to controls receiving the GS or lesion only as indicated by BBB score. The MSC-GS transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered c-fos expression in the grafted and lumbar spinal cord cells of the treated rats only. Our data suggest that MSC-derived neuron-like cells resulting from NT-3-TrkC-induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits. Copyright

  8. Stem cells regenerative properties on new rat spinal fusion model

    Czech Academy of Sciences Publication Activity Database

    Klíma, K.; Vaněček, Václav; Kohout, A.; Jiroušek, Ondřej; Foltán, R.; Štulík, J.; Machoň, V.; Pavlíková, G.; Jendelová, Pavla; Syková, Eva; Šedý, Jiří

    2015-01-01

    Roč. 64, č. 1 (2015), s. 119-128 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT13477; GA ČR(CZ) GAP304/10/0320 Institutional support: RVO:67985823 ; RVO:68378297 ; RVO:68378041 Keywords : mesenchymal stem cells * bone graft substitute * spinal fusion Subject RIV: FH - Neurology Impact factor: 1.643, year: 2015

  9. Study of the efficiency of transplantation of human neural stem cells to rats with spinal trauma: the use of functional load tests and BBB test.

    Science.gov (United States)

    Lebedev, S V; Karasev, A V; Chekhonin, V P; Savchenko, E A; Viktorov, I V; Chelyshev, Yu A; Shaimardanova, G F

    2010-09-01

    Human ensheating neural stem cells of the olfactory epithelium were transplanted to adult male rats immediately after contusion trauma of the spinal cord at T9 level rostrally and caudally to the injury. Voluntary movements (by a 21-point BBB scale), rota-rod performance, and walking along a narrowing beam were monitored weekly over 60 days. In rats receiving cell transplantation, the mean BBB score significantly increased by 11% by the end of the experiment. The mean parameters of load tests also regularly surpassed the corresponding parameters in controls. The efficiency of transplantation (percent of animals with motor function recovery parameters surpassing the corresponding mean values in the control groups) was 62% by the state of voluntary motions, 37% by the rota-rod test, and 32% by the narrowing beam test. Morphometry revealed considerable shrinking of the zone of traumatic damage in the spinal cord and activation of posttraumatic remyelination in animals receiving transplantation of human neural stem cells.

  10. The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats.

    Science.gov (United States)

    Sławińska, Urszula; Majczyński, Henryk; Dai, Yue; Jordan, Larry M

    2012-04-01

    Recent studies on the restoration of locomotion after spinal cord injury have employed robotic means of positioning rats above a treadmill such that the animals are held in an upright posture and engage in bipedal locomotor activity. However, the impact of the upright posture alone, which alters hindlimb loading, an important variable in locomotor control, has not been examined. Here we compared the locomotor capabilities of chronic spinal rats when placed in the horizontal and upright postures. Hindlimb locomotor movements induced by exteroceptive stimulation (tail pinching) were monitored with video and EMG recordings. We found that the upright posture alone significantly improved plantar stepping. Locomotor trials using anaesthesia of the paws and air stepping demonstrated that the cutaneous receptors of the paws are responsible for the improved plantar stepping observed when the animals are placed in the upright posture.We also tested the effectiveness of serotonergic drugs that facilitate locomotor activity in spinal rats in both the horizontal and upright postures. Quipazine and (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) improved locomotion in the horizontal posture but in the upright posture either interfered with or had no effect on plantar walking. Combined treatment with quipazine and 8-OH-DPAT at lower doses dramatically improved locomotor activity in both postures and mitigated the need to activate the locomotor CPG with exteroceptive stimulation. Our results suggest that afferent input from the paw facilitates the spinal CPG for locomotion. These potent effects of afferent input from the paw should be taken into account when interpreting the results obtained with rats in an upright posture and when designing interventions for restoration of locomotion after spinal cord injury.

  11. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats.

    Science.gov (United States)

    Kachadroka, Supatra; Hall, Alicia M; Niedzielko, Tracy L; Chongthammakun, Sukumal; Floyd, Candace L

    2010-03-01

    Several groups have recently shown that 17beta-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17beta-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17beta-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17beta-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5- or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax/Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17beta-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonad-intact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17beta-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17beta-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.

  12. Profound differences in spontaneous long-term functional recovery after defined spinal tract lesions in the rat

    NARCIS (Netherlands)

    Hendriks, William T J; Eggers, R.; Ruitenberg, Marc J; Blits, Bas; Hamers, Frank P T; Verhaagen, J.; Boer, Gerard J

    The purpose of this study was to compare spontaneous functional recovery after different spinal motor tract lesions in the rat spinal cord using three methods of analysis, the BBB, the rope test, and the CatWalk. We transected the dorsal corticospinal tract (CSTx) or the rubrospinal tract (RSTx) or

  13. Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats.

    Science.gov (United States)

    Gokce, Emre Cemal; Kahveci, Ramazan; Atanur, Osman Malik; Gürer, Bora; Aksoy, Nurkan; Gokce, Aysun; Sargon, Mustafa Fevzi; Cemil, Berker; Erdogan, Bulent; Kahveci, Ozan

    2015-11-01

    Ganoderma lucidum (G. lucidum) is a mushroom belonging to the polyporaceae family of Basidiomycota and has widely been used as a traditional medicine for thousands of years. G. lucidum has never been studied in traumatic spinal cord injury. The aim of this study is to investigate whether G. lucidum polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord injury. Rats were randomized into five groups of eight animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only a laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analysed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. After traumatic spinal cord injury, increases in caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. After the administration of GLPS, decreases were observed in tissue caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. Furthermore, GLPS treatment showed improved results in histopathological scores, ultrastructural scores, and functional tests. Biochemical, histopathological, and ultrastructural analyses and functional tests reveal that GLPS exhibits meaningful neuroprotective effects against spinal cord injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Secondary damage in the spinal cord after motor cortex injury in rats.

    Science.gov (United States)

    Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

    2010-08-01

    When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

  15. Intravenous Infusion of Magnesium Chloride Improves Epicenter Blood Flow during the Acute Stage of Contusive Spinal Cord Injury in Rats

    Science.gov (United States)

    Muradov, Johongir M.

    2013-01-01

    Abstract Vasospasm, hemorrhage, and loss of microvessels at the site of contusive or compressive spinal cord injury lead to infarction and initiate secondary degeneration. Here, we used intravenous injection of endothelial-binding lectin followed by histology to show that the number of perfused microvessels at the injury site is decreased by 80–90% as early as 20 min following a moderate T9 contusion in adult female rats. Hemorrhage within the spinal cord also was maximal at 20 min, consistent with its vasoconstrictive actions in the central nervous system (CNS). Microvascular blood flow recovered to up to 50% of normal volume in the injury penumbra by 6 h, but not at the epicenter. A comparison with an endothelial cell marker suggested that many microvessels fail to be reperfused up to 48 h post-injury. The ischemia was probably caused by vasospasm of vessels penetrating the parenchyma, because repeated Doppler measurements over the spinal cord showed a doubling of total blood flow over the first 12 h. Moreover, intravenous infusion of magnesium chloride, used clinically to treat CNS vasospasm, greatly improved the number of perfused microvessels at 24 and 48 h. The magnesium treatment seemed safe as it did not increase hemorrhage, despite the improved parenchymal blood flow. However, the treatment did not reduce acute microvessel, motor neuron or oligodendrocyte loss, and when infused for 7 days did not affect functional recovery or spared epicenter white matter over a 4 week period. These data suggest that microvascular blood flow can be restored with a clinically relevant treatment following spinal cord injury. PMID:23302047

  16. The effects of local insulin application to lumbar spinal fusions in a rat model.

    Science.gov (United States)

    Koerner, John D; Yalamanchili, Praveen; Munoz, William; Uko, Linda; Chaudhary, Saad B; Lin, Sheldon S; Vives, Michael J

    2013-01-01

    The rates of pseudoarthrosis after a single-level spinal fusion have been reported up to 35%, and the agents that increase the rate of fusion have an important role in decreasing pseudoarthrosis after spinal fusion. Previous studies have analyzed the effects of local insulin application to an autograft in a rat segmental defect model. Defects treated with a time-released insulin implant had significantly more new bone formation and greater quality of bone compared with controls based on histology and histomorphometry. A time-released insulin implant may have similar effects when applied in a lumbar spinal fusion model. This study analyzes the effects of a local time-released insulin implant applied to the fusion bed in a rat posterolateral lumbar spinal fusion model. Our hypothesis was twofold: first, a time-released insulin implant applied to the autograft bed in a rat posterolateral lumbar fusion will increase the rate of successful fusion and second, will alter the local environment of the fusion site by increasing the levels of local growth factors. Animal model (Institutional Animal Care and Use Committee approved) using 40 adult male Sprague-Dawley rats. Forty skeletally mature Sprague-Dawley rats weighing approximately 500 g each underwent posterolateral intertransverse lumbar fusions with iliac crest autograft from L4 to L5 using a Wiltse-type approach. After exposure of the transverse processes and high-speed burr decortication, a Linplant (Linshin Canada, Inc., ON, Canada) consisting of 95% microrecrystalized palmitic acid and 5% bovine insulin (experimental group) or a sham implant consisting of only palmitic acid (control group) was implanted on the fusion bed with iliac crest autograft. As per the manufacturer, the Linplant has a release rate of 2 U/day for a minimum of 40 days. The transverse processes and autograft beds of 10 animals from the experimental and 10 from the control group were harvested at Day 4 and analyzed for growth factors. The

  17. 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

  18. Systemic and Local Cytokine Profile following Spinal Cord Injury in Rats: A Multiplex Analysis

    Directory of Open Access Journals (Sweden)

    Yana O. Mukhamedshina

    2017-10-01

    Full Text Available Our study of the changes in cytokine profile in blood serum and in the spinal cord after traumatic spinal cord injury (SCI has shown that an inflammatory reaction and immunological response are not limited to the CNS, but widespread. This fact was confirmed by changes detected in a cytokine profile in blood serum samples [MIP-1α, interleukin 1 (IL-1 α, IL-2, IL-5, IL-1β, MCP-1, RANTES]. There were also changes in the levels of MIP-1α, IL-1α, IL-2, IL-5, IL-18, GM-colony-stimulating factor, IL-17α, IFN-γ, IL-10, IL-13, MCP-1, and GRO KC CINC-1 in samples of the rat injured spinal cord. The results underscore the complex cytokine network imbalance exhibited after SCI and show significant changes in the concentrations of 14 cytokines/chemokines with different inflammatory and immunological activities.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  20. Autoradiographic localization of substance P receptors in the rat and bovine spinal cord and the rat and cat spinal trigeminal nucleus pars caudalis and the effects of neonatal capsaicin

    Energy Technology Data Exchange (ETDEWEB)

    Mantyh, P.W.; Hunt, S.P. (Medical Research Council Centre, Cambridge (UK). Medical School, MRC Neurochemical Pharmacology Unit)

    1985-04-22

    Substance P (SP) is a putative neurotransmitter in the central nervous system. In the present report the authors have used autoradiographic receptor binding techniques to investigate the distribution of SP receptor binding sites in the rat and bovine spinal cord and in the rat and cat spinal trigeminal nucleus pars caudalis. Although some quantitative differences were evident, all species appeared to have a similar distribution of SP receptor binding sites in both the spinal cord and in the spinal trigeminal nucleus pars caudalis. In the spinal cord the heaviest concentration of SP receptors is located in lamina X, while moderate to heavy concentrations were found in laminae I, II and V-IX. Very low concentrations of SP receptors were present in laminae III and IV. Examination of the cat and rat spinal trigeminal nucleus pars caudalis revealed a moderate density of SP receptor binding sites in laminae I and II, very low concentrations in laminae III and IV, and low to moderate concentrations in lamina V. Rats treated neonatally with capsaicin showed a small (11%) but significant (P < 0.02) increase in the levels of SP receptor binding sites in laminae I and II of the cervical and lumbar spinal cord while in all other laminae the levels remained unchanged.

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

    Science.gov (United States)

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

    2008-07-01

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

  2. Characterization of thoracic spinal neurons with noxious convergent inputs from heart and lower airways in rats.

    Science.gov (United States)

    Qin, Chao; Foreman, Robert D; Farber, Jay P

    2007-04-13

    Respiratory symptoms experienced in some patients with cardiac diseases may be due to convergence of noxious cardiac and pulmonary inputs onto neurons of the central nervous system. For example, convergence of cardiac and respiratory inputs onto single solitary tract neurons may be in part responsible for integration of regulatory and defensive reflex control. However, it is unknown whether inputs from the lungs and heart converge onto single neurons of the spinal cord. The present aim was to characterize upper thoracic spinal neurons responding to both noxious stimuli of the heart and lungs in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer bradykinin (BK, 10 microg/ml, 0.2 ml, 1 min) as a noxious cardiac stimulus. The lung irritant, ammonia, obtained as vapor over a 30% solution of NH(4)OH was injected into the inspiratory line of the ventilator (0.5-1.0 ml over 20 s). Intrapericardial bradykinin (IB) altered activity of 58/65 (89%) spinal neurons that responded to inhaled ammonia (IA). Among those cardiopulmonary convergent neurons, 81% (47/58) were excited by both IA and IB, and the remainder had complex response patterns. Bilateral cervical vagotomy revealed that vagal afferents modulated but did not eliminate responses of individual spinal neurons to IB and IA. The convergence of pulmonary and cardiac nociceptive signaling in the spinal cord may be relevant to situations where a disease process in one organ influences the behavior of the other.

  3. Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway

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    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.

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

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    Ji-wei WANG

    2015-10-01

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

  5. Human fetal spinal stem cells improve locomotor function after spinal cord injury in the rat

    Czech Academy of Sciences Publication Activity Database

    Amemori, Takashi; Romanyuk, Nataliya; Jendelová, Pavla; Herynek, V.; Turnovcová, Karolína; Mareková, Dana; Kapcalová, Miroslava; Price, J.; Syková, Eva

    2011-01-01

    Roč. 59, S1 (2011), S84-S85 ISSN 0894-1491. [European meeting on Glia l Cells in Health and Disease /10./. 13.09.2011-17.09.2011, Prague] R&D Projects: GA MŠk(CZ) LC554; GA AV ČR IAA500390902; GA ČR GA203/09/1242 Grant - others:GA ČR(CZ) GD309/08/H079 Institutional research plan: CEZ:AV0Z50390703 Keywords : spinal cord injury Subject RIV: FH - Neurology

  6. Neonatal bee venom exposure induces sensory modality-specific enhancement of nociceptive response in adult rats.

    Science.gov (United States)

    Li, Mengmeng; Chen, Huisheng; Tang, Jiaguang; Chen, Jun

    2014-06-01

    Previous studies have shown that inflammatory pain at the neonatal stage can produce long-term structural and functional changes in nociceptive pathways, resulting in altered pain perception in adulthood. However, the exact pattern of altered nociceptive response and associated neurochemical changes in the spinal cord in this process is unclear. In this study, we used an experimental paradigm in which each rat first received intraplantar bee venom (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was followed 2 months later by a second intraplantar bee venom injection in the same rats to examine the difference in nociceptive responses. We found that neonatal inflammatory pain induced by the first BV injection significantly reduced baseline paw withdrawal mechanical threshold, but not baseline paw withdrawal thermal latency, when rats were examined 2 months from the first BV injection. Neonatal inflammatory pain also exacerbated mechanical, but not thermal, hyperalgesia in response to the second BV injection in these same rats. Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF, TrkA receptor, BDNF, TrkB receptor, IL-1β, and COX-2 expression following the second BV injection, especially with prior BV exposure on postnatal day 21 or 28. These results indicate that neonatal inflammation produces sensory modality-specific changes in nociceptive behavior and alters neurochemistry in the spinal cord of adult rats. These results also suggest that a prior history of inflammatory pain during the developmental period might have an impact on clinical pain in highly susceptible adult patients. Wiley Periodicals, Inc.

  7. A brain-machine-muscle interface for restoring hindlimb locomotion after complete spinal transection in rats.

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    Monzurul Alam

    Full Text Available A brain-machine interface (BMI is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics.

  8. Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho-associated kinase II in spinal cord injury rats

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    You-jiang Min

    2017-01-01

    Full Text Available Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase (ROCK signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan (GV3, Dazhui (GV14, Zusanli (ST36 and Ciliao (BL32 and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the mRNA and protein expression of Rho-A and Rho-associated kinase II (ROCKII of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKII. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKII. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of RhoA and ROCKII. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.

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

    Science.gov (United States)

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

    2018-01-01

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

  10. The Correlation of Gene Expression of Inflammasome Indicators and Impaired Fertility in Rat Model of Spinal Cord Injury: A Time Course Study.

    Science.gov (United States)

    Nikmehr, Banafsheh; Bazrafkan, Mahshid; Hassanzadeh, Gholamreza; Shahverdi, Abdolhossein; Sadighi Gilani, Mohammad Ali; Kiani, Sahar; Mokhtari, Tahmineh; Abolhassani, Farid

    2017-11-04

    Expression assessment of the inflammasome genes in the acute and the chronic phases of Spinal cord injury (SCI) on adult rat testis and examination of associations between inflammasome complex expression and sperm parameters. In this study, 25 adult male rats were randomly divided into 5 groups. SCI surgery was performed at T10-T11 level of rats' spinal cord in four groups (SCI1, SCI3, SCI7, and SCI56). They were sacrificed after 1day, 3days, 7days and 56 days post SCI, respectively. One group remained intact as control (Co).CASA analysis of sperm parameters and qRT-PCR (ASC and Caspase-1) were made in all cases. Our data showed a severe reduction in sperm count and motility, especially on day 3 and 7. ASC gene expression had a non-significant increase on day 1 and 56 after surgery compared to control group. Caspase-1 expression increased significantly on day 3 post injury versus the control group (P = .009). Moreover, Caspase-1 overexpression, had significant correlations with sperm count (r = -0.555, P = .01) and sperm progressive motility (r = -0.524, P = .02). Inflammasome complex expression increase following SCI induction. This overexpression correlates to low sperm parameters in SCI rats.

  11. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

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    Elphick Maurice R

    2009-07-01

    Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

  12. Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats.

    Science.gov (United States)

    Kim, Jae Hwan; Kim, Jae Young; Mun, Chin Hee; Suh, Minah; Lee, Jong Eun

    2017-10-01

    Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206 + & ED1 + cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.

  13. Selective retrograde transport of D-aspartate in spinal interneurons anc cortical neurons of rats

    International Nuclear Information System (INIS)

    Rustioni, A.; Cuenod, M.

    1982-01-01

    Retrograde labeling of neuronal elements in the brain and spinal cord has been investigated by autoradiographic techniques following injections of D-[ 3 H]aspartate (asp), [ 3 H]γ-aminobutyric acid (GABA) or horseradish peroxidase (HRP) in the medulla and spinal cord of rats. Twenty-four hours after D-[ 3 H]asp injections focused upon the cuneate nucleus, autoradiographic labeling is present over fibers in the pyramidal tract, internal capsule and over layer V pyramids in the forelimb representation of the sensorimotor cortex. After [ 3 H]GABA injections in the same nucleus no labeling attributable to retrograde translocation can be detected in spinal segments, brain stem or cortex. Conversely, injections of 30% HRP in the cuneate nucleus label neurons in several brain stem nuclei, in spinal gray and in layer V of the sensorimotor cortex. D-[ 3 H]Asp injections focused on the dorsal horn at cervical segments label a fraction of perikarya of the substantia gelatinosa and a sparser population of larger neurons in laminae IV to VI for a distance of 3-5 segments above and below the injection point. No brain stem neuronal perikarya appear labeled following spinal injections of D-[ 3 H]asp although autoradiographic grains overlie pyramidal tract fibers on the side contralateral to the injection. (Auth.)

  14. Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle

    OpenAIRE

    Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon; Chung, Jin Mo

    2011-01-01

    Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in res...

  15. Characterization of spinal afferent neurons projecting to different chambers of the rat heart.

    Science.gov (United States)

    Guić, Maja Marinović; Kosta, Vana; Aljinović, Jure; Sapunar, Damir; Grković, Ivica

    2010-01-29

    The pattern of distribution of spinal afferent neurons (among dorsal root ganglia-DRGs) that project to anatomically and functionally different chambers of the rat heart, as well as their morphological and neurochemical characteristics were investigated. Retrograde tracing using a patch loaded with Fast blue (FB) was applied to all four chambers of the rat heart and labeled cardiac spinal afferents were characterized by using three neurochemical markers. The majority of cardiac projecting neurons were found from T1 to T4 DRGs, whereas the peak was at T2 DRG. There was no difference in the total number of FB-labeled neurons located in ipsilateral and contralateral DRGs regardless of the chambers marked with the patch. However, significantly more FB-labeled neurons projected to the ventricles compared to the atria (859 vs. 715). The proportion of isolectin B(4) binding in FB-labeled neurons was equal among all neurons projecting to different heart chambers (2.4%). Neurofilament 200 positivity was found in greater proportions in DRG neurons projecting to the left side of the heart, whereas calretinin-immunoreactivity was mostly represented in neurons projecting to the left atrium. Spinal afferent neurons projecting to different chambers of the rat heart exhibit a variety of neurochemical phenotypes depending on binding capacity for isolectin B(4) and immunoreactivity for neurofilament 200 and calretinin, and thus represent important baseline data for future studies. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  16. Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat.

    Science.gov (United States)

    Yang, Cheng; Gao, Jie; Wu, Banglin; Yan, Nuo; Li, Hui; Ren, Yiqing; Kan, Yufei; Liang, Jiamin; Jiao, Yang; Yu, Yonghao

    2017-10-01

    We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats

    Science.gov (United States)

    Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

    2011-01-01

    Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level. PMID:21389301

  18. Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

    Science.gov (United States)

    Oza, Chintan S.

    2015-01-01

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. PMID:25948267

  19. Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

    Science.gov (United States)

    Oza, Chintan S; Giszter, Simon F

    2015-05-06

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. Copyright © 2015 the authors 0270-6474/15/357174-16$15.00/0.

  20. 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)

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

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

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

  2. Anti-apoptotic effect of insulin in the control of cell death and neurologic deficit after acute spinal cord injury in rats.

    Science.gov (United States)

    Wu, Xing-Huo; Yang, Shu-Hua; Duan, De-Yu; Cheng, Heng-Hui; Bao, Yu-Ting; Zhang, Yukun

    2007-09-01

    Recent studies confirmed that the new cell survival signal pathway of Insulin-PI3K-Akt exerted cyto-protective actions involving anti-apoptosis. This study was undertaken to investigate the potential neuroprotective effects of insulin in the pathogenesis of spinal cord injury (SCI) and evaluate its therapeutic effects in adult rats. SCI was produced by extradural compression using modified Allen's stall with damage energy of 40 g-cm force. One group of rats was subjected to SCI in combination with the administration of recombinant human insulin dissolved in 50% glucose solution at the dose of 1 IU/kg day, for 7 days. At the same time, another group of rats was subjected to SCI in combination with the administration of an equal volume of sterile saline solution. Functional recovery was evaluated using open-field walking, inclined plane tests, and motor evoked potentials (MEPs) during the first 14 days post-trauma. Levels of protein for B-cell lymphoma/leukemia-2 gene (Bcl-2), Caspase-3, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified in the injured spinal cord by Western blot analysis. Neuronal apoptosis was detected by TUNEL, and spinal cord blood flow (SCBF) was measured by laser-Doppler flowmetry (LDF). Ultimately, the data established the effectiveness of insulin treatment in improving neurologic recovery, increasing the expression of anti-apoptotic bcl-2 proteins, inhibiting caspase-3 expression decreasing neuronal apoptosis, reducing the expression of proinflammatory cytokines iNOS and COX-2, and ameliorating microcirculation of injured spinal cord after moderate contusive SCI in rats. In sum, this study reported the beneficial effects of insulin in the treatment of SCI, with the suggestion that insulin should be considered as a potential therapeutic agent.

  3. Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats.

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    Frost, Shawn B; Dunham, Caleb L; Barbay, Scott; Krizsan-Agbas, Dora; Winter, Michelle K; Guggenmos, David J; Nudo, Randolph J

    2015-11-01

    The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.

