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  1. Positron emission tomography for serial imaging of the contused adult rat spinal cord.

    NARCIS (Netherlands)

    Nandoe, R.D.S.; Yu, J.; Seidel, J.; Rahiem, S.T.; Hurtado, A.; Tsui, B.M.; Grotenhuis, J.A.; Pomper, M.G.; Oudega, M.

    2010-01-01

    We investigated whether small-animal positron emission tomography (PET) could be used in combination with computed tomography (CT) imaging techniques for longitudinal monitoring of the injured spinal cord. In adult female Sprague-Dawley rats (n = 6), the ninth thoracic (T9) spinal cord segment was e

  2. Repair of acutely injured spinal cord through constructing tissue-engineered neural complex in adult rats

    Institute of Scientific and Technical Information of China (English)

    PU Yu; GUO Qing-shan; WANG Ai-min; WU Si-yu; XING Shu-xing; ZHANG Zhong-rong

    2007-01-01

    Objective: To construct tissue-engineered neural complex in vitro and study its effect in repairing acutely injured spinal cord in adult rats. Methods: Neural stem cells were harvested from the spinal cord of embryo rats and propagated in vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds and co-cultured with extract of embryonic spinal cord in vitro. Immunofluorescence histochemistry and scanning electron microscope were used to observe the microstructure of this complex. Animal model of spine semi-transection was made and tissue-engineered neural complex was implanted by surgical intervention. Six weeks after transplantation, functional evaluation and histochemistry were applied to evaluate the functional recovery and anatomic reconstruction. Results: The tissue-engineered neural complex had a distinct structure, which contained neonatal neurons, oligodendrocytes and astrocytes. After tissue-engineered neural complex was implanted into the injured spinal cord, the cell components such as neurons, astrocytes and oligodendrocytes, could survive and keep on developing. The adult rats suffering from spinal cord injury got an obvious neurological recovery in motor skills. Conclusions: The tissue-engineered neural complex appears to have therapeutic effects on the functional recovery and anatomic reconstruction of the adult rats with spinal cord injury.

  3. Influences of olfactory ensheathing cells transplantation on axonal regeneration in spinal cord of adult rats

    Institute of Scientific and Technical Information of China (English)

    沈慧勇; 唐勇; 吴燕峰; 陈燕涛; 程志安

    2002-01-01

    To observe whether olfactory ensheathing cells could be used to promote axonal regeneration in a spontaneously nonregenerating system. Methods: After laminectomy at the lower thoracic level, the spinal cords of adult rats were exposed and completely transected at T10. A suspension of ensheathing cells was injected into the lesion site in 12 adult rats, and control D/F-12 (1∶1 mixture of DMEM and Hams F-12) was injected in 12 adult rats. Six weeks and ten weeks after cell transplantation, the rats were evaluated by climbing test and motor evoked potentials (MEPs) monitoring. The samples were procured and studied with histologicl and immunohistochemical methods. Results: At the 6th week after cell transplantation, all the rats in both the transplanted and control groups were paraplegic and the MEPs could not be recorded. At the 10th week after cell transplantation, of 7 rats in the control group, 2 rats had muscles contraction of the lower extremities, 2 rats had hips and/or knees active movement; and 5 rats MEPs could be recorded in the hind limbs in the transplanted group (n=7). None of the rats in the control group had functional improvement and no MEPs recorded (n=7). Numerous regenerating axons were observed through the transplantation and continued to regenerate into the denervated host tract. Cell labelling using anti-Myelin Basic Protein (MBP) and anti-Nerve Growth Factor Receptor (anti-NGFR) indicated that the regenerated axons were derived from the appropriate neuronal source and that donor cells migrated into the denervated host tract. But axonal degeneration existed and regenerating axons were not observed within the spinal cords of the adult rats with only D/F-12 injection. Conclusions: The axonal regeneration in the transected adult rat spinal cord is possible after ensheathing cells transplantation.

  4. Differentiation of endogenous neural precursors following spinal cord injury in adult rats

    Institute of Scientific and Technical Information of China (English)

    Bin Zhao; Hua Han; Shuanke Wang; Bingren Gao; Zhengyi Sun

    2008-01-01

    BACKGROUND:Studies have shown that cell death can activate proliferation of endogenous neural stem cells and promote newly generated cells to migrate to a lesion site.OBJECTIVE:To observe regeneration and differentiation of neural cells following spinal cord injury in adult rats and to quantitatively analyze the newly differentiated cells.DESIGN,TIME AND SETTING:A cell biology experiment was performed at the Institute of Orthopedics and Medical Experimental Center,Lanzhou University.between August 2005 and October 2007.MATERIALS:Fifty adult,Wistar rats of both sexes;5-bromodeoxyuridine(BrdU,Sigma,USA);antibodies against neuron-specific enolase,glial fibrillary acidic protein,and myelin basic protein(Chemicon,USA).METHODS:Twenty-five rats were assigned to the spinal cord injury group and received a spinal cord contusion injury.Materials were obtained at day 1,3,7,15,and 29 after injury,with 5 rats for each time point.Twenty-five rats were sham-treated by removing the lamina of the vertebral arch without performing a contusion.MAIN OUTCOME MEASURES:The phenotype of BrdU-labeled cells,i.e.,expression and distribution of surface markers for neurons(neuron-specific enolase),astrocytes(glial fibrillary acidic protein),and oligodendrocytes(myelin basic protein),were identified with immunofluorescence double-labeling.Confocal microscopy was used to detect double-labeled cells by immunofluorescence.Quantitative analysis of newly generated cells was performed with stereological counting methods.RESULTS:There was significant cell production and differentiation after adult rat spinal cord injury.The quantity of newly-generated BrdU-labeled cells in the spinal cord lesion was 75-fold greater than in the corresponding area of control animals.Endogenous neural precursor cells differentiated into astrocytes and oligodendrocytes,however spontaneous neuronal difierentiation was not detected.Between 7 and 29 d after spinal cord injury,newly generated cells expressed increasingly more

  5. Ependymal cell proliferation and apoptosis following acute spinal cord injury in the adult rat

    Institute of Scientific and Technical Information of China (English)

    Xu Wang; Jun Qian; Yanchao Ma; Guoxin Nan; Shuanke Wang; Yayi Xia; Youcheng Zhang

    2008-01-01

    BACKGROUND: Studies have reported that spinal cord injury can induce the reactive proliferation of ependymal cells and secondarily cause the apoptosis of nerve cells. However, there is no generally accepted theory on the apoptotic characteristics of ependymal cells in the injured spinal cord.OBJECTIVE: To observe the reactive proliferation and apoptosis of ependymal cells in adult rats following acute spinal cord injury.DESIGN, TIME AND SETTING: A randomized control study based on neuropathology was performed in the Third Military Medical University of Chinese PLA between 2005 and 2007.MATERIALS: Forty healthy, adult, Wistar rats were included in the present study.METHODS: Moderate spinal cord injury was established in twenty rats using Feeney's method, while the remaining 20 rats served as controls and were only treated with laminectomy. All rats were injected intraperitoneally with 1.25 mL of BrdU solution (10 mg BrdU/mL saline) 3 times at 4 hours intervals during the 12 hours prior to sacrifice.MAIN OUTCOME MEASURES: Ependymal cell proliferation and apoptosis in the rat spinal cord were determined by BrdU and nestin immunofluorescence double-labeling, as well as the TUNEL method, at 1, 3, 7, and 14 days after operation.RESULTS: In the moderate spinal cord injury rats, nestin expression was observed in the cytoplasm of ependymal cells. One day immediately following surgery, ependymal cells were BrdU-labeled. The number of BrdU-positive cells increased at 3 days, reached a peak at 7 days, and gradually reduced thereafter. The ependyma developed ti'om a constitutive monolayer cells to a multi-layer cell complex. Some BrdU/Nestin double-positive ependymal cells migrated out from the ependyma. TUNEL-positive cells were also detected in the ependyma in the central region, as well as ischemic regions of the injured spinal cord. In addition, TUNEL-positive cells were visible in the ependyma. No TUNEL-positive ependymal cells were observed in the normal spinal cord

  6. Influence of rat substrain and growth conditions on the characteristics of primary cultures of adult rat spinal cord astrocytes.

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    Codeluppi, Simone; Gregory, Ebba Norsted; Kjell, Jacob; Wigerblad, Gustaf; Olson, Lars; Svensson, Camilla I

    2011-04-15

    Primary astrocyte cell cultures have become a valuable tool for studies of signaling pathways that regulate astrocyte physiology, reactivity, and function; however, differences in culture preparation affect data reproducibility. The aim of this work was to define optimal conditions for obtaining primary astrocytes from adult rat spinal cord with an expression profile most similar to adult human spinal cord astrocytes. Hence, we examined whether different Sprague-Dawley substrains and culture conditions affect astrocyte culture quality. Medium supplemented with fetal bovine serum from three sources (Sigma, Gibco, Hyclone) or a medium with defined composition (AM medium) was used to culture astrocytes isolated from spinal cords of adult Harlan and Charles River Spraque-Dawley rats. Purity was significantly different between cultures established in media with different sera. No microglia were detected in AM or Hyclone cultures. Gene expression was also affected, with AM cultures expressing the highest level of glutamine synthetase, connexin-43, and glutamate transporter-1. Interestingly, cell response to starvation was substrain dependent. Charles River-derived cultures responded the least, while astrocytes derived from Harlan rats showed a greater decrease in Gfap and glutamine synthetase, suggesting a more quiescent phenotype. Human and Harlan astrocytes cultured in AM media responded similarly to starvation. Taken together, this study shows that rat substrain and growth medium composition affect purity, expression profile and response to starvation of primary astrocytes suggesting that cultures of Harlan rats in AM media have optimal astrocyte characteristics, purity, and similarity to human astrocytes.

  7. Stem cells in the adult rat spinal cord: plasticity after injury and treadmill training exercise.

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    Foret, Ariane; Quertainmont, Renaud; Botman, Olivier; Bouhy, Delphine; Amabili, Philippe; Brook, Gary; Schoenen, Jean; Franzen, Rachelle

    2010-02-01

    Ependymal cells located around the central canal of the adult spinal cord are considered as a source of neural stem cells (NSCs) and represent an interesting pool of endogenous stem cells for repair strategies. Physical exercise is known to increase ependymal cell proliferation, while improving functional recovery. In this work, we further characterized those endogenous NSCs within the normal and injured adult rat spinal cord and investigated the effects of treadmill training using immunohistochemical and behavioral studies. In uninjured untrained rats, Sox-2, a NSC marker, was detected in all ependymal cells of the central canal, and also scattered throughout the parenchyma of the spinal cord. Within the lesion, Sox-2 expression increased transiently, while the number of nestin-positive ependymal cells increased with a concomitant enhancement of proliferation, as indicated by the mitotic markers Ki67 and bromo-deoxyuridine. Exercise, which improved functional recovery and autonomous micturition, maintained nestin expression in both injured and uninjured spinal cords, with a positive correlation between locomotor recovery and the number of nestin-positive cells.

  8. EXCITATORY CONNECTIONS BETWEEN SPINAL MOTONEURONS IN THE ADULT RAT

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objectives. Dendro-dendritic and dendro-somatic projections are common between spinal motoneurons. We attempted to clarify whether there are functional connections through these projections.Methods. Motoneurons were antidromically stimulated by the muscle nerve and recorded intracellularly to examine the direct interaction between them, after the related dorsal roots had been cut.Results. Excitatory connections, demonstrated by depolarizing potentials in response to muscle nerve stimulation, were found between motoneurons innervating the same muscle or synergistic muscles, but never between motoneurons innervating antagonistic muscles. These potentials were finely graded in response to a series of increasing stimuli and resistant to high frequency (50Hz) stimulation.Conclusions.These results indicate that excitatory connections, with certain specificity of spatial and temporal distribution, occur in the spinal motoneurons. It is also suggested that electrical coupling should be involved in these connections and this mechanism should improve the excitability of the motoneurons in the same column.

  9. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord.

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    Jun Yan

    2007-02-01

    Full Text Available BACKGROUND: Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC transplants have shown either poor differentiation or a preferential choice of glial lineages. METHODS AND FINDINGS: In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. CONCLUSIONS: NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major

  10. Expression and role of PAK6 after spinal cord injury in adult rat

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    CHEN Xiang-dong

    2012-02-01

    Full Text Available 【Abstract】Objective: To observe p21-activated kinase 6 (PAK6 expression and its possible role after spinal cord injury (SCI in adult rat. Methods: Sprague-Dawley rats were subjected to spinal cord injury. To explore the pathological and physiological significance of PAK6, the expression patterns and distribution of PAK6 were observed by Western blot, immunohistochemistry and immunofluorescence. Results: Western blot analysis showed PAK6 protein level was significantly up-regulated on day 2 and day 4, then reduced and had no up-regulation till day 14. Immunohistochemistry analysis showed that the expression of PAK6 was significantly increased on day 4 compared with the control group. Besides, double immunofluorescence staining showed PAK6 was primarily expressed in the neurons and astrocytes in the control group. While after injury, the expression of PAK6 was increased significantly in the astrocytes and neurons, and the astrocytes were largely proliferated. We also examined the expression of proliferating cell nuclear antigen (PCNA and found its change was correlated with the expression of PAK6. Importantly, double immunofluorescence staining revealed that cell proliferation evaluated by PCNA appeared in many PAK6-expressing cells on day 4 after injury. Conclusion: The up-regulation of PAK6 in the injured spinal cord may be associated with glial proliferation. Key words: PAK6 protein, human; p21-activated kinases; Spinal cord injury; Astrocytes

  11. Vascularized peripheral nerve trunk autografted in the spinal cord: a new experimental model in adult rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the effect of vascularized peripheral nerve trunk autografted in spinal cord. Methods: With modern microsurgical technique,vascularized peripheral median and ulnar nerve trunk autografted in the upper thoracic region of the spinal cord were established in 20 female adult rats. The origin and the termination of axons in the graft were studied by retrograde neuronal labeling with horseradish peroxidase (HRP).Cord, nerve grafts and some normal median and ulnar nerves in the right upper limb were removed and sectioned for Bielschowsky's silver stain and haematoxylin and eosin (H&E) stain. Light and electron microscopic examination and electrophysiological examination were applied.Results: The grafts were innervated by many new fibers. Studies with HRP indicated that new axons in graft were originated from intrinsic central nervous system (CNS) neurons with their cell bodies from brain stem to sacral segments of spinal cord. Other axons arose from dorsal root ganglia at the level of graft and at least 19 distal segments to them. Together with electron microscopy, electrophysiological examination, silver and H&E stain, the results demonstrated that vascularized peripheral nerve trunk grafted in spinal cord attracted many neurons to grow into the nerve grafts.Conclusions: The findings implicate that CNS is able to regenerate much better in vascularized nerve autografted in spinal cord.

  12. 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...

  13. Mechanism of Forelimb Motor Function Restoration after Cervical Spinal Cord Hemisection in Rats: A Comparison of Juveniles and Adults

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    Atsushi Hasegawa

    2016-01-01

    Full Text Available The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS and Forelimb Locomotor Scale (FLS and by measuring the range of motion (ROM of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2±24.7% in juvenile rats and 34.0±19.8% in adult rats. FLS was 60.4±26.8% in juvenile rats and 46.5±26.9% in adult rats. ROM of the elbow and wrist were 88.9±20.6% and 44.4±24.1% in juvenile rats and 70.0±29.2% and 40.0±21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats.

  14. Response of ependymal progenitors to spinal cord injury or enhanced physical activity in adult rat.

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    Cizkova, Dasa; Nagyova, Miriam; Slovinska, Lucia; Novotna, Ivana; Radonak, Jozef; Cizek, Milan; Mechirova, Eva; Tomori, Zoltan; Hlucilova, Jana; Motlik, Jan; Sulla, Igor; Vanicky, Ivo

    2009-09-01

    Ependymal cells (EC) in the spinal cord central canal (CC) are believed to be responsible for the postnatal neurogenesis following pathological or stimulatory conditions. In this study, we have analyzed the proliferation of the CC ependymal progenitors in adult rats processed to compression SCI or enhanced physical activity. To label dividing cells, a single daily injection of Bromo-deoxyuridine (BrdU) was administered over a 14-day-survival period. Systematic quantification of BrdU-positive ependymal progenitors was performed by using stereological principles of systematic, random sampling, and optical Dissector software. The number of proliferating BrdU-labeled EC increased gradually with the time of survival after both paradigms, spinal cord injury, or increased physical activity. In the spinal cord injury group, we have found 4.9-fold (4 days), 7.1-fold (7 days), 4.9-fold (10 days), and 5.6-fold (14 days) increase of proliferating EC in the rostro-caudal regions, 4 mm away from the epicenter. In the second group subjected to enhanced physical activity by running wheel, we have observed 2.1-2.6 fold increase of dividing EC in the thoracic spinal cord segments at 4 and 7 days, but no significant progression at 10-14 days. Nestin was rapidly induced in the ependymal cells of the CC by 2-4 days and expression decreased by 7-14 days post-injury. Double immunohistochemistry showed that dividing cells adjacent to CC expressed astrocytic (GFAP, S100beta) or nestin markers at 14 days. These data demonstrate that SCI or enhanced physical activity in adult rats induces an endogenous ependymal cell response leading to increased proliferation and differentiation primarily into macroglia or cells with nestin phenotype.

  15. Regulation of neuropilin 1 by spinal cord injury in adult rats.

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    Agudo, Marta; Robinson, Michelle; Cafferty, William; Bradbury, Elizabeth J; Kilkenny, Carol; Hunt, Stephen P; McMahon, Stephen B

    2005-03-01

    Using RT-PCR, in situ hybridization, Western blotting, and immunofluorescence, we have analyzed the expression of neuropilin 1 (Np1) in two models of spinal cord injury (spinal cord hemisection and dorsal column crush) and following dorsal root rhizotomy in adult rats. Our results show that Np1 RNA and protein are up-regulated in the spinal cord after all these lesions but remain unaltered in the adjacent dorsal root ganglia. In control animals, Np1 levels in the spinal cord are low and appear to be localized mainly in blood vessels, motoneurons, and in the superficial layers of the dorsal horn. After DCC and rhizotomy, Np1 is expressed de novo around the injury and in the deafferentated dorsal horn, respectively, mainly by OX42-positive microglial cells. Both lesions affect the sensory projections, and interestingly a consistent increase of Np1 signal is additionally seen in the dorsal horn where these projections terminate. Unexpectedly, this increase is bilateral after unilateral rhizotomy.

  16. Ependymal cell reactions in spinal cord segments after compression injury in adult rat.

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    Takahashi, Masaki; Arai, Yasuhisa; Kurosawa, Hisashi; Sueyoshi, Noriyoshi; Shirai, Shunichi

    2003-02-01

    Recently, it has been suggested that neural stem cells and neural progenitor cells exist in the ependyma that forms the central canal of the spinal cord. In this study, we produced various degrees of thoracic cord injury in adult rats using an NYU-weight-drop device, assessed the degree of recovery of lower limb motor function based on a locomotor rating scale, and analyzed the kinetics of ependymal cell proliferation and differentiation by proliferating cell nuclear antigen (PCNA), nestin, glial fibrillary acidic protein (GFAP), or GAP-43 immunostaining. The results showed that the time course of the ependymal cell proliferation and differentiation reactions differed according to the severity of injury, and that the responses occurred not only in the neighborhood of the injury but in the entire spinal cord. An increase in the locomotor rating score was related to an increase in the number of PCNA-positive cells, and the differentiation of ependymal cells into reactive astrocytes was involved in injury repair. No apoptotic cells in the ependyma were detectable by the TUNEL method. These results indicate that the ependymal cells of the spinal central canal are themselves multipotent, can divide and proliferate according to the severity of injury, and differentiate into reactive astrocytes within the ependyma without undergoing apoptosis or cell death.

  17. Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult rats

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    Dubner Ronald

    2005-09-01

    Full Text Available Abstract Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan (CAR injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis (using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors to compare gene expression profiles in the lumbar spinal dorsal horn (LDH of adult (P60 male rats that received neonatal CAR treatment within (at postnatal day 3; P3 and outside (at postnatal 12; P12 of the sensitive period. The data were obtained both without inflammation (at baseline and during complete Freund's adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes (representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes (encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems in the LDH ipsilateral to the

  18. Neonatal local noxious insult affects gene expression in the spinal dorsal horn of adult rats.

    Science.gov (United States)

    Ren, Ke; Novikova, Svetlana I; He, Fang; Dubner, Ronald; Lidow, Michael S

    2005-09-22

    Neonatal noxious insult produces a long-term effect on pain processing in adults. Rats subjected to carrageenan (CAR) injection in one hindpaw within the sensitive period develop bilateral hypoalgesia as adults. In the same rats, inflammation of the hindpaw, which was the site of the neonatal injury, induces a localized enhanced hyperalgesia limited to this paw. To gain an insight into the long-term molecular changes involved in the above-described long-term nociceptive effects of neonatal noxious insult at the spinal level, we performed DNA microarray analysis (using microarrays containing oligo-probes for 205 genes encoding receptors and transporters for glutamate, GABA, and amine neurotransmitters, precursors and receptors for neuropeptides, and neurotrophins, cytokines and their receptors) to compare gene expression profiles in the lumbar spinal dorsal horn (LDH) of adult (P60) male rats that received neonatal CAR treatment within (at postnatal day 3; P3) and outside (at postnatal 12; P12) of the sensitive period. The data were obtained both without inflammation (at baseline) and during complete Freund's adjuvant induced inflammation of the neonatally injured paw. The observed changes were verified by real-time RT-PCR. This study revealed significant basal and inflammation-associated aberrations in the expression of multiple genes in the LDH of adult animals receiving CAR injection at P3 as compared to their expression levels in the LDH of animals receiving either no injections or CAR injection at P12. In particular, at baseline, twelve genes (representing GABA, serotonin, adenosine, neuropeptide Y, cholecystokinin, opioid, tachykinin and interleukin systems) were up-regulated in the bilateral LDH of the former animals. The baseline condition in these animals was also characterized by up-regulation of seven genes (encoding members of GABA, cholecystokinin, histamine, serotonin, and neurotensin systems) in the LDH ipsilateral to the neonatally-injured paw. The

  19. 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.)