  4. 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

  5. Therapeutic Effect of Platelet-Rich Plasma in Rat Spinal Cord Injuries

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    Nan-Fu Chen

    2018-04-01

    Full Text Available Platelet-rich plasma (PRP is prepared by centrifuging fresh blood in an anticoagulant state, and harvesting the platelet-rich portion or condensing platelets. Studies have consistently demonstrated that PRP concentrates are an abundant source of growth factors, such as platelet-derived growth factor (PDGF, transforming growth factor β (TGF-β, insulin-like growth factor 1 (IGF-1, and epithelial growth factor (EGF. The complex mechanisms underlying spinal cord injury (SCI diminish intrinsic repair and neuronal regeneration. Several studies have suggested that growth factor-promoted axonal regeneration can occur for an extended period after injury. More importantly, the delivery of exogenous growth factors contained in PRP, such as EGF, IGF-1, and TGF-β, has neurotrophic effects on central nervous system (CNS injuries and neurodegenerative diseases. However, only a few studies have investigated the effects of PRP on CNS injuries or neurodegenerative diseases. According to our review of relevant literature, no study has investigated the effect of intrathecal (i.t. PRP injection into the injured spinal cord and activation of intrinsic mechanisms. In the present study, we directly injected i.t. PRP into rat spinal cords and examined the effects of PRP on normal and injured spinal cords. In rats with normal spinal cords, PRP induced microglia and astrocyte activation and PDGF-B and ICAM-1 expression. In rats with SCIs, i.t. PRP enhanced the locomotor recovery and spared white matter, promoted angiogenesis and neuronal regeneration, and modulated blood vessel size. Furthermore, a sustained treatment (a bolus of PRP followed by a 1/3 dose of initial PRP concentration exerted more favorable therapeutic effects than a single dose of PRP. Our findings suggest by i.t. PRP stimulate angiogenesis, enhancing neuronal regeneration after SCI in rats. Although PRP induces minor inflammation in normal and injured spinal cords, it has many advantages. It is an

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

    Science.gov (United States)

    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

  7. Uptake of trace elements in adult and suckling rat lenses

    International Nuclear Information System (INIS)

    Nabekura, Tomohiro; Ito, Yoshimasa; Minami, Takeshi; Hirunuma, Rieko; Enomoto, Shuichi

    2001-01-01

    The uptake of trace elements in the lens was compared in adult and suckling rat lenses. Multitracers, including 15 trace elements, As, Be, Co, Fe, Mn, Rb, Rh, Ru, Sc, Se, Sr, Y, V, Zn, and Zr, were incubated with the lenses for 4 hr and their concentrations in the lens were measured. A high uptake rate of Zn was observed in the lenses of both adult and suckling rats in comparison with those of the other elements, and the Zn concentration in the lens of suckling rats was higher than that of adult rats. The uptake rate of Sr was higher in adult rats than in suckling rats. On the other contrary, Rb and Se concentrations in the lens were higher in suckling rats than in adult rats. The present study suggests that the different mechanisms depending on development serve to transport trace elements into the lens. (author)

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  9. Enhanced motor function by training in spinal cord contused rats following radiation therapy.

    Directory of Open Access Journals (Sweden)

    Ronaldo Ichiyama

    Full Text Available Weight-bearing stepping, without supraspinal re-connectivity, can be attained by treadmill training in an animal whose spinal cord has been completely transected at the lower thoracic level. Repair of damaged tissue and of supraspinal connectivity/circuitry following spinal cord injury in rat can be achieved by specific cell elimination with radiation therapy of the lesion site delivered within a critical time window, 2-3 weeks postinjury. Here we examined the effects of training in the repaired spinal cord following clinical radiation therapy. Studies were performed in a severe rat spinal cord contusion injury model, one similar to fracture/crush injuries in humans; the injury was at the lower thoracic level and the training was a combined hindlimb standing and stepping protocol. Radiotherapy, in a similar manner to that reported previously, resulted in a significant level of tissue repair/preservation at the lesion site. Training in the irradiated group, as determined by limb kinematics tests, resulted in functional improvements that were significant for standing and stepping capacity, and yielded a significant direct correlation between standing and stepping performance. In contrast, the training in the unirradiated group resulted in no apparent beneficial effects, and yielded an inverse correlation between standing and stepping performance, e.g., subject with good standing showed poor stepping capacity. Further, without any training, a differential functional change was observed in the irradiated group; standing capacity was significantly inhibited while stepping showed a slight trend of improvement compared with the unirradiated group. These data suggest that following repair by radiation therapy the spinal circuitries which control posture and locomotor were modified, and that the beneficial functional modulation of these circuitries is use dependent. Further, for restoring beneficial motor function following radiotherapy, training seems

  10. Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

    Science.gov (United States)

    Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

    2010-07-01

    Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

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

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    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

  12. Dose-volume effects in the rat cervical spinal cord after proton irradiation

    International Nuclear Information System (INIS)

    Bijl, Hendrik P.; Vuijk, Peter van; Coppes, Rob P.; Schippers, Jacobus M.; Konings, Antonius W.T.; Kogel, Albert J. van der

    2002-01-01

    Purpose: To estimate dose-volume effects in the rat cervical spinal cord with protons. Methods and Materials: Wistar rats were irradiated on the cervical spinal cord with a single fraction of unmodulated protons (150-190 MeV) using the shoot through method, which employs the plateau of the depth-dose profile rather than the Bragg peak. Four different lengths of the spinal cord (2, 4, 8, and 20 mm) were irradiated with variable doses. The endpoint for estimating dose-volume effects was paralysis of fore or hind limbs. Results: The results obtained with a high-precision proton beam showed a marginal increase of ED 50 when decreasing the irradiated cord length from 20 mm (ED 50 = 20.4 Gy) to 8 mm (ED 50 = 24.9 Gy), but a steep increase in ED 50 when further decreasing the length to 4 mm (ED 50 = 53.7 Gy) and 2 mm (ED 50 = 87.8 Gy). These results generally confirm data obtained previously in a limited series with 4-6-MV photons, and for the first time it was possible to construct complete dose-response curves down to lengths of 2 mm. At higher ED 50 values and shorter lengths irradiated, the latent period to paralysis decreased from 125 to 60 days. Conclusions: Irradiation of variable lengths of rat cervical spinal cord with protons showed steeply increasing ED 50 values for lengths of less than 8 mm. These results suggest the presence of a critical migration distance of 2-3 mm for cells involved in regeneration processes

  13. 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

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

    DEFF Research Database (Denmark)

    Petersen, Peter Christian Hvidberg; Berg, Rune W.

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

  16. Optimizing Filter-Probe Diffusion Weighting in the Rat Spinal Cord for Human Translation

    Directory of Open Access Journals (Sweden)

    Matthew D. Budde

    2017-12-01

    Full Text Available Diffusion tensor imaging (DTI is a promising biomarker of spinal cord injury (SCI. In the acute aftermath, DTI in SCI animal models consistently demonstrates high sensitivity and prognostic performance, yet translation of DTI to acute human SCI has been limited. In addition to technical challenges, interpretation of the resulting metrics is ambiguous, with contributions in the acute setting from both axonal injury and edema. Novel diffusion MRI acquisition strategies such as double diffusion encoding (DDE have recently enabled detection of features not available with DTI or similar methods. In this work, we perform a systematic optimization of DDE using simulations and an in vivo rat model of SCI and subsequently implement the protocol to the healthy human spinal cord. First, two complementary DDE approaches were evaluated using an orientationally invariant or a filter-probe diffusion encoding approach. While the two methods were similar in their ability to detect acute SCI, the filter-probe DDE approach had greater predictive power for functional outcomes. Next, the filter-probe DDE was compared to an analogous single diffusion encoding (SDE approach, with the results indicating that in the spinal cord, SDE provides similar contrast with improved signal to noise. In the SCI rat model, the filter-probe SDE scheme was coupled with a reduced field of view (rFOV excitation, and the results demonstrate high quality maps of the spinal cord without contamination from edema and cerebrospinal fluid, thereby providing high sensitivity to injury severity. The optimized protocol was demonstrated in the healthy human spinal cord using the commercially-available diffusion MRI sequence with modifications only to the diffusion encoding directions. Maps of axial diffusivity devoid of CSF partial volume effects were obtained in a clinically feasible imaging time with a straightforward analysis and variability comparable to axial diffusivity derived from DTI

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

    Science.gov (United States)

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

    2014-04-01

    Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in spinal cord injury (SCI), mainly based on in vitro and ex vivo evidence. Here, we demonstrate an increase of acrolein up to 300%; the elevation lasted at least 2 weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health. © 2013 International Society for Neurochemistry.

  18. Extraction of motor activity from the cervical spinal cord of behaving rats

    Science.gov (United States)

    Prasad, Abhishek; Sahin, Mesut

    2006-12-01

    Injury at the cervical region of the spinal cord results in the loss of the skeletal muscle control from below the shoulders and hence causes quadriplegia. The brain-computer interface technique is one way of generating a substitute for the lost command signals in these severely paralyzed individuals using the neural signals from the brain. In this study, we are investigating the feasibility of an alternative method where the volitional signals are extracted from the cervical spinal cord above the point of injury. A microelectrode array assembly was implanted chronically at the C5-C6 level of the spinal cord in rats. Neural recordings were made during the face cleaning behavior with forelimbs as this task involves cyclic forelimb movements and does not require any training. The correlation between the volitional motor signals and the elbow movements was studied. Linear regression technique was used to reconstruct the arm movement from the rectified-integrated version of the principal neural components. The results of this study demonstrate the feasibility of extracting the motor signals from the cervical spinal cord and using them for reconstruction of the elbow movements.

  19. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Norifumi; Nagaoka, Shunji; Nojima, Kumie

    2003-01-01

    We investigate effects of localized exposure of heavy ion to the lumbar 4th to 6th segments of the rat spinal cord on the properties of motoneurons and the innervated muscle fibers without surgical treatments. Twenty 7-week-old male Wistar rats were exposed to 5 mm spread-out Bragg peak (SOBP) carbon beam (290 MeV, linear energy transfer (LET)=130 keV/μm): Two doses (15 Gy or 20 Gy) were applied to each group of rats (n=5) in two different depths; one group was exposed only for ventral horn of the spinal cord while other for whole spinal cord. Five rats served as controls. The rats were exposed to carbon irons on October 26, 2002. We will sacrifice the rats soon after they show an abnormal behavior including posture and walking. Cell body size and oxidative enzyme activity of spinal motoneurons of the control and heavy-ion-exposed rats will be analyzed. In addition, cell size, oxidative enzyme activity, and expressions of myosin heavy chain isoforms of the gastrocnemius, soleus, plantaris, extensor digitorum longus, and tibialis anterior muscle fibers will be also determined. This study is performed to test our hypothesis that atrophy and a decrease in cross-sectional area of motoneurons and muscle fibers which they innervate, as well as a decrease in oxidative activity of motoneurons and muscle fibers, will be induced due to exposure to heavy ion. (author)

  20. Pathological changes in the white matter after spinal contusion injury in the rat.

    Directory of Open Access Journals (Sweden)

    C Joakim Ek

    Full Text Available It has been shown previously that after spinal cord injury, the loss of grey matter is relatively faster than loss of white matter suggesting interventions to save white matter tracts offer better therapeutic possibilities. Loss of white matter in and around the injury site is believed to be the main underlying cause for the subsequent loss of neurological functions. In this study we used a series of techniques, including estimations of the number of axons with pathology, immunohistochemistry and mapping of distribution of pathological axons, to better understand the temporal and spatial pathological events in white matter following contusion injury to the rat spinal cord. There was an initial rapid loss of axons with no detectable further loss beyond 1 week after injury. Immunoreactivity for CNPase indicated that changes to oligodendrocytes are rapid, extending to several millimetres away from injury site and preceding much of the axonal loss, giving early prediction of the final volume of white matter that survived. It seems that in juvenile rats the myelination of axons in white matter tracts continues for some time, which has an important bearing on interpretation of our, and previous, studies. The amount of myelin debris and axon pathology progressively decreased with time but could still be observed at 10 weeks after injury, especially at more distant rostral and caudal levels from the injury site. This study provides new methods to assess injuries to spinal cord and indicates that early interventions are needed for the successful sparing of white matter tracts following injury.

  1. Response of rat spinal cord to very small doses per fraction: lack of enhanced radiosensitivity

    International Nuclear Information System (INIS)

    Shun, Wong C.; Yong, Hao; Hill, Richard P.

    1995-01-01

    Our previous work with rat spinal cord demonstrated that the linear quadratic (LQ) model based on data for large fraction sizes ((α(β)) of 2.4 Gy) failed to predict isoeffective doses between 1 and 2 Gy per fraction, and under-estimated the sparing effect of small doses per fraction given once daily. In contrast, data from mouse skin and kidney, and recent in vitro results revealed a paradoxical increase in radiosensitivity at below 1 Gy per fraction. To assess whether enhanced radiosensitivity is present in the spinal cord below 1 Gy per fraction, the rat spinal cord (C2-T2) was irradiated initially with three daily doses of 10.25 Gy (top-up doses representing 90% of tolerance), followed by graded single doses or fractionated doses in 1.5, 1.0, 0.8, 0.6 or 0.4 Gy fractions given once daily. To limit the overall treatment time to ≤ 8 weeks, a small number of the 0.6- and 0.4-Gy fractions were given twice daily with an interfraction interval of 16 h. The end-point was forelimb paralysis secondary to white matter necrosis, confirmed histologically. The ED 50 values, excluding the top-up doses, were 5.8, 10.6, 14.8, 15.2, 15.9 and 19.1 Gy for a single dose and doses in 1.5-, 1.0-, 0.8-, 0.6- and 0.4-Gy fractions, respectively. The data gave an (α(β)) of 2.1 Gy (95% CI, 1.4, 2.7 Gy). Pooling the data separately, the (α(β)) value was 2.3 Gy (95% CI, 0.82, 3.7 Gy) for fraction sizes ≥ 1 Gy, and 1.2 Gy (95% CI, 0.16, 2.3 Gy) for the 0.8-, 0.6- and 0.4-Gy experiments. These results in which top-up doses were given initially are consistent with a large sparing effect of very small fraction sizes in rat spinal cord provided sufficient time is allowed for repair of sublethal damage between fractions, and provide no evidence for a paradoxical increase in radiosensitivity in the rat spinal cord below 1 Gy down to 0.4 Gy per fraction

  2. Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.

    Science.gov (United States)

    Gaudet, Andrew D; Ayala, Monica T; Schleicher, Wolfgang E; Smith, Elana J; Bateman, Emily M; Maier, Steven F; Watkins, Linda R

    2017-09-01

    Spinal cord injury (SCI) causes chronic pain in 65% of individuals. Unfortunately, current pain management is inadequate for many SCI patients. Rodent models could help identify how SCI pain develops, explore new treatment strategies, and reveal whether acute post-SCI morphine worsens chronic pain. However, few studies explore or compare SCI-elicited neuropathic pain in rats. Here, we sought to determine how different clinically relevant contusion SCIs in male and female rats affect neuropathic pain, and whether acute morphine worsens later chronic SCI pain. First, female rats received sham surgery, or 150kDyn or 200kDyn midline T9 contusion SCI. These rats displayed modest mechanical allodynia and long-lasting thermal hyperalgesia. Next, a 150kDyn (1s dwell) midline contusion SCI was performed in male and female rats. Interestingly, males, but not females showed SCI-elicited mechanical allodynia; rats of both sexes had thermal hyperalgesia. In this model, acute morphine treatment had no significant effect on chronic neuropathic pain symptoms. Unilateral SCIs can also elicit neuropathic pain that could be exacerbated by morphine, so male rats received unilateral T13 contusion SCI (100kDyn). These rats exhibited significant, transient mechanical allodynia, but not thermal hyperalgesia. Acute morphine did not exacerbate chronic pain. Our data show that specific rat contusion SCI models cause neuropathic pain. Further, chronic neuropathic pain elicited by these contusion SCIs was not amplified by our course of early post-trauma morphine. Using clinically relevant rat models of SCI could help identify novel pain management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

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

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

    2017-07-01

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

  5. Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats

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    Yang Jia-Le

    2012-05-01

    Full Text Available Abstract Background Spinal glia, particularly microglia and astrocytes, are of the utmost importance in the development and maintenance of chronic pain. A recent study from our laboratory revealed that gabapentin, a recommended first-line treatment for multiple neuropathic conditions, could also efficiently antagonize thermal hyperalgesia evoked by complete Freund's adjuvant (CFA-induced monoarthritis (MA. In the present study, we investigated whether the spinal glia are involved in the anti-hyperalgesic effect of gabapentin and how this event occurs. Results Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes. These cells exhibited large cell bodies, thick processes and increases in the ionized calcium binding adapter molecule 1 (Iba-1, a microglial marker or the glia fibrillary acidic protein (GFAP, an astrocytic marker. These cells also displayed immunoreactive signals, and an upregulation of the voltage-gated calcium channels (VGCCs α2/δ-1 subunit, CX3CL1 and CX3CR1 expression levels in the spinal cord. These changes were associated with the development of thermal hyperalgesia. Immunofluorescence staining showed that VGCC α2/δ-1 subunit, a proposed gabapentin target of action, was widely distributed in primary afferent fibers terminals and dorsal horn neurons. CX3CL1, a potential trigger to activate microglia, colocalized with VGCC α2/δ-1 subunits in the spinal dorsal horn. However, its receptor CX3CR1 was mainly expressed in the spinal microglia. Multiple intraperitoneal (i.p. gabapentin injections (100 mg/kg, once daily for 4 days with the first injection 60 min before intra-articular CFA suppressed the activation of spinal microglia, downregulated spinal VGCC α2/δ-1 subunits decreased CX3CL1 levels and blocked the development of thermal hyperalgesia in MA rats. Conclusions Here we provide the first evidence that gabapentin diminishes CX3CL1 signaling and spinal microglia

  6. Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin

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    Fang Li

    2006-03-01

    Full Text Available Abstract Background Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. Results In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in

  7. Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats.

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    Joanna M Lubieniecka

    Full Text Available One of the major challenges in management of spinal cord injury (SCI is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS analyses of cerebrospinal fluid (CSF collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.

  8. Biomarkers for Severity of Spinal Cord Injury in the Cerebrospinal Fluid of Rats

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    Lubieniecka, Joanna M.; Streijger, Femke; Lee, Jae H. T.; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K.; Coorssen, Jens R.; Foster, Leonard J.; Grigliatti, Thomas A.; Tetzlaff, Wolfram

    2011-01-01

    One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage. PMID:21559420

  9. Developmental Changes In Pain And Spinal Immune Gene Expression After Radicular Trauma In The Rat

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    Gordon Alfred Barr

    2016-12-01

    Full Text Available Neuropathic pain is an example of chronic pain that develops after nerve injury and is less frequent in infants and children than in adults. Likewise, in animal models of neuropathic pain, allodynia and hyperalgesia are non-existent or attenuated in the infant, with a switch during development by which acute nerve injury transitions to chronic pain. Concomitant with the delay in neuropathic pain, there is a parallel delay in the ability of nerve injury to activate the immune system. Models of neuropathic pain in the infant have used various ligation methods and find that neuropathic pain does not occur under after postnatal day 21-28 (PN21-PN28, linked to activation of immune processes and developmental regulation of anti-inflammatory cytokines. We applied a model of neuropathic pain in the adult using a transient compression of the cervical nerve or nerve root in infant rats (injured at 10, 14, 21 or 28 days of age to define transition periods during which injury results in no change in thermal and mechanical pain sensitivity or in short term changes in pain. There was little to no hyperalgesia when the injury was imposed at PN10, but significant thermal hyperalgesia and mechanical allodynia one day after compression injury when performed at PN14, 21 or 28. Thermal withdrawal latencies return to near baseline by 7 days post-surgery (PS7 when the injuries were at PN14, and lasted up to 14 days when imposed at PN28. There was mechanical allodynia following nerve injury at 7 or 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7 and 14 days post-injury at PN14, 21, and 28 showed that both the magnitude and duration of elevated immune markers and chemokines/cytokines were greater in the older animals, corresponding to the development of hyperalgesia. Thus we confirm the late onset of neuropathic pain but found no evidence of emergent hyperalgesia if the injury was before PN21/28. This may be due to the use of a transient

  10. Ryanodine receptors contribute to the induction of nociceptive input-evoked long-term potentiation in the rat spinal cord slice

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    Zhao Zhi-Qi

    2010-01-01

    Full Text Available Abstract Background Our previous study demonstrated that nitric oxide (NO contributes to long-term potentiation (LTP of C-fiber-evoked field potentials by tetanic stimulation of the sciatic nerve in the spinal cord in vivo. Ryanodine receptor (RyR is a downstream target for NO. The present study further explored the role of RyR in synaptic plasticity of the spinal pain pathway. Results By means of field potential recordings in the adult male rat in vivo, we showed that RyR antagonist reduced LTP of C-fiber-evoked responses in the spinal dorsal horn by tetanic stimulation of the sciatic nerve. Using spinal cord slice preparations and field potential recordings from superficial dorsal horn, high frequency stimulation of Lissauer's tract (LT stably induced LTP of field excitatory postsynaptic potentials (fEPSPs. Perfusion of RyR antagonists blocked the induction of LT stimulation-evoked spinal LTP, while Ins(1,4,5P3 receptor (IP3R antagonist had no significant effect on LTP induction. Moreover, activation of RyRs by caffeine without high frequency stimulation induced a long-term potentiation in the presence of bicuculline methiodide and strychnine. Further, in patch-clamp recordings from superficial dorsal horn neurons, activation of RyRs resulted in a large increase in the frequency of miniature EPSCs (mEPSCs. Immunohistochemical study showed that RyRs were expressed in the dorsal root ganglion (DRG neurons. Likewise, calcium imaging in small DRG neurons illustrated that activation of RyRs elevated [Ca2+]i in small DRG neurons. Conclusions These data indicate that activation of presynaptic RyRs play a crucial role in the induction of LTP in the spinal pain pathway, probably through enhancement of transmitter release.

  11. Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord

    International Nuclear Information System (INIS)

    Gonzales-Lima, F.

    1986-01-01

    The autoradiographic ( 14 C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. (author)

  12. Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord

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    Gonzales-Lima, F

    1986-04-24

    The autoradiographic (/sup 14/C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. 12 refs.

  13. Protective effect of bone marrow mesenchymal stem cells combined with erythropoietin therapy on spinal cord injury rat model

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    Peng Xie

    2016-01-01

    Full Text Available Objective: To study the protective effect of bone marrow mesenchymal stem cells combined with erythropoietin therapy on spinal cord injury rat model. Methods: SD rats were selected as experimental animals, spinal cord injury rat model was built by striking spinal cord with Hatteras Instruments PCI3000, and model rats were divided into control group, bone marrow mesenchymal stem cells (BMSCs group, erythropoietin (EPO group and BMSCs combined with EPO group according to different treatment methods. Then number of apoptotic cells in spinal cord tissue, contents of neural markers and neurotrophic factors as well as expression of apoptosis and injury molecules was detected. Results: Number of apoptotic cells as well as mRNA contents of Caspase-3 and c-fos of BMSCs group, EPO group and BMSCs+EPO group was lower than those of control group, and number of apoptotic cells as well as mRNA contents of Caspase-3 and c-fos of BMSCs+EPO group were lower than those of BMSCs group and EPO group; mRNA contents of NF-200 and MBP as well as protein contents of NGF and BDNF in spinal cord tissue of BMSCs group, EPO group and BMSCs+EPO group were higher than those of control group, and mRNA contents of NF-200 and MBP as well as protein contents of NGF and BDNF in spinal cord tissue of BMSCs+EPO group were higher than those of BMSCs group and EPO group. Conclusions: Bone marrow mesenchymal stem cells combined with erythropoietin therapy can inhibit cell apoptosis in the injured spinal cord tissue, increase neurotrophic factor levels and inhibit apoptosis and injury molecule expression; it has protective effect on spinal cord injury.

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

    Science.gov (United States)

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

    2018-03-08

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

  15. 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

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    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

  16. Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats.

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    Stone, A J; Copp, S W; Kaufman, M P

    2014-09-26

    Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100 μg in 10 μl), a COX-2-specific inhibitor Celecoxib (100 μg in 10 μl), an EP2 antagonist PF-04418948 (10 μg in 10 μl), and an EP4 antagonist L-161,982 (4 μg in 10 μl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100 μg in 10 μl), EP2 agonist Butaprost (4 ng in 10 μl), and EP4 agonist TCS 2510 (6.25 μg in 2.5 μl), respectively. Once effective doses were established, we statically contracted the hind limb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 ± 5 mmHg, after Ketorolac 14 ± 5 mmHg; preflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. The role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrate rats

    Science.gov (United States)

    Stone, Audrey J.; Copp, Steven W.; Kaufman, Marc P.

    2014-01-01

    Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide receptor (EP) 2 or EP4 receptors attenuated the exercise pressor reflex in decerebrate rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100ug in 10ul), a COX-2 specific inhibitor Celecoxib (100μg in 10μl), an EP2 antagonist PF-04418948 (10μg in 10μl), and an EP4 antagonist L-161,982 (4μg in 10μl) effectively attenuated the pressor responses to intrathecal injections of Arachidonic Acid (100μg in 10μl), EP2 agonist Butaprost (4ng in 10 μl), and EP4 agonist TCS 2510 (6.25μg in 2.5 μl), respectively. Once effective doses were established, we statically contracted the hindlimb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23±5 mmHg, after Ketorolac 14±5 mmHg; preflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors. PMID:25003710

  18. 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.