  20. PRDM5 Expression and Essential Role After Acute Spinal Cord Injury in Adult Rat.

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    Liu, Jie; Wu, Weijie; Hao, Jie; Yu, Mingchen; Liu, Jin; Chen, Xinlei; Qian, Rong; Zhang, Feng

    2016-12-01

    PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products that modulate cellular processes such as differentiation, cell growth and apoptosis. PRDM5 is a recently identified family member that functions as a transcriptional repressor and behaves as a putative tumor suppressor in different types of cancer. However, the expression and function of PRDM5 in spinal cord injury (SCI) are still unknown. In the present study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of PRDM5 expression in the spinal cord. We found that PRDM5 protein levels gradually increased, reaching a peak at day 5 and then gradually declined to a normal level at day 14 after SCI with Western blot analysis. Double immunofluorescence staining showed that PRDM5 immunoreactivity was found in neurons, astrocytes and microglia. However, the expression of PRDM5 was increased predominantly in neurons. Additionally, colocalization of PRDM5/active caspase-3 was been respectively detected in neurons. In vitro, we found that depletion of PRDM5 by short interfering RNA, obviously decreases neuronal apoptosis. In summary, this is the first description of PRDM5 expression in SCI. Our results suggested that PRDM5 might play crucial roles in CNS pathophysiology after SCI and this research will provide new drug targets for clinical treatment of SCI.

  1. Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

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    Nie, Mingbo; Chen, Liang; Gu, Yudong

    2012-06-01

    Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.

  2. The effect of treadmill training on motor recovery after a partial spinal cord compression-injury in the adult rat.

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    Multon, Sylvie; Franzen, Rachelle; Poirrier, Anne-Lise; Scholtes, Felix; Schoenen, Jean

    2003-08-01

    Locomotor training on a treadmill is a therapeutic strategy used for several years in human paraplegics in whom it was shown to improve functional recovery mainly after incomplete spinal cord lesions. The precise mechanisms underlying its effects are not known. Experimental studies in adult animals were chiefly performed after complete spinal transections. The objective of this experiment was to assess the effects of early treadmill training on recovery of spontaneous walking capacity after a partial spinal cord lesion in adult rats. Following a compression-injury by a subdurally inflated microballoon, seven rats were trained daily on a treadmill with a body weight support system, whereas six other animals were used as controls and only handled. Spontaneous walking ability in an open field was compared weekly between both groups by two blinded observers, using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Mean BBB score during 12 weeks was globally significantly greater in the treadmill-trained animals than in the control group, the benefit of training appearing as early as the 2nd week. At week 7, locomotor recovery reached a plateau in both animal groups, but remained superior in trained rats. Daily treadmill training started early after a partial spinal cord lesion in adult rats, which accelerates recovery of locomotion and produces a long-term benefit. These findings in an animal model mimicking the closed spinal cord injury occurring in most human paraplegics are useful for future studies of optimal locomotor training programs, their neurobiologic mechanisms, and their combination with other treatment strategies.

  3. Temporal response of endogenous neural progenitor cells following injury to the adult rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yilin eMao

    2016-03-01

    Full Text Available A pool of endogenous neural progenitor cells found in the ependymal layer and the sub-ependymal area of the spinal cord are reported to upregulate nestin in response to traumatic spinal cord injury. These cells could potentially be manipulated within a critical time period offering one innovative approach to the repair of spinal cord injury. However, little is known about the temporal response of endogenous neural progenitor cells following spinal cord injury. This study used a mild contusion injury in rat spinal cord and immunohistochemistry to determine the temporal response of ependymal neural progenitor cells following injury and their correlation to astrocyte activation at the lesion site. The results from the study demonstrated that Nestin staining intensity at the central canal peaked at 24 hours post-injury and then gradually declined over time. Reactive astrocytes double labelled by Nestin and GFAP were found at the lesion edge and commenced to form the glial scar from 1 week after injury. We conclude that the critical time period for manipulating endogenous neural progenitor cells following a spinal cord injury in rats is between 24 hrs when nestin expression in ependymal cells is increased and 1 week when astrocytes are activated in large numbers.

  4. Diagnostic accuracy of evoked potentials for functional impairment after contusive spinal cord injury in adult rats.

    Science.gov (United States)

    Thirumala, Parthasarathy; Zhou, James; Krishnan, Rohan; Manem, Nihita; Umredkar, Shreya; Hamilton, D K; Balzer, Jeffrey R; Oudega, Martin

    2016-03-01

    Iatrogenic spinal cord injury (SCI) is a cause of potentially debilitating post-operative neurologic complications. Currently, intra-operative neurophysiological monitoring (IONM) via somatosensory evoked potentials and motor-evoked potentials is used to detect and prevent impending SCI. However, no empirically validated interventions exist to halt the progression of iatrogenic SCI once it is detected. This is in part due to the lack of a suitable translational model that mimics the circumstances surrounding iatrogenic SCI detected via IONM. Here, we evaluate a model of simulated contusive iatrogenic SCI detected via IONM in adult female Sprague-Dawley rats. We show that transient losses of somatosensory evoked potentials responses are 88.24% sensitive (95% confidence interval [CI] 63.53-98.20) and 80% specific (95% CI 51.91-95.43) for significant functional impairment following simulated iatrogenic SCI. Similarly, we show that transient losses in motor-evoked potentials responses are 70.83% sensitive (95% CI 48.91-87.33) and 100% specific (95% CI 62.91-100.00) for significant functional impairment following simulated iatrogenic SCI. These results indicate that our model is a suitable replica of the circumstances surrounding clinical iatrogenic SCI.

  5. The Effects of Cyclosporin-A on Functional Outcome and Axonal Regrowth Following Spinal Cord Injury in Adult Rats

    Directory of Open Access Journals (Sweden)

    Hamdollah Delaviz

    2012-04-01

    Full Text Available It has been shown that the immunophilin ligands have the special advantage in spinal cord repair. In this study, the effects of cyclosporine A (CsA on functional recovery and histological outcome were evaluated following spinal cord injury in rats. After spinal cord hemisection in thirty six adult female Sprague-Dawley rats (200- 250 g, treatment groups received CsA (2.5 mg/kg i.p. at 15min and 24h after lesion (CsA 15min group and CsA 24h group daily, for 8 weeks. Control and sham groups received normal saline and in sham operated animals the spinal cord was exposed in the same manner as treatment groups, but was not hemisected. Hindlimb motor function was assessed in 1, 3, 5 and 7 weeks after lesion, using locomotive rating scale developed by Basso, Bresnahan and Beattie (BBB. Motor neurons were counted within the lamina IX of ventral horn and lesion size was measured in 5 mm of spinal lumbar segment with the epicenter of the lesion site. The mean number of motor neurons and the mean BBB scale in 3, 5 and 7 weeks in CsA 15min groups significantly increased compared to the control group. Although, the lesion size reduced in rats with CsA treatment compared to the control group, no significant difference was observed. Thus, it can be concluded that CsA can improve locomotor function and histological outcome in the partial spinal cord injury.

  6. Temporal Response of Endogenous Neural Progenitor Cells Following Injury to the Adult Rat Spinal Cord.

    Science.gov (United States)

    Mao, Yilin; Mathews, Kathryn; Gorrie, Catherine A

    2016-01-01

    A pool of endogenous neural progenitor cells (NPCs) found in the ependymal layer and the sub-ependymal area of the spinal cord are reported to upregulate Nestin in response to traumatic spinal cord injury (SCI). These cells could potentially be manipulated within a critical time period offering an innovative approach to the repair of SCI. However, little is known about the temporal response of endogenous NPCs following SCI. This study used a mild contusion injury in rat spinal cord and immunohistochemistry to determine the temporal response of ependymal NPCs following injury and their correlation to astrocyte activation at the lesion edge. The results from the study demonstrated that Nestin staining intensity at the central canal peaked at 24 h post-injury and then gradually declined over time. Reactive astrocytes double labeled by Nestin and glial fibrillary acidic protein (GFAP) were found at the lesion edge and commenced to form the glial scar from 1 week after injury. We conclude that the critical time period for manipulating endogenous NPCs following a spinal cod injury in rats is between 24 h when Nestin expression in ependymal cells is increased and 1 week when astrocytes are activated in large numbers.

  7. Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats.

    Directory of Open Access Journals (Sweden)

    Amar Karalija

    Full Text Available Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC and acetyl-L-carnitine (ALC can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day or ALC (0.9 mg/day was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2 in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes

  8. (-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

    Science.gov (United States)

    Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h.

  9. Morphological and electrophysiological evidence for regeneration of transected spinal cord fibers and restoration of motor functions in adult rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    After 2/3 transection of the right ninth thoracic spinal cord of an adult rat, a chitosan tube seeded with L-poly-lysine was implanted between the rostral and caudal end of the lesioned cord. Twelve months after the operation, regeneration of myelinated and non-myelinated axons and new blood vessels were observed along the wall of the chitosan tube implanted under an electron microscope. Somatosensory evoked potentials (SEP) could be consistently recorded from the left somatosensory cortex following electrical stimulation of the right hind limb, while transcranial magnetic stimulation of the left motor cortex could also evoke motor activity from the right hind limb. The present result suggests that implanted chitosan tube might be useful in regeneration of injured nerve fibers of the spinal cord resulting in a long-term restoration of motor functions.

  10. 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.

  11. Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat.

    Science.gov (United States)

    King, Von R; Henseler, Manuel; Brown, Robert A; Priestley, John V

    2003-08-01

    A variety of biological as well as synthetic implants have been used to attempt to promote regeneration into the damaged spinal cord. We have implanted mats made from fibronectin (FN) into the damaged spinal cord to determine their effectiveness as a substrate for regeneration of axons. These mats contain oriented pores and can take up and release growth factors. Lesion cavities 1 mm in width and depth and 2 mm in length were created on one side of the spinal cord of adult rats. FN mats containing neurotrophins or saline were placed into the lesion. Mats were well integrated into surrounding tissue and showed robust well-oriented growth of calcitonin gene-related peptide, substance P, GABAergic, cholinergic, glutamatergic, and noradrenergic axons into FN mats. Transganglionic tracing using cholera toxin B indicated large-diameter primary afferents had grown into FN implants. Schwann cells had also infiltrated FN mats. Electron microscopy confirmed the presence of axons within implants sites, with most axons either ensheathed or myelinated by Schwann cells. Mats incubated in brain-derived neurotrophic factor and neurotrophin-3 showed significantly more neurofilament-positive and glutamatergic fibers compared to saline- and nerve growth factor-incubated mats, while mats incubated with nerve growth factor showed more calcitonin gene-related peptide-positive axons. In contrast, neurotrophin treatment had no effect on PGP 9.5-positive axons. In addition, in some animals with neurotrophin-3-incubated mats, cholera toxin B-labelled fibers had grown from the mat into adjoining intact areas of spinal cord. The results indicate that FN mats provide a substrate that is permissive for robust oriented axonal growth in the damaged spinal cord, and that this growth is supported by Schwann cells.

  12. Electroacupuncture promotes the proliferation of endogenous neural stem cells and oligodendrocytes in the injured spinal cord of adult rats

    Institute of Scientific and Technical Information of China (English)

    Haiying Wu; Min Hu; Dekai Yuan; Yunhui Wang; Jing Wang; Tao Li; Chuanyun Qian

    2012-01-01

    A contusive model of spinal cord injury at spinal segment T8-9 was established in rats. Huantiao (GB30) and Huatuojiaji (Ex-B05) were punctured with needles, and endogenous neural stem cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) and NG2. Double immunofluorescence staining showed that electroacupuncture markedly increased the numbers of BrdU+/NG2+ cells at spinal cord tissue 15 mm away from the injury center in the rostral and caudal directions. The results suggest that electroacupuncture promotes the proliferation of endogenous neural stem cells and oligodendrocytes in rats with spinal cord injury.

  13. Neurotrophins and trk-receptors in adult rat spinal motoneurons : differences related to cell size but not to 'slow/fast' specialization

    NARCIS (Netherlands)

    Copray, S; Kernell, D

    2000-01-01

    We have studied the mRNA expression of the neurotrophins brain-derived neurotrophic factor (BDNF), NT-3 and NT-4 and of their receptors trkB and trkC in individual retrogradely labeled lumbar spinal motoneurons of the adult rat, using quantitative non-radioactive in situ hybridization (ISH). We meas

  14. Serotonin concentrations in the lumbosacral spinal cord of the adult rat following microinjection or dorsal surface application.

    Science.gov (United States)

    Brumley, Michele R; Hentall, Ian D; Pinzon, Alberto; Kadam, Brijesh H; Blythe, Anthony; Sanchez, Francisco J; Taberner, Annette M; Noga, Brian R

    2007-09-01

    Application of neuroactive substances, including monoamines, is common in studies examining the spinal mechanisms of sensation and behavior. However, affected regions and time courses of transmitter activity are uncertain. We measured the spatial and temporal distribution of serotonin [5-hydroxytryptamine (5-HT)] in the lumbosacral spinal cord of halothane-anesthetized adult rats, following its intraspinal microinjection or surface application. Carbon fiber microelectrodes (CFMEs) were positioned at various locations in the spinal cord and oxidation currents corresponding to extracellular 5-HT were measured by fast cyclic voltammetry. Intraspinal microinjection of 5-HT (100 microM, 1-3 microl) produced responses that were most pronounced at CFMEs positioned spinal cord.

  15. Rapid functional reorganization of the forelimb cortical representation after thoracic spinal cord injury in adult rats.

    Science.gov (United States)

    Sydekum, Esther; Ghosh, Arko; Gullo, Miriam; Baltes, Christof; Schwab, Martin; Rudin, Markus

    2014-02-15

    Thoracic spinal cord injured rats rely largely on forelimbs to walk, as their hindlimbs are dysfunctional. This increased limb use is accompanied by expansion of the cortical forelimb sensory representation. It is unclear how quickly the representational changes occur and whether they are at all related to the behavioral adaptation. Using blood oxygenation level dependent functional mangetic resonance imaging (BOLD-fMRI) we show that major plastic changes of the somato-sensory map can occur as early as one day after injury. The extent of map increase was variable between animals, and some animals showed a reduction in map size. However, at three or seven days after injury a significant enhancement of the forelimb representation was evident in all the animals. In a behavioral test for precise limb control, crossing of a horizontal ladder, the injured rats relied almost entirely on their forelimbs; they initially made more mistakes than at 7 days post injury. Remarkably, in the individual animals the behavioral performance seen at seven days was proportional to the physiological change present at one day after injury. The rapid increase in cortical representation of the injury-spared body part may provide the additional neural substrate necessary for high level behavioral adaptation.

  16. Upregulation of S100A4 after spinal cord transection in adult rats

    Institute of Scientific and Technical Information of China (English)

    Kai-hua ZHANG; Shu HAN; Pei-hua LU; Xiao-ming XU

    2004-01-01

    AIM: To investigate whether spinal cord transection induces changes of gene expression of S 100A4 protein.METHODS: In a spinal cord transection model, S 100A4 expression and cellular localization were examined using cDNA microarray, Northern blot, immunohistochemistry, and immunofluorescence double-labeling methods.RESULTS: There was very limited S 100A4 mRNA expression in the control spinal cord. However, S 100A4 mRNA expression was increased significantly in both the rostral and caudal spinal cord segments adjacent to the injury site.Specifically, S100A4 gene expression was substantially increased at d 2, peaked at d 7 and d 14, and remained high up to 28 d post-injury. During its peak expression, S100A4 protein was localized in astrocytes of the spinal cord within 5 mm from the site of spinal transection. CONCLUSION: Spinal cord transection induces prolonged S 100A4 expression at both mRNA and protein levels in areas close to the injury site. Increased expression of S100A4 in astrocytes after spinal cord transection may indicate that this molecule may play a role in astrocytic responses to injury.

  17. Studies on repairing of hemisected thoracic spinal cord of adult rats by using a chitosan tube filled with alginate fibers

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoguang; YANG Zhaoyang; YANG Yi

    2006-01-01

    A chitosan tube filled with alginate fibers was implanted into the injured spinal cord of a rat for repairing the damaged tissue. Twelve months after the operation, the morphological observation demonstrated that this chitosan tube could induce regeneration of myelinated and non-myelinated axons and blood vessels. The Basso-Beattie-Bresnahan (BBB) behavioral evaluation confirmed that the implants played a key role in the long-term restoration of rats motor functions. It is a promising start in the treatment of the patients with the injury of the spinal cord.

  18. Regeneration of the Adult Rat Spinal Cord in Response to Ensheathing Cells and Methylprednisolone

    Science.gov (United States)

    2002-01-01

    xv LIST OF ABBREVIATIONS A/P anterior/posterior BDNF brain-derived neurotrophic factor BDT biotin dextran tetramethylrhodamine bFGF basic...lateral funiculus. The axons of the CST terminate in the spinal cord on alpha motor neurons and on interneurons that synapse on alpha motor neurons. The...1998). Brain-derived neurotrophic factor ( BDNF ), both alone (Diener and Bregman, 1994) and in combination with embryonic spinal cord transplants

  19. Effects of long-term FK506 administration on functional and histopathological outcome after spinal cord injury in adult rat.

    Science.gov (United States)

    Saganová, Kamila; Orendácová, Judita; Sulla, Igor; Filipcík, Peter; Cízková, Dása; Vanický, Ivo

    2009-09-01

    FK506 (tacrolimus), a potent immunosuppressive drug primarily used for reduction of allograft rejection in organ transplantation, also offers neuroprotection after central nervous system injury. FK506-mediated immunosuppression and neuroprotection may occur through different mechanisms that could affect neurological recovery and the severity of spinal lesions where cells transplantation therapy is combined with FK506 application. We assessed effects of long-term FK506 administration using the same dose regiment (1 mg/kg/day for 6 weeks) as is used in spinal cord transplantation studies following a balloon-compression induced spinal cord injury (SCI). Body weight and locomotor recovery quantified by the BBB (Basso-Beattie-Bresnehan) locomotor rating scale were evaluated for up to 42 days post-injury. The area of the preserved spinal cord tissue within a 13 mm segment of the spinal cord (lesion epicenter and 6 mm rostral-caudal) was examined histologically. The results showed no significant effects of FK506 on spinal cord tissue sparing or improvement of locomotor recovery. However, body weight fell significantly (P < 0.05) with FK506 treatment when compared with placebo from day 7 until sacrifice. In our experimental design, long-term FK506 treatment did not affect the parameters of outcome following balloon-compression SCI in the rat; however, multiple effects of FK506 should be taken into account when evaluating the outcomes in transplantation studies.

  20. Repetitive transcranial magnetic stimulation improves open field locomotor recovery after low but not high thoracic spinal cord compression-injury in adult rats.

    Science.gov (United States)

    Poirrier, Anne-Lise; Nyssen, Yves; Scholtes, Felix; Multon, Sylvie; Rinkin, Charline; Weber, Géraldine; Bouhy, Delphine; Brook, Gary; Franzen, Rachelle; Schoenen, Jean

    2004-01-15

    Electromagnetic fields are able to promote axonal regeneration in vitro and in vivo. Repetitive transcranial magnetic stimulation (rTMS) is used routinely in neuropsychiatric conditions and as an atraumatic method to activate descending motor pathways. After spinal cord injury, these pathways are disconnected from the spinal locomotor generator, resulting in most of the functional deficit. We have applied daily 10 Hz rTMS for 8 weeks immediately after an incomplete high (T4-5; n = 5) or low (T10-11; n = 6) thoracic closed spinal cord compression-injury in adult rats, using 6 high- and 6 low-lesioned non-stimulated animals as controls. Functional recovery of hindlimbs was assessed using the BBB locomotor rating scale. In the control group, the BBB score was significantly better from the 7th week post-injury in animals lesioned at T4-5 compared to those lesioned at T10-11. rTMS significantly improved locomotor recovery in T10-11-injured rats, but not in rats with a high thoracic injury. In rTMS-treated rats, there was significant positive correlation between final BBB score and grey matter density of serotonergic fibres in the spinal segment just caudal to the lesion. We propose that low thoracic lesions produce a greater functional deficit because they interfere with the locomotor centre and that rTMS is beneficial in such lesions because it activates this central pattern generator, presumably via descending serotonin pathways. The benefits of rTMS shown here suggest strongly that this non-invasive intervention strategy merits consideration for clinical trials in human paraplegics with low spinal cord lesions.

  1. Effect of neural stem cell transplantation combined with erythropoietin injection on axon regeneration in adult rats with transected spinal cord injury.