  19. Effect of intravenous transplantation of bone marrow mesenchymal stem cells on neurotransmitters and synapsins in rats with spinal cord injury

    Science.gov (United States)

    Chen, Shaoqiang; Wu, Bilian; Lin, Jianhua

    2012-01-01

    Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3–5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time (1–5 weeks). Expressions of choline acetyltransferase, glutamic acid decarboxylase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury. PMID:25657678

  20. High-resolution three-dimensional visualization of the rat spinal cord microvasculature by synchrotron radiation micro-CT

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    Hu, Jianzhong; Cao, Yong; Wu, Tianding; Li, Dongzhe [Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008 (China); Lu, Hongbin, E-mail: hongbinlu@hotmail.com [Department of Sports Medicine, Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008 (China)

    2014-10-15

    Purpose: Understanding the three-dimensional (3D) morphology of the spinal cord microvasculature has been limited by the lack of an effective high-resolution imaging technique. In this study, synchrotron radiation microcomputed tomography (SRµCT), a novel imaging technique based on absorption imaging, was evaluated with regard to the detection of the 3D morphology of the rat spinal cord microvasculature. Methods: Ten Sprague-Dawley rats were used in this ex vivo study. After contrast agent perfusion, their spinal cords were isolated and scanned using conventional x-rays, conventional micro-CT (CµCT), and SRµCT. Results: Based on contrast agent perfusion, the microvasculature of the rat spinal cord was clearly visualized for the first time ex vivo in 3D by means of SRµCT scanning. Compared to conventional imaging techniques, SRµCT achieved higher resolution 3D vascular imaging, with the smallest vessel that could be distinguished approximately 7.4 μm in diameter. Additionally, a 3D pseudocolored image of the spinal cord microvasculature was generated in a single session of SRµCT imaging, which was conducive to detailed observation of the vessel morphology. Conclusions: The results of this study indicated that SRµCT scanning could provide higher resolution images of the vascular network of the spinal cord. This modality also has the potential to serve as a powerful imaging tool for the investigation of morphology changes in the 3D angioarchitecture of the neurovasculature in preclinical research.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-08-15

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

  3. Neonatal 6-hydroxydopamine treatment: Noradrenaline levels and in vitro 3H-catecholamine synthesis in discrete brain regions of adult rats

    NARCIS (Netherlands)

    Versteeg, D.H.G.; Ree, J.M. van; Provoost, Abraham P.; Jong, Wybren de

    1974-01-01

    Endogenous noradrenaline levels are elevated in medulla oblongata, mesencephalon, pons and thalamus of adult rats which had been treated with 6-hydroxydopamine on days 1, 2, 8 and 15 after birth. Levels in spinal cord, cerebellum, hippocampus/amygdala and cortex are depressed, whereas no significant

  4. Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats

    Directory of Open Access Journals (Sweden)

    Lin CM

    2015-08-01

    Full Text Available Chien-Min Lin,1,* Jo-Ting Tsai,2,* Chen Kuei Chang,1 Juei-Tang Cheng,3 Jia-Wei Lin11Department of Neurosurgery, 2Department of Radiation Oncology, Shuang Ho Hospital-Taipei Medical University, 3Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan City, Taiwan*These authors contributed equally to this workBackground: Decrease of peroxisome proliferator-activated receptors-δ (PPARδ expression has been observed after spinal cord injury (SCI. Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application.Methods: In the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage.Results: Recovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI.Conclusion: The obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.Keywords: PPARδ, AMPK, spinal cord injury, angiotensin receptor blocker, metformin

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

    Science.gov (United States)

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

    1998-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Subhra Prakash Hui

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

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

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    Jose L Serrano-Velez

    2014-06-01

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

  8. 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)

  9. In vivo PET imaging of the neuroinflammatory response in rat spinal cord injury using the TSPO tracer [18F]GE-180 and effect of docosahexaenoic acid

    International Nuclear Information System (INIS)

    Tremoleda, J.L.; Thau-Zuchman, O.; Davies, M.; Vadivelu, K.C.; Yip, P.K.; Michael-Titus, A.T.; Foster, J.; Sosabowski, J.; Khan, I.; Trigg, W.

    2016-01-01

    Traumatic spinal cord injury (SCI) is a devastating condition which affects millions of people worldwide causing major disability and substantial socioeconomic burden. There are currently no effective treatments. Modulating the neuroinflammatory (NI) response after SCI has evolved as a major therapeutic strategy. PET can be used to detect the upregulation of the 18-kDa translocator protein (TSPO), a hallmark of activated microglia in the CNS. We investigated whether PET imaging using the novel TSPO tracer [ 18 F]GE-180 can be used as a clinically relevant biomarker for NI in a contusion SCI rat model, and we present data on the modulation of NI by the lipid docosahexaenoic acid (DHA). A total of 22 adult male Wistar rats were subjected to controlled spinal cord contusion at the T10 spinal cord level. Six non-injured and ten T10 laminectomy only (LAM) animals were used as controls. A subset of six SCI animals were treated with a single intravenous dose of 250 nmol/kg DHA (SCI-DHA group) 30 min after injury; a saline-injected group of six animals was used as an injection control. PET and CT imaging was carried out 7 days after injury using the [ 18 F]GE-180 radiotracer. After imaging, the animals were killed and the spinal cord dissected out for biodistribution and autoradiography studies. In vivo data were correlated with ex vivo immunohistochemistry for TSPO. In vivo dynamic PET imaging revealed an increase in tracer uptake in the spinal cord of the SCI animals compared with the non-injured and LAM animals from 35 min after injection (P < 0.0001; SCI vs. LAM vs. non-injured). Biodistribution and autoradiography studies confirmed the high affinity and specific [ 18 F]GE-180 binding in the injured spinal cord compared with the binding in the control groups. Furthermore, they also showed decreased tracer uptake in the T10 SCI area in relation to the non-injured remainder of the spinal cord in the SCI-DHA group compared with the SCI-saline group (P < 0.05), supporting

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

    Science.gov (United States)

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

    2011-04-20

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

    Acrolein, an α,β-unsaturated aldehyde and a reactive product of lipid peroxidation, has been suggested as a key factor in neural post-traumatic secondary injury in SCI, mainly based on in vitro and ex vivo evidence. Here we demonstrate an increase of acrolein up to 300%; the elevation lasted at least two weeks in a rat SCI model. More importantly, hydralazine, a known acrolein scavenger can provide neuroprotection when applied systemically. Besides effectively reducing acrolein, hydralazine treatment also resulted in significant amelioration of tissue damage, motor deficits, and neuropathic pain. This effect was further supported by demonstrating the ability of hydralazine to reach spinal cord tissue at a therapeutic level following intraperitoneal application. This suggests that hydralazine is an effective neuroprotective agent not only in vitro, but in a live animal model of SCI as well. Finally, the role of acrolein in SCI was further validated by the fact that acrolein injection into the spinal cord caused significant SCI-like tissue damage and motor deficits. Taken together, available evidence strongly suggests a critical causal role of acrolein in the pathogenesis of spinal cord trauma. Since acrolein has been linked to a variety of illness and conditions, we believe that acrolein-scavenging measures have the potential to be expanded significantly ensuring a broad impact on human health. PMID:24286176

  13. Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord

    International Nuclear Information System (INIS)

    Sato, Miho; Nakahara, Keiko; Goto, Shintaro; Kaiya, Hiroyuki; Miyazato, Mikiya; Date, Yukari; Nakazato, Masamitsu; Kangawa, Kenji; Murakami, Noboru

    2006-01-01

    Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its protein were confirmed in rat fetal spinal cord tissues by RT-PCR and immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced significant proliferation of primary cultured cells from the fetal spinal cord. The proliferating cells were then double-stained using antibodies against the neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU), and the nestin-positive cells were also found to be co-stained with antibody against GHS-R. Furthermore, binding studies using [ 125 I]des-acyl ghrelin indicated the presence of a specific binding site for des-acyl ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin induce proliferation of neuronal precursor cells that is both dependent and independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord

  14. Oral Administration of α-Asarone Promotes Functional Recovery in Rats With Spinal Cord Injury

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    Min-Jae Jo

    2018-05-01

    Full Text Available α-asarone, a bioactive compound found in Acorus plant species, has been shown to exhibit neuroprotective, anti-oxidative, anti-inflammatory, and cognitive-enhancing effects. However, the effects of α-asarone on spinal cord injury (SCI have not yet been elucidated. The present study investigated the effects of α-asarone on the mRNA of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis in rats with compressive SCI. α-Asarone was orally administered (10 mg/kg once per day for 14 days following moderate static compression SCI. Compared to controls, α-asarone treatment significantly improved locomotor score, prevented neuroinflammation, and facilitated angiogenesis in the spinal cord at 14 days after SCI. Furthermore, α-asarone significantly reduced the TNF-α, IL-1β, IL-6, monocyte chemoattractant protein 1 (MCP-1, macrophage inflammatory protein 2 (MIP-2, and inducible nitric oxide synthase (iNOS levels but increased the IL-4, IL-10, and arginase 1 levels at 24 h after SCI. At 7 and 14 days after SCI, immunohistochemistry showed reduced reactive gliosis and neuroinflammation and an increased expression of M2 macrophage markers and angiogenesis. The results suggest that the inhibition of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis by α-asarone may be some of the mechanisms underlying the α-asarone-mediated neuroprotective effects on an injured spinal cord.

  15. Effect of a muscle relaxant, chlorphenesin carbamate, on the spinal neurons of rats.

    Science.gov (United States)

    Kurachi, M; Aihara, H

    1984-09-01

    The effects of chlorphenesin carbamate (CPC) and mephenesin on spinal neurons were investigated in spinal rats. CPC (50 mg/kg i.v.) inhibited the mono-(MSR) and poly-synaptic reflex (PSR), the latter being more susceptible than the former to CPC depression. Mephenesin also inhibited MSR and PSR, though the effects were short in duration. CPC had no effect on the dorsal root potential evoked by the stimulation of the dorsal root, while mephenesin reduced the dorsal root-dorsal root reflex. The excitability of motoneuron was reduced by the administration of CPC or mephenesin. The excitability of primary afferent terminal was unchanged by CPC, while it was inhibited by mephenesin. Neither CPC nor mephenesin influenced the field potential evoked by the dorsal root stimulation. Both CPC and mephenesin had no effect on the synaptic recovery. These results suggest that both CPC and mephenesin inhibit the firing of motoneurons by stabilizing the neuronal membrane, while mephenesin additionally suppresses the dorsal root reflex and the excitability of the primary afferent terminal. These inhibitory actions of CPC on spinal activities may contribute, at least partly, to its muscle relaxing action.

  16. GABA, not glycine, mediates inhibition of latent respiratory motor pathways after spinal cord injury

    OpenAIRE

    Zimmer, M. Beth; Goshgarian, Harry G.

    2006-01-01

    Previous work has shown that latent respiratory motor pathways known as crossed phrenic pathways are inhibited via a spinal inhibitory process; however, the underlying mechanisms remain unknown. The present study investigated whether spinal GABA-A and/or glycine receptors are involved in the inhibition of the crossed phrenic pathways after a C2 spinal cord hemisection injury. Under ketamine/xylazine anesthesia, adult, female, Sprague Dawley rats were hemisected at the C2 spinal cord level. Fo...

  17. Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury.

    Science.gov (United States)

    Lee, Yee-Shuan; Funk, Lucy H; Lee, Jae K; Bunge, Mary Bartlett

    2018-04-01

    Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage

  18. Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

    Science.gov (United States)

    Lee, Yee-Shuan; Funk, Lucy H.; Lee, Jae K.; Bunge, Mary Bartlett

    2018-01-01

    Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage

  19. Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

    Directory of Open Access Journals (Sweden)

    Yee-Shuan Lee

    2018-01-01

    Full Text Available Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP, and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with

  20. Segmental neuropathic pain does not develop in male rats with complete spinal transections.

    Science.gov (United States)

    Hubscher, Charles H; Kaddumi, Ezidin G; Johnson, Richard D

    2008-10-01

    In a previous study using male rats, a correlation was found between the development of "at-level" allodynia in T6-7 dermatomes following severe T8 spinal contusion injury and the sparing of some myelinated axons within the core of the lesion epicenter. To further test our hypothesis that this sparing is important for the expression of allodynia and the supraspinal plasticity that ensues, an injury that severs all axons (i.e., a complete spinal cord transection) was made in 15 male rats. Behavioral assessments were done at level throughout the 30-day recovery period followed by terminal electrophysiological recordings (urethane anesthesia) from single medullary reticular formation (MRF) neurons receiving convergent nociceptive inputs from receptive fields above, at, and below the lesion level. None of the rats developed signs of at-level allodynia (versus 18 of 26 male rats following severe contusion). However, the terminal recording (206 MRF neurons) data resembled those obtained previously post-contusion. That is, there was evidence of neuronal hyper-excitability (relative to previous data from intact controls) to high- and low-threshold mechanical stimulation for "at-level" (dorsal trunk) and "above-level" (eyelids and face) cutaneous territories. These results, when combined with prior data on intact controls and severe/moderate contusions, indicate that (1) an anatomically incomplete injury (some lesion epicenter axonal sparing) following severe contusion is likely important for the development of allodynia and (2) the neuronal hyper-excitability at the level of the medulla is likely involved in nociceptive processes that are not directly related to the conscious expression of pain-like avoidance behaviors that are being used as evidence of allodynia.

  1. 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 ...

  2. 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 ...

  3. Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

    Science.gov (United States)

    Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

    2013-01-01

    Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

  4. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

    Directory of Open Access Journals (Sweden)

    Khaled Abdallah

    Full Text Available Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG, into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project. These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

  5. 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.

  6. Electroacupuncture improves microcirculation and neuronal morphology in the spinal cord of a rat model of intervertebral disc extrusion

    Directory of Open Access Journals (Sweden)

    Dai-xun Jiang

    2015-01-01

    Full Text Available Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral surface of T 13 . Electroacupuncture was used to stimulate the bilateral Zusanli point (ST36 and Neiting point (ST44 for 14 days. Compared with control animals, blood flow in the first lumbar vertebra (L 1 was noticeably increased in rats given electroacupuncture. Microvessel density in the T 13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved significantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.

  7. Evaluation of purinergic mechanism for the treatment of voiding dysfunction: a study in conscious spinal cord-injured rats.

    Science.gov (United States)

    Lu, Shing-Hwa; Groat, William C de; Lin, Alex T L; Chen, Kuang-Kuo; Chang, Luke S

    2007-10-01

    To investigate the effect of a selective P2X(3-)P2X(2/3) purinergic receptor antagonist (a-317491) on detrusor hyperreflexia in conscious chronic spinal cord-injured female rats. Six chronic spinal cord-transected female Sprague-Dawley rats (290-336 g) were used in this study. Spinal transection at the T8-T9 segmental level was performed using aseptic techniques under halothane anesthesia. Fourteen to 16 weeks after spinal transection, A-317491, a selective P2X(3-)P2X(2/3) purinergic receptor antagonist, was administered intravenously in cystometry studies at increasing doses of 0.03, 0.1, 0.3, 1, 3, 10 and 30 micromol/kg at 40-50 minute intervals. Cystometrograms (CMGs) were performed before and after the administration of each dose of the drug. The continuous filling of CMGs revealed a large number of small-amplitude (> 8 cmH(2)O), non-voiding contractions (NVCs) (average, 9.7 per voiding cycle) preceding voiding contractions (mean amplitude, 31 cmH(2)O; duration, 2.5 minutes), which occurred at an interval of 539 seconds and at a pressure threshold of 5.7 cmH(2)O. When tested in a range of doses (0.03-30 micromol/kg, intravenous), A-317491 in doses between 1 and 30 micromol/kg significantly (p spinal cord injury in rats.

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

    Science.gov (United States)

    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.

  9. Effects of spinal transection on presynaptic markers for glutamatergic neurons in the rat

    International Nuclear Information System (INIS)

    Singer, H.S.; Coyle, J.T.; Frangia, J.; Price, D.L.

    1981-01-01

    To evaluate the hypothesis that glutamic acid may be the neurotransmitter of descending, excitatory supraspinal pathways, the uptake and release of L-[3H] glutamate and the levels of endogenous glutamate were measured in preparations from rat lumbar spinal cord following complete mid-thoracic transection. Following transection, the activity of the synaptosomal high-affinity glutamate uptake process was increased in both dorsal and ventral halves of lumbar cord between 1 and 14 days after transection and returned to control levels by 21 days posttransection. At 7 days, the increased activity of the uptake process for L-[3H]glutamate resulted in elevation of Vmax with no significant alteration in KT as compared to age-matched controls. Depolarization-induced release of L-[3H]glutamate from prelabeled slices did not differ significantly from control in the lesioned rat except at 21 days after lesion when the amount of tritium release was significantly greater in the transected preparations than in control. Amino acid analysis of the lumbar cord from control and transected rats indicated only a 10% decrease in the level of endogenous glutamate and no alterations in the concentration of GABA and glycine 7 days after lesion. These findings do not support the hypothesis that glutamate serves as a major excitatory neurotransmitter in supraspinal pathways innervating the lumbar cord of the rat

  10. Pathological activity in mediodorsal thalamus of rats with spinal cord injury pain.

    Science.gov (United States)

    Whitt, Jessica L; Masri, Radi; Pulimood, Nisha S; Keller, Asaf

    2013-02-27

    Spinal cord injury (SCI) results not only in motor deficits, but produces, in many patients, excruciating chronic pain (SCI pain). We have previously shown, in a rodent model, that SCI causes suppression of activity in the GABAergic nucleus, the zona incerta (ZI), and concomitant increased activity in one of its main targets, the posterior nucleus of the thalamus (PO); the increased PO activity is correlated with the maintenance and expression of hyperalgesia after SCI. Here, we test the hypothesis that SCI causes a similar pathological increase in other thalamic nuclei regulated by the ZI, specifically the mediodorsal thalamus (MD), which is involved in the emotional-affective aspects of pain. We recorded single and multiunit activity from MD of either anesthetized or awake rats, and compared data from rats with SCI with data from sham-operated controls (anesthetized experiments) or with data from the same animals prelesion (awake experiments). Consistent with our hypothesis, MD neurons from rats with SCI show significant increases in spontaneous firing rates and in the magnitude and duration of responses to noxious stimuli. In a subset of anesthetized animals, similar changes in activity of MD neurons were produced by pharmacologically inactivating ZI in naive rats, suggesting that the changes in the MD after SCI are related to suppressed inhibition from the ZI. These data support our hypothesis that SCI pain results, at least in part, from a loss of inhibition to thalamic nuclei associated with both the sensory-discriminative and emotional-affective components of pain.

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

    Directory of Open Access Journals (Sweden)

    Bartanusz Viktor

    2012-09-01

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

  12. Longitudinal study on diffusion tensor imaging and diffusion tensor tractography following spinal cord contusion injury in rats.

    Science.gov (United States)

    Zhao, Can; Rao, Jia-Sheng; Pei, Xiao-Jiao; Lei, Jian-Feng; Wang, Zhan-Jing; Yang, Zhao-Yang; Li, Xiao-Guang

    2016-06-01

    Diffusion tensor imaging (DTI) as a potential technology has been used in spinal cord injury (SCI) studies, but the longitudinal evaluation of DTI parameters after SCI, and the correlation between DTI parameters and locomotor outcomes need to be defined. Adult Wistar rats (n = 6) underwent traumatic thoracic cord contusion by an NYU impactor. DTI and Basso-Beattie-Bresnahan datasets were collected pre-SCI and 1, 3, 7, 14, and 84 days post-SCI. Diffusion tensor tractography (DTT) of the spinal cord was also generated. Fractional anisotropy (FA) and connection rate of fibers at the injury epicenter and at 5 mm rostral/caudal to the epicenter were calculated. The variations of these parameters after SCI were observed by one-way analysis of variance and the correlations between these parameters and motor function were explored by Pearson's correlation. FA at the epicenter decreased most remarkably on day 1 post-SCI (from 0.780 ± 0.012 to 0.330 ± 0.015), and continued to decrease slightly by day 3 post-SCI (0.313 ± 0.015), while other parameters decreased significantly over the first 3 days after SCI. DTT showed residual fibers concentrated on ventral and ventrolateral sides of the cord. Moreover, FA at the epicenter exhibited the strongest correlation (r = 0.887, p = 0.000) with the locomotion performance. FA was sensitive to degeneration in white matter and DTT could directly reflect the distribution of the residual white matter. Moreover, days 1 to 3 post-SCI may be the optimal time window for SCI examination and therapy.

  13. Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission.

    Science.gov (United States)

    Mondaca, Mauricio; Hernández, Alejandro; Valladares, Luis; Sierralta, Walter; Noseda, Rodrigo; Soto-Moyano, Rubén

    2004-02-01

    There is evidence that melatonin and its metabolites could bind to nuclear sites in neurones, suggesting that this hormone is able to exert long-term functional effects in the central nervous system via genomic mechanisms. This study was designed to investigate (i) whether systemically administered melatonin can exert long-term effects on spinal cord windup activity, and (ii) whether blockade of melatonin degradation with eserine could prevent this effect. Rats receiving melatonin (10 mg/kg ip), the same dose of melatonin plus eserine (0.5 mg/kg ip), or saline were studied. Seven days after administration of the drugs or saline, spinal windup of rats was assessed in a C-fiber reflex response paradigm. Results show that rats receiving melatonin exhibited a reduction in spinal windup activity. This was not observed in the animals receiving melatonin plus eserine or saline, suggesting a role for melatonin metabolites in long-term changes of nociceptive transmission in the rat spinal cord.

  14. Evaluation of Purinergic Mechanism for the Treatment of Voiding Dysfunction: A Study in Conscious Spinal Cord-injured Rats

    Directory of Open Access Journals (Sweden)

    Shing-Hwa Lu

    2007-10-01

    Conclusion: These results indicate that purinergic mechanisms, presumably involving P2X3 or P2X2/3 receptors on bladder C-fiber afferent nerves, play an important role in the detrusor hyperreflexia that occurs after spinal cord injury in rats.

  15. Radiation effects in the rat spinal cord: evaluation with apparent diffusion coefficient versus T2 at serial MR imaging.

    NARCIS (Netherlands)

    Philippens, M.E.P.; Gambarota, G.; Kogel, A.J. van der; Heerschap, A.

    2009-01-01

    PURPOSE: To prospectively determine whether apparent diffusion coefficients (ADCs) are more sensitive to radiation-induced changes in the rat spinal cord than T2 relaxation times. MATERIALS AND METHODS: The study was approved by the institutional ethical committee on animal welfare. One centimeter

  16. Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat.

    Science.gov (United States)

    Sagar, D R; Nwosu, L; Walsh, D A; Chapman, V

    2015-06-01

    Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

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

    2015-06-29

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

  18. 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.

  19. Action of naftopidil on spinal serotonergic neurotransmission for inhibition of the micturition reflex in rats.

    Science.gov (United States)

    Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki; Hattori, Tsuyoshi

    2017-03-01

    We examined the mechanism of action of naftopidil, an α1D/A blocker, on spinal descending serotonergic neurotransmission for the micturition reflex. We examined (1) urinary 5-hydroxyindole acetic acid (5-HIAA) after intraperitoneal administration of saline, para-chlorophenylalanine (PCPA; a serotonin synthetic enzyme inhibitor), and/or 5-hydroxytryptophan (5-HTP; a serotonin precursor); (2) isovolumetric cystometry after intraperitoneal administration of saline, PCPA, and/or 5-HTP and intravenous injection of naftopidil; and (3) isovolumetric cystometry before and after intrathecal administration of serotonin (5-HT) receptor antagonists and intravenous injection of naftopidil. PCPA decreased and 5-HTP increased urinary 5-HIAA/creatinine. Intraperitoneal injection of PCPA did not influence cystometric parameters. Intraperitoneal injection of 5-HTP significantly shortened the interval between bladder contractions. Intravenous injection of naftopidil transiently abolished bladder contractions. However, the duration of abolishment of bladder contractions after injection of naftopidil in rats given PCPA was significantly shorter than that in rats given vehicle, but significantly longer than that in rats given PCPA and 5-HTP. Intrathecal injection of 5-HT1B, 5-HT3, or 5-HT7 receptor antagonists significantly prolonged the interval between bladder contractions. Intrathecal injection of 5-HT1D or 5-HT2B receptor antagonists significantly shortened the interval between bladder contractions. Combined administration of the maximum non-effective dose of 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, or 5-HT3 receptor antagonists and intravenous injection of naftopidil significantly shortened the duration of abolishment of bladder contraction compared to intravenous injection of naftopidil alone. Naftopidil may inhibit the micturition reflex via 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT3 receptors in the spinal cord. Neurourol. Urodynam. 36:604-609, 2017. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2016-04-01

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

  1. Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

    Science.gov (United States)

    Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

    2016-09-02

    Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase

  2. Electrophysiological characterization of activation state-dependent Ca(v)2 channel antagonist TROX-1 in spinal nerve injured rats.

    Science.gov (United States)

    Patel, R; Rutten, K; Valdor, M; Schiene, K; Wigge, S; Schunk, S; Damann, N; Christoph, T; Dickenson, A H

    2015-06-25

    Prialt, a synthetic version of Ca(v)2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Ca(v)2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Ca(v)2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  4. Panax ginseng Improves Functional Recovery after Contusive Spinal Cord Injury by Regulating the Inflammatory Response in Rats: An In Vivo Study

    Directory of Open Access Journals (Sweden)

    Young Ock Kim

    2015-01-01

    Full Text Available Spinal cord injury (SCI results in permanent loss of motor function below the injured site. Neuroinflammatory reaction following SCI can aggravate neural injury and functional impairment. Ginseng is well known to possess anti-inflammatory effects. The present study investigated the neuroprotective effects of Panax ginseng C.A. Mayer (P. ginseng after SCI. A spinal contusion was made at the T11-12 spinal cord in adult male Sprague-Dawley rats (n=47 using the NYU impactor. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB score in P. ginseng (0.1, 0.5, 1, 3, and 5 mg/kg or vehicle (saline treated after SCI. We also assessed the protein expression of cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS at the lesion site by western blot and then measured the cavity area using luxol fast blue/cresyl violet staining. P. ginseng treated group in SCI showed a significant improvement in locomotor function after the injury. The protein expression of COX-2 and iNOS at the lesion site and the cavity area were decreased following SCI by P. ginseng treatment. These results suggest that P. ginseng may improve the recovery of motor function after SCI which provides neuroprotection by alleviating posttraumatic inflammatory responses.

  5. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

    1982-01-01

    The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED 50 dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and γ-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED 50 dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair

  6. Predicting Neuroinflammation in Morphine Tolerance for Tolerance Therapy from Immunostaining Images of Rat Spinal Cord.

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    Shinn-Long Lin

    Full Text Available Long-term morphine treatment leads to tolerance which attenuates analgesic effect and hampers clinical utilization. Recent studies have sought to reveal the mechanism of opioid receptors and neuroinflammation by observing morphological changes of cells in the rat spinal cord. This work proposes a high-content screening (HCS based computational method, HCS-Morph, for predicting neuroinflammation in morphine tolerance to facilitate the development of tolerance therapy using immunostaining images for astrocytes, microglia, and neurons in the spinal cord. HCS-Morph first extracts numerous HCS-based features of cellular phenotypes. Next, an inheritable bi-objective genetic algorithm is used to identify a minimal set of features by maximizing the prediction accuracy of neuroinflammation. Finally, a mathematic model using a support vector machine with the identified features is established to predict drug-treated images to assess the effects of tolerance therapy. The dataset consists of 15 saline controls (1 μl/h, 15 morphine-tolerant rats (15 μg/h, and 10 rats receiving a co-infusion of morphine (15 μg/h and gabapentin (15 μg/h, Sigma. The three individual models of astrocytes, microglia, and neurons for predicting neuroinflammation yielded respective Jackknife test accuracies of 96.67%, 90.00%, and 86.67% on the 30 rats, and respective independent test accuracies of 100%, 90%, and 60% on the 10 co-infused rats. The experimental results suggest that neuroinflammation activity expresses more predominantly in astrocytes and microglia than in neuron cells. The set of features for predicting neuroinflammation from images of astrocytes comprises mean cell intensity, total cell area, and second-order geometric moment (relating to cell distribution, relevant to cell communication, cell extension, and cell migration, respectively. The present investigation provides the first evidence for the role of gabapentin in the attenuation of morphine tolerance from

  7. Contribución de fibras mielínicas provenientes de los nervios espinales lumbares L4, L5 y L6 al nervio ciático de rata adulta y sus ramas principales Contribution of myelunated fibers from spinal L4, L5 and L6 nerves to the sciatic nerve and its main branches in the adult rat

    Directory of Open Access Journals (Sweden)

    Hernán Hurtado

    2000-04-01

    Full Text Available El nervio ciático de la rata está formado por los nervios espinales (ne lumbares L4, L5 y L6. Sin embargo, aún no se ha definido el aporte en fibras mielínicas de estos nervios espinales a lo largo del tronco nervioso. En este estudio se transectaron selectivamente los NE L4, L5 y L4-L5. Luego de una semana se disecaron los nervios ciático, tibial, sural y peroneal. Estas muestras se fijaron y procesaron para microscopía óptica y a partir de cortes coloreados con azul de toluidina se contaron las fibras mielínicas degeneradas y normales. L4 contribuyó con fibras mielínicas principalmente al nervio peroneal y L5 a los nervios ciático, tibial y sural. En general, el aporte de L6 fue menor y variable a lo largo del tronco nervioso comparado con las otras dos ramas espinales. Nuestros resultados brindan información valiosa para posteriores estudios que busquen correlacionar la contribución de los nervios espinales que componen el ciático y sus ramas principales con la función de la extremidad inferior. The rat sciatic nerve is composed by the L4, L5 and L6 lumbar spinal nerves. However, the contribution in myelinated fibers originating from these nerves along this nervous trunk has not yet been defined. In the present study, the L4, L5 and L4-L5 spinal nerves were selectively transected. After one week the sciatic, tibial, sural and peroneal nerves were dissected. These samples were fixed and processed for optical microscopy, and both degenerated and normal myelinated fibers were counted in toluidine blue-stained semi-thin sections. L4 contributed with myelinated fibers mainly to the peroneal nerve, and L5 to the sciatic, tibial and sural nerves. In general, the contribution of L6 was smaller and variable along the nervous trunk in comparison to the other two spinal branches. Our results give key information for further studies looking to correlate the contribution of spinal nerves making part of the sciatic nerve and its main

  8. Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle

    Science.gov (United States)

    Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

    2011-01-01

    Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in response to plantarflexion and inversion of the foot or ankle compression were recorded from the medial part of the deep dorsal horn, laminae IV-VI, in normal and ankle-sprained rats. One day after ankle sprain, rats showed significantly reduced WBRs on the affected foot, and this reduction was partially restored by systemic morphine. The majority of deep dorsal horn neurons responded to a single ankle stimulus modality. After ankle sprain, the mean evoked response rates were significantly increased, and afterdischarges were developed in recorded dorsal horn neurons. The ankle sprain-induced enhanced evoked responses were significantly reduced by morphine, which was reversed by naltrexone. The data indicate that movement-specific dorsal horn neuron responses were enhanced after ankle sprain in a morphine-dependent manner, thus suggesting that hyperactivity of dorsal horn neurons is an underlying mechanism of pain after ankle sprain. PMID:21389306

  9. Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats.

    Science.gov (United States)

    Melo, Fernanda Rosene; Bressan, Raul Bardini; Forner, Stefânia; Martini, Alessandra Cadete; Rode, Michele; Delben, Priscilla Barros; Rae, Giles Alexander; Figueiredo, Claudia Pinto; Trentin, Andrea Gonçalves

    2017-07-01

    Spinal cord injury (SCI) is a devastating neurologic disorder with significant impacts on quality of life, life expectancy, and economic burden. Although there are no fully restorative treatments yet available, several animal and small-scale clinical studies have highlighted the therapeutic potential of cellular interventions for SCI. Mesenchymal stem cells (MSCs)-which are conventionally isolated from the bone marrow-recently emerged as promising candidates for treating SCI and have been shown to provide trophic support, ameliorate inflammatory responses, and reduce cell death following the mechanical trauma. Here we evaluated the human skin as an alternative source of adult MSCs suitable for autologous cell transplantation strategies for SCI. We showed that human skin-derived MSCs (hSD-MSCs) express a range of neural markers under standard culture conditions and are able to survive and respond to neurogenic stimulation in vitro. In addition, using histological analysis and behavioral assessment, we demonstrated as a proof-of-principle that hSD-MSC transplantation reduces the severity of tissue loss and facilitates locomotor recovery in a rat model of SCI. Altogether, the study provides further characterization of skin-derived MSC cultures and indicates that the human skin may represent an attractive source for cell-based therapies for SCI and other neurological disorders. Further investigation is needed to elucidate the mechanisms by which hSD-MSCs elicit tissue repair and/or locomotor recovery.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  11. Effects of hyperthermia applied to previously irradiated cervical spinal cord in the rat

    International Nuclear Information System (INIS)

    Sminia, P.; Haveman, J.; Koedoder, C.

    1991-01-01

    Rat cervical spinal cord was X-ray irradiated at doses of 15, 18, 20 and 26 Gy. Approximately the same part of the spinal cord was heated by means of a 434 MHz microwave applicator 90 days later. After treatment, animals were observed for 18 months, for expression of neurological complications. These could either be result of the heat or of the radiation treatment. The time course showed 3 distinct peaks in the incidence of neurological symptoms. The 1st peak was due to the acute response to hyperthermia. The ED 50 value for neurological complications one day after treatment at 42.3±0.4 o C was 74 ±2 min. Previous X-ray irradiation of spinal cord with 18, 20 and 26 Gy reduced ED 50 to 57±7,65±4 and 55±5 min (12-26% of control), resp. Recovery from heat-induced neurological complications was diminished in previously irradiated animals. The 2nd peak (150-300 days after X-rays) concerned expression of 'early-delayed' radiation damage. Hyperthermia given in 90 days after irradiation did not influence either the percentage of animals with paralysis or the latent period. Neurological symptoms developing after day 300 were due to the late delayed radiation response. Significant difference was not observed in data on paralysis induced by radiation alone or radiation followed by heat. The late radiation-induced minor neurological symptoms, were however, influenced by retreatment with heat. (author). 30 refs., 6 figs., 3 tabs

  12. Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion

    Directory of Open Access Journals (Sweden)

    Wu Junfang

    2012-07-01

    Full Text Available Abstract Background Traumatic spinal cord injury (SCI induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model. Methods Adult male rats were subjected to moderate spinal cord contusion injury at T8 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 weeks or 4 months post-injury, and processed for protein expression and lesion volume. Functional recovery was assessed over the 4 months after injury. Results Immunoblot analysis demonstrated a marked continued upregulation of cell cycle-related proteins − including cyclin D1 and E, CDK4, E2F5 and PCNA − for 4 months post-injury that were highly expressed by GFAP+ astrocytes and microglia, and co-localized with inflammatory-related proteins. CR8 administrated systemically 3 h post-injury and continued for 7 days limited the sustained elevation of cell cycle proteins and immunoreactivity of GFAP, Iba-1 and p22PHOX − a key component of NADPH oxidase − up to 4 months after SCI. CR8 treatment significantly reduced lesion volume, which typically progressed in untreated animals between 1 and 4 months after trauma. Functional recovery was also significantly improved by CR8 treatment after SCI from week 2 through week 16. Conclusions These data demonstrate that cell cycle-related proteins are chronically upregulated after SCI and may contribute to astroglial scar

  13. 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 cord and medulla oblongata is reduced. PMID:16097052

  14. Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

    NARCIS (Netherlands)

    Ritfeld, G.J.; Nandoe Tewarie, R.D.S.; Rahiem, S.T.; Hurtado, A.; Roos, R.A.; Grotenhuis, A.; Oudega, M.

    2010-01-01

    We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in

  15. 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

  16. The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation

    Science.gov (United States)

    Machova Urdzikova, Lucia; Karova, Kristyna; Ruzicka, Jiri; Kloudova, Anna; Shannon, Craig; Dubisova, Jana; Murali, Raj; Kubinova, Sarka; Sykova, Eva; Jhanwar-Uniyal, Meena; Jendelova, Pavla

    2015-01-01

    Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9–T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury. PMID:26729105

  17. 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

  18. The effect of small radiation doses on the rat spinal cord: the concept of partial tolerance

    International Nuclear Information System (INIS)

    Ang, K.K.; Van Der Kogel, A.J.; Van Der Schueren, E.

    1983-01-01

    To evaluate the tolerance of the rat spinal cord to small radiation doses per fraction, an increasing number of fractions is required for induction of paralysis. The assessment of doses of 1-2 Gy, as used in the clinic, would require that over 100 fractions be given. The validity of replacing part of a fractionated irradiation of the spinal cord by a single large dose has been tested. Fractionated irradiation doses with 18 MeV X rays were followed by a ''top-up'' dose of 15 Gy as a single treatment. This is the fraction size of a treatment with two irradiation doses leading to paralysis in 50% of the animals (ED 50). Fractionated treatments were carried out with 2, 5, 10 and 20 fractions followed by the top-up dose of 15 Gy. the isoeffect curve, as a function of the number of fractions, has the same slope as experiments performed without top-up dose. The results show that the quality and quantity of cellular repair is not modified when part of a multifractionated exposure is replaced by a larger top-dose. An important consequence of this finding is, that in treatments with unequal fraction sizes, the partial tolerances can simply be added. Since a top-up dose can replace a sizable number of irradiation treatments, its application will allow investigations of the extent of sublethal damage repair for fraction sizes as low as 1 Gy

  19. Cervical spinal demyelination with ethidium bromide impairs respiratory (phrenic) activity and forelimb motor behavior in rats

    Science.gov (United States)

    Nichols, Nicole L.; Punzo, Antonio M.; Duncan, Ian D.; Mitchell, Gordon S.; Johnson, Rebecca A.

    2012-01-01

    Although respiratory complications are a major cause of morbidity/mortality in many neural injuries or diseases, little is known concerning mechanisms whereby deficient myelin impairs breathing, or how patients compensate for such changes. Here, we tested the hypothesis that respiratory and forelimb motor function are impaired in a rat model of focal dorsolateral spinal demyelination (ethidium bromide, EB). Ventilation, phrenic nerve activity and horizontal ladder walking were performed 7-14 days post-C2 injection of EB or vehicle (SHAM). EB caused dorsolateral demyelination at C2-C3 followed by signficant spontaneous remyelination at 14 days post-EB. Although ventilation did not differ between groups, ipsilateral integrated phrenic nerve burst amplitude was significantly reduced versus SHAM during chemoreceptor activation at 7 days post-EB but recovered by 14 days. The ratio of ipsi- to contralateral phrenic nerve amplitude correlated with cross-sectional lesion area. This ratio was significantly reduced 7 days post-EB versus SHAM during baseline conditions, and versus SHAM and 14 day groups during chemoreceptor activation. Limb function ipsilateral to EB was impaired 7 days post-EB and partially recovered by 14 days post-EB. EB provides a reversible model of focal, spinal demyelination, and may be a useful model to study mechanisms of functional impairment and recovery via motor plasticity, or the efficacy of new therapeutic interventions to reduce severity or duration of disease. PMID:23159317

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

    Directory of Open Access Journals (Sweden)

    Friedly Janna L

    2012-03-01

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

  1. Ultrastructural study of myelinating cells and sub-pial astrocytes in developing rat spinal cord.

    Science.gov (United States)

    Nagashima, K

    1979-12-01

    The anterior funiculus of the spinal cervical cord of post-natal rats was examined ultrastructurally. The myelinating cells found one day after brith contained a large amount of evenly distributed ribosomes up to the outer tongue of mesaxons, representing the cytoplasmic density. These cells were separated by astrocytic processes from the pial basement membrane, even when they were located on the pial surface. Astrocytes contained glial fibrils from one day onwards and often attached their processes to the pial basement membrane. Although the cytoplasmic processes of astrocytes occasionally wrapped axons, they were never shown to form the initial layer of myelin sheaths. However, the tenuous processes of the sub-pial astrocytes were occasionally rolled in myelin lamellae, as if a part of the myelin sheaths was constructed by astrocytic processes. The interpretation for this finding is discussed in relation to function and potency of the astrocytes, and variations and anomalies of nervous ontogeny.

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

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

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

  3. 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.

  4. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

    Directory of Open Access Journals (Sweden)

    Kummer Wolfgang

    2006-07-01

    Full Text Available Abstract Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1 and ASIC3 (acid sensing ion channel-3 respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons, and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative were significantly more frequent among pleural (35% than pulmonary afferents (20%. TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung and 48% (pleura of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive. Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.

  5. Signaling pathways involved in HSP32 induction by hyperbaric oxygen in rat spinal neurons

    Directory of Open Access Journals (Sweden)

    Guoyang Huang

    2016-12-01

    Full Text Available Spinal cord injury (SCI is a debilitating disease, effective prevention measures are in desperate need. Our previous work found that hyperbaric oxygen (HBO preconditioning significantly protected rats from SCI after stimulated diving, and in vitro study further testified that HBO protected primary cultured rat spinal neurons from oxidative insult and oxygen glucose deprivation injury via heat shock protein (HSP 32 induction. In this study, underlying molecular mechanisms were further investigated. The results showed that a single exposure to HBO significantly increased intracellular levels of reactive oxygen species (ROS and nitric oxide (NO and activated MEK1/2, ERK1/2, p38 MAPK, CREB, Bach1 and Nrf2. The induction of HSP32 by HBO was significantly reversed by pretreatment neurons with ROS scavenger N-Acetyl-L-cysteine, p38 MAPK inhibitor or Nrf2 gene knockdown, enhanced by MEK1/2 inhibitors or gene knockdown but not by ERK1/2 inhibitor. CREB knockdown did not change the expression of HSP32 induced by HBO. N-Acetyl-L-cysteine significantly inhibited the activation of MEK1/2, ERK1/2, p38 MAPK, and Nrf2. Activation of Nrf2 was significantly inhibited by p38 MAPK inhibitor and the nuclear export of Bach1 was significantly enhanced by MEK1/2 inhibitor. The results demonstrated that HBO induces HSP32 expression through a ROS/p38 MAPK/Nrf2 pathway and the MEK1/2/Bach1 pathway contributes to negative regulation in the process. More importantly, as we know, this is the first study to delineate that ERK1/2 is not the only physiological substrates of MEK1/2.

  6. Intravenous dextromethorphan/quinidine inhibits activity of dura-sensitive spinal trigeminal neurons in rats.

    Science.gov (United States)

    Sokolov, A Y; Lyubashina, O A; Berkovich, R R; Panteleev, S S

    2015-09-01

    Migraine is a chronic neurological disorder characterized by episodes of throbbing headaches. Practically all medications currently used in migraine prophylaxis have a number of substantial disadvantages and use limitations. Therefore, the further search for principally new prophylactic antimigraine agents remains an important task. The objective of our study was to evaluate the effects of a fixed combination of dextromethorphan hydrobromide and quinidine sulphate (DM/Q) on activity of the spinal trigeminal neurons in an electrophysiological model of trigemino-durovascular nociception. The study was performed in 15 male Wistar rats, which were anaesthetized with urethane/α-chloralose and paralysed using pipecuronium bromide. The effects of cumulative intravenous infusions of DM/Q (three steps performed 30 min apart, 15/7.5 mg/kg of DM/Q in 0.5 mL of isotonic saline per step) on ongoing and dural electrical stimulation-induced neuronal activities were tested in a group of eight rats over 90 min. Other seven animals received cumulative infusion of equal volumes of saline and served as control. Cumulative administration of DM/Q produced steady suppression of both the ongoing activity of the spinal trigeminal neurons and their responses to electrical stimulation of the dura mater. It is evident that the observed DM/Q-induced suppression of trigeminal neuron excitability can lead to a reduction in nociceptive transmission from meninges to higher centres of the brain. Since the same mechanism is believed to underlie the pharmacodynamics of many well-known antimigraine drugs, results of the present study enable us to anticipate the potential efficacy of DM/Q in migraine. © 2014 European Pain Federation - EFIC®

  7. Effect of intra-peritoneal fludarabine on rat spinal cord tolerance to fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gregoire, V; Ruifrok, A C.C.; Price, R E; Brock, W A; Hittelman, W N; Plunkett, W K; Ang, K K

    1995-07-01

    The effect of fludarabine (9-{beta}-d-arabinosyl-2-fluoroadenine-5'-monophosphate), an adenine nucleoside analogue, on the tolerance of the spinal cord to fractionated irradiation was studied in a rat model. Anesthesized female Fisher 344 rats received irradiation to 2 cm of the cervical spine with a telecobalt unit (dose rate 1.14 Gy/min). Radiation was administered in two, four or eight fractions spread over a 48-h period with or without fludarabine. Animals assigned to combined therapy received two daily intraperitoneal injections of fludarabine (150 mg/kg) given 3 h prior to the first daily radiation fraction. It was found that fludarabine reduced the iso-effect dose required to induce leg paresis at 9 months after irradiation for all fractionation schedules. Dose modification factors of 1.23, 1.29 and greater than 1.27 were obtained for two, four and eight fractions, respectively. Fitting the data with the direct analysis method of Thames et al. with an incomplete repair model [18] showed that the potentiating effect of fludarabine may be mediated through reduction in the number of 'tissue-rescuing units' (lnK). Alpha and {beta} values were slightly but not significantly decreased, whereas the ({alpha}({beta})) ratio was unchanged. These features suggest that fludarabine did not significantly inhibit cellular repair processes but rather reduced the spinal cord tolerance by a fixed additive toxic effect on the same target cells. In rodent models, the combination of fludarabine and fractionated radiation has previously been found to yield a therapeutic gain, i.e., the drug enhanced tumor response to a greater extent than it reduced normal tissue tolerance. However, given our results, caution should be exercised in extrapolating these findings to the clinic. Normal tissue reactions will have to be monitored rigorously in phase I clinical studies.

  8. Assessment of the neuroprotective effects of Lavandula angustifolia extract on the contusive model of spinal cord injury in Wistar rats

    Directory of Open Access Journals (Sweden)

    Gholamreza eKaka

    2016-02-01

    Full Text Available IntroductionSpinal cord injury (SCI involves a primary trauma and secondary cellular processes that can lead to severe damage to the nervous system, resulting in long-term spinal deficits. At the cellular level, SCI causes astrogliosis, of which glial fibrillary acidic protein (GFAP is a major index. ObjectiveThe aim of this study was to investigate the neuroprotective effects of Lavandula angustifolia (Lav on the repair of spinal cord injuries in Wistar rats.Materials and MethodsForty-five female rats were randomly divided into six groups of seven rats each: the intact, sham, control (SCI, Lav 100, Lav 200, and Lav 400 groups. Every week after SCI onset, all animals were evaluated for behavior outcomes by the Basso, Beattie, and Bresnahan (BBB score. H&E staining was performed to examine the lesions post-injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP testing was performed to detect the recovery of neural conduction.Results BBB scores were significantly increased and delayed responses on sensory tests were significantly decreased in the Lav 200 and Lav 400 groups compared to the control group. The greatest decrease of GFAP was evident in the Lav 200 and Lav 400 groups. EMG results showed significant improvement in the hindlimbs in the Lav 200 and Lav 400 groups compared to the control group. Cavity areas significantly decreased and the number of ventral motor neurons significantly increased in the Lav 200 and Lav 400 groups.ConclusionLav at doses of 200 mg/kg and 400 mg/kg can promote structural and functional recovery after SCI. The neuroprotective effects of L. angustifolia can lead to improvement in the contusive model of spinal cord injury in Wistar rats.Keywords Spinal cord injury (SCI; Lavandula angustifolia; neuroprotection; Basso, Beattie, and Bresnahan (BBB; glial fibrillary acidic protein (GFAP; somatosensory evoked potential (SEP

  9. 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.

  10. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

    Czech Academy of Sciences Publication Activity Database

    van Gorp, S.; Leerink, M.; Kakinohana, O.; Platoshyn, O.; Santucci, C.; Galik, J.; Joosten, E. A.; Hruška-Plocháň, Marian; Goldberg, D.; Marsala, S.; Johe, K.; Ciacci, J. D.; Marsala, M.