    Science.gov (United States)

    Zhao, Y; Zuo, Y; Wang, X L; Huo, H J; Jiang, J M; Yan, H B; Xiao, Y L

    2015-12-22

    We investigated the effect of neural stem cells (NSC) and erythropoietin (EPO) on axon regeneration in adult rats with transected spinal cord injury, and provided an experimental basis for clinical treatment. Forty Wistar rats with T10-transected spinal cord injury were randomly divided into four groups of ten rats: a control group (group A), an NSC-transplant group (group B), an NSC-transplant and EPO group (group C), and an EPO group (group D). Biotinylated dextran amines (BDA) anterograde corticospinal cord neuronal tracing and Fluoro-Gold (FG) retrograde tracing were carried out at the 8th week after operation to observe the regeneration of nerve fibers. The Basso, Beattie, and Bresnahan (BBB) locomotor score was used to evaluate restoration. 1) BDA and FG immunofluorescence staining: in group C, a large number of regenerated axons were observed and some penetrated the injured area. In group B, only a small number of regenerated axons were observed and none penetrated the injured area. In group D, only sporadic regenerated nerve fibers were observed occasionally, while in group A, no axonal regeneration was observed. In group C, a small number of cones and axons emitted yellow fluorescence, and no FG-labeled cells were observed in the other groups. 2) The BBB scores for group C were higher than those for the other groups, and the differences were statistically significance (P EPO intraperitoneal injection may benefit axon regeneration in rats with transected spinal cord injury, and accelerate the functional recovery of the hindlimb locomotor.

  2. Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot.

    Science.gov (United States)

    Fenrich, Keith K; May, Zacincte; Torres-Espín, Abel; Forero, Juan; Bennett, David J; Fouad, Karim

    2016-02-15

    Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury.

  3. Release properties and functional integration of noradrenergic-rich tissue grafted to the denervated spinal cord of the adult rat.

    Science.gov (United States)

    Leanza, G; Cataudella, T; Dimauro, R; Monaco, S; Stanzani, S

    1999-05-01

    Noradrenaline- (NA-) containing grafts of central (embryonic locus coeruleus, LC) or peripheral (juvenile adrenal medullary, AM, autologous superior cervical ganglionic, SCG) tissue were implanted unilaterally into rat lumbar spinal cord previously depleted of its NA content by 6-hydroxydopamine (6-OHDA) intraventricularly. A microdialysis probe was implanted in the spinal cord 3-4 months after transplantation, and extracellular levels of noradrenaline were monitored in freely moving animals during basal conditions and following administration of pharmacological or behavioural stimuli. Age-matched normal and lesioned animals both served as controls. Morphometric analyses were carried out on horizontal spinal sections processed for dopamine-beta-hydroxylase (DBH) immunocitochemistry, in order to assess lesion- or graft-induced changes in the density of spinal noradrenergic innervation, relative to the normal patterns. In lesioned animals, the entire spinal cord was virtually devoid of DBH-positive fibers, resulting in a dramatic 88% reduction in baseline NA, compared with that in controls, which did not change in response to the various stimuli. LC and SCG grafts reinstated approximately 80% and 50% of normal innervation density, respectively, but they differed strikingly in their release ability. Thus, LC grafts restored baseline NA levels up to 60% of those in controls, and responded with significantly increased NA release to KCl-induced depolarization, neuronal uptake blockade and handling. In contrast, very low NA levels and only poor and inconsistent responses to the various stimuli were observed in the SCG-grafted animals. In AM-grafted animals, spinal extracellular NA levels were restored up to 45% of those in controls, probably as a result of nonsynaptic, endocrine-like release, as grafted AM cells retained the chromaffine phenotype, showed no detectable fibre outgrowth and did not respond to any of the pharmacological or behavioural challenges. Thus, both a

  4. Effects of C8 ventral root avulsion or transection on spinal alpha motoneurons in adult rats A qualitative light and electron microscopic study

    Institute of Scientific and Technical Information of China (English)

    Khulood M.AL-Khater; Bassem Y.Sheikh

    2008-01-01

    BACKGROUND:Nerve root avulsion is a frequent finding in patients with brachial plexus injury following road traffic accidents or as a result of severe arm traction during complicated deliveries.This injury constitutes a challenging clinical and surgical problem.The orphological characteristics of motoneurons after nerve root avulsion deserve further analysis.OBJECTIVE:To study the different morphological changes of u -motoneurons under light and electron microscopy after C8 spinal ventral rootlets avulsion and transection at various stages.DESIGN:Controlled animal study.SETTING:Department of Anatomy,King Faisal University.MATERIALS:The experiment was carried out at the Department of Anatomy,College of Medicine,King Faisal University between January 2005 and March 2006.Six adult Sprague Dawley rats weighing 200-350 g, irrespective of gender,were used for this study.The animals were bred at the animal house,College of Medicine,King Faisal University,and fed on rat maintenance diet.Water and standard diet were supplied ad libitum.Animal interventions were carried out according to animal ethical standards.METHODS:Three animals were randomly chosen for avulsion of the right ventral rootlets of C8 spinal nerves.The other three received transection of the right ventral rootlets of C8 spinal nerves.①Avulsion experiment:After rats were anesthetized,the right ventral rootlets of C8 spinal nerves were identified.The ventral rootlets were avulsed from the spinal cord by traction with a fine hook(Fine Science Tools Inc.,No. 10031-13,Germany).Traction was exerted in a direction parallel to the course of the spinal root.Under the operating microscope,the Cs segment was exactly located.After checking the successfulness of the surgical procedure,the Ca segment was separated from the spinal cord.The outcome of the avulsion procedure was as follows:two animals had true avulsion,i.e.,no remaining stump was attached to the spinal cord surface.One rat had a stump still attached

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

    Science.gov (United States)

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

    2013-02-01

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

  6. Tanshinone IIA attenuates the inflammatory response and apoptosis after traumatic injury of the spinal cord in adult rats.

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    Xin Yin

    Full Text Available BACKGROUND: Spinal cord injury (SCI, including immediate mechanical injury and secondary injury, is associated with the inflammatory response, apoptosis and oxidative stress in response to traumatic injury. Tanshinone IIA (TIIA is one of the major extracts obtained from Salvia miltiorrhiza BUNGE, which has anti-inflammatory and anti-apoptotic effects on many diseases. However, little is known about the effects of TIIA treatment on SCI. Therefore, the aim of the present study is to evaluate the pharmacological action of TIIA on secondary damage and the underlying mechanisms of experimental SCI in rats. METHODOLOGY/PRINCIPAL FINDINGS: SCI was generated using a weight drop device on the dorsal spinal cord via a two-level T9-T11 laminectomy. SCI in rats resulted in severe trauma, characterized by locomotor disturbance, edema, neutrophil infiltration, the production of astrocytes and inflammatory mediators, apoptosis and oxidative stress. TIIA treatment (20 mg/kg, i.p. after SCI induced significant effects: (1 improved motor function (Basso, Beattie and Bresnahan scores, (2 reduced the degree of tissue injury (histological score, neutrophil infiltration (myeloperoxidase activity and the expression of astrocytes, (3 inhibited the activation of SCI-related pathways, such as NF-κB and MAPK signaling pathways, (4 decreased the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6 and iNOS, (5 reduced apoptosis (TUNEL staining, and Bcl-2 and caspase-3 expression and (6 reversed the redox state imbalance. CONCLUSIONS/SIGNIFICANCE: The results clearly show that TIIA has a prominent protective effect against SCI through inhibiting the inflammatory response and apoptosis in the spinal cord tissue after SCI.

  7. Regulation of DM-20 mRNA expression and intracellular translocation of glutathione-S-transferase pi isoform during oligodendrocyte differentiation in the adult rat spinal cord.

    Science.gov (United States)

    Kitada, Masaaki; Takeda, Kazuya; Dezawa, Mari

    2016-07-01

    We previously demonstrated that NG2-positive oligodendrocyte precursor cells (OPCs) do not express DM-20 mRNA and identified a distinct DM-20 mRNA-positive cell population expressing glutathione-S-transferase pi isoform (GST-pi) in the nucleus (GST-pi(Nuc)) of the adult rat spinal cord. As GST-pi intranuclear localization correlates with progenitor cell properties, we examined the differentiation status of this cell population under the intensive 5-bromo-2'-deoxyuridine (BrdU) administration method, consisting of intraperitoneal BrdU injections every 2 h for 48 h. We observed that a certain population of proliferating/proliferated cells expressed DM-20 mRNA, and sometimes two proliferating/proliferated cells were observed still attached to each other. We performed triple staining for BrdU, DM-20 mRNA, and NG2 and found pairs of neighboring BrdU-positive cells, which were considered to originate from the same progenitor cells and where both cells expressed DM-20 mRNA. Triple staining for BrdU, DM-20 mRNA, and GST-pi detected proliferating/proliferated cells exhibiting the GST-pi(Nuc)/DM-20 mRNA-positive expression pattern. These findings suggested the presence of a GST-pi(Nuc)/DM-20 mRNA-positive oligodendrocyte-lineage progenitor cell population in the adult rat spinal cord. However, we did not find any pair of neighboring BrdU-positive cells with this expression pattern. These observations collectively support the idea that GST-pi(Nuc)/DM-20 mRNA-expressing cells are the progeny of NG2-positive OPCs rather than a novel type of oligodendrocyte-lineage progenitor cells and that DM-20 mRNA expression is dynamically regulated during differentiation of OPCs into oligodendrocytes.

  8. Proliferation and differentiation of reactive nestin~+/GFAP~+ cells in an adult rat model of compression-induced spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Pinglin Yang; Xijing He; Haopeng Li; Binshang Lan; Guoyu Wang; Yiheng Liu

    2009-01-01

    days.The majority of cells in the ependymal region around the central canal were nestin~+/GFAP~- cells,while the gray and white matter around the ependymal region were full of nestin~+/GFAP~+ cells,with an astrocytic-like appearance.A large number of nestin~+/GFAP~+ cells were observed in the model group cell culture,and the cells formed clonal spheres and displayed strong nestin-positive immunofluorescence staining.Following induced differentiation,a large number of GaLC-nestin,β-tubulin Ⅲ-nestin,and GFAP-nestin positive cells were observed.However,no obvious changes were seen in the control group.Cells in S stage,as well as the percentage of proliferating cells,in the model group were significantly greater than in the control group (P<0.01).CONCLUSION:Spinal cord injury in the adult rat induced high expression of nestin~+/GFAP~+ in the gray and white matter around the ependymal region of the central canal.These nestin~+/GFAP~+ cells displayed the potential to self-renew and differentiate into various cells.The cells could be neural stem cells of the central nervous system.GFAP~

  9. Role of ERK1/2, Akt, and PLCy pathways in proliferation and neuronal differentiation in the adult rat spinal cord neural stem/progenitor cell culture

    Directory of Open Access Journals (Sweden)

    Wai Si eChan

    2013-08-01

    Full Text Available Proliferation of endogenous neural stem/progenitor cells (NSPCs has been identified in both normal and injured adult mammalian spinal cord. Yet the signaling mechanisms underlying the regulation of adult spinal cord NSPCs proliferation and commitment toward a neuronal lineage remain undefined. In this study, the role of three growth factor-mediated signaling pathways in proliferation and neuronal differentiation was examined. Adult spinal cord NSPCs were enriched in the presence of fibroblast growth factor 2 (FGF2. We observed an increase in the number of cells expressing the microtubule-associated protein 2 (MAP2 over time, indicating neuronal differentiation in the culture. Inhibition of the mitogen-activated protein kinase or extracellular signal-regulated kinase (ERK kinase 1 and 2/ERK 1 and 2 (MEK/ERK1/2 or the phosphoinositide 3-kinase (PI3K/Akt pathways suppressed active proliferation in adult spinal cord NSPC cultures; whereas neuronal differentiation was negatively affected only when the ERK1/2 pathway was inhibited. Inhibition of the phospholipase C gamma (PLCy pathway did not affect proliferation or neuronal differentiation. Finally, we demonstrated that the blockade of either the ERK1/2 or PLCy signaling pathways reduced neurite branching of MAP2+ cells derived from the NSPC cultures. Many of the MAP2+ cells expressed synaptophysin and had a glutamatergic phenotype, indicating that over time adult spinal cord NSPCs had differentiated into mostly glutamatergic neurons. Our work provides new information regarding the contribution of these pathways to the proliferation and neuronal differentiation of NSPCs derived from adult spinal cord cultures, and emphasizes that the contribution of these pathways is dependent on the origin of the NSPCs.

  10. Vitamin A deficiency induces congenital spinal deformities in rats.

    Directory of Open Access Journals (Sweden)

    Zheng Li

    Full Text Available Most cases of congenital spinal deformities were sporadic and without strong evidence of heritability. The etiology of congenital spinal deformities is still elusive and assumed to be multi-factorial. The current study seeks to elucidate the effect of maternal vitamin A deficiency and the production of congenital spinal deformities in the offsping. Thirty two female rats were randomized into two groups: control group, which was fed a normal diet; vitamin A deficient group, which were given vitamin A-deficient diet from at least 2 weeks before mating till delivery. Three random neonatal rats from each group were killed the next day of parturition. Female rats were fed an AIN-93G diet sufficient in vitamin A to feed the rest of neonates for two weeks until euthanasia. Serum levels of vitamin A were assessed in the adult and filial rats. Anteroposterior (AP spine radiographs were obtained at week 2 after delivery to evaluate the presence of the skeletal abnormalities especially of spinal deformities. Liver and vertebral body expression of retinaldehyde dehydrogenase (RALDHs and RARs mRNA was assessed by reverse transcription-real time PCR. VAD neonates displayed many skeletal malformations in the cervical, thoracic, the pelvic and sacral and limbs regions. The incidence of congenital scoliosis was 13.79% (8/58 in the filial rats of vitamin A deficiency group and 0% in the control group. Furthermore, vitamin A deficiency negatively regulate the liver and verterbral body mRNA levels of RALDH1, RALDH2, RALDH3, RAR-α, RAR-β and RAR-γ. Vitamin A deficiency in pregnancy may induce congenital spinal deformities in the postnatal rats. The decreases of RALDHs and RARs mRNA expression induced by vitamin A deprivation suggest that vertebral birth defects may be caused by a defect in RA signaling pathway during somitogenesis.

  11. APOPTOSIS AFTER SPINAL CORD INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  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. Experiment Study of Human Hair Keratin Transplanted To Adult Rats After Spinal Cord Cross-Injury%人发角蛋白修复大鼠脊髓横断损伤的实验研究

    Institute of Scientific and Technical Information of China (English)

    倪江东; 宋德业; 谢宏明; 李贺君; 谭进

    2003-01-01

    Objective:To study the function of human hair keratin [HHK] in repairing acute spinal cord cross-injury (SCCI) of SD adult rats.Methods:18 adult female SD rats were selected and devided into three groups (control group, HHK group, SCCI group). Movement and sensation of SD adult rats were evaluated.The samples from spinal cord at injuryed or insertion site,9 and 11 precessus spinosus were observed with optical microscope and electronic microscope in 1, 3, 6 weeks after operation.Results:Campared with SCCI group,HHK group recovered better in sensation, motion and histological changes.Conclusions:HHK can repair spinal cord injury and promote the function recovery. HHK can boost the regeneration of nervous cord and reduce necrosis of nerve cells. This study is the base of clinical practices in treating spinal cord injury with HHK.%目的:研究人发角蛋白(HHK)在大鼠脊髓横断损伤(SCCI)修复中的作用.方法:选用18只SD大鼠,建立正常对照组、SCCI组,SCCI后植入HHK组.于术后1W,3W,6W对大鼠的运动,感觉进行评估;并在横断部位及近,远断3个断面分别取材,用HE,铀铅双染,在光镜及电子显微镜下观察其组织学结构.结果:大鼠脊髓横断损伤后植入HHK,运动,感觉逐渐好转,术后6W基本恢复正常;而未植入HHK大鼠无明显变化.光镜观察:植入HHK组白质有明显的神经纤维沿着HHK再生,部分区域有坏死,无明显的空洞形成;灰质有部分异常神经元,大部分形态正常.未植入HHK组断面有神经呈编织状再生,未见纤维超过离断面,有大面积坏死和空洞形成;灰质神经元大量坏死,形态异常.结论:HHK对横断脊髓的功能及形态恢复有促进作用,本实验为HHK应用于临床奠定基础.

  14. Rat hair follicle stem cells differentiate and promote recovery following spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Nowruz Najafzadeh; Maliheh Nobakht; Bagher Pourheydar; Mohammad Ghasem Golmohammadi

    2013-01-01

    Emerging studies of treating spinal cord injury (SCI) with adult stem cells led us to evaluate the effects of transplantation of hair fol icle stem cells in rats with a compression-induced spinal cord lesion. Here, we proposed a hypothesis that rat hair fol icle stem celltransplantation can promote the recovery of injured spinal cord. Compression-induced spinal cord injury was induced in Wistar rats in this study. The bulge area of the rat vibrissa fol icles was isolated, cultivated and characterized with nestin as a stem cellmarker. 5-Bromo-2′-deoxyuridine (BrdU) labeled bulge stem cells were transplanted into rats with spinal cord injury. Immunohistochemical staining results showed that some of the grafted cells could survive and differentiate into oligodendrocytes (receptor-interacting protein positive cells) and neuronal-like cells (βIII-tubulin positive cells) at 3 weeks after transplantation. In addition, recovery of hind limb locomotor function in spinal cord injury rats at 8 weeks fol owing celltransplantation was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The results demon-strate that the grafted hair fol icle stem cells can survive for a long time period in vivo and differentiate into neuronal- and glial-like cells. These results suggest that hair fol icle stem cells can promote the recovery of spinal cord injury.

  15. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats.

    Science.gov (United States)

    Bundesen, Liza Q; Scheel, Tracy Aber; Bregman, Barbara S; Kromer, Lawrence F

    2003-08-27

    The present study provides the first evidence that signaling occurs between B-ephrins and EphB receptors in the adult CNS in response to injury. Specifically, our combined histological and biochemical data indicate that two members of the B-class of ephrins and Eph receptors, ephrin-B2 and EphB2, are expressed by astrocytes and meningeal fibroblasts, respectively, in the adult spinal cord. In response to thoracic spinal cord transection lesions, ephrin-B2 and EphB2 protein levels exhibit an initial decrease (1 d after lesion), followed by a significant increase by day 14. Immunohistochemical data indicate that ephrin-B2 is expressed by reactive CNS astrocytes, and EphB2 is present on fibroblasts invading the lesion site from the adjacent meninges. During the first 3 d after injury, there is intermingling of ephrin-B2-expressing reactive astrocytes at the lesion surface with EphB2-containing fibroblasts that is concurrent with bidirectional activation (phosphorylation) of ephrin-B2 and EphB2. By 7 d, both cell types are establishing restricted cellular domains containing dense networks of cells and interweaving processes. This astroglial-meningeal fibroblast scar is fully developed by day 14 when there is strict segregation of ephrin-B2-expressing astrocytes from EphB2-positive meningeal fibroblasts. These morphological changes are concomitant with a simultaneous decrease in ephrin-B2 and EphB2 activation. These observations provide strong evidence that cell contact-mediated bidirectional signaling between ephrin-B2 on reactive astrocytes and EphB2 on meningeal fibroblasts is an early event in the cellular cascades that result in the development of the glial scar and the exclusion of meningeal fibroblasts from the injured spinal cord.

  16. The effect of microgene pSVPoMcat to modify Schwann cell on GAP- 43 expression after spinal cord injury in adult rats%微基因修饰雪旺氏细胞移植对大鼠脊髓损伤后GAP-43表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈礼刚; 高立达; 毛伯镛; 杨立斌; 李开慧

    2001-01-01

    Objective To study the effect of microgene pSVPoMcat implanted to modify schwann cell on growth associated protein-43(GAP-43) expression after spinal cord injury in adult rats.Method Hemisected of the T8 segment of the spinal cord was performed for all the experiment rats.The rats were randomly divided into three groups as follows:Group A with microgene pSVPoMcat implanted to genetically modify SC;Group B with SC implanted ;Group C with hemisection of the spinal cord only.The changes of expression of GAP-43 in spinal cord were observed by immunochemistry with antibodies against GAP-43 .Simultaneous,the combined behavioral scores(CBS)was measured.Result There were not any different(P >0.05)among the three groups in first week and 12 week.There were significant diffeence(P<0.05)among three groups in 2nd,8th,and more dxpression of GAP-43 at the 2nd week in group A.The neurofunctional recovery was best in group A.Conclusion The microgene pSVPoMcat implanted to modify schwann cell can promote the expression of GAP-43 in spinal cord and functional recovery in adults rats after SCI.

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

    Science.gov (United States)

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

    2013-03-01

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

  18. 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 injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

  19. Nestin- and Doublecortin-Positive Cells Reside in Adult Spinal Cord Meninges and Participate in Injury-Induced Parenchymal Reaction

    OpenAIRE

    2011-01-01

    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...

  20. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    OpenAIRE

    Beatriz Paniagua-Torija; Angel Arevalo-Martin; Isidro Ferrer; Eduardo Molina-Holgado; Daniel Garcia-Ovejero

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqma...

  1. Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat.

    Science.gov (United States)

    Mothe, A J; Tator, C H

    2005-01-01

    Ependymal cells of the adult mammalian spinal cord exhibit stem/progenitor cell properties following injury. In the present study, we utilized intraventricular injection of 1,1'-dioctadecyl-6,6'-di(4-sulfophenyl)-3,3,3',3'-tetramethylindocarbocyanine (DiI) to label the ependyma lining the central canal to allow tracking of the migration of endogenous ependymal cells and their progeny after spinal cord injury (SCI). We developed a minimal injury model that preserved the integrity of the central canal and did not interfere with ependymal cell labeling. Three days following SCI, there was an 8.6-fold increase in the proliferative labeling index of the ependymal cells at the level of the needle track based on bromodeoxyuridine labeling, compared with 1 day post-injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells were not detected in the ependyma or surrounding gray matter, indicating that ependymal cells do not undergo apoptosis in response to minimal injury. Nestin was rapidly induced in the ependyma by 1 day and expression peaked by 7 days post-injury. We quantitated the number and distance of ependymal cell migration following minimal injury. The number of ependymal cells migrating from the region of the central canal increased by 3 days following minimal injury and DiI-labeled glial fibrillary acidic protein expressing cells were detected 14 days post-SCI, most of which migrated within 70 microm of the region of the central canal. These results show that a minimal SCI adjacent to the ependyma is sufficient to induce an endogenous ependymal cell response where ependymal stem/progenitor cells proliferate and migrate from the region of the central canal, differentiating primarily into astrocytes.

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

    Science.gov (United States)

    Franz, Steffen; Ciatipis, Mareva; Pfeifer, Kathrin; Kierdorf, Birthe; Sandner, Beatrice; Bogdahn, Ulrich; Blesch, Armin; Winner, Beate; Weidner, Norbert

    2014-01-01

    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.

  3. 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.

  4. Injury-induced class 3 semaphorin expression in the rat spinal cord

    NARCIS (Netherlands)

    Gispen, W.H.; Winter, F. de; Oudega, M.; Lankhorst, A.J.; Hamers, F.P.; Blits, B.; Ruitenberg, M.J.; Pasterkamp, R.J.; Verhaagen, J.

    2002-01-01

    In this study we evaluate the expression of all members of the class 3 semaphorins and their receptor components following complete transection and contusion lesions of the adult rat spinal cord. Following both types of lesions the expression of all class 3 semaphorins is induced in fibroblast in th

  5. Effect of hyperbaric oxygen on MMP9/2 expression and motor function in rats with spinal cord injury.

    Science.gov (United States)

    Hou, Ying-Nuo; Ding, Wen-Yuan; Shen, Yong; Yang, Da-Long; Wang, Lin-Feng; Zhang, Peng

    2015-01-01

    To study the effect of hyperbaric oxygen intervention on the microenvironment of nerve regeneration after spinal cord injury modeling and to explore the possible mechanism of nerve regeneration and functional recovery in rats with spinal cord injury. In 98 adult female SD rats, 90 successful models were obtained, which were divided into sham group, spinal cord injury group and hyperbaric oxygen group using randomized block method, 30/group. Spinal cord injury rat model was established in accordance with the modified Allen method. Motor function was assessed at the time points of before modeling, one day, three days, one week, two weeks, three weeks and four weeks after modeling respectively by BBB rating, inclined plane test and improved Tarlov score. At 3 days after modeling, apoptosis of neuronal cells in spinal cord injury region in experimental group was detected by TUNEL method; gene and protein expression of MMP9/2 in spinal cord injury and surrounding tissues was detected by RT-PCR and Western blot assay. At 4 weeks after modeling, histopathological morphological changes in spinal cord injury were observed by HE staining; fluorogold retrograde tracing was used to observe the regeneration and distribution of spinal cord nerve fibers and axon regeneration was observed by TEM. The three motor function scores in hyperbaric oxygen group at each time point after two weeks of treatment were significantly increased compared with spinal cord injury group (P hyperbaric oxygen group were significantly lower than those in spinal cord injury group (P hyperbaric oxygen group was significantly lower (P hyperbaric oxygen group and spinal cord injury group in order; the differences among the groups were statistically significant (P hyperbaric oxygen group; unmyelinated and myelinated nerve fibers in hyperbaric oxygen group were more than those in spinal cord injury group. Hyperbaric oxygen therapy played a protective effect on spinal cord injury through reducing apoptosis of

  6. Trigeminally induced cardiovascular reflex responses in spinalized rats.

    Science.gov (United States)

    Ideguchi, S; Hotta, H; Suzuki, A; Umino, M

    2000-03-15

    The effects on cardiovascular functions of noxious stimulation to the orofacial areas innervated by trigeminal afferent nerves were analyzed in urethane-anesthetized, spinal cord-intact rats and in rats acutely spinalized at the second cervical level. In the spinal cord-intact rats, pinching of the upper lip produced increases in both heart rate (HR) and mean arterial pressure (MAP). Both responses were considered to be due to activation of sympathetic efferent nerves to the cardiovascular organs. Both responses were attenuated but did not disappear after spinalization at the C2 level. In spinalized rats, sympathetic preganglionic neurons emerging from the thoracolumbar spinal cord could not receive any neural influences from the brain. The HR response in the spinal rats was abolished after either bilateral vagotomy or intravenous injection of a peripherally acting muscarinic cholinergic receptor antagonist, methylatropine. This suggests that the increase in HR was elicited via vagal cholinergic efferent fibers, probably by decreasing tonic activity of vagus nerves to the heart. In spinal rats, neither vagotomy nor cholinergic blockade affected the increase in MAP, but i.v. injection of the vasopressin V1 receptor antagonist, OPC-21268, abolished the response of MAP. This suggests that the response of MAP was due to peripheral vasoconstriction elicited by vasopressin secreted from the posterior pituitary lobe. The present study demonstrated that, in rats acutely spinalized at the C2 level, noxious stimulation of orofacial areas innervated by the trigeminal nerve could produce reflex increases both in HR, by decreasing cholinergic vagal nerve activity to the heart, and blood pressure, by secreting vasopressin from the pituitary gland, even though sympathetic efferent innervation to the cardiovascular organs could not be directly affected by trigeminal afferent nerve excitation.

  7. Spinal Cord Blood Flow after Ischemic Preconditioning in a Rat Model of Spinal Cord Ischemia

    Directory of Open Access Journals (Sweden)

    David Zvara

    2004-01-01

    Full Text Available Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8, and control (CTRL, n = 8. Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7, ischemic preconditioning (IPC, n = 7, and time control (TC, n = 4. Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.

  8. A Surgery Protocol for Adult Zebrafish Spinal Cord Injury

    Institute of Scientific and Technical Information of China (English)

    Ping Fang; Jin-Fei Lin; Hong-Chao Pan; Yan-Qin Shen; Melitta Schachner

    2012-01-01

    Adult zebrafish has a remarkable capability to recover from spinal cord injury,providing an excellent model for studying neuroregeneration.Here we list equipment and reagents,and give a detailed protocol for complete transection of the adult zebrafish spinal cord.In this protocol,potential problems and their solutions are described so that the zebrafish spinal cord injury model can be more easily and reproducibly performed.In addition,two assessments are introduced to monitor the success of the surgery and functional recovery:one test to assess free swimming capability and the other test to assess extent of neuroregeneration by in vivo anterograde axonal tracing.In the swimming behavior test,successful complete spinal cord transection is monitored by the inability of zebrafish to swim freely for 1 week after spinal cord injury,followed by the gradual reacquisition of full locomotor ability within 6 weeks after injury.As a morphometric correlate,anterograde axonal tracing allows the investigator to monitor the ability of regenerated axons to cross the lesion site and increasingly extend into the gray and white matter with time after injury,confirming functional recovery.This zebrafish model provides a paradigm for recovery from spinal cord injury,enabling the identification of pathways and components of neuroregeneration.

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

    Directory of Open Access Journals (Sweden)

    Bhatoe H

    2000-07-01

    Full Text Available 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 cervical spondylosis. Following trauma, these patients had weakness of all four limbs. They were evaluated by MRI (CT scan in one patient, which showed hypo / isointense lesion in the cord on T1 weighted images, and hyperintensity on T2 weighted images, suggesting cord contusion or oedema. MRI was normal in two patients. With conservative management, fifteen patients showed neurological improvement, one remained quadriplegic and one died. With increasing use of MRI in the evaluation of traumatic myelopathy, such injuries will be diagnosed more often. The mechanism of injury is probably acute stretching of the cord as in flexion and torsional strain. Management is essentially conservative and prognosis is better than that seen in patients with fracture or dislocation of cervical spine.

  10. Establishment and evaluation of a rat model of complete transected spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Xuejun Li; Chunhai Huang; Shangming Liu; Xianrui Yuan

    2008-01-01

    BACKGROUND: The establishment of a rat model of complete transected spinal cord injury lacks technological specifications. The current models lack concordance and reliability, and the death rate of the experimental animals is high. Therefore, there is a great need for a reliable model to apply clinical applications of therapy.OBJECTIVE: To construct a rat model of complete transected spinal cord injury characterized by stability, reproducibility, and a high animal survival rate. DESIGN: Completely randomized controlled study.SETTING: Department of Neurosurgery, Xiangya Hospital of Central South University.MATERIALS: Fifty-five healthy specific pathogen free grade adult female Sprague Dawley rats were provided by the Experimental Animal Department, Xiangya Medical College, Central South University. Olympus BX51 imaging collecting analytic system was provided by Olympus Company, Japan; and SEN-7203 Nihon-Kohden electrical stimulator by Nihon Kohden, Japan. METHODS: This study was performed at the Laboratory of Neurosurgery, Xiangya Hospital of Central South University from April to June 2006. Experimental grouping: 55 rats were randomly divided into model group (n = 40) and sham surgery group (n = 15). In the model group, a self-made sliver hook was passed through the ventral side to support the spinal cord at the T12 segment and to shear it off. A complete transected spinal cord, 2 mm in length, was resected. In the sham surgery group, the spinal cord was identically exposed. The dura mater of the spinal cord was cut open, but the spinal cord was not damaged. MAIN OUTCOME MEASURES: Histopathological changes after spinal cord injury at L2 segment were observed subsequent to hematoxylin and eosin staining under optical microscopy. Olympus BX51 imaging collecting analytic system was used to count spinal cord ventral horn neurons. Motor function of rat hindlimb was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. Paraplegia was evaluated as 0 point, and

  11. Establishment of intramedullary spinal cord glioma model in rats

    Institute of Scientific and Technical Information of China (English)

    REN Tian-jian; WANG Zhong-cheng; ZHANG Ya-zhuo; LI Dan; WANG Hong-yun; LI Zhen-zong

    2010-01-01

    Background Treating intramedullary spinal cord gliomas is a big challenge because of limited options, high recurrence rate and poor prognosis. An intramedullary glioma model is prerequisite for testing new treatments. This paper describes the establishment of a rodent intramedullary glioma model and presents functional progression, neuroimaging and histopathological characterization of the tumour model.Methods Fischer344 rats (n=24) were randomized into two groups. Group 1 (n=16) received a 5 μl intramedullary implantation of 9L gliosarcomal (105) cells. Group 2 (n=8) received a 5 μl intramedullary injection of Dulbecco's modified Eagle medium. The rats were anesthetized, the spinous process of the T10 vertebra and the ligamentum flavum were removed to expose the T10-11 intervertebral space and an intramedullary injection was conducted into the spinal cord. The rats were evaluated preoperatively and daily postoperatively for neurological deficits using the Basso, Beattie and Bresnahan scale. High resolution magnetic resonance images were acquired preoperatively and weekly postoperatively.When score equal to 0, rats were sacrificed for histopathological examination.Results Rats implanted with 9L gliosarcoma cells had a statistically significant median onset of hind limb paraplegia at (16.0±0.4) days, compared with rats in the control group in which neurological deficits were absent. Imaging and pathological cross sections confirmed intramedullary 9L gliosarcoma invading the spinal cord. Rats in the control group showed no significant functional, radiological or histopathological findings of tumour.Conclusions Rats implanted with 9L cells regularly develop paraplegia in a reliable and reproducible manner. The progression of neurological deficits, neuroimaging and histopathological characteristics of intramedullary spinal cord gliomas in rats is comparable with the behaviour of infiltrative intramedullary spinal cord gliomas in patients.

  12. Forelimb EMG-based trigger to control an electronic spinal bridge to enable hindlimb stepping after a complete spinal cord lesion in rats

    Directory of Open Access Journals (Sweden)

    Gad Parag

    2012-06-01

    Full Text Available Abstract Background A complete spinal cord transection results in loss of all supraspinal motor control below the level of the injury. The neural circuitry in the lumbosacral spinal cord, however, can generate locomotor patterns in the hindlimbs of rats and cats with the aid of motor training, epidural stimulation and/or administration of monoaminergic agonists. We hypothesized that there are patterns of EMG signals from the forelimbs during quadrupedal locomotion that uniquely represent a signal for the “intent” to step with the hindlimbs. These observations led us to determine whether this type of “indirect” volitional control of stepping can be achieved after a complete spinal cord injury. The objective of this study was to develop an electronic bridge across the lesion of the spinal cord to facilitate hindlimb stepping after a complete mid-thoracic spinal cord injury in adult rats. Methods We developed an electronic spinal bridge that can detect specific patterns of EMG activity from the forelimb muscles to initiate electrical-enabling motor control (eEmc of the lumbosacral spinal cord to enable quadrupedal stepping after a complete spinal cord transection in rats. A moving window detection algorithm was implemented in a small microprocessor to detect biceps brachii EMG activity bilaterally that then was used to initiate and terminate epidural stimulation in the lumbosacral spinal cord. We found dominant frequencies of 180–220 Hz in the EMG of the forelimb muscles during active periods, whereas these frequencies were between 0–10 Hz when the muscles were inactive. Results and conclusions Once the algorithm was validated to represent kinematically appropriate quadrupedal stepping, we observed that the algorithm could reliably detect, initiate, and facilitate stepping under different pharmacological conditions and at various treadmill speeds.

  13. Neural stem cell transplantation combined with erythropoietin for the treatment of spinal cord injury in rats.

    Science.gov (United States)

    Zhao, Yan; Zuo, Yuan; Jiang, Jianming; Yan, Huibo; Wang, Xiliang; Huo, Hunjun; Xiao, Yulong

    2016-10-01

    Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group). Morphological alterations associated with axonal regeneration were detected using neurofilament (NF)-200 immunohistochemistry and immunofluorescence staining after 8 weeks. Basso, Beattie and Bresnahan (BBB) scoring was used to evaluate the recovery of hindlimb function. A total of 5 rats died following surgery, including 2 control rats and 1 rat each in the EPO, NSC and NSC + EPO groups. NSCs labeled with bromodeoxyuridine were observed to have survived and migrated in the spinal cord tissue after 8 weeks. Significant histomorphological differences were observed in the NSC and NSC + EPO groups compared with the EPO and control groups. Furthermore, the rats of the NSC + EPO group exhibited significantly enhanced axonal regeneration in the SCI area compared with the NSC group rats. The rats of the NSC and NSC + EPO groups exhibited significantly improved BBB scores compared with the EPO and control group rats at 7 days after treatment (PEPO group were significantly improved compared with those of the three other groups at 7 days after surgery (PEPO may benefit the survival and regeneration of injured axons, and accelerate the repair of injured spinal cord tissue, thus facilitating the functional recovery of hindlimb locomotor function in rats.

  14. 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...... reported with significant variability and have not been measured as a primary endpoint in any prospective, multicenter, observational study. METHODS: The primary outcome measure was the change in American Spinal Injury Association (ASIA) Lower Extremity Motor Scores (LEMS) obtained preoperatively...... with a preoperative neurologic deficit, a significant portion of patients with ASD experienced postoperative decline in LEMS. Measures that can anticipate and reduce the risk of postoperative neurologic complications are warranted. LEVEL OF EVIDENCE: 3....

  15. 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.

  16. 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.

  17. Locally transplanted enteric gila improve functional and structural recovery in a rat model of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Shucui Jiang; Mohammad I.Khan; James R.Bain; Cai Jiang; Christopher R.Hansebout; Zesheng Yu; Yuqing Liu; Michel P.Rathbone

    2009-01-01

    BACKGROUND: We have previously reported that adult enteric gila (EG) facilitate the growth of transected dorsal root axons into the uninjured spinal cord to form functional connections with their targets. OBJECTIVE: The present study investigated the effects of EG on spinal cord function, tissue injury, and axonal regeneration following transplantation into injured rat spinal cords, according to histological and functional outcomes. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at McMaster University, Canada from January 2006 to March 2008.MATERIALS: EG were isolated from rat intestine. METHODS: One week following spinal cord crush, female Wistar rats were injected with an EG suspension (2 μL, 1 x 10 5/μL, n=10) or with the same volume of fresh culture medium alone (control animals, n=11). The third group did not receive any injection following laminectomy and served as the sham-operated controls (n=5). MAIN OUTCOME MEASURES: Behavior was tested prior to transplantation and weekly following transplantation, with nine behavioral examinations in total. Open field, hind limb placement response, foot orientation response, and inclined plane test were utilized. Immediately following the final behavioral examination, spinal cord T9 to L1 segments were harvested for immunohistochemical and hematoxylin-eosin staining to determine astroglial scarring, axonal regeneration and spinal cord lesion size. RESULTS: Rats with EG transplantation exhibited significantly better locomotor function with reduced tissue damage, compared with the control rats. Cystic cavities were present 2 months after injury in spinal cords from both control groups. In contrast, rats injected with EG did not present with cystic lesions. In addition, the injury site consisted of cellular material and nerve fibers, and axonal regeneration was apparent, with dense labeling of neurofilament-positive axons within the injury site. Moreover, regenerating axons were

  18. Spinal pharmacology of tactile allodynia in diabetic rats

    OpenAIRE

    1997-01-01

    Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown.Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by ass...

  19. Neuromodulation of motor-evoked potentials during stepping in spinal rats.

    Science.gov (United States)

    Gad, Parag; Lavrov, Igor; Shah, Prithvi; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie; Gerasimenko, Yury

    2013-09-01

    The rat spinal cord isolated from supraspinal control via a complete low- to midthoracic spinal cord transection produces locomotor-like patterns in the hindlimbs when facilitated pharmacologically and/or by epidural electrical stimulation. To evaluate the role of epidural electrical stimulation in enabling motor control (eEmc) for locomotion and posture, we recorded potentials evoked by epidural spinal cord stimulation in selected hindlimb muscles during stepping and standing in adult spinal rats. We hypothesized that the temporal details of the phase-dependent modulation of these evoked potentials in selected hindlimb muscles while performing a motor task in the unanesthetized state would be predictive of the potential of the spinal circuitries to generate stepping. To test this hypothesis, we characterized soleus and tibialis anterior (TA) muscle responses as middle response (MR; 4-6 ms) or late responses (LRs; >7 ms) during stepping with eEmc. We then compared these responses to the stepping parameters with and without a serotoninergic agonist (quipazine) or a glycinergic blocker (strychnine). Quipazine inhibited the MRs induced by eEmc during nonweight-bearing standing but facilitated locomotion and increased the amplitude and number of LRs induced by eEmc during stepping. Strychnine facilitated stepping and reorganized the LRs pattern in the soleus. The LRs in the TA remained relatively stable at varying loads and speeds during locomotion, whereas the LRs in the soleus were strongly modulated by both of these variables. These data suggest that LRs facilitated electrically and/or pharmacologically are not time-locked to the stimulation pulse but are highly correlated to the stepping patterns of spinal rats.

  20. Spinal pharmacology of tactile allodynia in diabetic rats

    Science.gov (United States)

    Calcutt, Nigel A; Chaplan, Sandra R

    1997-01-01

    Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown.Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by assessing the efficacy of agents that inhibit specific components of spinal nociceptive processing.Dose-dependent inhibition of tactile allodynia in diabetic rats was noted with the N-type calcium channel antagonist SNX 239, the α2-adrenoceptor agonist dexmedetomidine, the μ-opioid receptor agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and the non-NMDA receptor antagonist NBQX.No effect on tactile allodynia was noted after intrathecal administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the cyclo-oxygenase inhibitor ketorolac, the L-type calcium channel inhibitor diltiazem or any vehicle.These data suggest that the tactile allodynia of diabetic rats involves spinal glutamatergic pathways but is not associated with spinal release of nitric oxide or prostaglandins. PMID:9421298

  1. Antioxidation of melatonin against spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    刘锦波; 唐天驷; 杨惠林; 肖德生

    2004-01-01

    Background The iron catalyzed lipid peroxidation plays an important role in the autodestruction of the injured spinal cord. This study was to detect the antioxidation of melatonin against spinal cord injury (SCI) in rats.Methods Sity Sprague-Dawley rats were randomly divided into four groups: group A (n = 15) for laminectomyanly, group B (n = 15) for laminectomy with SCI, group C (n = 15) for SCI and intraperitoneal injection of a bolus of 100 mg/kg melatonin, and group D (n = 15) for SCI and intraperitoneal injection of saline containing 5% ethanol. The SCI of animal model was made using modified Allen's method on T12. Six rats of each group were sacrificed 4 hours after injury, and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by the bleomycin assay and thiobarbituric acid (TBA) separately. Functional recovery of the spinal cord was assessed by Modified Tarlov's scale and the inclined plane method at 1,3, 7, 14, 21 days after SCI. The histologic changes of the damaged spinal cord were also examined at 7 days after SCl.Results After SCI, the levels of free iron and MDA were increased significantly and the modified Tarlov's score and inclined plane angle decreased significantly in groups B and D. In group C, the Tarlov's score and inclined plane angle were increased significantly at 7, 14 and 21 days, with histological improvement.Conclusion: Melatonin can reduce the level of lipid peroxidation and prevent damage to the spinal cord of rat.