    2013-01-01

    Roč. 4, č. 57 (2013) ISSN 1757-6512 Institutional support: RVO:67985904 Keywords : spinal cord injury * human neural stem cells * spinal grafting * functional recovery * rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.634, year: 2013

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

    Science.gov (United States)

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

    2018-05-01

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

  12. Lavandula angustifolia Extract Improves the Result of Human Umbilical Mesenchymal Wharton’s Jelly Stem Cell Transplantation after Contusive Spinal Cord Injury in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Kayvan Yaghoobi

    2016-01-01

    Full Text Available Introduction. The primary trauma of spinal cord injury (SCI results in severe damage to nervous functions. At the cellular level, SCI causes astrogliosis. Human umbilical mesenchymal stem cells (HUMSCs, isolated from Wharton’s jelly of the umbilical cord, can be easily obtained. Previously, we showed that the neuroprotective effects of Lavandula angustifolia can lead to improvement in a contusive SCI model in rats. Objective. The aim of this study was to investigate the effect of L. angustifolia (Lav on HUMSC transplantation after acute SCI. Materials and Methods. Sixty adult female rats were randomly divided into eight groups. Every week after SCI onset, all animals were evaluated for behavior outcomes. H&E staining was performed to examine the lesions after injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP testing was performed to detect the recovery of neural conduction. Results. Behavioral tests showed that the HUMSC group improved in comparison with the SCI group, but HUMSC + Lav 400 was very effective, resulting in a significant increase in locomotion activity. Sensory tests and histomorphological and immunohistochemistry analyses verified the potentiation effects of Lav extract on HUMSC treatment. Conclusion. Transplantation of HUMSCs is beneficial for SCI in rats, and Lav extract can potentiate the functional and cellular recovery with HUMSC treatment in rats after SCI.

  13. Lavandula angustifolia Extract Improves the Result of Human Umbilical Mesenchymal Wharton's Jelly Stem Cell Transplantation after Contusive Spinal Cord Injury in Wistar Rats

    Science.gov (United States)

    Yaghoobi, Kayvan; Kaka, Gholamreza; Mansouri, Korosh; Davoodi, Shaghayegh; Sadraie, Seyed Homayoon; Hosseini, Seyed Ruhollah

    2016-01-01

    Introduction. The primary trauma of spinal cord injury (SCI) results in severe damage to nervous functions. At the cellular level, SCI causes astrogliosis. Human umbilical mesenchymal stem cells (HUMSCs), isolated from Wharton's jelly of the umbilical cord, can be easily obtained. Previously, we showed that the neuroprotective effects of Lavandula angustifolia can lead to improvement in a contusive SCI model in rats. Objective. The aim of this study was to investigate the effect of L. angustifolia (Lav) on HUMSC transplantation after acute SCI. Materials and Methods. Sixty adult female rats were randomly divided into eight groups. Every week after SCI onset, all animals were evaluated for behavior outcomes. H&E staining was performed to examine the lesions after injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. Results. Behavioral tests showed that the HUMSC group improved in comparison with the SCI group, but HUMSC + Lav 400 was very effective, resulting in a significant increase in locomotion activity. Sensory tests and histomorphological and immunohistochemistry analyses verified the potentiation effects of Lav extract on HUMSC treatment. Conclusion. Transplantation of HUMSCs is beneficial for SCI in rats, and Lav extract can potentiate the functional and cellular recovery with HUMSC treatment in rats after SCI. PMID:27057171

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

    Science.gov (United States)

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

    2017-06-01

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

  15. Changes in galanin immunoreactivity in rat lumbosacral spinal cord and dorsal root ganglia after spinal cord injury.

    Science.gov (United States)

    Zvarova, K; Murray, E; Vizzard, M A

    2004-08-02

    Alterations in the expression of the neuropeptide galanin were examined in micturition reflex pathways 6 weeks after complete spinal cord transection (T8). In control animals, galanin expression was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the superficial dorsal horn; (3) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (L6-S1); and (4) the lateral collateral pathway in lumbosacral spinal segments. Densitometry analysis demonstrated significant increases (P < or = 0.001) in galanin immunoreactivity (IR) in these regions of the S1 spinal cord after spinal cord injury (SCI). Changes in galanin-IR were not observed at the L4-L6 segments except for an increase in galanin-IR in the dorsal commissure in the L4 segment. In contrast, decreases in galanin-IR were observed in the L1 segment. The number of galanin-IR cells increased (P < or = 0.001) in the L1 and S1 dorsal root ganglia (DRG) after SCI. In all DRG examined (L1, L2, L6, and S1), the percentage of bladder afferent cells expressing galanin-IR significantly increased (4-19-fold) after chronic SCI. In contrast, galanin expression in nerve fibers in the urinary bladder detrusor and urothelium was decreased or eliminated after SCI. Expression of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) was altered in the spinal cord after SCI. A significant increase in BDNF expression was present in spinal cord segments after SCI. In contrast, NGF expression was only increased in the spinal segments adjacent and rostral to the transection site (T7-T8), whereas spinal segments (T13-L1; L6-S1), distal to the transection site exhibited decreased NGF expression. Changes in galanin expression in micturition pathways after SCI may be mediated by changing neurotrophic factor expression, particularly BDNF. These changes may contribute to

  16. Effectiveness of minocycline and FK506 alone and in combination on enhanced behavioral and biochemical recovery from spinal cord injury in rats.

    Science.gov (United States)

    Ahmad, Mohammad; Zakaria, Abdulrahim; Almutairi, Khalid M

    2016-06-01

    Injury to the spinal cord results in immediate physical damage (primary injury) followed by a prolonged posttraumatic inflammatory disorder (secondary injury). The present study aimed to investigate the neuroprotective effects of minocycline and FK506 (Tacrolimus) individually and in combination on recovery from experimental spinal cord injury (SCI). Young adult male rats were subjected to experimental SCI by weight compression method. Minocycline (50mg/kg) and FK506 (1mg/kg) were administered orally in combination and individually to the SCI group daily for three weeks. During these three weeks, the recovery was measured using behavioral motor parameters (including BBB, Tarlov and other scorings) every other day for 29days after SCI. Thereafter, the animals were sacrificed and the segment of the spinal cord centered at the injury site was removed for the histopathological studies as well as for biochemical analysis of monoamines such as 5-hydroxytryptamine (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) and some oxidative stress indices, such as thiobarbituric acid-reactive substances (TBARS), total glutathione (GSH) and myeloperoxidase (MPO). All behavioral results indicated that both drugs induced significant recovery from SCI with respect to time. The biochemical and histopathological results supported the behavioral findings, revealing significant recovery in the regeneration of the injured spinal tissues, the monoamine levels, and the oxidative stress indices. Overall, the effects of the tested drugs for SCI recovery were as follows: FK506+minocycline>minocycline>FK506 in all studied parameters. Thus, minocycline and FK506 may prove to be a potential therapy cocktail to treat acute SCI. However, further studies are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Origin and neurochemical properties of bulbospinal neurons projecting to the rat lumbar spinal cord via the medal longitudinal fasciculus and caudal ventrolateral medulla

    Directory of Open Access Journals (Sweden)

    Zilli eHuma

    2014-04-01

    Full Text Available Bulbospinal systems (BS originate from various regions of the brainstem and influence spinal neurons by classical synaptic and modulatory mechanisms. Our aim was to determine the brainstem locations of cells of origin of BS pathways passing through the medial longitudinal fasciculus (MLF and the caudal ventrolateral medulla (CVLM. We also examined the transmitter content of spinal terminations of the CVLM pathway. Six adult rats received Fluorogold (FG injections to the right intermediate grey matter of the lumbar cord (L1-L2 and the b-subunit of cholera toxin (CTb was injected either into the MLF or the right CVLM (3 animals each. Double-labelled cells were identified within brainstem structures with confocal microscopy and mapped onto brainstem diagrams. An additional 3 rats were injected with CTb in the CVLM to label axon terminals in the lumbar spinal cord. Double-labelled cells projecting via the MLF or CVLM were found principally in reticular regions of the medulla and pons but small numbers of cells were also located within the midbrain. CVLM projections to the lumbar cord were almost exclusively ipsilateral and concentrated within the intermediate grey matter. Most (62% of terminals were immunoreactive for the vesicular glutamate transporter 2 while 23% contained the vesicular GABA transporter. The inhibitory subpopulation was glycinergic, GABAergic or contained both transmitters. The proportions of excitatory and inhibitory axons projecting via the CVLM to the lumbar cord are similar to those projecting via the MLF. Unlike the MLF pathway, CVLM projections are predominantly ipsilateral and concentrated within intermediate grey but do not extend into motor nuclei or laminia VIII. Terminations of the CVLM pathway are located in a region of the grey matter that is rich in premotor interneurons; thus its primary function may be to coordinate activity of premotor networks.

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

    Science.gov (United States)

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

    2017-12-01

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

  19. The use of recombinant nAG protein In spinal cord crush injury in a rat model

    International Nuclear Information System (INIS)

    Al-Qattan, M.M.; Al-Motairi, M.; Ah-Habib, A.

    2017-01-01

    Objective: To evaluate the therapeutic properties of nAG protein during the recovery following acute spinal cord injuries in the rat. Study Design: An experimental study. Place and Duration of Study: King Saud University, Riyadh, Saudi Arabia, from September 2014 to September 2015. Methodology: Eight rats were studied (4 control rats and 4 experimental rats; and hence 50% were controls and 50% were experimental). All rats were subjected to an acute spinal cord injury using the aneurysmal clip injury model. Immediately after the injury, a single intra-dural injection of either normal saline (in the control group) or the nAG protein (in the experimental group) was done. Assessment of both groups was done over a 6-week period with regard to weight maintenance, motor recovery scores, MRI and histopathology of the injury site. Results: Weight maintenance was seen in the experimental and not in the control rats. Starting at 3 weeks after injury, the motor recovery was significantly (p<0.05) better in the experimental group. MRI assessment at 6 weeks showed better maintenance of cord continuity and less fluid accumulation at the injury site in the nAG-treated group. Just proximal to the injury site, there was less gliosis in the experimental group compared to the control group. At the crush injury site, there was less tissue architecture distortion, less vacuole formation, and less granulation tissue formation in the experimental group. Conclusion: The local injection nAG protein enhances neuro-restoration, reduces gliosis, and reduces vacuole/ granulation tissue formation following acute spinal cord crush injury in the rat aneurysmal clip animal model. (author)

  20. Long-term effects of ionizing radiation on the rat spinal cord: intramedullary connective tissue formation

    International Nuclear Information System (INIS)

    Gilmore, S.A.

    1973-01-01

    Light microscopy was used to evaluate the effects of ionizing radiation on spinal cords of rats irradiated when three days of age and killed at intervals up to 28 months after irradiation. The amounts of x-rays administered (2,000 R; 1,000 R; 500 R) were those which had been demonstrated by short-term studies to cause either no histopathologic changes or only transient, reparable alterations. The most significant and previously unreported finding was the development, usually restricted to the gray matter, of elongated, spindle-shaped cells that produce prodigious amounts of fibers clearly demonstrated by the Wilder's reticular stain. In cases where extensive cellular development had occurred, these cells were oriented around the perikarya of the large ventral motor neurons and formed a well-developed capsule of reticular fibers. This phenomenon occurred more frequently in rats receiving the greater amounts of radiation and killed 12 months or more after exposure. The other observation of interest was the development of lesser amounts of connective tissue-producing cells in the dorsal gray matter, where these cells were seen initially in the substantia gelatinosa. The significance of these changes is discussed in relation to previously reported long-term effects of ionizing radiation on the central nervous system

  1. Action of hypo- and hyperthyroidism on the postmortal decay of acetylcholine in the rat spinal cord.

    Science.gov (United States)

    Molinengo, L; Cassone, M C; Oggero, L

    1986-01-01

    The postmortal decay of acetylcholine (Ach) was studied in the cervical spinal cords of rats in conditions of hyper- and hypothyroidism. The modifications of thyroid function were achieved either by chronic (20-25 days) administration of l-thyroxine or of methimazole. The basal metabolic rate and plasma T4 concentration were measured to estimate the degree of modification of thyroid activity. The levels of Ach at the start of postmortal decay were evaluated by extrapolation to time 0 of the curves of the postmortal decay of Ach and the levels of Ach at stabilization were estimated from the means of all the measures made at lapses of time over 100-200 s from death. In low and high hypothyroidism a reduction (53 and 72%, respectively) of the levels of Ach was found. A similar effect was found in hyperthyroidism: a 73 and 63% reduction of Ach levels in high and low hyperthyroidism, respectively. The level of Ach at stabilization of the postmortal decay increased only in hyperthyroid rats. The process by which Ach is destroyed is not modified in hyper- or hypothyroidism.

  2. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    International Nuclear Information System (INIS)

    Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

    2010-01-01

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response.

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

    Science.gov (United States)

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

    2017-09-01

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

  4. Lack of evidence for increased tolerance of rat spinal cord with decreasing fraction doses below 2 Gy

    International Nuclear Information System (INIS)

    Ang, K.K.; van der Kogel, A.J.; van der Schueren, E.

    1985-01-01

    The radiation tolerance of the spinal cord, both in man and in rats, has been shown to depend strongly on the size of the dose per fraction. With fraction doses down to about 2 Gy, the spinal cord tolerance can be predicted by a modified Ellis formula. More recently alternative isoeffect formulas were based on the linear-quadratic (LQ) model of cell survival where the effect of dose fractionation is characterized by the ratio α/β which varies from tissue to tissue. For the spinal cord, as well as for other late responding tissues, the ratio α/β is small, in contrast to most acutely responding tissues. Both the Ellis-type formula, and to a lesser extent the LQ-model, predict a continuously increasing tolerance dose with decreasing fraction size. From previous experiments on the rat cervical spinal cord with doses per fraction down to about 2 Gy, the ratio α/β was determined to be 1.7 Gy, and the LQ-model would predict a rise in tolerance with a reduction in fraction size to far below 2 Gy. Based on these predictions clinical studies have been initiated assuming a significantly increased tolerance by reduction of fraction size to about 1 Gy. However, in the present experiments no evidence was found for such an increase in tolerance with fraction sizes below 2 Gy

  5. Neuronal regeneration in injured rat spinal cord after human dental pulp derived neural crest stem cell transplantation.

    Science.gov (United States)

    Kabatas, S; Demir, C S; Civelek, E; Yilmaz, I; Kircelli, A; Yilmaz, C; Akyuva, Y; Karaoz, E

    2018-01-01

    This study aimed to analyze the effect of human Dental Pulp-Neural Crest Stem Cells (hDP-NCSCs) delivery on lesion site after spinal cord injury (SCI), and to observe the functional recovery after transplantation. Neural Crest Stem Cells (NCSCs) were isolated from human Dental Pulp (hDP). The experimental rat population was divided into four groups (n = 6/24). Their behavioral motility was scored regularly. After 4-weeks, rats were sacrificed, and their spinal cords were examined for Green Fluorescent Protein (GFP) labeled hDP-NCSCs by immunofluorescence (IF) staining. In early post-injury (p.i) period, the ultrastructure of spinal cord tissue was preserved in Group 4. The majority of cells forming the ependymal region around the central canal were found to be hDP-NCSCs. While the grey-and-white-matter around the ependymal region was composed of e.g. GFP cells, with astrocytic-like appearance. The scores showed significant motor recovery in hind limb functions in Group 4. However, no obvious change was observed in other groups. Cells e.g., mesenchymal (Vimentin+) which express GFP+ cells in the gray-and-white-matter around the ependymal region could indicate the potential to self-renewal and plasticity. Thus, transplantation of hDP-NCSCs might be an effective strategy to improve functional recovery following spinal cord trauma (Fig. 10, Ref. 32).

  6. Distribution of networks generating and coordinating locomotor activity in the neonatal rat spinal cord in vitro: a lesion study

    DEFF Research Database (Denmark)

    Kjaerulff, O; Kiehn, O

    1996-01-01

    The isolated spinal cord of the newborn rat contains networks that are able to create a patterned motor output resembling normal locomotor movements. In this study, we sought to localize the regions of primary importance for rhythm and pattern generation using specific mechanical lesions. We used...... ventral root recordings to monitor neuronal activity and tested the ability of various isolated parts of the caudal thoraciclumbar cord to generate rhythmic bursting in a combination of 5-HT and NMDA. In addition, pathways mediating left/right and rostrocaudal burst alternation were localized. We found......, these pathways were distributed along the lumbar enlargement. Both lateral and ventral funiculi were sufficient to coordinate activity in the rostral and caudal regions. We conclude that the networks organizing locomotor-related activity in the spinal cord of the newborn rat are distributed....

  7. Organization of projections from the spinal trigeminal subnucleus oralis to the spinal cord in the rat: a neuroanatomical substrate for reciprocal orofacial-cervical interactions.

    Science.gov (United States)

    Devoize, Laurent; Doméjean, Sophie; Melin, Céline; Raboisson, Patrick; Artola, Alain; Dallel, Radhouane

    2010-07-09

    The organization of efferent projections from the spinal trigeminal nucleus oralis (Sp5O) to the spinal cord in the rat was studied using the anterograde tracer Phaseolus vulgaris leucoagglutinin. Sp5O projections to the spinal cord are restricted to the cervical cord. No labeled terminal can be detected in the thoracic and lumbar cord. The organization of these projections happens to critically depend on the dorso-ventral location of the injection site. On the one hand, the dorsal part of the Sp5O projects to the medial part of the dorsal horn (laminae III-V) at the C1 level, on the ipsilateral side, and to the ventral horn, on both sides but mainly on the ipsilateral one. Ipsilateral labeled terminals are distributed throughout laminae VII to IX but tend to cluster around the dorso-medial motor nuclei, especially at C3-C5 levels. Within the contralateral ventral horn, label terminals are found particularly in the region of the ventro-medial motor nucleus. This projection extends as far caudally as C3 or C4 level. On the other hand, the ventral part of the Sp5O projects to the lateral part of the dorsal horn (laminae III-V) at the C1 level, on the ipsilateral side, and to the ventral horn, on both sides but mainly on the contralateral one. Contralateral labeled terminals are distributed within the region of the dorso- and ventro-medial motor nuclei at C1-C4 levels whereas they are restricted to the dorso-medial motor nucleus at C5-C8 levels. These findings suggest that Sp5O is involved in the coordination of neck movements and in the modulation of incoming sensory information at the cervical spinal cord. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. Extracellular magnesium enhances the damage to locomotor networks produced by metabolic perturbation mimicking spinal injury in the neonatal rat spinal cord in vitro.

    Science.gov (United States)

    Margaryan, G; Mladinic, M; Mattioli, C; Nistri, A

    2009-10-06

    An acute injury to brain or spinal cord produces profound metabolic perturbation that extends and exacerbates tissue damage. Recent clinical interventions to treat this condition with i.v. Mg(2+) to stabilize its extracellular concentration provided disappointing results. The present study used an in vitro spinal cord model from the neonatal rat to investigate the role of extracellular Mg(2+) in the lesion evoked by a pathological medium mimicking the metabolic perturbation (hypoxia, aglycemia, oxidative stress, and acid pH) occurring in vivo. Damage was measured by taking as outcome locomotor network activity for up to 24 h after the primary insult. Pathological medium in 1 mM Mg(2+) solution (1 h) largely depressed spinal reflexes and suppressed fictive locomotion on the same and the following day. Conversely, pathological medium in either Mg(2+)-free or 5 mM Mg(2+) solution evoked temporary network depression and enabled fictive locomotion the day after. While global cell death was similar regardless of extracellular Mg(2+) solution, white matter was particularly affected. In ventral horn the number of surviving neurons was the highest in Mg(2+) free solution and the lowest in 1 mM Mg(2+), while motoneurons were unaffected. Although the excitotoxic damage elicited by kainate was insensitive to extracellular Mg(2+), 1 mM Mg(2+) potentiated the effect of combining pathological medium with kainate at low concentrations. These results indicate that preserving Mg(2+) homeostasis rendered experimental spinal injury more severe. Furthermore, analyzing ventral horn neuron numbers in relation to fictive locomotion expression might provide a first estimate of the minimal size of the functional locomotor network.

  9. 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.

  10. Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

    Directory of Open Access Journals (Sweden)

    Schmitz Beate

    2008-08-01

    Full Text Available Abstract Background Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology. In the present study we focused on two cathepsins, CATS and CATX, and studied their spatiotemporal expression and activity during the development and progression of neuropathic pain in the CNS of the rat 5th lumbar spinal nerve transection model (L5T. Results Immediately after the lesion, both cathepsins, CATS and CATX, were upregulated in the spinal cord. Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T. The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain. The cellular distribution of CATS and CATX was, however, considerably different. Conclusion The cellular distribution and the spatio-temporal development of the altered expression of CATS and CATX suggest that these proteins are important players in the spinal mechanisms involved in chronic pain induction and maintenance.

  11. Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats.

    Science.gov (United States)

    Kathe, Claudia; Hutson, Thomas Haynes; McMahon, Stephen Brendan; Moon, Lawrence David Falcon

    2016-10-19

    Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.

  12. Regulation of Neurotrophin-3 and Interleukin-1β and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats

    Directory of Open Access Journals (Sweden)

    Wenzhan Tu

    2015-01-01

    Full Text Available Growing evidence indicates that neurotrophin-3, interleukin-1β, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1β in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1β. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1β production and spinal glial activity.

  13. [Effects of small needle knife on the substance P in the dorsal root ganglion and spinal cord of rats].

    Science.gov (United States)

    Wang, Jin-Rong; Wang, Yong-Zhi; Dong, Fu-Hui; Zhong, Hong-Gang; Wang, De-Long; Wang, Xuan

    2010-09-01

    To study the mechanism of synthesis of substance P (SP) in the dorsal root ganglion (DRG) and the release of it in the dorsal horn of the spinal cord of rats after compression of skeletal muscle, and to observe the influence of small needle knife. Sustained pressure of 70 kPa was applied to rats, muscular tissues for 2 hours. The rats were divided into three groups: normal, control and experiment group respectively. In all rats except the six normal ones, the lower legs were compressed once one day. The left leg was considered as the control group, the right left was experiment group, which were divided into the 1st day, the 2nd day and the 3rd day within the two groups. Experiment group was treated with small needle knife after the muscular tissue was compressed. After completing the stimulation, the DRG related to the muscle and part of spinal cord were removed for the qualification of SP-like immunoreactivity using immunohistochemistry. The dark brown stains on the DRG and on the REXed laminae I and II in the dorsal horn of the spinal cord were counted by Image-Pro Plus software. SP-like immunoreactivity in the side treated by the small needle knife was enhanced comparing with the counterpart in DRG in normal group (P DRG in the experiment group were significantly reduced compared with the control group (P DRG, and shows no effects on the release of SP from the spinal cord in short-term (3 days).

  14. Specific involvement of atypical PKCζ/PKMζ in spinal persistent nociceptive processing following peripheral inflammation in rat

    Directory of Open Access Journals (Sweden)

    Marchand Fabien

    2011-11-01

    Full Text Available Abstract Background Central sensitization requires the activation of various intracellular signalling pathways within spinal dorsal horn neurons, leading to a lowering of activation threshold and enhanced responsiveness of these cells. Such plasticity contributes to the manifestation of chronic pain states and displays a number of features of long-term potentiation (LTP, a ubiquitous neuronal mechanism of increased synaptic strength. Here we describe the role of a novel pathway involving atypical PKCζ/PKMζ in persistent spinal nociceptive processing, previously implicated in the maintenance of late-phase LTP. Results Using both behavioral tests and in vivo electrophysiology in rats, we show that inhibition of this pathway, via spinal delivery of a myristoylated protein kinase C-ζ pseudo-substrate inhibitor, reduces both pain-related behaviors and the activity of deep dorsal horn wide dynamic range neurons (WDRs following formalin administration. In addition, Complete Freund's Adjuvant (CFA-induced mechanical and thermal hypersensitivity was also reduced by inhibition of PKCζ/PKMζ activity. Importantly, this inhibition did not affect acute pain or locomotor behavior in normal rats and interestingly, did not inhibited mechanical allodynia and hyperalgesia in neuropathic rats. Pain-related behaviors in both inflammatory models coincided with increased phosphorylation of PKCζ/PKMζ in dorsal horn neurons, specifically PKMζ phosphorylation in formalin rats. Finally, inhibition of PKCζ/PKMζ activity decreased the expression of Fos in response to formalin and CFA in both superficial and deep laminae of the dorsal horn. Conclusions These results suggest that PKCζ, especially PKMζ isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation.

  15. Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

    OpenAIRE

    Kachadroka, Supatra; Hall, Alicia M.; Niedzielko, Tracy L.; Chongthammakun, Sukumal; Floyd, Candace L.

    2010-01-01

    Several groups have recently shown that 17β-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17β-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17β-estradiol-mediated protection by evaluating a delayed administration over a clinically relevan...

  16. The number of postsynaptic currents necessary to produce locomotor- related cyclic information in neurons in the neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Raastad, Morten; Johnson, Bruce R.; Kiehn, Ole

    1996-01-01

    To understand better how synaptic signaling contributes to network activity, we analyzed the potential contribution of putative unitary postsynaptic currents (PSCs) to locomotor-related information received by spinal interneurons in neonatal rats. The average cyclic modulation of the whole-cell c......-5) of the synapses contributing to the cyclic information need to be active simultaneously. This suggests that individual presynaptic cells in a central locomotor network can have a powerful influence on other neurons....

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

    Science.gov (United States)

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

    2013-12-01

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

  18. Granulocyte-colony stimulating factor (G-CSF improves motor recovery in the rat impactor model for spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Tanjew Dittgen

    Full Text Available Granulocyte-colony stimulating factor (G-CSF improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function.

  19. Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats

    Science.gov (United States)

    Muradov, Johongir M.; Ewan, Eric E.; Hagg, Theo

    2013-01-01

    The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and a ~70% loss of the sensory axons, by 24 hours. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 hours. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 µg/µl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 hours. EB also caused an ~72% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R2 = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons. PMID:23978615

  20. Feasibility of 3.0 T diffusion-weighted nuclear magnetic resonance imaging in the evaluation of functional recovery of rats with complete spinal cord injury

    Directory of Open Access Journals (Sweden)

    Duo Zhang

    2015-01-01

    Full Text Available Diffusion tensor imaging is a sensitive way to reflect axonal necrosis and degeneration, glial cell regeneration and demyelination following spinal cord injury, and to display microstructure changes in the spinal cord in vivo. Diffusion tensor imaging technology is a sensitive method to diagnose spinal cord injury fiber tractography visualizes the white matter fibers, and directly displays the structural integrity and resultant damage of the fiber bundle. At present, diffusion tensor imaging is restricted to brain examinations, and is rarely applied in the evaluation of spinal cord injury. This study aimed to explore the fractional anisotropy and apparent diffusion coefficient of diffusion tensor magnetic resonance imaging and the feasibility of diffusion tensor tractography in the evaluation of complete spinal cord injury in rats. The results showed that the average combined scores were obviously decreased after spinal cord transection in rats, and then began to increase over time. The fractional anisotropy scores after spinal cord transection in rats were significantly lower than those in normal rats (P <0.05 the apparent diffusion coefficient was significantly increased compared with the normal group (P < 0.05. Following spinal cord transection, fractional anisotropy scores were negatively correlated with apparent diffusion coefficient values (r = -0.856, P < 0.01, and positively correlated with the average combined scores (r = 0.943, P < 0.01, while apparent diffusion coefficient values had a negative correlation with the average combined scores (r = -0.949, P < 0.01. Experimental findings suggest that, as a non-invasive examination, diffusion tensor magnetic resonance imaging can provide qualitative and quantitative information about spinal cord injury. The fractional anisotropy score and apparent diffusion coefficient have a good correlation with the average combined scores, which reflect functional recovery after spinal cord injury.

  1. [Expressions of neuropathic pain-related proteins in the spinal cord dorsal horn in rats with bilateral chronic constriction injury].

    Science.gov (United States)

    Shen, Le; Li, Xu; Wang, Hai-tang; Yu, Xue-rong; Huang, Yu-guang

    2013-12-01

    To evaluate the pain-related behavioral changes in rats with bilateral chronic constriction injury(bCCI)and identify the expressions of neuropathic pain-related proteins. The bCCI models were established by ligating the sciatic nerves in female Sprague Dawley rats. Both mechanical hyperalgesia and cold hyperalgesia were evaluated through electronic von Frey and acetone method. Liquid chromatography-mass spectrometry/mass spectrometry was applied to characterize the differentially expressed proteins. Both mechanical withdrawal threshold and cold hyperalgesia threshold decreased significantly on the postoperative day 7 and 14, when compared with na ve or sham rats(P <0.05). Twenty five differentially expressed proteins associated with bilateral CCI were discovered, with eighteen of them were upregulated and seven of them downregulated. The bCCT rats have remarkably decreased mechanical and cold hyperalgesia thresholds. Twenty five neuropathic pain-related proteins are found in the spinal cord dorsal horn.

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

    Directory of Open Access Journals (Sweden)

    Volker Kroehne

    2017-09-01

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

  3. Radiation-induced nerve root degeneration and hypertrophic neuropathy in the lumbosacral spinal cord of rats: The relation with changes in aging rats

    International Nuclear Information System (INIS)

    Kogel, A.J. van der

    1977-01-01

    Three-month-old WAG Rij rats were irradiated with 300 kV X-rays on the lumbar region of the spinal column with doses below the level for causing paralysis due to radiation radiculomyelopathy. 8-9 months after irradiation. degeneration of predominantly the ventral nerve roots of the cauda equina was observed. Three stages were distinguishable: I) Demyelination and proliferation of Schwann cells: II) Local swelling of ventral nerve roots, with concentric layers of Schwann cells resembling hypertrophic neuropathy: III) Malignant Schwannoma, invading roots and spinal cord. It is concluded that the degenerative and proliferative lesions represent a continuous series of stages of slowly progressive lesions. The ventral nerve root degeneration (Ist stage) is similar to that observed in aging, unirradiated rats, normally developing at the age of 18-20 months. (orig.) [de

  4. Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats.

    Science.gov (United States)

    Joo, Min Cheol; Jang, Chul Hwan; Park, Jong Tae; Choi, Seung Won; Ro, Seungil; Kim, Min Seob; Lee, Moon Young

    2018-02-01

    Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10 th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord.

  5. Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

    Science.gov (United States)

    Joo, Min Cheol; Jang, Chul Hwan; Park, Jong Tae; Choi, Seung Won; Ro, Seungil; Kim, Min Seob; Lee, Moon Young

    2018-01-01

    Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord. PMID:29557386

  6. 9 Expression in Rats with Acute Spinal Cord Injury by Cantharidin

    African Journals Online (AJOL)

    Purpose: To demonstrate the anti-apoptotic effects of cantharidin in mice with acute spinal cord injury. (ASCI). Methods: In total, 30 ... were obtained from the Shanghai Laboratory .... prevent the development of secondary spinal injury in mice ...

  7. Electroacupuncture in the repair of spinal cord injury: inhibiting the Notch signaling pathway and promoting neural stem cell proliferation

    Directory of Open Access Journals (Sweden)

    Xin Geng

    2015-01-01

    Full Text Available Electroacupuncture for the treatment of spinal cord injury has a good clinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Dawley rats was clamped for 60 seconds. Dazhui (GV14 and Mingmen (GV4 acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expression of serum inflammatory factors was apparently downregulated in rat models of spinal cord injury after electroacupuncture. Hematoxylin-eosin staining and immunohistochemistry results demonstrated that electroacupuncture contributed to the proliferation of neural stem cells in rat injured spinal cord, and suppressed their differentiation into astrocytes. Real-time quantitative PCR and western blot assays showed that electroacupuncture inhibited activation of the Notch signaling pathway induced by spinal cord injury. These findings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem cells.

  8. 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

  9. Mild Moxibustion Decreases the Expression of Prokineticin 2 and Prokineticin Receptor 2 in the Colon and Spinal Cord of Rats with Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Cili Zhou

    2014-01-01

    Full Text Available It has been proven that prokineticin 2 (PK2 and its receptor PKR2 play an important role in hyperalgesia, while mild moxibustion can relieve visceral hypersensitivity in a rat model of irritable bowel syndrome (IBS. The goal of the present study was to determine the effects of mild moxibustion on the expression of PK2 and PKR2 in colon and spinal cord in IBS rat model, which was induced by colorectal distension using inflatable balloons. After mild moxibustion treatment, abdominal withdrawal reflex (AWR scores were assessed by colorectal distension; protein and mRNA expression of PK2 and PKR2 in rat colon and spinal cord was determined by immunohistochemistry and fluorescence quantitative PCR. Compared with normal rats, the AWR scores of rats and the expressions of PK2/PKR2 proteins and mRNAs in colon and spinal cord tissue were significantly increased in the model group; compared with the model group, the AWR scores of rats and the expressions of PK2/PKR2 proteins and mRNAs in colon and spinal cord tissue were significantly decreased in the mild moxibustion group. These findings suggest that the analgesia effect of mild moxibustion may be associated with the reduction of the abnormally increased expression of the PK2/PKR2 proteins and mRNAs in the colon and spinal cord.

  10. Curcumin attenuates morphine antinociceptive tolerance through suppressing up-regulation of spinal Toll-like receptor 4 in rats

    Directory of Open Access Journals (Sweden)

    Fei GAO

    2017-12-01

    Full Text Available Objective To investigate the effects of curcumin (Cur on activation of spinal Toll-like receptor 4 (TLR4 and on the chronic antinociceptive tolerance of morphine. Methods Sixty male Sprague-Dawley rats with successful intrathecal catheterization were randomly divided into four groups (n=15: saline (NS group; morphine (MOR group; curcumin (Cur group and morphine plus curcumin (MOR+Cur group. A morphine tolerance model of rats was induced by intrathecal injection of morphine 15μg, once a day for 7 consecutive days in MOR and MOR+Cur group; 100μg curcumin was administered intrathecally once a day for 7 consecutive days in Cur and MOR+Cur group, 10μl saline was administered intrathecally once a day for 7 consecutive days in NS group. The effect of curcumin intrathecal catheterization on morphine antinociceptive tolerance was explored by the tail flick latency (TFL method and mechanical withdrawal threshold (MWT, and then the maximum possible potential effect (MPE was calculated. The immunofluorescence staining method was applied to detect the effect of curcumin on the activation of lumbar spinal microglia. Real-time PCR and Western blotting were used to evaluate the effect of curcumin on the expression of mRNA and protein of spinal TLR4. Results The %MPE TFL and %MPE MWT increased significantly in MOR+Cur group than in MOR group (P0.05. The lumbar spinal microglia increased markedly and the expressions of polyclonal antibody IBA-1 and TLR4 were significantly up-regulated in MOR group than in NS group (P0.05. Conclusion Curcumin may attenuate chronic morphine antinociceptive tolerance through inhibiting spinal TLR4 up-regulation. DOI: 10.11855/j.issn.0577-7402.2017.12.06

  11. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    International Nuclear Information System (INIS)

    Rodrigues, L.P.; Iglesias, D.; Nicola, F.C.; Steffens, D.; Valentim, L.; Witczak, A.; Zanatta, G.; Achaval, M.; Pranke, P.; Netto, C.A.

    2011-01-01

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10 6 cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10 6 cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation

  12. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, L.P. [Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Iglesias, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Nicola, F.C. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Steffens, D. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Valentim, L.; Witczak, A.; Zanatta, G. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Achaval, M. [Departamento de Ciências Morfológicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Pranke, P. [Laboratório de Hematologia e Células-Tronco, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Netto, C.A. [Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2011-12-23

    Cell transplantation is a promising experimental treatment for spinal cord injury. The aim of the present study was to evaluate the efficacy of mononuclear cells from human umbilical cord blood in promoting functional recovery when transplanted after a contusion spinal cord injury. Female Wistar rats (12 weeks old) were submitted to spinal injury with a MASCIS impactor and divided into 4 groups: control, surgical control, spinal cord injury, and one cell-treated lesion group. Mononuclear cells from umbilical cord blood of human male neonates were transplanted in two experiments: a) 1 h after surgery, into the injury site at a concentration of 5 x 10{sup 6} cells diluted in 10 µL 0.9% NaCl (N = 8-10 per group); b) into the cisterna magna, 9 days after lesion at a concentration of 5 x 10{sup 6} cells diluted in 150 µL 0.9% NaCl (N = 12-14 per group). The transplanted animals were immunosuppressed with cyclosporin-A (10 mg/kg per day). The BBB scale was used to evaluate motor behavior and the injury site was analyzed with immunofluorescent markers to label human transplanted cells, oligodendrocytes, neurons, and astrocytes. Spinal cord injury rats had 25% loss of cord tissue and cell treatment did not affect lesion extension. Transplanted cells survived in the injured area for 6 weeks after the procedure and both transplanted groups showed better motor recovery than the untreated ones (P < 0.05). The transplantation of mononuclear cells from human umbilical cord blood promoted functional recovery with no evidence of cell differentiation.

  13. 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.

  14. Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury

    Directory of Open Access Journals (Sweden)

    F.C. Nicola

    2016-01-01

    Full Text Available Spinal cord injury (SCI is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10; SCI (laminectomy followed by SCI, n=12; SHEDs (SCI treated with SHEDs, n=11; TT (SCI treated with treadmill training, n=11; SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10. Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action.

  15. Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury.

    Science.gov (United States)

    Nicola, F C; Rodrigues, L P; Crestani, T; Quintiliano, K; Sanches, E F; Willborn, S; Aristimunha, D; Boisserand, L; Pranke, P; Netto, C A

    2016-08-08

    Spinal cord injury (SCI) is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs) transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10); SCI (laminectomy followed by SCI, n=12); SHEDs (SCI treated with SHEDs, n=11); TT (SCI treated with treadmill training, n=11); SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10). Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action.

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms.

    Science.gov (United States)

    Sakai, Kiyoshi; Yamamoto, Akihito; Matsubara, Kohki; Nakamura, Shoko; Naruse, Mami; Yamagata, Mari; Sakamoto, Kazuma; Tauchi, Ryoji; Wakao, Norimitsu; Imagama, Shiro; Hibi, Hideharu; Kadomatsu, Kenji; Ishiguro, Naoki; Ueda, Minoru

    2012-01-01

    Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

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

    Science.gov (United States)

    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.

  19. Behavioral and physiological methods for early quantitative assessment of spinal cord injury and prognosis in rats

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    C.A. Giglio

    2006-12-01

    Full Text Available Methods for reliable evaluation of spinal cord (SC injury in rats at short periods (2 and 24 h after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a anesthesia, b dissection of soft prevertebral tissue, and c laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their

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

    OpenAIRE

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

    2015-01-01

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

  1. Hypertension after bilateral kidney irradiation in young and adult rats

    International Nuclear Information System (INIS)

    Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

    1987-01-01

    The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    2018-03-30

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

  4. Cross-organ sensitization of thoracic spinal neurons receiving noxious cardiac input in rats with gastroesophageal reflux.

    Science.gov (United States)

    Qin, Chao; Malykhina, Anna P; Thompson, Ann M; Farber, Jay P; Foreman, Robert D

    2010-06-01

    Gastroesophageal reflux (GER) frequently triggers or worsens cardiac pain or symptoms in patients with coronary heart disease. This study aimed to determine whether GER enhances the activity of upper thoracic spinal neurons receiving noxious cardiac input. Gastric fundus and pyloric ligations as well as a longitudinal myelotomy at the gastroesophageal junction induced acute GER in pentobarbital-anesthetized, paralyzed, and ventilated male Sprague-Dawley rats. Manual manipulations of the stomach and lower esophagus were used as surgical controls in another group. At 4-9 h after GER surgery, extracellular potentials of single neurons were recorded from the T3 spinal segment. Intrapericardial bradykinin (IB) (10 microg/ml, 0.2 ml, 1 min) injections were used to activate cardiac nociceptors, and esophageal distensions were used to activate esophageal afferent fibers. Significantly more spinal neurons in the GER group responded to IB compared with the control group (69.1 vs. 38%, P neurons in the superficial laminae of GER animals was significantly different from those in deeper layers (1/8 vs. 46/60, P 0.05). Excitatory responses of spinal neurons to IB in the GER group were greater than in the control group [32.4 +/- 3.5 impulses (imp)/s vs. 13.3 +/- 2.3 imp/s, P neurons responded to cardiac input and ED, which was higher than the control group (61.5%, P neurons in deeper laminae of the dorsal horn to noxious cardiac stimulus.

  5. INFLAMMATION IS INCREASED WITH ANXIETY- AND DEPRESSION-LIKE SIGNS IN A RAT MODEL OF SPINAL CORD INJURY

    Science.gov (United States)

    Maldonado-Bouchard, Sioui; Peters, Kelsey; Woller, Sarah A.; Madahian, Behrouz; Faghihi, Usef; Patel, Shivani; Bake, Shameena; Hook, Michelle A

    2015-01-01

    Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet, despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease it remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in psychological well-being. To test this hypothesis, we used a battery of established behavioral tests to assess depression and anxiety in spinally contused rats. The behavioral tests, and subsequent statistical analyses, revealed three cohorts of subjects that displayed behavioral characteristics of 1) depression, 2) depression and anxiety, or 3) no signs of decreased psychological well-being. Subsequent molecular analyses demonstrated that the psychological cohorts differed not only in behavioral symptoms, but also in peripheral (serum) and central (hippocampi and spinal cord) levels of pro-inflammatory cytokines. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. These data support the hypothesis that inflammatory changes are associated with decreased psychological well-being following SCI. PMID:26296565

  6. Protective effects of two constituents of Chinese herbs on spinal motor neurons from embryonic rats with hypoxia injury.

    Science.gov (United States)

    Chen, Jian-Feng; Fan, Jian; Tian, Xiao-Wu; Tang, Tian-Si

    2012-01-01

    Neuroprotective agents are becoming significant tools in the repair of central nervous system injuries. In this study, we determined whether ginkgolides (Gin, extract of GinkgoBiloba) and Acanthopanax senticosus saponins (ASS, flavonoids extracted from Acanthopanax herbal preparations) have protective effects on rat spinal cords exposed to anoxia and we explored the mechanisms that underlie the protective effects. Spinal motor neurons (SMNs) from rat spinal cords were obtained and divided into five groups with 10 wells in each group. In control group, SMNs suffered no injury under normal oxygen; in hypoxia- inducible (HI) group, SMNs suffered injury from hypoxia; in Gin group, 37.5µg/ml Gin were used before 24 hrs of hypoxia; in ASS group, 50µg/ml ASS were used before 24 hrs of hypoxia;in glial cell-lined derived neurotrophic factor (GDNF) group, 0.1µg/ml GDNF were used before 24 hrs of hypoxia. Changes in morphology, neuron viability, and lactate dehydrogenase (LDH) release were observed. In addition, the expression of HIF-1α induced by hypoxia was measured. The neuronal viability in the Gin, ASS, and GDNF pretreated groups was higher than that in the HI group (P0.05). The quantity of LDH released in the three pretreated groups was lower than that in the HI group (Phypoxic neurons.

  7. Determination of Urine 3-HPMA, a Stable Acrolein Metabolite in a Rat Model of Spinal Cord Injury

    Science.gov (United States)

    Zheng, Lingxing; Park, Jonghyuck; Walls, Michael; Tully, Melissa; Jannasch, Amber; Cooper, Bruce

    2013-01-01

    Abstract Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significantly elevated in a dose-dependent manner when acrolein was injected into rats IP or directly into the spinal cord, but not when acrolein scavengers were co-incubated with acrolein solution. A nonlinear mathematic relationship is established between acrolein injected directly into the spinal cord and a correlated dose-dependent increase of 3-HPMA, suggesting the increase of 3-HPMA becomes less apparent as the level of injected acrolein increases. The elevation of 3-HPMA was further detected in the rat spinal cord injury, a pathological condition known to be associated with elevated endogenous acrolein. This finding was further validated by concomitant confirmation of increased acrolein-lysine adducts using established dot immunoblotting techniques. The noninvasive nature of measuring 3-HPMA concentrations in urine allows for long-term monitoring of acrolein in the same animal and ultimately in human clinical studies. Due to wide spread involvement of acrolein in human health, the benefits of this study have the potential to enhance human health significantly. PMID:23697633

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

    Directory of Open Access Journals (Sweden)

    Jakub Krejčí

    2016-03-01

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

  9. Assessment of the Neuroprotective Effects of Lavandula angustifolia Extract on the Contusive Model of Spinal Cord Injury in Wistar Rats

    Science.gov (United States)

    Kaka, Gholamreza; Yaghoobi, Kayvan; Davoodi, Shaghayegh; Hosseini, Seyed R.; Sadraie, Seyed H.; Mansouri, Korosh

    2016-01-01

    Introduction: Spinal cord injury (SCI) involves a primary trauma and secondary cellular processes that can lead to severe damage to the nervous system, resulting in long-term spinal deficits. At the cellular level, SCI causes astrogliosis, of which glial fibrillary acidic protein (GFAP) is a major index. Objective: The aim of this study was to investigate the neuroprotective effects of Lavandula angustifolia (Lav) on the repair of spinal cord injuries in Wistar rats. Materials and Methods: Forty-five female rats were randomly divided into six groups of seven rats each: the intact, sham, control (SCI), Lav 100, Lav 200, and Lav 400 groups. Every week after SCI onset, all animals were evaluated for behavior outcomes by the Basso, Beattie, and Bresnahan (BBB) score. H&E staining was performed to examine the lesions post-injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. Results: BBB scores were significantly increased and delayed responses on sensory tests were significantly decreased in the Lav 200 and Lav 400 groups compared to the control group. The greatest decrease of GFAP was evident in the Lav 200 and Lav 400 groups. EMG results showed significant improvement in the hindlimbs in the Lav 200 and Lav 400 groups compared to the control group. Cavity areas significantly decreased and the number of ventral motor neurons significantly increased in the Lav 200 and Lav 400 groups. Conclusion: Lav at doses of 200 and 400 mg/kg can promote structural and functional recovery after SCI. The neuroprotective effects of L. angustifolia can lead to improvement in the contusive model of SCI in Wistar rats. PMID:26903793

  10. Radiation response of the rat cervical spinal cord after irradiation at different ages: Tolerance, latency and pathology

    International Nuclear Information System (INIS)

    Ruifrok, A.C.C.; Van Der Kogel, A.J.; Stephens, L.C.

    1994-01-01

    Investigation of the age dependent single-dose radiation tolerance, latency to radiation myelopathy, and the histopathological changes after irradiation of the rat cervical spinal cord is presented. Rats were irradiated with graded single doses of 4 MV photons to the cervical spinal cord. When the rats showed definite signs of paresis of the forelegs, they were killed and processed for histological examination. The radiation dose resulting in paresis due to white matter damage in 50% of the animals (ED 50 ) after single dose irradiation was about 21.5 Gy at all ages ≥ 2 weeks. Only the Ed 50 at 1 week was significantly lower. The latency to the development of paresis clearly changed with the age at irradiation, from about 2 weeks after irradiation at 1 week to 6-8 months after irradiation at age ≥ 8 weeks. The white matter damage was similar in all symptomatic animals studied. The most prominent were areas with diffuse demyelination and swollen axons, often with focal necrosis, accompanied by glial reaction. This was observed in all symptomatic animals, irrespective of the age at irradiation. Expression of vascular damage appeared to depend on the age at irradiation. Although the latency to myelopathy is clearly age dependent, single dose tolerance is not age dependent at age ≥ 2 weeks in the rat cervical spinal cord. The white matter damage is similar in all symptomatic animals studied, but the vasculopathies appear to be influenced by the age at irradiation. It is concluded that white matter damage and vascular damage are separate phenomena contributing to the development of radiation myelopathy, expression of which may depend on the radiation dose applied and the age at irradiation. 28 refs., 5 figs., 3 tabs

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

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    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.

  12. Boron neutron capture irradiation of the rat spinal cord: effects of variable doses of borocaptate sodium

    International Nuclear Information System (INIS)

    Morris, Gerard M.; Coderre, Jeffrey A.; Hopewell, John W.; Micca, Peggy L.; Fisher, Craig

    1996-01-01

    The Fischer 344 rat spinal cord model has been used to evaluate the response of the central nervous system to boron neutron capture irradiation with variable doses of the neutron capture agent, borocaptate sodium (BSH). Three doses of BSH, 190, 140 and 80 mg/kg body weight, administered by i.p. injection, were used to establish the time course of 10 B accumulation in and removal from the blood. After administration of the two lower doses of BSH, blood 10 B levels peaked at 0.5 h after injection, with no significant (P > 0.1) change at 1 h after injection. Beyond this time point, levels of 10 B in the blood began to decrease after a dose of 80 mg/kg BSH, but remained constant until 3 h after administration after the two higher doses of BSH. Myelopathy developed after latent intervals of 20.4 ± 0.1, 20.8 ± 1.4, 15.0 ± 0.8, 15.4 ± 0.4 and 15.6 ± 0.4 weeks, following irradiation with thermal neutrons in combination with BSH at doses of 20, 40, 80, 140 and 190 mg/kg body weight, respectively. The radiation-induced lesion in the spinal cord was white matter necrosis. ED 50 values for myelopathy were calculated from probit-fitted dose-effect curves. Expressed as total physical absorbed doses, these values were 20.7 ± 1.9, 24.9 ± 1.2, 27.2 ± 0.9, 28.4 ± 0.6 and 32.4 ± 1.9 Gy after irradiation with thermal neutrons in the presence of 20, 40, 80, 140 and 190 mg/kg body weight of BSH, respectively. The compound biological effectiveness (CBE) factor values, estimated from this data, were in the range 0.49-0.55. There was no significant (P >0.1) variation in the CBE factor for BSH as a function of increasing 10 B concentration in the blood. It was concluded that there was no significant synergistic interaction between the low and high linear energy transfer (LET) components of the boron neutron capture (BNC) radiation field

  13. Serial Diffusion Tensor Imaging In Vivo Predicts Long-Term Functional Recovery and Histopathology in Rats following Different Severities of Spinal Cord Injury

    Science.gov (United States)

    Patel, Samir P.; Smith, Taylor D.; VanRooyen, Jenna L.; Powell, David; Cox, David H.; Sullivan, Patrick G.