  2. Mechanical characterization of the injured spinal cord after lateral spinal hemisection injury in the rat.

    Science.gov (United States)

    Saxena, Tarun; Gilbert, Jeremy; Stelzner, Dennis; Hasenwinkel, Julie

    2012-06-10

    The glial scar formed at the site of traumatic spinal cord injury (SCI) has been classically hypothesized to be a potent physical and biochemical barrier to nerve regeneration. One longstanding hypothesis is that the scar acts as a physical barrier due to its increased stiffness in comparison to uninjured spinal cord tissue. However, the information regarding the mechanical properties of the glial scar in the current literature is mostly anecdotal and not well quantified. We monitored the mechanical relaxation behavior of injured rat spinal cord tissue at the site of mid-thoracic spinal hemisection 2 weeks and 8 weeks post-injury using a microindentation test method. Elastic moduli were calculated and a modified standard linear model (mSLM) was fit to the data to estimate the relaxation time constant and viscosity. The SLM was modified to account for a spectrum of relaxation times, a phenomenon common to biological tissues, by incorporating a stretched exponential term. Injured tissue exhibited significantly lower stiffness and elastic modulus in comparison to uninjured control tissue, and the results from the model parameters indicated that the relaxation time constant and viscosity of injured tissue were significantly higher than controls. This study presents direct micromechanical measurements of injured spinal cord tissue post-injury. The results of this study show that the injured spinal tissue displays complex viscoelastic behavior, likely indicating changes in tissue permeability and diffusivity.

  3. Effect of electro-acupuncture on the expression of heat shock protein-70 gene in rat spinal cords following spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:It is generally believed that the mechanism by which heat shock protein-70(HSP70) protects cells is related to its effectiveness in maintaining the normal stereochemical structure of intracellular proteins,and in participating in the process of cell apoptosis.Whether electro-acupuncture participates in HSP70 expression and produces neuroprotective effects remain unclear.OBJECTIVE:This study aimed at detecting HSP70 expression after electro-acupuncture in rats with transected spinal cord,in order to further validate the mechanism of electro-acupuncture-induced effects in the treatment of spinal cord injury.DESIGN:A controlled observational experiment.SETTING:Shanghai University of Traditional Chinese Medicine and Toho University,School of Medicine.MATERIALS:Seventy adult male Sprague-Dawley rats of SPF grade,weighing 200±20g,were provided by the Laboratory Animal Center of Shanghai University of Traditional Chinese Medicine,with permission No.SYXK(hu)2004-2005.The animals were handled in accordance with the requests from Animal Ethics Committees for guidance.A G6805-2 multiple purpose treatment machine was used (Shanghai Medical Instruments High-Tech Co.,Ltd.,Shanghai,China).METHODS:This study was carried out in the state level laboratories of Shanghai University of Traditional Chinese Medicine and Toho University,School of Medicine between January 2005 and July 2007.The rats were randomly divided into the electro-acupuncture treated group,which received electro-acupuncture treatment in addition to spinal cord surgery and the control group,which received only spinal cord surgery,with 35 rats in each group.All the rats underwent the same surgery consisting of spinal cord transection at the T10 level.If the spinal cord was completely transected and the two posterior limbs were completely paralyzed,then the surgery was considered successful and the animal was kept for further analysis and testing.After surgery,rats in the experimental group were electro

  4. 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.

  5. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    Science.gov (United States)

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  6. Impaired formalin-evoked changes of spinal amino acid levels in diabetic rats.

    Science.gov (United States)

    Malmberg, Annika B; O'Connor, William T; Glennon, Jeffery C; Ceseña, Rose; Calcutt, Nigel A

    2006-10-18

    To investigate mechanisms by which diabetes alters sensory processing, we measured levels of amino acid neurotransmitters in spinal dialysates from awake, unrestrained control and diabetic rats under resting conditions and following hind paw formalin injection. Under resting conditions, glutamate concentrations in spinal dialysates were significantly (Phyperalgesia in diabetic rats does not appear to be secondary to enhanced glutamatergic input to the spinal cord.

  7. Use of robotics in assessing the adaptive capacity of the rat lumbar spinal cord.

    Science.gov (United States)

    de Leon, Ray D; Reinkensmeyer, David J; Timoszyk, Wojciech K; London, Nicolas J; Roy, Roland R; Edgerton, V Reggie

    2002-01-01

    We have developed a robotic device that can record the trajectory of the hindlimb movements in rats. The robotic device can also impose programmed forces on the limbs during stepping. In the present paper we describe experiments using this robotic device, i.e. the rat stepper, to determine whether step training improves the locomotor capacity of adult rats that received complete spinal cord transections as neonates. We also determined to what extent the locomotor patterns can be maintained when the step cycle is physically perturbed by the robotic device. The results of the present study demonstrate that a robotic device can be used effectively to quantify the improvements in the locomotor capacity of spinal transected rats that occurs over a period of step training. The present results also demonstrate that when an external force is imposed to disrupt the step cycle, the spinal cord has the neural control elements necessary to normalize the kinematics over a number of steps, in the face of the disrupted forces.

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

    OpenAIRE

    Stavros eMalas; Elena ePanayiotou

    2013-01-01

    Spinal cord injury is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following spinal cord injury activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient nu...

  9. Motor recovery following olfactory ensheathing cell transplantation in rats with spinal cord injury

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    George Tharion

    2011-01-01

    Full Text Available Background: Olfactory ensheathing cells (OEC are considered to be the most suitable cells for transplantation therapy in the central nervous system (CNS because of their unique ability to help axonal regrowth and remyelination in the CNS. However, there are conflicting reports about the success rates with OEC. Aim: This study was undertaken to evaluate the therapeutic effect of OEC in rat models using different cell dosages. Material and Methods: OECs harvested from the olfactory mucosa of adult white Albino rats were cultured. Spinal cord injury (SCI was inflicted at the lower thoracic segment in a control and test group of rats. Two weeks later, OECs were delivered in and around the injured spinal cord segment of the test group of the rats. The outcome in terms of locomotor recovery of limb muscles was assessed on a standard rating scale and by recording the motor-evoked potentials from the muscles during transcranial electrical stimulation. Finally, the animals were sacrificed to assess the structural repair by light microscopy. Statistical Analysis: Wilcoxon signed rank test and Mann-Whitney U-test were used to compare the data in the control and the test group of animals. A P value of <0.05 was considered significant. Results: The study showed a moderate but significant recovery of the injured rats after OEC transplantation (P=0.005. Conclusion: Transplantation of OECs along with olfactory nerve fibroblasts improved the motor recovery in rat models with SCI.

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

    Institute of Scientific and Technical Information of China (English)

    Kan XU; Qi-xin CHEN; Fang-cai LI; Wei-shan CHEN; Min LIN; Qiong-hua WET

    2009-01-01

    Objective: To determine whether spinal cord decompression plays a role in neural cell apoptosis after spinal cord injury. Study design: We used an animal model of compressive spinal cord injury with incomplete paraparesis to evaluate neural cell apoptosis after decompression. Apoptosis and cellular damage were assessed by staining with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) and immunostaining for caspase-3, Bcl-2 and Bax. Methods: Experiments were conducted in male Spragne-Dawley rats (n=78) weighing 300-400 g. The spinal cord was compressed posteriorly at T10 level using a custom-made screw for 6 h, 24 h or continuously, followed by decompression by removal of the screw. The rats were sacrificed on Day 1 or 3 or in Week 1 or 4 post-decompression. The spinal cord was removed en bloc and examined at lesion site, rostral site and caudal site (7.5 mm away from the lesion). Results: The numbers of TUNEL-positive cells were significantly lower at the site of decompression on Day l, and also at the rostral and caudal sites between Day 3 and Week 4 post-decompression, compared with the persistently compressed group. The numbers of cells between Day 1 and Week 4 were immunoreactive to caspase-3 and B-cell lymphoma-2 (Bcl-2)-associated X-protein (Bax), but not to Bcl-2, correlated with those of TUNEL-positive cells. Conclusion: Our results suggest that decompression reduces neural cell apoptosis following spinal cord injury.

  11. Effects of Epidural Spinal Cord Stimulation and Treadmill Training on Locomotion Function and Ultrastructure of Spinal Cord Anterior Horn after Moderate Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WANG Yizhao; HUANG Xiaolin; XU Jiang; XU Tao; FANG Zhengyu; XU Qi; TU Xikai; YANG Peipei

    2009-01-01

    Objective:To investigate the effects of epidural spinal cord stimulation (ESCS) and treadmill training on the locomotion function and ultrastructure of spinal cord anterior horn after moderate spinal cord injury in rats. (IT, n=3). All rats received a moderate spinal cord injury surgery. Four weeks after surgery, rats in SE group received an electrode implantation procedure, with the electrode field covering spinal cord segments L2-S1. Four weeks after electrode implantation, rats received subthreshold ESCS for 30 min/d. Rats in TY group received 4cm/s treadmill training for 30min/d. Rats in SI group received no intervention, as a control group. All procedures in these three groups lasted four weeks.The open field Basso,Beattie and Bresnahan (BBB) scale was used before and after intervention to evaluate rats' hindlimb motor function. Result:After four weeks intervention, rats in TT group improved their open field locomotion scores to 20. In contrast, no significant improvement was observed in groups SI and SE. The morphology of synapses and neurons were similar regardless of whether rats had undergone ESCS, treadmill training or not. Conclusion:ESCS alone was not sufficient to improve the walking ability of spinal cord injured rats. ESCS or treadmill training alone might not contribute to the changes of ultrastructure in anterior horn of spinal cord that underlie the recovery of walking ability. Further research is needed to understand the contributions of combination of ESCS and treadmill training to the rehabilitation of spinal cord injured rats.

  12. EZH2 regulates spinal neuroinflammation in rats with neuropathic pain.

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    Yadav, Ruchi; Weng, Han-Rong

    2017-02-28

    Alteration in gene expression along the pain signaling pathway is a key mechanism contributing to the genesis of neuropathic pain. Accumulating studies have shown that epigenetic regulation plays a crucial role in nociceptive process in the spinal dorsal horn. In this present study, we investigated the role of enhancer of zeste homolog-2 (EZH2), a subunit of the polycomb repressive complex 2, in the spinal dorsal horn in the genesis of neuropathic pain in rats induced by partial sciatic nerve ligation. EZH2 is a histone methyltransferase, which catalyzes the methylation of histone H3 on K27 (H3K27), resulting in gene silencing. We found that levels of EZH2 and tri-methylated H3K27 (H3K27TM) in the spinal dorsal horn were increased in rats with neuropathic pain on day 3 and day 10 post nerve injuries. EZH2 was predominantly expressed in neurons in the spinal dorsal horn under normal conditions. The number of neurons with EZH2 expression was increased after nerve injury. More strikingly, nerve injury drastically increased the number of microglia with EZH2 expression by more than sevenfold. Intrathecal injection of the EZH2 inhibitor attenuated the development and maintenance of mechanical and thermal hyperalgesia in rats with nerve injury. Such analgesic effects were concurrently associated with the reduced levels of EZH2, H3K27TM, Iba1, GFAP, TNF-α, IL-1β, and MCP-1 in the spinal dorsal horn in rats with nerve injury. Our results highly suggest that targeting the EZH2 signaling pathway could be an effective approach for the management of neuropathic pain.

  13. Human neural stem cells promote corticospinal axons regeneration and synapse reformation in injured spinal cord of rats

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    LIANG Peng; JIN Lian-hong; LIANG Tao; LIU En-zhong; ZHAO Shi-guang

    2006-01-01

    Background Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord.Methods NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n=15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group,NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA.Results NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P< 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P< 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression

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

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    Sharyn L Rossi

    Full Text Available BACKGROUND: Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  15. Intrathecal MK-801 inhibits formalin-induced activation of spinal p38-MAPK in rats

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    Zhifeng Peng; Xin Zhao; Xing Jin; Xiaochun Yan; Xiaorong Yang; Ce Zhang

    2008-01-01

    BACKGROUND: p38 mitogen-activated protein kinase (MAPK) plays an instrumental role in signal transduction from the cell surface to the nucleus, while subcutaneous injection of formalin can induce increased activation of spinal p38 MAPK. However, the mechanisms underlying the formalin-induced activation of spinal p38 MAPK in rats are unclear. OBJECTIVE: To observe the effects of N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 on the formalin-induced activation of spinal p38 MAPK in rats. DESIGN, TIME AND SETTING: This randomized grouping, controlled animal experiment was performed at the Department of Physiology and Neurobiology, Shanxi Medical University between May and November 2007. MATERIALS: Forty eight healthy, adult Wistar rats were randomly divided into two groups: formalin + normal saline (n = 12) and formalin + MK-801 (n = 36). The formalin + MK-801 group was further divided into three subgroups according to the dosage of MK-801 (10, 50, and 100 nmol/L, 12 rats for each subgroup) METHODS: Following anesthesia, polyethylene tubing filled with sterile normal saline was implanted into the subarachnoid cavity. On postoperative days 5-8, rats received a 15 minute perfusion of normal saline or MK-801 (10, 50, and 100 nmol/L) in the formalin + normal saline and formalin + MK-801 groups, respectively, followed by formalin injection for the induction of nociceptive behavior. MAIN OUTCOME MEASURES: Detection of total p38 MAPK and of phosphorylated p38 MAPK by western Blot analysis; observation of nociceptive behaviors in the 1 hour after formalin injection. RESULTS: Western Blot analysis revealed that injection of formalin had no effect on total p38 MAPK expression but resulted in increased phosphorylation of p38 MAPK in the spinal cord. This increase was apparent after 5 minutes, peaked at 20 minutes, and thereafter descended and reached control levels after 45 minutes. Pretreatment with MK-801 (10, 50, 100 nmol/L) resulted in a dose-dependent reduction

  16. 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.

  17. Antioxidation of quercetin against spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Jin-bo; TANG Tian-si; YANG Hui-lin

    2006-01-01

    Objective: To observe the effect of quercetin on experimental spinal cord injury (SCI) in rats.Methods: Sixty Sprague-Dawley rats were randomly divided into four groups: Group A only for laminectomy,Group B for laminectomy with SCI, Group C for SCI and intraperitoneal injection with a bolus of 200 mg/kg quercetin and Group D for SCI and intraperitoneal injection of saline. SCI model was made by using modified Allen's method on T12. Six rats of each group were killed at4 h after injury and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by bleomycin and thiobarbituric acid (TBA) assays separately. The recovery of hind limb function was assessed by Modified Tarlov's scale and inclined plane method at 7 d,14 d and 21 d after SCI. The histological changes of the damaged spinal cord were also examined at 7 d after SCI.Results: After SCI, the levels of free iron and MDA were significantly increased in Groups B and D, while not in Group C. The Modified Tarlov's score and the inclined plane angles were significantly decreased in Groups B, C and D. The histological findings were not improved.Conclusions: After SCI, quercetin can reduce the level of lipid peroxidation, but not improve recovery of function.

  18. Chronic spinal infusion of loperamide alleviates postsurgical pain in rats.

    Science.gov (United States)

    Kumar, Rakesh; Reeta, K H; Ray, Subrata Basu

    2014-04-01

    Plantar incision in rat generates spontaneous pain behaviour. The opioid drug, morphine used to treat postsurgical pain produces tolerance after long-term administration. Loperamide, a potent mu-opioid agonist, has documented analgesic action in various pain conditions. However, loperamide analgesia and associated tolerance following continuous spinal administration in postsurgical pain has not been reported. Chronic spinal infusion of drugs was achieved using intrathecal catheters connected to osmotic minipump. Coinciding with the onset of spinal infusion of loperamide or morphine, rats were subjected to plantar incision. Pain-related behaviour was assessed by Hargreaves apparatus (thermal hyperalgesia) and von Frey filaments (mechanical allodynia). Morphine and loperamide (0.5, 1 and 2 microL/h) induced analgesia was observed until 7th day post-plantar incision in Sprague-Dawley rats. Morphine and loperamide produced dose-dependent analgesia. Loperamide, in the highest dose, produced analgesia till 7th day. However, the highest dose of morphine produced inhibition of thermal hyperalgesia till 5th day and mechanical allodynia only till 3rd day post-plantar incision. Morphine and loperamide produced analgesia in postsurgical pain, which may be mediated through different mechanisms. Longer duration of analgesia with loperamide could probably be due sustained blockade of calcium channels.

  19. 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.

  20. 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.

  1. Immune therapy with cultured microglia grafting into the injured spinal cord promoting the recovery of rat's hind limb motor function

    Institute of Scientific and Technical Information of China (English)

    YU Teng-bo; CHENG Yong-shuai; ZHAO Peng; KOU De-wei; SUN Kang; CHEN Bo-hua; WANG Ai-min

    2009-01-01

    Objective: To study the effect of activated microglia grafting on rats' hind limb motor function recovery after spinal cord injury.Methods: Microglia were separated from primary culture and subcultured for 3 generations. Lipopolysaccharide was added to the culture medium with the terminal concentrition of 10 μl/L for microglia activation 3 days before transplantation. Totally 80 adult Wistar rats were divided into transplantation group and control group, with 40 rats in each group. Spinal cord injury model of rats was set by hitting onto the spinal cord using a modified Allen impactor. With a 5 μl micro-syringe, the activated microglia suspension was injected into the injured area 7 days after the first operation. Basso, Beattie and Bresnahan (BBB) scoring for hind limb motor function was taken on the 1st, 7th, 14th, 21st, and 28th day after microglia transplantation, and 8 rats were sacrificed at each time point mentioned above, respectively. Frozen sections of the spinal cord were made for haematoxylin-eosin (HE) and Naoumenko-Feigin stainings. SPSS 11.0 software was used for statistical analysis.Results: BBB scores for hind limb motor function on the 14th, 21 st, and 28th day were significantly higher compared with the control group. Most liquefaction necrosis areas disappeared and only a few multicystic cavities surrounded by aggregated microglia remained in the transplantation group. Naoumenko-Feigin staining for microglia showed that the transplantation group had significantly more positive cells (P<0.05).Conclusions: Grafting of activated microglia into the injured spinal cord can significantly promote the hind limb motor function recovery in rats with spinal cord injury and reduce the size of liquefaction necrosis area. The extent of lower limb motor function improvement has a positive correlation with the number of aggregated microglia.

  2. Vasoactive intestinal polypeptide (VIP) immunoreactivity in the ependymal cells of the rat spinal cord.

    Science.gov (United States)

    Chung, K; Lee, W T

    1988-12-19

    Vasoactive intestinal polypeptide (VIP) was demonstrated immunohistochemically in the entire ependymal and subependymal cells in all levels (cervical: C, thoracic: T, lumbar: L and sacral: S) of normal adult rat spinal cord. The VIP-immunoreactive basal processes from the apical ependymal cells coursed dorsally or ventrally along the median plane and reached the pia mater of the dorsal and ventral median septa. Many VIP-immunoreactive basal processes terminated on the blood vessels in the neuropil around the central canal. A few microvilli of the ependymal cells that project into the central canal also demonstrated intense VIP immunoreactivity. These observations suggest that ependymal cells may be involved in the modulation of VIP levels in the cerebrospinal fluid and regulation of vascular tone of the blood vessels in the spinal cord.

  3. Transplantation of human amniotic epithelial cells improves hindlimb function in rats with spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    WU Zhi-yuan; HUI Guo-zhen; LU Yi; WU Xin; GUO Li-he

    2006-01-01

    Background Human amniotic epithelial cells (HAECs), which have several characteristics similar to stem cells,therefore could possibly be used in cell therapy without creating legal or ethical problems. In this study, we transplanted HEACs into the injured spinal cord of rats to investigate if the cells can improve the rats' hindlimb motor function.Methods HAECs were obtained from a piece of fresh amnion, labeled with Hoechst33342, and transplanted into the site of complete midthoracic spinal transections in adult rats. The rats (n=21) were randomly divided into three groups: Sham-operation group (n=7), cells-graft group (n=7), and PBS group (n=7). One rat of each group was killed for histological analysis at the second week after the transplantation. The other six rats of each group were killed for histological analysis after an 8-week behavioral testing. Hindlimb motor function was assessed by using the open-field BBB scoring system. Survival rate of the graft cells was observed at second and eighth weeks after the transplantation. We also detected the myelin sheath fibers around the lesions and the size of the axotomized red nucleus. A one-way ANOVA was used to compare the means among the groups. The significance level was set at P<0.05.Results The graft HAECs survived for a long time (8 weeks) and integrated into the host spinal cord without immune rejection. Compared with the control group, HAECs can promote the regeneration and sprouting of the axons, improve the hindlimb motor function of the rats (BBB score: cells-graft group 9.0± 0.89 vs PBS group 3.7± 1.03, P<0.01), and inhibit the atrophy of axotomized red nucleus [cells-graft group (526.47 ± 148.42) μm2 vs PBS group (473.69±164.73) μm2, P<0.01].Conclusion Transplantation of HAECs can improve the hindlimb motor function of rats with spinal cord injury.

  4. Substance P mRNA expression in the rat spinal cord following selective brachial plexus injury

    Institute of Scientific and Technical Information of China (English)

    Na Liu; Longju Chen; Feng Li; Wutian Wu

    2008-01-01

    BACKGROUND: The neuropeptide, substance P, has various bioactivities and is widely distributed in the central nervous system. Substance P participates in neural transmission in the spinal cord and plays an important role in regeneration and repair of nerve injury.OBJECTIVE: To investigate substance P mRNA expression in the anterior horn of the spinal cord following brachial plexus injury.DESIGN, TIME AND SETTING: A molecular cell biology randomized controlled study was performed at the Department of Anatomy, Zhongshan Medical College, Sun Yat-sen University and the DaAn Gene Laboratory in May 2005.MATERIALS: A total of 29 adult male Sprague Dawley rats were randomly assigned to a control group (n=5) and an injury group (n = 24).METHODS: The injury group was divided into three subgroups. In subgroup A, the right seventh cervical vertebra (C7) anterior root was avulsed, and the residual nerve root at the distal end was removed. In subgroup B, the right C7 anterior root was avulsed, and the right C5 first thoracic vertebrae (TO posterior root was incised. Thus afferent pathways of the posterior root that connected with the anterior horn motor neurons were blocked. In subgroup C, the right C7 anterior root was avulsed, and a right C5-6 hemisection was performed. Thus the descending fiber pathways of the cortex that connected with anterior horn motor neurons were blocked. In the control group, the C5-T1 vertebral plate was opened, and then the skin was sutured.MAIN OUTCOME MEASURE: Substance P mRNA expression in the anterior horn of the spinal cord was quantified using fluorescent quantitative reverse transcription-polymerase chain reaction.RESULTS: Substance P mRNA expression was low in the anterior horn of the rat spinal cord in the control group. Substance P mRNA expression in the anterior horn of the spinal cord was upregulated and was significantly higher in the injury group compared with the control group (P < 0.01 ). Substance P mRNA expression was highest in

  5. 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.

  6. Effect of nitric oxide on spinal evoked potentials and survival rate in rats with decompression sickness

    DEFF Research Database (Denmark)

    Randsøe, Thomas; Meehan, Claire Francesca; Broholm, Helle

    2015-01-01

    evaluated by means of spinal evoked potentials (SEPs). Anesthetized rats were decompressed from a 1-h hyperbaric air dive at 506.6 kPa (40 m of seawater) for 3 min and 17 s, and spinal cord conduction was studied by measurements of SEPs. Histological samples of the spinal cord were analyzed for lesions...

  7. Culture and differentiation of neural stem cells from the injured spinal cord in adult rats%成年脊髓损伤大鼠脊髓神经干细胞的体外培养及分化研究

    Institute of Scientific and Technical Information of China (English)

    叶正旭; 李静; 黄景辉; 闫铭; 梁伟; 杨旻; 罗卓荆

    2009-01-01

    目的 探讨大鼠脊髓损伤后脊髓神经干细胞的分离培养方法及分化情况.方法 采用Allen法制作大鼠脊髓损伤模型,利用无血清培养和单细胞克隆技术在成年脊髓损伤7 d大鼠脊髓中分离具有单细胞克隆能力的神经干细胞,并进行培养鉴定.结果 从成年脊髓损伤7 d大鼠脊髓中成功分离出神经干细胞,该细胞具有连续克隆能力,可传代培养,表达神经巢蛋白抗原.分化后的细胞表达神经元细胞、星形胶质细胞和少突胶质细胞的特异性抗原.结论 致伤7 d的成年大鼠脊髓组织体外町培养出神经十细胞,并分化为神经无细胞、星形胶质细胞和少突胶质细胞,有可能参与脊髓损伤的修复过程.%Objective To investigate culture and differentiation of neural stem cells from the injured spinal cord in adult rats.Methods The spinal cord of male SD rats was injured by Allen's weight dropping on T8.Procedures of floating neural stem cell culture were carried out.Results Neurospheres of neural stem cells emerged after plating for 1 week.They had potent serf-renewing ability and could be passaged repeatedly,Immunohistochemistry data showed that these neurospheres strongly expressed nestin.A characteristic intermediate filament was seen in neural stem cells.The stem cells were further induced to differentiate into cells expressing β-tubulin,glial fibrillary acidic protein (GFAP) and myelin associated glycopretein (MAG),suggesting their differentiating potencies into neurons,astrocytes and oligodendrocytes.Conclusion In adult rats after spinal cord injury the neural stem cells can be isolated and cultured in vitro and induced to differentiate into neurons,astrocytes and oligodendrocytes,so the neural stem cells may participate in repair of spinal cord injury.

  8. The Effect of Fetal Olfactory Mucosa on Tissue Sparing and Locomotor Recovery after Spinal Cord Hemisection in Rats

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    Hamdollah Delaviz

    2008-01-01

    Full Text Available Objective: Olfactory ensheathing cells (OECs has been shown to have a neuroprotectiveeffect after transplanted in brain and spinal cord injury (SCI. This study was conductedto determine the possible beneficial results of transplantation of fetal olfactorymucosa (FOM that was the source of OECs in the recovery of locomotor function andin spinal tissue sparing after spinal cord hemisection.Materials and Methods: Forty-eight adult female Sprague-Dawley rats were spinallyhemisected at the L1 level and were randomized into the three groups of 16 animals.The first group, immunosuppressed injured animals were received cyclosporine A (CsAand FOM graft. The second group was received CsA and fetal respiratory mucosa(FRM graft, and the control group; non-immunosuppressed rats were received salineand gel foam. Locomotor performance was assessed weekly for 8 weeks after lesion,using locomotive rating scale developed by Basso, Bresnahan and Beattie (BBB. Afterbehavioral assessment, the spinal cord was examined by a histologist for spinal tissuesparing.Results: From weeks 6-8, the functional recovery of the FOM rats significantly increasedin comparison to the FRM, although a significant difference in tissue sparing was not apparent.From weeks, 2-8 the functional recovery of the FOM and FRM groups as well astissue sparing of the FOM group increased significantly compared to the control group.Conclusion: Thus, the FOM treatment may be effective to promote functional recoveryand partially preserving tissue sparing.

  9. Research progress in three-dimensional reconstruction of the rat spinal tract

    Institute of Scientific and Technical Information of China (English)

    Huiqun Wu; Guangming Lü

    2008-01-01

    BACKGROUND: Recently, three-dimensional (3D) reconstruction of the corticospinal tract has been attempted in treatment for corticospinal tract injury. However, results remain unsatisfactory. OBJECTIVE: This manuscript reviews technique progress and problems in 3D reconstruction of rat spinal tracts, as well as 3D reconstruction of human spinal tracts. RETRIEVAL STRATEGY: Using the keywords "rat, spinal tracts, three-dimensional reconstruction", the PubMed database was searched for English articles pertaining to 3D reconstruction of the rat spinal tract that were published between January 1996 and January 2007. Meanwhile, the above-mentioned keywords in Chinese were also used to search the CNKI database for articles that were published between January 1999 and January 2007. Inclusion criteria: manuscripts that addressed the study of 3D reconstruction of the rat spinal tract and review articles. Exclusion criteria: old and repetitive articles. All manuscripts were initially evaluated, followed by extensive review.LITERATURE EVALUATION: A total of 154 related manuscripts were collected; a total of 27 were evaluated and reviewed for the present review. One manuscript assessed rat behavioral functions, four were experimental reports addressing micro-3D reconstruction techniques, ten were experiment reports about image analysis of rat corticospinal tracts, and twelve were experiment articles related to image processing of serial spinal cord sections. DATA SYNTHESIS: Rat spinal cord sections were obtained through section staining or magnetic resonance imaging (MRI) techniques, specifically localizing the inner tracts. Software was used to construct 3D reconstruction from the serial sections to observe and analyze rat spinal cord structures. The rat spinal cord is small, with complicated inner tracts, which makes accurate 3D reconstruction difficult.CONCLUSION: The assembly of 3D reconstructions from rat spinal cord serial sections and the visualization of the inner tracts

  10. Human mesenchymal cells from adipose tissue deposit laminin and promote regeneration of injured spinal cord in rats.

    Science.gov (United States)

    Menezes, Karla; Nascimento, Marcos Assis; Gonçalves, Juliana Pena; Cruz, Aline Silva; Lopes, Daiana Vieira; Curzio, Bianca; Bonamino, Martin; de Menezes, João Ricardo Lacerda; Borojevic, Radovan; Rossi, Maria Isabel Doria; Coelho-Sampaio, Tatiana

    2014-01-01

    Cell therapy is a promising strategy to pursue the unmet need for treatment of spinal cord injury (SCI). Although several studies have shown that adult mesenchymal cells contribute to improve the outcomes of SCI, a description of the pro-regenerative events triggered by these cells is still lacking. Here we investigated the regenerative properties of human adipose tissue derived stromal cells (hADSCs) in a rat model of spinal cord compression. Cells were delivered directly into the spinal parenchyma immediately after injury. Human ADSCs promoted functional recovery, tissue preservation, and axonal regeneration. Analysis of the cord tissue showed an abundant deposition of laminin of human origin at the lesion site and spinal midline; the appearance of cell clusters composed of neural precursors in the areas of laminin deposition, and the appearance of blood vessels with separated basement membranes along the spinal axis. These effects were also observed after injection of hADSCs into non-injured spinal cord. Considering that laminin is a well-known inducer of axonal growth, as well a component of the extracellular matrix associated to neural progenitors, we propose that it can be the paracrine factor mediating the pro-regenerative effects of hADSCs in spinal cord injury.

  11. Diffusion Tensor Imaging in Rat Spinal Cord In-Vivo

    Science.gov (United States)

    Al-Rekabi, Zeinab

    2008-05-01

    Diffusion Tensor Imaging (DTI), an MRI technique based on probing the structure of tissues at a microscopic level is used to determine regional values of Fractional Anisotropy (FA) and mean diffusivity (Dav) of excised and in-vivo rat spinal cords. Two pulse sequences: Spin Echo (SE) and Echo Planar Imaging (EPI) are optimized to provide the best image quality, signal-to-noise ratio (SNR) and the greatest spatial resolution at reasonable acquisition times in the rat spinal cord. The study was conducted using a 7T BRUKER BioSpec MRI animal scanner. In the ex-vivo experiments images with the spatial resolution of 100 μm and the SNR of 1.938 ± 0.010 were acquired in 2 minutes. After optimization both methods were applied in-vivo. The values of FA and Dav acquired in this study showed good correlation with the literature values. Furthermore, results from these studies should provide the necessary baseline data for serial DTI in injured spinal cord in future studies.

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

    Directory of Open Access Journals (Sweden)

    Stavros eMalas

    2013-11-01

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

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

    OpenAIRE

    Panayiotou, Elena; Malas, Stavros

    2013-01-01

    Spinal cord injury (SCI) is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following SCI activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient number to l...

  14. Expression of PirB in Normal and Injured Spinal Cord of Rats

    Institute of Scientific and Technical Information of China (English)

    周迎春; 迁荣军; 饶竞; 翁密霞; 易序霞

    2010-01-01

    The expression of paired immunoglobulin-like receptor B (PirB) in normal and injured spinal cord of rats was investigated. The SD rat hemi-sectioned spinal cord injury (SCI) model was established. Before and 1, 3, 7, 10 days after SCI, the spinal cord tissues were harvested, and Western blot and immunohistochemistry were used to examine the expression and location of PirB. The results showed that the expression level of PirB in the normal spinal cord of SD rats was low. At the first day after SCI, the expre...

  15. Acellular spinal cord scaffold seeded with mesenchymal stem cells promotes long-distance axon regeneration and functional recovery in spinal cord injured rats.

    Science.gov (United States)

    Liu, Jia; Chen, Jian; Liu, Bin; Yang, Cuilan; Xie, Denghui; Zheng, Xiaochen; Xu, Song; Chen, Tianyu; Wang, Liang; Zhang, Zhongmin; Bai, Xiaochun; Jin, Dadi

    2013-02-15

    The stem cell-based experimental therapies are partially successful for the recovery of spinal cord injury (SCI). Recently, acellular spinal cord (ASC) scaffolds which mimic native extracellular matrix (ECM) have been successfully prepared. This study aimed at investigating whether the spinal cord lesion gap could be bridged by implantation of bionic-designed ASC scaffold alone and seeded with human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) respectively, and their effects on functional improvement. A laterally hemisected SCI lesion was performed in adult Sprague-Dawley (SD) rats (n=36) and ASC scaffolds seeded with or without hUCB-MSCs were implanted into the lesion immediately. All rats were behaviorally tested using the Basso-Beattie-Bresnahan (BBB) test once a week for 8weeks. Behavioral analysis showed that there was significant locomotor recovery improvement in combined treatment group (ASC scaffold and ASC scaffold+hUCB-MSCs) as compared with the SCI only group (pspinal cord cavity and promote long-distance axon regeneration and functional recovery in SCI rats.

  16. Selective control by posterior spinal nerve roots of micturition and erection in rats

    Institute of Scientific and Technical Information of China (English)

    Wenting Wang; Mouwang Zhou; Genying Zhu; Tao Li; Nan Liu

    2012-01-01

    The posterior rootlets in L6 and S1 spinal cord of adult male Sprague-Dawley rats underwent electrostimulation. The bladder pressure, urethral perfusion pressure and intracavernous pressure were recorded. When some posterior rootlets of L6 and S1 were electrostimulated, the intracavernous pressure peaked rapidly, but the bladder pressure and the urethral perfusion pressure curve did not show great change. When other rootlets were stimulated, the bladder pressure changed greatly, but the urethral perfusion pressure and the intracavernous pressure did not show great change. When different rootlets were stimulated, the urethral perfusion pressure changed maximally, but there were no great changes in bladder pressure or intracavernous pressure. Furthermore, stimulation of some rootlets produced simultaneous changes in two or three different pressure measures mentioned above. The results demonstrate that regulation by L6 and S1 posterior rootlets of the rat bladder detrusor, external urethral sphincter and penis cavernous body are significantly distinct. Different rootlets can be distinguished by electrostimulation.

  17. Isobolographic analysis of caramiphen and lidocaine on spinal anesthesia in rats.

    Science.gov (United States)

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

    2010-01-18

    The aims of the study were to evaluate the spinal anesthetic effect of caramiphen and also assess spinal anesthetic interactions of caramiphen with lidocaine. Lidocaine, a common local anesthetic, was used as control. Dose-dependent responses of intrathecal caramiphen on spinal anesthesia were compared with lidocaine in rats. The interactions of caramiphen with lidocaine were evaluated via an isobolographic analysis. Caramiphen and lidocaine produced a dose-dependent local anesthetic effect as spinal anesthesia. On a 50% effective dose (ED(50)) basis, the spinal anesthetic effect of caramiphen was more potent than lidocaine (P<0.01 for each comparison). Co-administration of caramiphen with lidocaine produced an additive effect. Caramiphen and lidocaine are known to have local anesthetic effects as spinal anesthesia in rats. The spinal anesthetic effects of adding caramiphen to lidocaine are similar to the combinations of other anesthetics with lidocaine.

  18. 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.

  19. FUNCTIONAL AND STRUCTURAL RECOVERY OF INJURED SPINAL CORD FOLLOWING DELAYED X-IRRADIATION IN RATS

    Institute of Scientific and Technical Information of China (English)

    Xin-gang Li; De-ze Jia; Dong-hai Wang; Yu-hang Su; Qing-lin Zhang

    2007-01-01

    Objective To test the hypothesis that delayed X-irradiation can enhance the functional and structural recovery of the injured spinal cord in rats,Methods Seventy Sprague-Dawley rats were randomly divided into two groups, 35 rats in each. The control group sustained a one-minute clip compression (force of clip was 30 g) injury of the spinal cord at the T2 level, without X-irradiation. The experimental group received X-irradiation 14 days after injury. Neurological function was assessed by the modified Tarlov method, including hind limbs movement, inclined plane, and pain withdrawal. These tests were performed in a blinded fashion at 3, 7, 14, 21, 28, 35 , and 42 days after injury. At 43 days after injury, histological examination of the injured spinal cord was performed following decapitation of the rats.Results Sixty-two rats met the experimental requirements (spinal cord injury was similar), 32 rats in experimental group and 30 rats in control group. Statistically significant difference was observed between the two groups in hind limbs movement and inclined plane (P <0.01), but not in the pain withdrawal test The edema and necrosis areas of injured spinal cords in experimental group were less than those in control group, and axons in experimental group were significantly more than those in control group (P < 0.01).Conclusion Delayed X-irradiation following spinal cord injury may enhance functional recovery by improving and restoring structural integrity of the injured spinal cord in rats.

  20. Potentiation of excitatory transmission in substantia gelatinosa neurons of rat spinal cord by inhibition of estrogen receptor alpha

    Directory of Open Access Journals (Sweden)

    Li Kai-Cheng

    2010-12-01

    Full Text Available Abstract Background It has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission. One of the estrogen receptor (ER subtypes, estrogen receptor alpha (ERα, is expressed in the spinal laminae I-V, including substantia gelatinosa (SG, lamina II. However, it is unclear how ERs are involved in the modulation of nociceptive transmission. Results In the present study, a selective ERα antagonist, methyl-piperidino-pyrazole (MPP, was used to test the potential functional roles of spinal ERα in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of MPP on SG neurons in the dorsal root-attached spinal cord slice prepared from adult rats. We found that MPP increased glutamatergic excitatory postsynaptic currents (EPSCs evoked by the stimulation of either Aδ- or C-afferent fibers. Further studies showed that MPP treatment dose-dependently increased spontaneous EPSCs frequency in SG neurons, while not affecting the amplitude. In addition, the PKC was involved in the MPP-induced enhancement of synaptic transmission. Conclusions These results suggest that the selective ERα antagonist MPP pre-synaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive transmission evoked by Aδ- and C-fiber stimulation could be potentiated by blocking ERα in the spinal neurons. Thus, the spinal estrogen may negatively regulate the nociceptive transmission through the activation of ERα.

  1. A non-opioid pathway for dynorphin-caused spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Yu Chen; Liangbi Xiang; Jun Liu; Dapeng Zhou; Hailong Yu; Qi Wang; Wenfeng Han; Mingming Guo

    2012-01-01

    Intrathecal injection of dynorphin into rats via subarachnoid catheter induces damage to spinal cord tissue and motor function. Injection of the kappa opioid receptor antagonist nor-binaltorphine, or the excitatory amino acid N-methyl-D-aspartate receptor antagonist MK-801 into rats alleviated the pathological changes of dynorphin-caused spinal cord tissue injury and reduced the acid phosphatase activity in the spinal cord. The experimental findings indicate that there are opioid and non-opioid pathways for dynorphin-induced spinal cord injury, and that the non-opioid receptor pathway may be mediated by the excitatory amino acid N-methyl-D-aspartate receptor.

  2. Comparison of the effect of adult neural stem cells derived from different origins in treatment of rat spinal cord injury%不同来源成体神经干细胞促进大鼠脊髓损伤功能修复的比较研究

    Institute of Scientific and Technical Information of China (English)

    蔡颖谦; 张洪钿; 姜晓丹; 徐如祥; 郭琳琅

    2009-01-01

    Objective To evaluate the therapeutic effects of adult neural stem cells derived from the brain, adipose tissue and bone marrow on spinal cord injuries in adult rats. Methods The brain subventricular zone (SVZ), adipose tissue and bone marrow from the same rat were obtained to induce the neural stem cells (NSCs). In 72 SD rats with spinal contusive injury, the NSCs from the 3 origins were grafted into the injured spinal cord one week after the injury, with 24 rats as the saline control group and another 24 as the sham-operated group. The locomotor recovery of the rats was evaluated according to the BBB scores, and the cell survival, distribution, migration and differentiation in the injured spinal cord were evaluated by immunohistochemistry. Results Compared with the rats in sham-operated and saline groups, the rats receiving transplantation of NSCs of different origins all showed significantly increased BBB scores. At 9 weeks after the transplantation, the rats receiving brain SVZ-derived NSCs (SVZ-NSs) exhibited significantly improved locomotor function compared with those grafted with the other two NSCs (P0.05). Conclusion Grafting of the NSCs derived form the brain SVZ, adipose tissue and bone marrow all help improve the locomotor recovery of the rats following spinal cord injury, and the SVZ-NSs has the most obvious effect. But AD-NSs may seem a better option than those of other origins for repairing the injured spinal cord due to their abundant sources and strong proliferation ability.s%目的 评价大脑、骨髓和脂肪组织3种不同来源的神经干细胞对大鼠脊髓挫伤的治疗效果.方法 选取来源于同一大鼠成体中大脑、骨髓和脂肪的3个部位的组织,分离、诱导分化为不同来源的神经干细胞;应用自由落体损伤模型装置造成大鼠脊髓挫伤.将不同来源的神经干细胞分别移植入大鼠脊髓损伤部位,通过BBB评分比较修复脊髓损伤功能的效果,应用免疫荧光染色检测

  3. Estrogens Suppress Spinal Endomorphin 2 Release in Female Rats in Phase with the Estrous Cycle

    Science.gov (United States)

    Kumar, Arjun; Storman, Emiliya M.; Liu, Nai-Jiang; Gintzler, Alan R.