    2016-01-01

    Abstract The current study demonstrates the feasibility of using serial magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in vivo to quantify temporally spinal cord injury (SCI) pathology in adult female Sprague-Dawley rats that were scanned prior to a moderate or severe upper lumbar contusion SCI. Injured rats were behaviorally tested for hind limb locomotion (Basso, Beattie, Bresnahan [BBB] scores) weekly for 4 weeks and scanned immediately after each session, ending with terminal gait analyses prior to euthanasia. As a measure of tissue integrity, fractional anisotropy (FA) values were significantly lower throughout the spinal cord in both injury cohorts at all time-points examined versus pre-injury. Moreover, FA values were significantly lower following severe versus moderate SCI at all time-points, and FA values at the injury epicenters at all time-points were significantly correlated with both spared white and gray matter volumes, as well as lesion volumes. Critically, quantified FA values at subacute (24 h) and all subsequent time-points were highly predictive of terminal behavior, reflected in significant correlations with both weekly BBB scores and terminal gait parameters. Critically, the finding that clinically relevant subacute (24 h) FA values accurately predict long-term functional recovery may obviate long-term studies to assess the efficacy of therapeutics tested experimentally or clinically. In summary, this study demonstrates a reproducible serial MRI procedure to predict the long-term impact of contusion SCI on both behavior and histopathology using subacute DTI metrics obtained in vivo to accurately predict multiple terminal outcome measures, which can be particularly valuable when comparing experimental interventions. PMID:26650623

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

    Directory of Open Access Journals (Sweden)

    Yi-Liang Kuo

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

  15. Observations on the interactions of Schwann cells and astrocytes following x irradiation of neonatal rat spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Blakemore, W F; Patterson, R C

    1975-10-01

    Myelination was inhibited in the spinal cord of three day-old rats with 2000 rads of x irradiation. Myelination subsequently occurred as a result of caudal migration of oligodendrocytes and extensive invasion of the cord by Schwann cells. Although oligodendrocytes were present in areas containing Schwann cells, astrocytes were absent. The presence of Schwann cells in the neuropil of the spinal cord did not stimulate production of basement membrane by astrocytes, so no new glial limiting membrane was formed. Evidence is presented which suggests that if astrocytes do not form a glial limiting membrane when opposed by large numbers of Schwann cells they are destroyed by the invading cells. It is suggested that the glial limiting membrane normally inhibits entry of Schwann cells into the central nervous system; if this is destroyed and not reconstituted, Schwann cells can migrate freely into the neuropil.

  16. Evidence for spinal N-methyl-d-aspartate receptor involvement in prolonged chemical nociception in the rat.

    Science.gov (United States)

    Haley, Jane E; Dickenson, Anthony H

    2016-08-15

    We used in vivo electrophysiology and a model of more persistent nociceptive inputs to monitor spinal cord neuronal activity in anaesthetised rats to reveal the pharmacology of enhanced pain signalling. The study showed that all responses were blocked by non-selective antagonism of glutamate receptors but a selective and preferential role of the N-methyl-d-aspartate (NMDA) receptor in the prolonged plastic responses was clearly seen. The work lead to many publications, initially preclinical but increasingly from patient studies, showing the importance of the NMDA receptor in central sensitisation within the spinal cord and how this could relate to persistent pain states. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

    OpenAIRE

    Oza, Chintan S.; Giszter, Simon F.

    2015-01-01

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we e...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-15

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

  19. Comparison of histopathologic changes following X-irradiation of mid-thoracic and lumbosacral levels of neonatal rat spinal cord

    International Nuclear Information System (INIS)

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

    1985-01-01

    Light microscopic changes were studied in the dorsal funiculi of spinal cords from rats irradiated (4000 R) at 3 days of age and killed from 9-60 days postirradiation (P-I). The irradiated site was limited to a 5-mm length of mid-thoracic spinal cord (T only) in one group of rats, to a 5-mm length of lumbosacral spinal cord (L only) in a second group, and to 5-mm lengths of both mid-thoracic and lumbosacral spinal cord (T/L) in the third group. Changes in the lumbosacral regions were essentially the same in both L only and T/L irradiated groups. These changes included a decreased neuroglial population and a concurrent state of hypomyelination from 9-30 days P-I. In contrast, in the mid-thoracic regions of T only and T/L irradiated groups the decrease in the neuroglial population was obvious only through 13 days P-I, and by 30 days this population resembled that of the controls. The irradiated mid-thoracic areas were hypomyelinated, with the fasciculus gracilis showing a greater degree of hypomyelination than the fasciculus cuneatus. By 25 days P-I, myelination appeared to be normal in these areas. Scattered hemorrhages were noted in both lumbosacral and mid-thoracic regions, but necrotic areas occurred only at the lumbosacral level. In general, the mid-thoracic area appeared to be less sensitive to x-radiation at 3 days of age than the lumbosacral area. These data suggest that there may be marked differences in the developmental states of cells at these two levels at 3 days of age

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

    Science.gov (United States)

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

    2017-08-15

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

  1. Distribution of calcium channel Ca(V)1.3 immunoreactivity in the rat spinal cord and brain stem.

    Science.gov (United States)

    Sukiasyan, N; Hultborn, H; Zhang, M

    2009-03-03

    The function of local networks in the CNS depends upon both the connectivity between neurons and their intrinsic properties. An intrinsic property of spinal motoneurons is the presence of persistent inward currents (PICs), which are mediated by non-inactivating calcium (mainly Ca(V)1.3) and/or sodium channels and serve to amplify neuronal input signals. It is of fundamental importance for the prediction of network function to determine the distribution of neurons possessing the ion channels that produce PICs. Although the distribution pattern of Ca(V)1.3 immunoreactivity (Ca(V)1.3-IR) has been studied in some specific central nervous regions in some species, so far no systematic investigations have been performed in both the rat spinal cord and brain stem. In the present study this issue was investigated by immunohistochemistry. The results indicated that the Ca(V)1.3-IR neurons were widely distributed across different parts of the spinal cord and the brain stem although with variable labeling intensities. In the spinal gray matter large neurons in the ventral horn (presumably motoneurons) tended to display higher levels of immunoreactivity than smaller neurons in the dorsal horn. In the white matter, a subset of glial cells labeled by an oligodendrocyte marker was also Ca(V)1.3-positive. In the brain stem, neurons in the motor nuclei appeared to have higher levels of immunoreactivity than those in the sensory nuclei. Moreover, a number of nuclei containing monoaminergic cells, for example the locus coeruleus, were also strongly immunoreactive. Ca(V)1.3-IR was consistently detected in the neuronal perikarya regardless of the neuronal type. However, in the large neurons in the spinal ventral horn and the cranial motor nuclei the Ca(V)1.3-IR was clearly detectable in first and second order dendrites. These results indicate that in the rat spinal cord and brain stem Ca(V)1.3 is probably a common calcium channel used by many kinds of neurons to facilitate the neuronal

  2. Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-fallypride

    International Nuclear Information System (INIS)

    Kaur, Jasmeet; Khararjian, Armen; Coleman, Robert A.; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

    2014-01-01

    Objectives: The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-fallypride and 11 C-fallypride. Methods: Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-fallypride scan or a 11 C-fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results: In vitro studies showed 18 F-fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-fallypride and 11 C-fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-fallypride in spinal cord sections. Conclusions: Our studies showed 18 F-fallypride and 11 C-fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord

  3. Propofol combined with bone marrow mesenchymal stem cell transplantation improves electrophysiological function in the hindlimb of rats with spinal cord injury better than monotherapy

    Directory of Open Access Journals (Sweden)

    Yue-xin Wang

    2015-01-01

    Full Text Available The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

  4. Influx mechanisms in the embryonic and adult rat choroid plexus

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...

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

    Science.gov (United States)

    Wilbanks, Susan R; Ivankova, Nataliya V

    2015-01-01

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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Exendin-4 Plays a Protective Role in a Rat Model of Spinal Cord Injury Through SERCA2

    Directory of Open Access Journals (Sweden)

    Zhonglei Sun

    2018-05-01

    Full Text Available Background/Aims: Current therapies for spinal cord injury (SCI have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2 plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2. Methods: To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen’s method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6-carboxyfluorescein diacetate N-succinimidyl ester (CE. Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test. Results: Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes. Conclusion: These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI.

  10. Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal Cord Injury in Rat Model.

    Science.gov (United States)

    O'Connor, Gregory; Jeffrey, Elisabeth; Madorma, Derik; Marcillo, Alexander; Abreu, Maria T; Deo, Sapna K; Dietrich, W Dalton; Daunert, Sylvia

    2018-03-23

    Although there has been a significant amount of research focused on the pathophysiology of Spinal Cord Injury (SCI), there is limited information on the consequences of SCI on remote organs. SCI can produce significant effects on a variety of organ systems, including the gastrointestinal tract. Patients with SCI often suffer from severe, debilitating bowel dysfunction in addition to their physical disabilities, which is of major concern for these individuals due to the adverse impact on their quality of life. Herein, we report on our investigation into the effects of SCI and subsequent antibiotic treatment on the intestinal tissue and microbiota. For that, we employed a thoracic SCI rat model and investigated changes to the microbiota, pro-inflammatory cytokine levels, and bacterial communication molecule levels post injury and gentamicin treatment for seven days. We discovered significant changes, the most interesting being the differences in the gut microbiota beta diversity of 8-week SCI animals compared to control animals at the family, genus, and species level. Specifically, 35 Operational Taxonomic Units (OTUs) were enriched in the SCI animal group and 3 were identified at species level; Lactobacillus intestinalis, Clostridium disporicum, and Bifidobacterium choerinum. In contrast, Clostridium saccharogumia was identified as depleted in the SCI animal group. Pro-inflammatory cytokines IL-12, MIP-2, and TNF-α, were found to be significantly elevated in intestinal tissue homogenate 4-weeks post-SCI compared to 8-weeks post-injury. Further, levels of IL-1β, IL-12, and MIP-2 significantly correlated with changes in beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the early effects of SCI on the microbiota and gastrointestinal tract, highlighting the need for further investigation to elucidate the mechanism underlying these effects.

  11. Radiation injuries of the spinal marrow of rats after irradiation with fast electrons

    International Nuclear Information System (INIS)

    Bruce-Micah, B.

    1973-01-01

    Twenty rats were fractionated irradiated on five days of the week with fast electrons of 42 MeV energy with a single dose of 200 r/day. After 1,000 r, 2,000 r, 3,000 r and 4,000 r HD, the animals were supravitally fixed and the spinal marrow was removed. The histological investigation already showed after 1,000 r HD distinct changes of the nerve cells and nerve fibers whereas the vessels appeared not to be injured. After 2,000 r HD, vessel changes with edemas occured for the first time. After 3,000 r HD, all nerve cells were severely injured, the glia tissue was denser and the vessels were enlarged despite endothelial proliferations. Furthermore, there were big edemas around the vessels and a beginning of demyelinisation in the dorsal column. After 4,000 r HD, a great part of the nerve cells and also a few glia cells were destroyed. The remaining glia cells were pyknotic and had partly several nucleoli. The tractus of the white matter consisted almost only now of a glia felt. With a survival time of six weeks, the glia had greatly regenerated and numerous new capillaries had sprouted in the grey matter. The white matter was strongly demyelinised. In the front lateral column, small round necrosis centres were visible. 18 weeks after irradiation, the glia tissue had greatly rebuilt itself. There were only very few nerve cells present. The strong sprouting of new capillaries in the grey matter was most noticeable. The results show that the application of fast electrons is of no advantage as regards injuring the nerve tissue compared to X-rays. (orig./LH) [de

  12. Exogenous Acrolein intensifies sensory hypersensitivity after spinal cord injury in rat.

    Science.gov (United States)

    Butler, Breanne; Acosta, Glen; Shi, Riyi

    2017-08-15

    Acrolein, an α,β-unsaturated aldehyde associated with oxidative stress, is also a major toxic component of tobacco cigarette smoke, which has been reported in the clinic to coincide with the exacerbation of neuropathic pain after SCI. Previous reports have shown that acrolein involvement in spinal cord injury (SCI) is crucial to the development and persistence of neuropathic pain. Through the activation and upregulation of the transient receptor protein ankyrin-1 (TRPA1) cation channel, acrolein is capable of sensitizing the central nervous system in the acute and chronic stages of SCI. Here, we report that the acute or delayed nasal exposure of acrolein, apart from cigarette smoke but at concentrations similar to that found in cigarette smoke, resulted in increased neuropathic pain behaviors in a rat model of contusion SCI. We also found that this hyperalgesia occurred concurrently with an augmentation in systemic acrolein, detected by an acrolein-glutathione metabolite in the urine. The application of an acrolein scavenger, phenelzine, was shown to reduce the hyperalgesic effect of acrolein inhalation. The previously determined ability of acrolein to bind to and activate the TRPA1 channel and elicit algesic responses may be a mechanism of the phenomenon seen in this study. Upon the exposure to actual cigarette smoke after SCI, intensified neuropathic pain behaviors were also observed and persisted for at least 1week after the cessation of the exposure period. Taken together, these results indicate that cigarette smoke, through mechanisms involving acrolein, poses a threat to the vulnerable CNS after SCI and can contribute to neuropathic pain. This investigation also provides further evidence for the potential utility of acrolein scavengers as a therapeutic strategy in SCI-resultant neuropathic pain. Copyright © 2017. Published by Elsevier B.V.

  13. Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn.

    Science.gov (United States)

    Peng, H-Z; Ma, L-X; Lv, M-H; Hu, T; Liu, T

    2016-04-05

    Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

    Brace, Jacalyn A; Schubart, Jane R

    2010-08-01

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

  15. [Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

    Science.gov (United States)

    Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

    2017-12-01

    Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

  16. Robust upregulation of serotonin 2A receptors after chronic spinal transection of rats: An immunohistochemical study

    DEFF Research Database (Denmark)

    Kong, Xiang-Yu; Wienecke, Jacob; Hultborn, Hans

    2010-01-01

    It is well known that spinal motoneurons below a spinal transection become supersensitive to a systemic administration of serotonin (5-HT) precursors, such as 5-hydroxytryptophan. This supersensitivity has been implicated in both the process of functional recovery following chronic lesions, and a...

  17. Plasticity of Signaling by Spinal Estrogen Receptor α, κ-Opioid Receptor, and Metabotropic Glutamate Receptors over the Rat Reproductive Cycle Regulates Spinal Endomorphin 2 Antinociception: Relevance of Endogenous-Biased Agonism.

    Science.gov (United States)

    Liu, Nai-Jiang; Murugaiyan, Vijaya; Storman, Emiliya M; Schnell, Stephen A; Kumar, Arjun; Wessendorf, Martin W; Gintzler, Alan R

    2017-11-15

    We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous μ-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle: minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and κ-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated metabotropic glutamate receptor 1 (mGluR 1 ) signaling, are critical to the transition from an EM2 nonresponsive state (during diestrus) to an analgesically responsive state (during proestrus). Differential signaling by mGluR 1 , depending on its activation by membrane estrogen receptor α (mERα; during diestrus) versus glutamate (during proestrus), concomitant with the ebb and flow of spinal dynorphin/KOR signaling, functions as a switch, preventing or promoting, respectively, spinal EM2 antinociception. Importantly, EM2 and glutamate-containing varicosities appose spinal neurons that express MOR along with mGluRs and mERα, suggesting that signaling mechanisms regulating analgesic effectiveness of intrathecally applied EM2 also pertain to endogenous EM2. Regulation of spinal EM2 antinociception by both the nature of the endogenous mGluR 1 activator (i.e., endogenous biased agonism at mGluR 1 ) and changes in spinal dynorphin/KOR signaling represent a novel mechanism for modulating analgesic responsiveness to endogenous EM2 (and perhaps other opioids). This points the way for developing noncanonical pharmacological approaches to pain management by harnessing endogenous opioids for pain relief. SIGNIFICANCE STATEMENT The current prescription opioid abuse epidemic underscores the urgency to develop alternative pharmacotherapies for managing pain. We find that the magnitude of spinal endomorphin 2 (EM2) antinociception not only

  18. Effects of bone marrow stromal cell transplantation through CSF on the subacute and chronic spinal cord injury in rats.

    Directory of Open Access Journals (Sweden)

    Norihiko Nakano

    Full Text Available It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs through the cerebrospinal fluid (CSF has beneficial effects on acute spinal cord injury (SCI in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury, and/or chronic (4-week post-injury SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0-3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle-injection subgroups, it increased only from 0.5-4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF.

  19. Effects of Bone Marrow Stromal Cell Transplantation through CSF on the Subacute and Chronic Spinal Cord Injury in Rats

    Science.gov (United States)

    Nakano, Norihiko; Nakai, Yoshiyasu; Seo, Tae-Beom; Homma, Tamami; Yamada, Yoshihiro; Ohta, Masayoshi; Suzuki, Yoshihisa; Nakatani, Toshio; Fukushima, Masanori; Hayashibe, Miki; Ide, Chizuka

    2013-01-01

    It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs) through the cerebrospinal fluid (CSF) has beneficial effects on acute spinal cord injury (SCI) in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury), and/or chronic (4-week post-injury) SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly) into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0–3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle)-injection subgroups, it increased only from 0.5–4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF. PMID:24039961

  20. Involvement of ERK phosphorylation of trigeminal spinal subnucleus caudalis neurons in thermal hypersensitivity in rats with infraorbital nerve injury.

    Directory of Open Access Journals (Sweden)

    Ikuko Suzuki

    Full Text Available To evaluate the involvement of the mitogen-activated protein kinase (MAPK cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK in trigeminal spinal subnucleus caudalis (Vc neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction nerve injury of the infraorbital nerve (ION-CCI. The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynamic range neurons to noxious mechanical and thermal stimulation in ION-CCI rats were significantly depressed following i.t. administration of PD98059, whereas responses to non-noxious mechanical and thermal stimulation were not altered. The present findings suggest that pERK-IR neurons in the Vc play a pivotal role in the development of thermal hypersensitivity in the face following trigeminal nerve injury.

  1. [Effect of electroacupuncture on the expression of oligodendrocyte precursor cells in rats with compressed spinal cord injury].

    Science.gov (United States)

    Huang, Si-qin; Qi, Wei; Zeng, Zhi-hua; Wang, Ke-jian; Wu, Xiu-yu

    2014-11-01

    To investigate the effect of electroacupuncture on the expression of oligodendrocyte precursor cells in rats with compressed spinal cord injury (CSCI) and to explore the mechanism of remyelinization. Thirty-six SD rats were randomly divided into a control group and three treatment groups with 3 d, 7 d and 14 d of treatment respectively. Acupuncture was given to rats in the treatment groups through jiaji point, double zusanli (ST36), and double taixi (KI3). Electroacupuncture (continuous wave, 2 Hz/1. 5 V, 30 min) was applied for the double zusanli (ST36) and double taixi (KI3). Ethological alterations of the rats were observed with quantitative assessment of neurologic function. The ultrastructure changes of nerve fibers in white matter were determined under electronic microscope. Expressions of NG2 protein, an OPC marker, was observed by Western blot. No significant changes in neurologic function and G-ratio were observed after three days and seven days of electroacupuncture treatment (P>0. 05). However, 14 d of electroacupuncture treatment made a significant change compared to the 7 d treatment group and the control group (PElectroacupuncture can improve inflammation and edema in the injured nerve fibers and up regulate NG2 expression and remyelination of the injured nerve fibers in rats with CSCI.

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

    Science.gov (United States)

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

    2011-03-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  5. Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats

    Science.gov (United States)

    Chen, Bo; He, Jianyu; Yang, Hao; Zhang, Qian; Zhang, Lingling; Zhang, Xian; Xie, En; Liu, Cuicui; Zhang, Rui; Wang, Yi; Huang, Linhong; Hao, Dingjun

    2015-03-01

    There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.

  6. Long-term organ culture of adult rat colon

    DEFF Research Database (Denmark)

    Shamsuddin, A.K.M.; Barrett, L.A.; Autrup, Herman

    1978-01-01

    . The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial......Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants...

  7. Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model

    Directory of Open Access Journals (Sweden)

    Doaa M. Samy

    2016-09-01

    Full Text Available Secondary damage after acute spinal cord compression injury (SCCI exacerbates initial insult. Nuclear factor kappa-B (NF-κB-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm showed neuroprotection against various CNS injuries. However, Agm impact on NF-κB signaling in acute SCCI remains to be investigated. The present study compared the effectiveness of Agm therapy and decompression laminectomy (DL in functional recovery, oxidative stress, inflammatory and apoptotic responses, and modulation of NF-κB activation in acute SCCI rat model. Rats were either sham-operated or subjected to SCCI at T8–9, using 2-Fr. catheter. SCCI rats were randomly treated with DL at T8–9, intraperitoneal Agm (100 mg/kg/day, combined (DL/Agm treatment or saline (n = 16/group. After 28-days of neurological follow-up, spinal cords were either subjected to biochemical measurement of oxidative stress and inflammatory markers or histopathology and immuno-histochemistry for NF-κB-p65 and caspase-3 expression (n = 8/group. Agm was comparable to DL in facilitating neurological functions recovery, reducing inflammation (TNF-α/interleukin-6, and apoptosis. Agm was distinctive in combating oxidative stress. Agm neuroprotective effects were paralleled with inhibition of NF-κB-p65 nuclear translocation. Combined pharmacological and surgical interventions were proved superior in functional recovery. In conclusion, present research suggested a new mechanism for Agm neuroprotection in rats SCCI through inhibition of NF-κB activation.

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

    Science.gov (United States)

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

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

  9. Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats (the 3rd report)

    International Nuclear Information System (INIS)

    Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Wang, Xiao Dong; Nagaoka, Shunji; Nojima, Kumie

    2005-01-01

    The effects of acute exposure of heavy ion on the properties of spinal motoneurons and their innervating muscle fibers were investigated. A 15, 20, 40, 50, or 70 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in 8-week-old male rats. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of spinal motoneurons innervating the soleus and plantaris muscles were analyzed by a computer-assisted image processing system. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no differences in the number of spinal motoneurons innervating the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in spinal motoneurons of the heavy-ion-exposed rats at the dose levels of 40, 50, and 70 Gy. There were no differences in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. It is concluded that more than 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there are no influences on the properties of muscle fibers which they innervate. (author)

  10. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

    Directory of Open Access Journals (Sweden)

    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  11. 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

  12. [Curcumin down-regulates CX3CR1 expression in spinal cord dorsal horn and DRG in neuropathic pain rats].

    Science.gov (United States)

    Zheng, Jinwei; Zheng, Changjian; Cao, Hong; Li, Jun; Lian, Qingquan

    2011-09-01

    To investigate the effects of curcumin on the behavior of chronic constrictive injury (CCI) rats and the CX3CR1 expression in spinal cord dorsal horn and dorsal root ganglia (DRG). Seventy-two male SD rats were randomly divided into 4 groups: 1) Sham operation group (Sham); 2) Chronic constrictive injury group (CCI); 3) Curcumin treated group (Cur), administrated with curcumin 100 mg x kg(-1) x d(-1) ip for 14 days after CCI; 4) Solvent contrast group (SC), administrated with an equal volume of solvent for 14 days after CCI. Paw thermal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) were measured on 2 pre-operative and 1, 3, 5, 7, 10, 14 post-operative days respectively. The lumbar segments L4-5 of the spinal cord and the L4, L5 DRG were removed at 3, 7, 14 days after surgery. The expression of CX3CR1 was determined by immunohistochemical staining. Compared with Sham group, PTWL and PMWT in CCI group were significantly lower on each post-operative day (PDRG. In Cur group, PTWL were higher than in CCI group on 7, 10, 14 post-operative day (Pdorsal root ganglia.