    2015-01-01

    Background/Aims Male and female rats differ in their ability to utilize spinal endomorphin 2 (EM2; the predominant mu-opioid receptor ligand in spinal cord) and in the mechanisms that underlie spinal EM2 analgesic responsiveness. We investigated the relevance of spinal estrogen receptors (ERs) to the in vivo regulation of spinal EM2 release. Methods ER antagonists were administered directly to the lumbosacral spinal cord of male and female rats, intrathecal perfusate was collected, and resulting changes in EM2 release were quantified using a plate-based radioimmunoassay. Results Intrathecal application of an antagonist of either estrogen receptor-α (ERα) or the ER GPR30 failed to alter spinal EM2 release. Strikingly, however, the concomitant blockade of ERα and GPR30 enhanced spinal EM2 release. This effect was sexually dimorphic, being absent in males. Furthermore, the magnitude of the enhancement of spinal EM2 release in females was dependent upon estrous cycle stage, suggesting a relationship with circulating levels of 17β-estradiol. The rapid onset of enhanced EM2 release following intrathecal application of ERα/GPR30 antagonists (within 30–40 min) suggests mediation via ERs in the plasma membrane, not the nucleus. Notably, both ovarian and spinally synthesized estrogens are essential for membrane ER regulation of spinal EM2 release. Conclusion These findings underscore the importance of estrogens for the regulation of spinal EM2 activity and, by extension, endogenous spinal EM2 antinoci-ception in females. Components of the spinal estrogenic mechanism(s) that suppress EM2 release could represent novel drug targets for improving utilization of endogenous spinal EM2, and thereby pain management in women. PMID:25925013

  4. FOS EXPRESSION IN LUMBARSACRAL SPINAL CORD AND MEDULLA OBLONGATA INDUCED BY CHRONIC COLONIC INFLAMMATION IN RATS

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To investigate Fos expression in rat lumbarsacral spinal cord and medulla oblongata induced by chronic colonic inflammation. Methods Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group: colonic inflammation was induced in seventeen rats by intraluminal administration of trinitrobenzenesulfonic acid (TNBS); control group: saline was administered intraluminally in sixteen rats; After 3, 7, 14 and 28 days of administration, lumbarsacral spinal cord and medulla oblongata were removed and processed for Fos immunohistochemistry. Results Fos-immunoreactive (Fos-IR) neurons induced by TNBS administration were primarily distributed in deep laminae (laminae Ⅲ-Ⅳ,Ⅴ-Ⅵ) in the spinal dorsal horn and in medullary visceral zone (MVZ) in the medulla oblongata. The number of Fos-IR cells in the spinal cord and MVZ in rats after 7 and 14 days of TNBS administration were significantly higher than that in the control rats (P<0.05). After 28 days of TNBS instillation, the number of Fos-IR neurons in MVZ decreased and became comparable to the control group. However, the number of Fos cells in the spinal cord in some rats were still significantly increased compared with the control rats (P<0.05). Conclusion Fos-IR neurons after colonic inflammation recovery may play an important role in the development of visceral hypersensitivity. Medulla oblongata was a less important structure than the spinal cord in inducing visceral hypersensitivity after chronic colonic inflammation.

  5. Dexmedetomidine Attenuates Blood-Spinal Cord Barrier Disruption Induced by Spinal Cord Ischemia Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Bo Fang

    2015-05-01

    Full Text Available Background/Aims: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB disruption induced by spinal cord I/R injury. Methods: Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9, Angiopoietin-1 (Ang1 and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence. Results: Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury. Conclusions: Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.

  6. Lidocaine for prolonged and intensified spinal anesthesia by coadministration of propranolol in the rat.

    Science.gov (United States)

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

    2011-09-26

    Although the coadministration of lidocaine with propranolol interferes with the metabolic profile (pharmacokinetics), its pharmacodynamics is still unclear. In this report, we investigate whether propranolol can potentiate the effect of lidocaine. Rats received spinal anesthesia with lidocaine co-injected with propranolol. After intrathecal injections of drugs in rats, three neurobehavioral examinations (motor function, proprioception, and nociception) were performed. We showed that lidocaine and propranolol elicited a spinal blockade in motor function, proprioception, and nociception. Propranolol at the dose of 0.82 μmol/kg produced no spinal anesthesia. Co-administration of lidocaine [50% effective dose (ED(50)) or ED(95)] and propranolol (0.82 μmol/kg) produced greater spinal anesthesia than lidocaine (ED(50) or ED(95)), respectively. These preclinical findings demonstrated that propranolol and lidocaine displayed spinal anesthesia. When combined with propranolol, lidocaine elicited a supra-additive effect of spinal anesthesia.

  7. Elevated spinal cyclooxygenase and prostaglandin release during hyperalgesia in diabetic rats.

    Science.gov (United States)

    Freshwater, Jason D; Svensson, Camilla I; Malmberg, Annika B; Calcutt, Nigel A

    2002-07-01

    Diabetic rats display exaggerated hyperalgesic behavior in response to noxious stimuli that may model aspects of painful diabetic neuropathy. This study examined the contribution of spinal prostaglandin production to this exaggerated hyperalgesic behavior. Rats were implanted with spinal dialysis probes and received noxious stimulation to the hind paw by subcutaneous injection of 0.5% formalin solution. Prostaglandin E(2) (PGE(2)) was measured in dialysates of lumbar spinal cerebrospinal fluid concurrent with behavioral responses to formalin injection. In separate experiments, formalin-evoked behavioral responses were measured after intrathecal delivery of either a cyclooxygenase inhibitor or an EP(1) receptor antagonist, and cyclooxygenase protein was measured in spinal cord homogenates. Diabetic rats exhibited exaggerated behavioral responses to paw formalin injection and a concurrent prolongation of formalin-evoked PGE(2) release. Formalin-evoked behavioral responses were dose-dependently reduced in diabetic rats by spinal delivery of a cyclooxygenase inhibitor or an EP(1) receptor antagonist. Protein levels of cyclooxygenase-2 were elevated in the spinal cord of diabetic rats, whereas cyclooxygenase-1 protein was reduced. Hyperalgesic behavior in diabetic rats is associated with both increased cyclooxygenase-2 protein and cyclooxygenase-mediated PGE(2) release. Spinal delivery of selective inhibitors of cyclooxygenase-2 or antagonists of prostaglandin receptors may have therapeutic potential for treating painful diabetic neuropathy.

  8. 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...

  9. SOX2 expression is upregulated in adult spinal cord after contusion injury in both oligodendrocyte lineage and ependymal cells.

    Science.gov (United States)

    Lee, Hyun Joon; Wu, Junfang; Chung, Jumi; Wrathall, Jean R

    2013-02-01

    The upregulation of genes normally associated with development may occur in the adult after spinal cord injury (SCI). To test this, we performed real-time RT-PCR array analysis of mouse spinal cord mRNAs comparing embryonic day (E)14.5 spinal cord with intact adult and adult cord 1 week after a clinically relevant standardized contusion SCI. We found significantly increased expression of a large number of neural development- and stem cell-associated genes after SCI. These included Sox2 (sex determining region Y-box 2), a transcription factor that regulates self-renewal and potency of embryonic neural stem cells and is one of only a few key factors needed to induce pluripotency. In adult spinal cord of Sox2-EGFP mice, Sox2-EGFP was found mainly in the ependymal cells of the central canal. After SCI, both mRNA and protein levels of Sox2 were significantly increased at and near the injury site. By 1 day, Sox2 was upregulated in NG2(+) oligodendrocyte progenitor cells (OPC) in the spared white matter. By 3 days, Sox2-EGFP ependymal cells had increased proliferation and begun to form multiple layers and clusters of cells in the central lesion zone of the cord. Expression of Sox2 by NG2(+) cells had declined by 1 week, but increased numbers of other Sox2-expressing cells persisted for at least 4 weeks after SCI in both mouse and rat models. Thus, SCI upregulates many genes associated with development and neural stem cells, including the key transcription factor Sox2, which is expressed in a pool of cells that persists for weeks after SCI.

  10. Expression of PirB in normal and injured spinal cord of rats.

    Science.gov (United States)

    Zhou, Yingchun; Qian, Rongjun; Rao, Jing; Weng, Mixia; Yi, Xuxia

    2010-08-01

    The expression of paired immunoglobulin-like receptor B (PirB) in normal and injured spinal cord of rats was investigated. The SD rat hemi-sectioned spinal cord injury (SCI) model was established. Before and 1, 3, 7, 10 days after SCI, the spinal cord tissues were harvested, and Western blot and immunohistochemistry were used to examine the expression and location of PirB. The results showed that the expression level of PirB in the normal spinal cord of SD rats was low. At the first day after SCI, the expression of PirB was obviously increased, and that in the injured spinal cord from the first day to the 10th day was significantly higher than in the normal spinal cord. The positive expression of PirB in neurons from different regions of gray matter of the injured spinal cord was seen. It was concluded that the expression of PirB in the normal spinal cord of rats was low. The expression of PirB in SCI was significantly increased till at least the 10th day.

  11. 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 cor

  12. Evidence for the presence of both peroxisome proliferator-activated receptors alpha and beta in the rat spinal cord.

    Science.gov (United States)

    Benani, A; Krémarik-Bouillaud, P; Bianchi, A; Netter, P; Minn, A; Dauça, M

    2003-01-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. Different subtypes of PPARs (alpha, beta, and gamma) have been described. Their distinct physiological functions depend on their differential ligand activation profiles but also on their specific tissue expression. Previous studies have described their presence in the central nervous system. However, their expression in the adult rat spinal cord in normal physiological conditions has never been investigated. We demonstrated by using reverse-transcription-polymerase chain reaction, and Western blotting, the mRNA and protein expression of PPARalpha and PPARbeta, but not PPARgamma in cervical, thoracic, and lumbar segments of the spinal cord. Using immunohistochemistry, we also showed for the first time the specific cellular distribution of these transcription factors in the different segments of the spinal cord. In the gray matter, the distribution of PPARalpha was homogenous whereas PPARbeta was specifically localized in motoneurons and in medial part of laminae IV, V, VI, VII, VIII, and X. These latter areas are known as nociceptive afferent pathways to supra-spinal structures such as the medulla reticular nucleus and the thalamus. In the white matter, PPARalpha was localized exclusively in astrocytes while PPARbeta was present in oligodendrocytes. The possible functions of PPARalpha and PPARbeta expressed in both white and gray matters of the spinal cord will be discussed but need further studies.

  13. Evaluation of the excopula ejaculatory potentials of Bersama engleriana in spinal male rats

    Institute of Scientific and Technical Information of China (English)

    Pierre Watcho; Miguel Carro-Juarez

    2009-01-01

    tive ejaculation in spinal male rat is mediated through dopaminergic and oxytocinergic pathways. This prolonged ejaculatory latency caused by B. Engleriana could support its potential use in patients with rapid ejaculation.

  14. 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

  15. Ginkgo biloba leaf extract effects on inducible nitric oxide synthase, Bcl-2, and Bax expression in rat models of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Jiejun Jiao; Bin Du

    2008-01-01

    BACKGROUND: Ginkgo biloba leaf extract exhibits neuroprotective effects in spinal cord injury. However,the mechanisms of action remain unclear.OBJECTIVE: To investigate inducible nitric oxide synthase (iNOS) and Bcl-2/Bax expression in the injured spinal cord, and to explore the neuroprotective mechanisms of ginkgo biloba leaf extract in rats with spinal cord injury.DESIGN, TIME AND SETTING: The randomized, controlled, cell molecular biology experiment was performed at Soochow University, China from March 2007 to March 2008.MATERIALS: A total of 120 healthy, adult Sprague Dawley rats were selected for this study. Rat models of moderate acute thoracic (T9) spinal cord injury were established using the modified Allen method.Shuxuening injection was obtained from Zhenbaodao Pharmaceutical Co., Ltd., China. Methylprednisolone was purchased from North China Pharmaceutical Co., Ltd.METHODS: All rats were equally and randomly divided into four groups. Only the spinal cord was exposed in the sham operation group rats. In the trauma group, rats were not treated with drugs following spinal cord injury. Rats in the hormone group were intraperitoneally injected with 30 mg/kg methylprcdnisolone following spinal cord injury. Rats in the ginkgo biloba leaf extract group were intraperitoneally infused with a 1.0 mL/kg Shuxuening injection per day.MAIN OUTCOME MEASURES: At l hour, as well as 1, 3, 5, 7, and 14 days after spinal cord injury,iNOS- and Bcl-2/Bax-positive cells were quantified with immunohistochemistry. Pathological changes were detected using hematoxylin-eosin staining under an optical microscope.RESULTS: Spinal cord injury in the ginkgo biloba leaf extract and hormone groups was milder compared with the trauma group. Demyelination was significantly ameliorated and the necrotic cavity was obviously reduced in the injured spinal cord of rats in the ginkgo biloba leaf extract and hormone groups at each time point, iNOS expression was increased in the injured spinal cord

  16. Lumbar spinal mobility changes among adults with advancing age

    Directory of Open Access Journals (Sweden)

    Ismaila Adamu Saidu

    2011-01-01

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

  17. FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE SPINAL CORD DURING SENSORY STIMULATION IN DIABETIC RATS

    Science.gov (United States)

    Malisza, Krisztina L.; Jones, Cheryl; Gruwel, Marco L.H.; Foreman, Derek; Fernyhough, Paul; Calcutt, Nigel A.

    2009-01-01

    Purpose To determine if differences exist between control and diabetic rats in functional MRI activity of the spinal cord and if fMRI can provide a means of early detection of diabetic neuropathy. Materials and Methods fMRI of the spinal cord, using noxious electrical stimulation (15 V (~8 mA), 0.3 ms, 3 Hz) of the hind paw, was performed in groups of control and streptozotocin (STZ)-induced type 1 diabetic rats. Results Diabetic rats were lighter, hyperglycemic and had lower blood pH than controls. FMRI activity at the lumbar enlargement of the spinal cord was identified in the dorsal horn ipsilateral to stimulus of all animals. Signal intensity changes across the lumbar spinal cord during periods of activity were not significantly different between control and diabetic rats, with a trend towards greater signal changes in controls. When specific regions of the spinal cord were analyzed, control rats exhibited significantly increased BOLD fMRI activity in both ipsilateral and contralateral dorsal horn compared to diabetic rats. Conclusion The results of this study are consistent with reports that primary afferent input to the spinal cord is diminished by diabetes, and suggest that BOLD fMRI may be useful in early detection of diabetic neuropathy. PMID:19629995

  18. A PARYLENE-BASED MICROELECTRODE ARRAY IMPLANT FOR SPINAL CORD STIMULATION IN RATS.

    Science.gov (United States)

    Nandra, Mandheerej S; Lavrov, Igor A; Edgerton, V Reggie; Tai, Yu-Chong

    2011-01-23

    The design and fabrication of an epidural spinal cord implant using a parylene-based microelectrode array is presented. Rats with hindlimb paralysis from a complete spinal cord transection were implanted with the device and studied for up to eight weeks, where we have demonstrated recovery of hindlimb stepping functionality through pulsed stimulation. The microelectrode array allows for a high degree of freedom and specificity in selecting the site of stimulation compared to wire-based implants, and triggers varied biological responses that can lead to an increased understanding of the spinal cord and locomotion recovery for victims of spinal cord injury.

  19. Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.

    Directory of Open Access Journals (Sweden)

    Jose A Corleto

    Full Text Available The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI. The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9 complete transection model of muscle spasticity in Sprague-Dawley (SD rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i ankle-rotation-evoked peripheral muscle resistance (PMR and corresponding electromyography (EMG activity, ii Hoffmann reflex, and iii EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist, tizanidine (α2-adrenergic agonist and NGX424 (AMPA receptor antagonist was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the

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

    Science.gov (United States)

    Panayiotou, Elena; Malas, Stavros

    2013-11-28

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

  1. 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 various levels along the cranio-caudal axis of the rat spinal cord revealed differences in the heavy metal content. The Timm sulfide silver staining method has demonstrated that metals in the spinal cord have a distinct regional distribution. To obtain a differentiation between the stainable metals...

  2. Effects of nerve growth factor on neuronal nitric oxide production after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    汤长华; 曹晓建; 王道新

    2002-01-01

    To explore the protective effects of nerve growth factor (NGF) on injured spinal cord. Methods: The spinal cord injury (SCI) model of Wistar rats was established by a 10 g×2.5 cm impact force on the T8 spinal cord. NGF (60 μg/20 μl) was given to the rats of the treatment group immediately and at 2, 4, 8, 12, 24 hours after SCI. The level of neuronal constitutive nitric oxide synthase (ncNOS) and the expression of ncNOS mRNA in the spinal cord were detected by the immunohistochemistry assay and in situ hybridization method. Results: Abnormal expression of ncNOS was detected in the spinal ventral horn motorneuron in injured rats. The levels of ncNOS protein in the NGF group were significantly lower than those in the normal saline group (P<0.05 ). The ncNOS mRNA expression was found in the spinal ventral horn motorneuron in injured rats and the expression in the NGF group was significantly decreased compared with that in the normal saline group (P<0.01). Conclusions: NGF can protect the injured tissue of the spinal cord by prohibiting abnormal expression of nitric oxide synthase and the neurotoxicity of nitric oxide.

  3. Expression of adrenomedullin in rats after spinal cord injury and intervention effect of recombinant human erythropoietin

    Science.gov (United States)

    Zhao, Liang; Jing, Yu; Qu, Lin; Meng, Xiangwei; Cao, Yang; Tan, Huibing

    2016-01-01

    The expression of adrenomedullin (ADM) in injured tissue of rat spinal cord was observed and the effect of recombinant human erythropoietin was analyzed. A total of 45 Sprague-Dawley rats were selected and divided into 3 equal groups including, a sham-operation group in which rats received an excision of vertebral plate; a spinal cord injury model group and a recombinant human erythropoietin group in which rats with spinal cord injury received a caudal vein injection of 300 units recombinant human erythropoietin after injury. Hematoxylin and eosin staining was performed to observe the spinal cord injury conditions. Immunohistochemical staining was performed to observe the expression of ADM. Pathologic changes in the group of recombinant human erythropoietin at various times were significantly less severe than those in the group of spinal cord injury model. The expression of ADM was increased particularly in the group of recombinant human erythropoietin (P<0.01). The improved Tarlov scores of the group of spinal cord injury model and the group of recombinant human erythropoietin were lower than those of the sham-operation group at 3, 6 and 9 days (P<0.01). Thus, the recombinant human erythropoietin is capable of alleviating the secondary injury of spinal cord. One of the mechanisms may be achieved by promoting the increase of ADM expression. PMID:28101163

  4. Immunofluorescence laser confocal expression and localization study of rat nerve growth guidance cues Netrin-1 and Slit2 after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    LU Yao-jun; XU Nan-wei; YANG Wen-qiang

    2008-01-01

    To observe the expression and distribution of adult rat axon guidance cues Netrin-1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axons.Methods:Twenty adult Sprague Dawley(SD)rats were divided randomly into five groups with 4 in each.Four groups of them were used to make Allen's spinal cord punch models and we took materials randomly from one of them on the 2nd,4th,7th and 14th day respectively after operation.The left one group was taken as the control group.Immunofluorescence laser confocal scan was used to examine the co-expression and localization of Netrin-1 and Slit2 proteins in the injured site of the spinal cord.Results:Within two weeks after SCI,the expression of Netrin-1 and Slit2 proteins increased temporarily and there was co-expression of them on the neuron plasma membrane.Conclusions:Synchronous high expression and co-expression of axon attractant Netrin-1 and repellent Slit2 are found in the adult rat injured spinal cord in the damaged local and vicinity parts,and probably,they act as the key regulators of axon guidance regeneration.

  5. Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

    Science.gov (United States)

    Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

    2017-02-01

    Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords.NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a

  6. Salvianolic acid B promotes survival of transplanted mesenchymal stem cells in spinal cord-injured rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-bin BI; Yu-bin DENG; Dan-hui GAN; Ya-zhu WANG

    2008-01-01

    Aim: Stem cells hold great promise for brain and spinal cord injuries (SCI), but cell survival following transplantation to adult central nervous system has been poor. Salvianolic acid B (Sal B) has been shown to improve functional recovery in brain-injured rats. The present study was designed to determine whether Sal B could improve transplanted mesenchymal stem cell (MSC) survival in SCI rats. Methods: SCI rats were treated with Sal B. The Basso-Beatie-Bresnahan (BBB) scale was used to test the functional recovery. Sal B was used to protect MSC from being damaged by TNF-α in vitro. Bromodeoxyuridine-labeled MSC were transplanted into SCI rats with Sal B intraperitoneal injection, simul-taneously. MSC were examined, and the functional recovery of the SCI rats was tested. Results: Sal B treatment significantly reduced the lesion area from 0.26±0.05 mm2 to 0.15±0.03 mm2 (P<0.01) and remarkably raised the BBB scores on d 28, post-injury, from 7.3±0.9 to 10.5±1.3 (P<0.05), compared with the phosphate-buffered saline (PBS) control group. MSC were protected from the damage of TNF-α by Sal B. The number of surviving MSC in the MSC plus Sal B groups were 1143.3± 195.6 and 764.0±81.3 on d 7 and 28, post-transplantation, more than those in the MSC group, which was 569.3±72.3 and 237.0±61.3, respectively (P<0.05). Rats with MSC trans-planted and Sal B injected obtained higher BBB scores than those with MSC transplanted alone (P<0.05) and PBS (P<0.01). Conclusion: Sal B provides neuroprotection to SCI and promotes the survival of MSC in vitro and after cell transplantation to the injured spinal cord in vivo.

  7. Persistent beneficial impact of H-reflex conditioning in spinal cord-injured rats.

    Science.gov (United States)

    Chen, Yi; Chen, Lu; Wang, Yu; Wolpaw, Jonathan R; Chen, Xiang Yang

    2014-11-15

    Operant conditioning of a spinal cord reflex can improve locomotion in rats and humans with incomplete spinal cord injury. This study examined the persistence of its beneficial effects. In rats in which a right lateral column contusion injury had produced asymmetric locomotion, up-conditioning of the right soleus H-reflex eliminated the asymmetry while down-conditioning had no effect. After the 50-day conditioning period ended, the H-reflex was monitored for 100 [±9 (SD)] (range 79-108) more days and locomotion was then reevaluated. After conditioning ended in up-conditioned rats, the H-reflex continued to increase, and locomotion continued to improve. In down-conditioned rats, the H-reflex decrease gradually disappeared after conditioning ended, and locomotion at the end of data collection remained as impaired as it had been before and immediately after down-conditioning. The persistence (and further progression) of H-reflex increase but not H-reflex decrease in these spinal cord-injured rats is consistent with the fact that up-conditioning improved their locomotion while down-conditioning did not. That is, even after up-conditioning ended, the up-conditioned H-reflex pathway remained adaptive because it improved locomotion. The persistence and further enhancement of the locomotor improvement indicates that spinal reflex conditioning protocols might supplement current therapies and enhance neurorehabilitation. They may be especially useful when significant spinal cord regeneration becomes possible and precise methods for retraining the regenerated spinal cord are needed.