  13. Combined effects of rat Schwann cells and 17β-estradiol in a spinal cord injury model.

    Science.gov (United States)

    Namjoo, Zeinab; Moradi, Fateme; Aryanpour, Roya; Piryaei, Abbas; Joghataei, Mohammad Taghi; Abbasi, Yusef; Hosseini, Amir; Hassanzadeh, Sajad; Taklimie, Fatemeh Ranjbar; Beyer, Cordian; Zendedel, Adib

    2018-04-15

    Spinal cord injury (SCI) is a devastating traumatic event which burdens the affected individuals and the health system. Schwann cell (SC) transplantation is a promising repair strategy after SCI. However, a large number of SCs do not survive following transplantation. Previous studies demonstrated that 17β-estradiol (E2) protects different cell types and reduces tissue damage in SCI experimental animal model. In the current study, we evaluated the protective potential of E2 on SCs in vitro and investigated whether the combination of hormonal and SC therapeutic strategy has a better effect on the outcome after SCI. Primary SC cultures were incubated with E2 for 72 h. In a subsequent experiment, thoracic contusion SCI was induced in male rats followed by sustained administration of E2 or vehicle. Eight days after SCI, DiI-labeled SCs were transplanted into the injury epicenter in vehicle and E2-treated animals. The combinatory regimen decreased neurological and behavioral deficits and protected neurons and oligodendrocytes in comparison to vehicle rats. Moreover, E2 and SC significantly decreased the number of Iba-1+ (microglia) and GFAP + cells (astrocyte) in the SCI group. In addition, we found a significant reduction of mitochondrial fission-markers (Fis1) and an increase of fusion-markers (Mfn1 and Mfn2) in the injured spinal cord after E2 and SC treatment. These data demonstrated that E2 protects SCs against hypoxia-induced SCI and improves the survival of transplanted SCs.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

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

    2010-11-01

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

  16. γ-diketone central neuropathy: quantitative morphometric analysis of axons in rat spinal cord white matter regions and nerve roots

    International Nuclear Information System (INIS)

    LoPachin, Richard M.; Jortner, Bernard S.; Reid, Maria L.; Das, Soma

    2003-01-01

    A quantitative analytical method was used to measure myelinated axon morphometric parameters (e.g., axon area, ratio of axon area/fiber area, and index of circularity) in rat nervous tissue during intoxication with 2,5-hexanedione (HD). Parameters were assessed in nerve roots (dorsal and ventral) and in ascending (gracile fasciculus and spinocerebellar tract) and descending (corticospinal and rubrospinal tracts) spinal cord white matter tracts (L4-L5) of rats intoxicated with HD at two different daily dose-rates (175 or 400 mg HD/kg/day, gavage). For each dose-rate, tissue was sampled at four neurological endpoints: unaffected, slight, moderate, and severe toxicity, as determined by gait analysis and measurements of grip strength. Results indicate that, regardless of the HD dose-rate, axon atrophy (reduced axon area) was a widespread, abundant effect that developed in concert with neurological deficits. The atrophy response occurred contemporaneously in both ascending and descending spinal tracts, which suggests that loss of caliber developed simultaneously along the proximodistal axon axis. In contrast, swollen axons were a numerically small component and were present in nerve roots and spinal tracts only during subchronic intoxication at the lower HD dose-rate (i.e., 175 mg/kg/day). Intoxication at the higher dose-rate (400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. These observations in conjunction with our previous studies of HD-induced peripheral neuropathy (Toxicol. Appl. Pharmacol. 135 (1995) 58; and Toxicol. Appl. Pharmacol. 165 (2000) 127) indicate that axon atrophy, and not axonal swelling, is a primary neuropathic phenomenon

  17. Subdural infusion of dexamethasone inhibits leukomyelitis after acute spinal cord injury in a rat model

    Czech Academy of Sciences Publication Activity Database

    Kwiecien, J. M.; Jarocz, B.; Urdzíková, Lucia; Rola, R.; Dabrowski, W.

    2015-01-01

    Roč. 53, č. 1 (2015), s. 41-51 ISSN 1641-4640 Institutional support: RVO:68378041 Keywords : spinal cord injury * leukomyelitis * macrophage s * subdural infusion * dexamethasone Subject RIV: FH - Neurology Impact factor: 1.233, year: 2015

  18. Feasibility of Diffusion Tensor Imaging for Assessing Functional Recovery in Rats with Olfactory Ensheathing Cell Transplantation After Contusive Spinal Cord Injury (SCI).

    Science.gov (United States)

    Gu, Mengchao; Gao, Zhengchao; Li, Xiaohui; Zhao, Feng; Guo, Lei; Liu, Jiantao; He, Xijing

    2017-06-17

    BACKGROUND Olfactory ensheathing cell transplantation is a promising treatment for spinal cord injury. Diffusion tensor imaging has been applied to assess various kinds of spinal cord injury. However, it has rarely been used to evaluate the beneficial effects of olfactory ensheathing cell transplantation. This study aimed to explore the feasibility of diffusion tensor imaging in the evaluation of functional recovery in rats with olfactory ensheathing cell transplantation after contusive spinal cord injury. MATERIAL AND METHODS Immunofluorescence staining was performed to determine the purity of olfactory ensheathing cells. Rats received cell transplantation at week 1 after injury. Basso, Beattie, and Bresnahan score was used to assess the functional recovery. Magnetic resonance imaging was applied weekly, including diffusion tensor imaging. Diffusion tensor tractography was reconstructed to visualize the repair process. RESULTS The results showed that olfactory ensheathing cell transplantation increased the functional and histological recovery and restrained the secondary injury process after the initial spinal cord injury. The fractional anisotropy values in rats with cell transplantation were significantly higher than those in the control group, while the apparent diffusion coefficient values were significantly lower. Basso, Beattie, and Bresnahan score was positively and linearly correlated with fractional anisotropy value, and it was negatively and linearly correlated with apparent diffusion coefficient value. CONCLUSIONS These findings suggest that diffusion tensor imaging parameters are sensitive biomarker indices for olfactory ensheathing cell transplantation interventions, and diffusion tensor imaging scan can reflect the functional recovery promoted by the olfactory ensheathing cell transplantation after contusive spinal cord injury.

  19. Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats

    OpenAIRE

    Kim, Jae Hwan; Kim, Jae Young; Mun, Chin Hee; Suh, Minah; Lee, Jong Eun

    2017-01-01

    Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macropha...

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

    Directory of Open Access Journals (Sweden)

    Shang Yuze

    2008-04-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

  2. Post-spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG.

    Science.gov (United States)

    Povysheva, Tatyana; Shmarov, Maksim; Logunov, Denis; Naroditsky, Boris; Shulman, Ilya; Ogurcov, Sergey; Kolesnikov, Pavel; Islamov, Rustem; Chelyshev, Yuri

    2017-07-01

    OBJECTIVE The most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor ( VEGF) and angiogenin ( ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI. METHODS Spinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction. RESULTS Partial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal

  3. Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase activity in inflammatory hyperalgesia

    OpenAIRE

    Gregus, Ann M.; Dumlao, Darren S.; Wei, Spencer C.; Norris, Paul C.; Catella, Laura C.; Meyerstein, Flore G.; Buczynski, Matthew W.; Steinauer, Joanne J.; Fitzsimmons, Bethany L.; Yaksh, Tony L.; Dennis, Edward A.

    2013-01-01

    Previously, we observed significant increases in spinal 12-lipoxygenase (LOX) metabolites, in particular, hepoxilins, which contribute to peripheral inflammation-induced tactile allodynia. However, the enzymatic sources of hepoxilin synthase (HXS) activity in rats remain elusive. Therefore, we overexpressed each of the 6 rat 12/15-LOX enzymes in HEK-293T cells and measured by LC-MS/MS the formation of HXB3, 12-HETE, 8-HETE, and 15-HETE from arachidonic acid (AA) at baseline and in the presenc...

  4. Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

    Science.gov (United States)

    Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

    2018-01-01

    Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the

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

    Directory of Open Access Journals (Sweden)

    Guillon Hélène

    2011-10-01

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

  6. Some behavioral aspects of adult rats irradiated prenatally

    International Nuclear Information System (INIS)

    Vekovishcheva, O.Yu.; Blagova, O.E.; Borovitskaya, A.E.; Evtushenko, V.I.; Khanson, K.P.

    1992-01-01

    This is a study of the effects of prenatal irradiation on the behavior of rats. The experiments were performed on 42 eighteen month old rats of both sexes. Eight of the males and thirteen females had been irradiated prenatally. The results of this experiment indicated that in general, the activation of behavior, the appearance of aggression and the increase in chaos along with the presence of behavior poses were typical of the suppressed condition of the prenatal irradiated animal. Also, among prenatally irradiated animals, there was a greater degree of anxiety, a slow rate of adjustment to unfamiliar situations and unfriendly relationships between animals of the same sex. These results were compared with the results of behavioral experiments on irradiated adult rats

  7. Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R

    1990-01-01

    Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... of epitopes recognized by these MAb. The ubiquitous presence of these epitopes in the basement membranes of nearly all adult rat tissues demonstrates that at least one CSPG is a constituent of most basement membranes, and by virtue of its unique distribution is distinct from other chondroitin and dermatan...

  8. Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: an in vivo electrophysiological study.

    Science.gov (United States)

    Dalmolin, Gerusa D; Bannister, Kirsty; Gonçalves, Leonor; Sikandar, Shafaq; Patel, Ryan; Cordeiro, Marta do Nascimento; Gomez, Marcus Vinícius; Ferreira, Juliano; Dickenson, Anthony H

    2017-07-01

    Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Tx3-3 (0.3-100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Aδ-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

  9. Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

    Directory of Open Access Journals (Sweden)

    L. D. Wang

    2016-01-01

    Full Text Available Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

  10. [Effect of electroacupuncture on phosphorylation of NR2B at Tyr 1742 site in the spinal dorsal horn of CFA rats].

    Science.gov (United States)

    Liang, Yi; Fang, Jian-Qiao; Fang, Jun-Fan; Du, Jun-Ying; Qiu, Yu-Jie; Liu, Jin

    2013-10-01

    To observe the effect of electroacupuncture (EA) on phosphorylation of spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly divided into normal group (N group, n = 10), the model group (CFA group, n = 15), and the EA group (n = 15). The inflammatory pain model was established by subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day post-injection were detected using immunohistochemical assay. PWTs in the CFA group were significantly lower than those of the N group at every detective time point post-injection (P CFA group at 25 h and 3rd day post-injection (P CFA group was up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA group. EA might effectively inhibit CFA-induced inflammatory pain possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn.

  11. Protective effects of Naringin in a rat model of spinal cord ischemia ...

    African Journals Online (AJOL)

    generation and downregulating inflammatory markers in an SCI rat model. Keywords: Naringin ... intestinal microflora to yield a metabolite called naringenin ... disease (PD). Moreover .... CAT was significantly reduced in SCII rats compared ...

  12. Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

    Science.gov (United States)

    Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

    2010-01-01

    Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

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

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Amaral Barreto

    2015-06-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Farah M. Shroff

    2015-01-01

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

  16. Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex.

    Science.gov (United States)

    Sikandar, Shafaq; West, Steven J; McMahon, Stephen B; Bennett, David L; Dickenson, Anthony H

    2017-07-01

    Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes. © 2017 University College London. Physiological Reports published by Wiley Periodicals

  17. Supraspinal and spinal effects of L-trans-PDC, an inhibitor of glutamate transporter, on the micturition reflex in rats.

    Science.gov (United States)

    Honda, Masashi; Yoshimura, Naoki; Hikita, Katsuya; Hinata, Nobuyuki; Muraoka, Kuniyasu; Saito, Motoaki; Chancellor, Michael B; Takenaka, Atsushi

    2013-09-01

    Glutamate is a major excitatory transmitter in the central nervous system, controlling lower urinary tract function. Five types of glutamate transporters such as GLAST (EAAT1), GLT-1 (EAAT2), EAAC-1 (EAAT3), EAAT4, and EAAT5 have been cloned so far. In the current study we tested whether L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), a non-selective inhibitor of glutamate transporters that increases endogenous glutamate concentration, can affect the micturition reflex in urethane anesthetized rats. Continuous cystometrograms (CMG, 0.04 ml/min infusion rate) were performed in two groups of urethane-anesthetized rats. A group of 18 rats was used for intrathecal administration of 1-10 µg of L-trans-PDC via an intrathecal catheter. In the second group of 18 rats, 1-10 µg of L-trans-PDC were administered intracerebroventricularly via a catheter inserted into the lateral ventricle. Micturition parameters were recorded and compared before and after drug administration. Intrathecal administration of L-trans-PDC at 1, 3, and 10 µg (n = 6 per dose) increased intercontraction intervals in dose dependent fashion, but did not affect postvoid residual or basal pressure at any doses tested. Intracerebroventricular administration of L-trans-PDC at 1, 3, and 10 µg (n = 6 per dose) also increased intercontraction intervals in dose dependent fashion, but did not affect postvoid residual or basal pressure at any doses tested. The current results show that, in urethane-anesthetized rats, suppression of glutamate transporters by L-trans-PDC has an inhibitory effect on the micturition reflex at supraspinal and spinal sites, possibly via activation of glutamate-mediated inhibitory pathways. Copyright © 2012 Wiley Periodicals, Inc.

  18. Tailless-like (TLX) protein promotes neuronal differentiation of dermal multipotent stem cells and benefits spinal cord injury in rats.

    Science.gov (United States)

    Wang, Tao; Ren, Xiaobao; Xiong, Jianqiong; Zhang, Lei; Qu, Jifu; Xu, Wenyue

    2011-04-01

    Spinal cord injury (SCI) remains a formidable challenge in the clinic. In the current study, we examined the effects of the TLX gene on the proliferation and neuronal differentiation of dermal multipotent stem cells (DMSCs) in vitro and the potential of these cells to improve SCI in rats in vivo. DMSCs were stably transfected with TLX-expressing plasmid (TLX/DMSCs). Cell proliferation was examined using the MTT assay, and neuronal differentiation was characterized by morphological observation combined with immunocytochemical/immunofluorescent staining. The in vivo functions of these cells were evaluated by transplantation into rats with SCI, followed by analysis of hindlimb locomotion and post-mortem histology. Compared to parental DMSCs, TLX/DMSCs showed enhanced proliferation and preferential differentiation into NF200-positive neurons in contrast to GFAP-positive astrocytes. When the undifferentiated cells were transplanted into rats with SCI injury, TLX/DMSCs led to significant improvement in locomotor recovery and healing of SCI, as evidenced by reduction in scar tissues and cavities, increase in continuous nerve fibers/axons and enrichment of NF200-positive neurons on the histological level. In conclusion, TLX promotes the proliferation and neuronal differentiation of DMSCs and thus, may serve as a promising therapy for SCI in the clinic.

  19. High dose rate (HDR) and low dose rate (LDR) interstitial irradiation (IRT) of the rat spinal cord

    International Nuclear Information System (INIS)

    Pop, Lucas A.M.; Plas, Mirjam van der; Skwarchuk, Mark W.; Hanssen, Alex E.J.; Kogel, Albert J. van der

    1997-01-01

    Purpose: To describe a newly developed technique to study radiation tolerance of rat spinal cord to continuous interstitial irradiation (IRT) at different dose rates. Material and methods: Two parallel catheters are inserted just laterally on each side of the vertebral bodies from the level of Th 10 to L 4 . These catheters are afterloaded with two 192 Ir wires of 4 cm length each (activity 1-2.3 mCi/cm) for the low dose rate (LDR) IRT or connected to the HDR micro-Selectron for the high dose rate (HDR) IRT. Spinal cord target volume is located at the level of Th 12 -L 2 . Due to the rapid dose fall-off around the implanted sources, a dose inhomogeneity across the spinal cord thickness is obtained in the dorso-ventral direction. Using the 100% reference dose (rate) at the ventral side of the spinal cord to prescribe the dose, experiments have been carried out to obtain complete dose response curves at average dose rates of 0.49, 0.96 and 120 Gy/h. Paralysis of the hind-legs after 5-6 months and histopathological examination of the spinal cord of each irradiated rat are used as experimental endpoints. Results: The histopathological damage seen after irradiation is clearly reflected the inhomogeneous dose distribution around the implanted catheters, with the damage predominantly located in the dorsal tract of the cord or dorsal roots. With each reduction in average dose rate, spinal cord radiation tolerance is significantly increased. When the dose is prescribed at the 100% reference dose rate, the ED 50 (induction of paresis in 50% of the animals) for the HDR-IRT is 17.3 Gy. If the average dose rate is reduced from 120 Gy/h to 0.96 or 0.49 Gy/h, a 2.9- or 4.7-fold increase in the ED 50 values to 50.3 Gy and 80.9 Gy is observed; for the dose prescribed at the 150% reference dose rate (dorsal side of cord) ED 50 values are 26.0, 75.5 and 121.4 Gy, respectively. Using different types of analysis and in dependence of the dose prescription and reference dose rate, the

  20. 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.

  1. 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.

  2. 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.

  3. Optimization of low-level light therapy's illumination parameters for spinal cord injury in a rat model

    Science.gov (United States)

    Shuaib, Ali; Bourisly, Ali

    2018-02-01

    Spinal cord injury (SCI) can result in complete or partial loss of sensation and motor function due to interruption along the severed axonal tract(s). SCI can result in tetraplegia or paraplegia, which can have prohibitive lifetime medical costs and result in shorter life expectancy. A promising therapeutic technique that is currently in experimental phase and that has the potential to be used to treat SCI is Low-level light therapy (LLLT). Preclinical studies have shown that LLLT has reparative and regenerative capabilities on transected spinal cords, and that LLLT can enhance axonal sprouting in animal models. However, despite the promising effects of LLLT as a therapy for SCI, it remains difficult to compare published results due to the use of a wide range of illumination parameters (i.e. different wavelengths, fluences, beam types, and beam diameter), and due to the lack of a standardized experimental protocol(s). Before any clinical applications of LLLT for SCI treatment, it is crucial to standardize illumination parameters and efficacy of light delivery. Therefore, in this study we aim to evaluate the light fluence distribution on a 3D voxelated SCI rat model with different illumination parameters (wavelengths: 660, 810, and 980 nm; beam types: Gaussian and Flat; and beam diameters: 0.1, 0.2, and 0.3 cm) for LLLT using Monte Carlo simulation. This study provides an efficient approach to guide researchers in optimizing the illumination parameters for LLLT spinal cord injury in an experimental model and will aid in quantitative and qualitative standardization of LLLT-SCI treatment.

  4. Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord

    Directory of Open Access Journals (Sweden)

    Guiqin Zhu

    2016-01-01

    Full Text Available Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI in rat tibia (TCI cancer pain model. Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy. Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG was detected by RT-PCR. Concentrations of cAMP, IL-1β, and TNF-α as well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1β and TNF-α in the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.

  5. Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats.

    Science.gov (United States)

    Li, Ye; Hu, Haifeng; Liu, Jingchen; Zhu, Qingsan; Gu, Rui

    2018-02-01

    To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP-treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet-dry weights method was applied to measure the water content of the spinal cord. The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues.

  6. HDR- and LDR-interstitial irradiation (IRT) in rat spinal cord: the effect of decreasing the dose rate and the impact of a rapid dose fall off over the spinal cord

    International Nuclear Information System (INIS)

    Pop, L.A.M.; Plas, M. van der; Hanssen, A.E.J.; Kogel, A.J. van der

    1996-01-01

    Introduction: Detailed knowledge of radiobiological parameters of the different tissues involved are warranted before HDR- and recently PDR-brachytherapy can be successfully introduced in clinical practice as an alternative to LDR- brachytherapy. The purpose of this study is to determine the α/β ratio and half time of repair of rat spinal cord during continuous irradiation at different dose rates and to investigate the impact of a rapid dose fall off over the spinal cord thickness. Material and methods: Two parallel catheters are inserted on each side of the vertebral bodies from the level of Th 10 to L 4 . These catheters were afterloaded with two 192 Ir- wires of 4 cm length each (activity 1- 10 mCi/cm) or connected to the HDR-microSelectron. Serial experiments have been carried out to obtain complete dose response curves at 5 different dose rates, resp. 0.5, 0.9, 1.6, 2.6 and 120 Gy/h. Paralysis of the hindlegs after 5-6 months and histopathological examination of the spinal cord of each animal are used as experimental endpoints. Dose-volume histograms of each irradiated rat have been analysed to evaluate the correlation between dose distribution and biological response and the histopathological damage seen. Results: The distribution of the histological damage was a good reflection of the rapid dose fall-off over the spinal cord, with white matter necrosis or demyelination predominantly seen in the dorsal tracts of the spinal cord or dorsal roots. With each reduction of the dose rate, spinal cord tolerance was significantly increased, with a maximum dose rate factor of 4.3 if the dose rate was reduced from 120 Gy/h to 0.53 Gy/h. Estimates of the repair parameters using different types of analysis revealed an α/β ratio of 2.44 Gy and a (mono- exponential) half time of repair (=t (1(2)) ) of 1.43 hours; for the maximum of 150 % of the prescribed dose these values were 3.67 Gy and 1.43 hours respectively. Conclusions: Spinal cord radiation tolerance is

  7. Activation of Spinal α2-Adrenoceptors Using Diluted Bee Venom Stimulation Reduces Cold Allodynia in Neuropathic Pain Rats

    Directory of Open Access Journals (Sweden)

    Suk-Yun Kang

    2012-01-01

    Full Text Available Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV reduced cold allodynia in sciatic nerve chronic constriction injury (CCI rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg was performed into Zusanli acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg was injected for 2 weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low dose (0.25 mg/kg did not produce any anticold allodynic effect, while a high dose of DBV (2.5 mg/kg significantly reduced cold allodynia. Moreover, this effect of high-dose DBV was completely blocked by intrathecal pretreatment of idazoxan (α2-adrenoceptor antagonist, but not prazosin (α1-adrenoceptor antagonist or propranolol (nonselective β-adrenoceptor antagonist. In addition, coadministration of low-dose DBV (0.25 mg/kg and intrathecal clonidine (α2-adrenoceptor agonist synergically reduced cold allodynia. On the other hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably suppressed cold allodynia from 7 days after DBV treatment. This effect was also reversed by intrathecal idazoxan injection. These findings demonstrated that single or repetitive stimulation of DBV could alleviate CCI-induced cold allodynia via activation of spinal α2-adrenoceptor.

  8. Functional exploration of the thyroid gland on the rat at the third day after a spinal section at high level

    International Nuclear Information System (INIS)

    Agnius-Delord, C.; Caine, S.; Tanche, M.; Rinaldi, R.

    1969-01-01

    We have studied on animals having two different diets, the one with iodine, the other without iodine, the influence of a spinal section at high level on the thyroid fixation, this latter being measured after an injection of iodine 131 carried out 72 h after the section. In this case, and for all animals, our results show an increase of the thyroid fixation with regard to the control animals. However this increase is not significant; only is significant the difference between the rates of fixation for the injections carried out 15 mn and 24 h after section and these measured 48 h and 72 h after section. Concerning the hormonal discharge, it is always significantly decreased with regard to the controls, as we had found it for the animals treated 15 mn, 24 h and 48 h after section. We have also entered upon a study of the thyroid fixation and of the hormonal discharge on rats subjected to a simple laminectomy at level where are effected the spinal sections. Yet the results obtained have not permitted us to display significant differences between the control animals and the animals subjected to such an operation. (authors) [fr

  9. Biochemical Monitoring of Spinal Cord Injury by FT-IR Spectroscopy—Effects of Therapeutic Alginate Implant in Rat Models

    Science.gov (United States)

    Uckermann, Ortrud; Sitoci-Ficici, Kerim H.; Later, Robert; Beiermeister, Rudolf; Doberenz, Falko; Gelinsky, Michael; Leipnitz, Elke; Schackert, Gabriele; Koch, Edmund; Sablinskas, Valdas; Steiner, Gerald; Kirsch, Matthias

    2015-01-01

    Spinal cord injury (SCI) induces complex biochemical changes, which result in inhibition of nervous tissue regeneration abilities. In this study, Fourier-transform infrared (FT-IR) spectroscopy was applied to assess the outcomes of implants made of a novel type of non-functionalized soft calcium alginate hydrogel in a rat model of spinal cord hemisection (n = 28). Using FT-IR spectroscopic imaging, we evaluated the stability of the implants and the effects on morphology and biochemistry of the injured tissue one and six months after injury. A semi-quantitative evaluation of the distribution of lipids and collagen showed that alginate significantly reduced injury-induced demyelination of the contralateral white matter and fibrotic scarring in the chronic state after SCI. The spectral information enabled to detect and localize the alginate hydrogel at the lesion site and proved its long-term persistence in vivo. These findings demonstrate a positive impact of alginate hydrogel on recovery after SCI and prove FT-IR spectroscopic imaging as alternative method to evaluate and optimize future SCI repair strategies. PMID:26559822

  10. Biochemical Monitoring of Spinal Cord Injury by FT-IR Spectroscopy--Effects of Therapeutic Alginate Implant in Rat Models.

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    Sandra Tamosaityte

    Full Text Available Spinal cord injury (SCI induces complex biochemical changes, which result in inhibition of nervous tissue regeneration abilities. In this study, Fourier-transform infrared (FT-IR spect