  8. Transsynaptic tracing of CNS neural circuitry involved in the innervation of bladder function in the adult rat brainstem and spinal cord%大鼠脊髓及脑干内膀胱支配中枢的跨突触示踪研究

    Institute of Scientific and Technical Information of China (English)

    盛珺; 肖燎原; 张月雷; 林浩东; 侯春林

    2013-01-01

    Objective To identify the CNS neural circuitry involved in the innervation of bladder function in the adult rat brainstem and spinal cord using pseudorabies virus,a transsynaptic tracer,so as to lay down the basis for further studying of brain functional reorganization after bladder function reconstruction.Methods GFP-PRV 4.5ul (1 × 108 PFU/ml)was injected into the bladder wall of 15 adult female SD rats at 3 different sites.The distribution of virus-infected neurons in the brainstem,spinal cord and dorsal root ganglion were observed under fluorescent microscope at various intervals (72h,84h,96h,108h,120h) following the PRV injection.Results Fluorescence positive neurons were mainly present in L6~S1,L1~L2 dorsal root ganglion;sacral parasympathetic nucleus,intermediolateral cell column and dorsal commissural in L6~S1 and L1~L2 spinal cord segments; Barrington's nucleus,nucleus raphe magnus,the gigantocelluar reticular nucleus,the parapyramidal reticular formation,noradrenergic cell groups A5 and A7,locus coeruleus,periaqueductal gray and the ventral region of red nucleus in brainstem.Conclusion The structures labeled in spinal cord and brainstern are synaptically connected with the bladder and presumably involved in the neural control of the bladder.%目的 跨突触示踪正常大鼠脊髓和脑干内膀胱支配相关中枢,为进一步阐明膀胱功能重建术后中枢重塑奠定研究基础. 方法 成年雌性SD大鼠l5只,膀胱壁内分三个点共注射GFP-PRV 4.5μl(1×108 PFU/ml).注射后不同时间(72、84、96、108、120h)分别取大脑、脊髓及背根神经节,荧光显微镜下观察标记结果. 结果 病毒注射后72~120 h,阳性神经元主要分布于L6~S1、L1~L2脊神经背根神经节;L6~S1、L1~L2脊髓节段骶副交感核、中间外侧核及后连合核;脑干的巴氏核、中缝巨细胞核、巨细胞网状核、锥旁网状结构、去甲肾上腺素能细胞群A5及A7、蓝斑、中脑导水管周

  9. Inflammation unmasks gabapentin's effect on Aδ-fiber evoked excitatory postsynaptic currents in substantia gelatinosa neurons of rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    刘智良; 徐如祥; 杨鲲

    2003-01-01

    ObjectiveTo study the analgesic mechanism of gabapentin, an anticonvulsant, during antinociceptive clinical treatment. MethodsWhole-cell voltage-clamp recordings were taken from adult rat spinal cord slices to investigate the effect of gabapentin on primary afferent Aδ-fiber evokedexcitatory postsynaptic currents (EPSCs) to substantia gelatinosa (SG) neurons in normal and inflamed (established by plantar injection of carrageenan) rats. Results Gabapentin (5-20 μmol/L for 5 min) depressed dorsal root Aδ fiber evoked polysynaptic, but not monosynaptic EPSCs to SG experiencing inflammation by about 25ptic or monosynaptic EPSCs in normal rats. Gabapentin failed to block a glutamate receptor subtype, N-methyl-D-aspartate (NMDA), -induced slow excitatory currents on SG neurons.ConclusionsInflammation, at least in part, unmasks the gabapentin depression on nociception transmission in the dorsal horn, and this depression is not due to the blockade of postsynaptic NMDA receptor.

  10. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats.

    Science.gov (United States)

    Vavrek, R; Girgis, J; Tetzlaff, W; Hiebert, G W; Fouad, K

    2006-06-01

    Although regeneration of injured axons is inhibited within the adult CNS, moderate recovery can be found in patients and animals with incomplete spinal cord injury (SCI). This can be partly attributed to sprouting of spared and injured axons, rostral and caudal to the lesion, respectively. Recently, it has been reported that following a thoracic SCI such sprouting can result in indirect reconnections of the lesioned axons to caudal targets via propriospinal interneurons (PrI). Here, we attempted to further promote this spontaneous repair mechanism by applying the neurotrophic factor BDNF (brain-derived neurotrophic factor), in the vicinity of the cell bodies of lesioned corticospinal neurons or NT-3, intrathecally to the cervical spinal cord. We performed a dorsal over-hemisection at the thoracic spinal cord sparing only the left ventrolateral quadrant. This type of lesion did not promote sprouting of injured corticospinal axons or re-routing via commissural PrI. Also, in rats that received NT-3 at the cervical enlargement, no increase in sprouting was found. However, animals receiving BDNF at the cell bodies of lesioned corticospinal neurons showed a significant increase in collateral sprouting and in the number of contacts with PrI. This was not observed when BDNF was administered to unlesioned animals. Although no statistical difference in the horizontal ladder walking was found between the groups, the increase in collateral sprouting and in the number of contacts correlated with the functional recovery. Hence, cell body treatment can promote plasticity of the injured CNS and may be a valuable treatment approach in conjunction with local regeneration promoting strategies.

  11. Repair of spinal cord injury by neural stem cells modified with BDNF gene in rats

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Wen-Qin CAI; Cheng-Ren LI

    2006-01-01

    Objective To explore repair of spinal cord injury by neural stem cells (NSCs) modified with brain derived neurotrophic factor (BDNF) gene (BDNF-NSCs) in rats. Methods Neural stem cells modified with BDNF gene were transplanted into the complete transection site of spinal cord at the lumbar 4 (L4) level in rats. Motor function of rats'hind limbs was observed and HE and X-gal immunocytochemical staining, in situ hybridization, and retrograde HRP tracing were also performed. Results BDNF-NSCs survived and integrated well with host spinal cord. In the transplant group, some X-gal positive, NF-200 positive, GFAP positive, BDNF positive, and BDNF mRNA positive cells, and many NF-200 positive nerve fibers were observed in the injury site. Retrograde HRP tracing through sciatic nerve showed some HRP positive cells and nerve fibers near the rostral side of the injury one month after transplant and with time, they increased in number. Examinations on rats' motor function and behavior demonstrated that motor function of rats' hind limbs improved better in the transplant group than the injury group. Conclusion BDNF-NSCs can survive, differentiate,and partially integrate with host spinal cord, and they significantly ameliorate rats ' motor function of hind limbs, indicating their promising role in repairing spinal cord injury.

  12. Neuroprotective effect of estrogen after chronic spinal cord injury in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: At present, there is still lack of effective drugs for chronic spinal cord injury, whereas it is found recently that estrogen has a neuroprotective effect on brain and spinal cord injuries.OBJECTIVE: To observe the effect of estrogen on the apoptosis of nerve cells after gradual chronic spinal cord injury in ovariectomized rats.DESIGN: A randomized controlled animal trial.SETTING: Institute of Orthopaedics, the Second Hospital of Lanzhou University.MATERIALS: Sixty-five female Wistar rats of common degree, weighing 220 - 250 g, were provided by the experimental animal center of Lanzhou University. The rats were randomly divided into sham-operated group (n =5), estrogen-treated group (n =30) and saline control group (n =30), and the latter two groups were observed at 1, 3, 7, 14, 28 and 60 days respectively, and 5 rats for each time point.METHODS: All the rats were treated with bilateral oophorectomy 2 weeks before the experiment. T10 vertebral lamina was revolved into using plastic screw. The spinal canal impingement was not induced initially. After that, the original incision was opened to expose the screw every 7 - 10 days.MAIN OUTCOME MEASURES: The apoptosis and Caspase-3 positive cells in the damaged spinal cord were detected using terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) method and Caspase-3 immunohistochemical staining at 1, 3, 7, 14, 28 and 60 days after chronic spinal cord injury respectively.RESULTS: Totally 65 rats were used, and the deleted ones during the experiment were supplemented by others. Changes of Caspase-3 expression after spinal cord injury: In the sham-operated group, only a small amount of Caspase-3 proteins were observed in the rat spinal cord, mainly located in motor neurons of spinal cord anterior horn. In the estrogen-treated group and saline control group, positive cells expressed occasionally at 1 day postoperatively, began to increase obviously at 7 days after injury, strongly

  13. Acupuncture inhibition on neuronal activity of spinal dorsal horn induced by noxious colorectal distention in rat

    Institute of Scientific and Technical Information of China (English)

    Pei-Jing Rong; Bing Zhu; Qi-Fu Huang; Xin-Yan Gao; Hui Ben; Yan-Hua Li

    2005-01-01

    AIM: To observe how acupuncture stimulation influences the visceral nociception in rat and to clarify the interactions between acupuncture or somatic input and visceral nociceptive inputs in the spinal dorsal horn. These will provide scientific base for illustrating the mechanism of acupuncture on visceral pain.METHODS: Experiments were performed on SpragueDawley rats and the visceral nociceptive stimulus was generated by colorectal distention (CRD). Unit discharges from individual single neuron were recorded extracellularly with glass-microelectrode in L1-3 spinal dorsal horn.Acupuncture stimulation was applied at contralateral heterotopic acupoint and ipsilateral homotopic acupoint,both of which were innervated by the same segments that innervate also the colorectal-gut.RESULTS: The visceral nociception could be inhibited at the spinal level by the heterotopic somatic mechanical stimulation and acupuncture. The maximal inhibition was induced by acupuncture or the somatic noxious stimulation at spinal dorsal horn level with inhibiting rate of 68.61%and 60.79%, respectively (P<0.01 and <0.001). In reversible spinalized rats (cervical-thoracic cold block)both spontaneous activity and responses to CRD increased significantly in 16/20 units examined, indicating the existence of tonic descending inhibition. The inhibition of acupuncture on the noxious CRD disappeared totally in the reversible spinalized rats (P<0.001).CONCLUSION: The inputs of noxious CRD and acupuncture may interact at the spinal level. The nociceptive visceral inputs could be inhibited by acupuncture applied to hetero-topic acupoint. The effect indicates that the spinal dorsal horn plays a significant role in mediating the inhibition of acupuncture and somatic stimulation on the neuronal response to the noxious visceral stimulation and the inhibition is modulated by upper cervical cord and/or supra-spinal center.

  14. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    Science.gov (United States)

    Jolivalt, Corinne G.; Lee, Corinne A.; Ramos, Khara M.; Calcutt, Nigel A.

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABAA receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats while levels of NKCC1 and the GABAA receptor were unchanged. Spinal delivery of the GABAA receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABAA receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally-mediated hyperalgesia in diabetes. PMID:18755547

  15. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters.

    Science.gov (United States)

    Jolivalt, Corinne G; Lee, Corinne A; Ramos, Khara M; Calcutt, Nigel A

    2008-11-15

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored the role of the GABA(A) receptor in rats with painful diabetic neuropathy. KCC2 protein levels were significantly reduced in the spinal cord of diabetic rats, while levels of NKCC1 and the GABA(A) receptor were unchanged. Spinal delivery of the GABA(A) receptor antagonist bicuculline reduced formalin-evoked flinching in diabetic rats and also dose-dependently alleviated tactile allodynia. GABA(A) receptor-mediated rate-dependent depression of the spinal H reflex was absent in the spinal cord of diabetic rats. Control rats treated with the KCC2 blocker DIOA, mimicked diabetes by showing increased formalin-evoked flinching and diminished rate- dependent depression. The ability of bicuculline to alleviate allodynia and formalin-evoked hyperalgesia in diabetic rats is consistent with a reversal of the properties of GABA predicted by reduced spinal KCC2 and suggests that reduced KCC2 expression and increased GABA release contribute to spinally mediated hyperalgesia in diabetes.

  16. 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.

  17. Effect of valproic acid on endogenous neural stem cell proliferation in a rat model of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Guoxin Nan; Ming Li; Weihong Liao; Jiaqiang Qin; Yujiang Cao; Youqiong Lu

    2009-01-01

    BACKGROUND: Valproic acid has been reported to decrease apoptosis, promote neuronal differentiation of brain-derived neural stem cells, and inhibit glial differentiation of brain-derived neural stem cells.OBJECTIVE: To investigate the effects of valproic acid on proliferation of endogenous neural sterm cells in a rat model of spinal cord injury.DESIGN, TIME AND SETTING: A randomized, controlled, neuropathological study was performed at Key Laboratory of Trauma, Buming, and Combined Injury, Research Institute of Surgery, Daping Hospital, the Third Military Medical University of Chinese PLA between November 2005 and February 2007.MATERIALS: A total of 45 adult, Wistar rats were randomly divided into sham surgery (n=5), injury(n=20), and valproic acid (n=20) groups. Valproic acid was provided by Sigma, USA.METHODS: Injury was induced to the T10 segment in the injury and valproic acid groups using the metal weight-dropping method. The spinal cord was exposed without contusion in the sham surgery group. Rats in the valproic acid group were intraperitoneally injected with 150 mg/kg valproic acid every 12 hours (twice in total).MAIN OUTCOME MEASURES: Nestin expression (5 mm from injured center) was detected using immunohistochemistry at 1, 3 days, 1, 4, and 8 weeks post-injury.RESULTS: Low expression of nestin was observed in the cytoplasm, but rarely in the white matter of the spinal cord in the sham surgery group. In the injury group, nestin expression was observed in the ependyma and pia mater one day after injury, and expression reached a peak at 1 week (P<0.05).Expression was primarily observed in the ependymal cells, which expanded towards the white and gray matter of the spinal cord. Nestin expression rapidly decreased by 4 weeks post-injury, and had almost completely disappeared by 8 weeks. At 24 hours after spinal cord injury, there was nosignificant difference in nestin expression between the valproic acid and injury groups. At 1 week,there was a significant

  18. The reparative response to cross-linked collagen-based scaffolds in a rat spinal cord gap model.

    Science.gov (United States)

    Cholas, Rahmatullah H; Hsu, Hu-Ping; Spector, Myron

    2012-03-01

    Prior work demonstrated the improvement of peripheral nerve regeneration in gaps implanted with collagen scaffold-filled collagen tubes, compared with nerve autografts, and the promise of such implants for treating gaps in spinal cord injury (SCI) in rats. The objective of this study was to investigate collagen implants alone and incorporating select therapeutic agents in a 5-mm full-resection gap model in the rat spinal cord. Two studies were performed, one with a 6-week time point and one with a 2-week time point. For the 6-week study the groups included: (1) untreated control, (2) dehydrothermally (DHT)-cross-linked collagen scaffold, (3) DHT-cross-linked collagen scaffold seeded with adult rat neural stem cells (NSCs), and (4) DHT-cross-linked collagen scaffold incorporating plasmid encoding glial cell line-derived neurotropic factor (pGDNF). The 2-week study groups were: (1) nontreated control, (2) DHT-cross-linked collagen scaffold; (3) DHT-cross-linked collagen scaffold containing laminin; and (4) carbodiimide-cross-linked collagen scaffold containing laminin. The tissue filling the defect of all groups at 6 weeks was largely composed of fibrous scar; however, the tissue was generally more favorably aligned with the long axis of the spinal cord in all of the treatment groups, but not in the control group. Quantification of the percentage of animals per group containing cystic cavities in the defect showed a trend toward fewer rats with cysts in the groups in which the scaffolds were implanted compared to control. All of the collagen implants were clearly visible and mostly intact after 2 weeks. A band of fibrous tissue filling the control gaps was not seen in the collagen implant groups. In all of the groups there was a narrowing of the spinal canal within the gap as a result of surrounding soft tissue collapse into the defect. The narrowing of the spinal canal occurred to a greater extent in the control and DHT scaffold alone groups compared to the DHT

  19. 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.

  20. Delayed remyelination in rat spinal cord following ethidium bromide injection.

    Science.gov (United States)

    Graça, D L; Blakemore, W F

    1986-01-01

    Areas of demyelination were produced by injecting ethidium bromide into the white matter of the lumbar spinal cord of rats. There was variation in the nature of the process of demyelination and a difference in the speed with which Schwann cells remyelinated the demyelinated axons. In some lesions, or areas within lesions, myelin debris was rapidly processed by macrophages and axons were rapidly remyelinated by Schwann cells, while in other lesions of similar duration, or in areas within the same lesion, the myelin was transformed into lattices of membranous profiles which persisted around axons for long periods of time. In the lesions containing such myelin derived membranes, there were few macrophages and remyelination by Schwann cells was delayed compared to that seen in the more rapidly resolving lesions. It was concluded that the slow resolution of some lesions resulted from the delay between intoxication and cell disintegration (7-10 days) which meant that the cell responses to demyelination took place in a glial free area which could not support cell movement needed for removal of myelin debris and remyelination. This study indicates that the tempo and results of demyelination can be altered by the cellular events which accompany degeneration of oligodendrocytes.

  1. 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.

  2. Isobolographic analysis of interaction between nisoxetine- and mepivacaine-induced spinal blockades in rats.

    Science.gov (United States)

    Leung, Yuk-Man; Chu, Chin-Chen; Kuo, Chang-Shin; Chen, Yu-Wen; Hung, Ching-Hsia; Wang, Jhi-Joung

    2014-02-01

    Although nisoxetine has been shown to elicit cutaneous (peripheral) anesthesia, spinal (central) anesthesia with nisoxetine was not exposed. The aim of this study was to examine spinal anesthesia of nisoxetine and its influence on the antinociceptive action of mepivacaine. We compared nisoxetine with an established local anesthetic mepivacaine for spinal anesthesia after rats were intrathecally injected with drugs. The drugs were spinally administered alone as well as in combination, and their potencies were compared via dose-response curves and isobolographic analysis. We showed that nisoxetine, as well as mepivacaine elicited spinal anesthesia in dose-dependent manners. On a 50% effective dose (ED₅₀) basis, the spinal block effect of nisoxetine in motor function, proprioception, and nociception [0.99 (0.91-1.10), 0.85 (0.76-0.95), 0.82 (0.74-0.89)] was more potent (P < 0.05) than that of mepivacaine [1.28 (1.21-1.34), 1.14 (1.07-1.22), 0.99 (0.93-1.05)], respectively. Furthermore, the nociceptive/sensory blockade (ED₅₀) was greater than the motor blockade in both nisoxetine and mepivacaine groups (P < 0.05). Saline group (vehicle) produced no spinal anesthesia. Coadministration of nisoxetine with mepivacaine displayed an additive effect. Our data reported nisoxetine produced significant anesthesia at spinal level, and additive interaction with the local anesthetic, mepivacaine. Intrathecal nisoxetine elicited more potent spinal anesthesia than mepivacaine.

  3. 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

    ]Epibatidine in concentrations of 1, 10 and 100 nM was dissolved in Ringer's solution and administered through the dialysis membrane into the dorsal region of the cervical spinal cord. First, the outflow of [(3)H]epibatidine from the probe into the spinal cord was examined with respect to different concentrations and changes...

  4. 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

    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......, 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.......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....

  5. Simvastatin protects bladder and renal functions following spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    Schuler Thomas C

    2010-04-01

    Full Text Available Abstract Background Urinary bladder and renal dysfunction are secondary events associated with spinal cord injury (SCI in humans. These secondary events not only compromise quality of life but also delay overall recovery from SCI pathophysiology. Furthermore, in experimental models the effects of SCI therapy on bladder and renal functions are generally not evaluated. In this study, we tested whether simvastatin improves bladder and renal functions in a rat model of experimental SCI. Methods SCI was induced by controlled contusion of T9-T10 in adult female rats. Simvastatin (5 mg/Kg body weight was administered at two hours after SCI and repeated every 24 hours until the end point. Simvastatin-treated SCI animals (simvastatin group were compared with vehicle-treated SCI animals (vehicle group in terms of the Basso Beattie Bresnahan score, tissue morphology, cell death, and bladder/renal functions. Results The urinary bladder of vehicle animals showed a 4.3-fold increase in size and a 9-fold increase in wet weight compared to sham animals. Following SCI, the urine to plasma osmolality ratio increased initially but decreased 1 week after SCI. Hematoxylin and eosin staining of bladder tissue showed transitional epithelial hyperplasia, degeneration of lamina propria, and enlargement of tunica adventia in addition to detrusor muscle hypertrophy. Rats treated with simvastatin for 14 days displayed remarkable recovery by showing decreased bladder size and maintenance of a normal urine/plasma osmolality ratio, in addition to improved locomotion. The muscularis layer of the bladder also regained its compact nature in simvastatin animals. Moreover, SCI-induced renal caspase-3 activity was significantly decreased in the simvastatin group indicating the ability of simvastatin to reduce the renal tubular apoptosis. Conclusion Post-injury administration of simvastatin ameliorates bladder and renal dysfunction associated with SCI in rats.

  6. Phosphoproteomics and Bioinformatics Analyses of Spinal Cord Proteins in Rats with Morphine Tolerance

    OpenAIRE

    Wen-Jinn Liaw; Cheng-Ming Tsao; Go-Shine Huang; Chin-Chen Wu; Shung-Tai Ho; Jhi-Joung Wang; Yuan-Xiang Tao; Hao-Ai Shui

    2014-01-01

    INTRODUCTION: Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. METHODS: To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal c...

  7. Survival of transplanted neurotrophin-3 expressing human neural stem cells and motor function in a rat model of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Peiqiang Cai; Guangyun Sun; Peishu Cai; Martin Oudega; Rui Xiao; Xuewen Wang; Wei Li; Yunbing Shu; Cheng Cai; Haihao Yang; Xuebing Shan; Wuhua Luo

    2009-01-01

    BACKGROUND: Many methods have been attempted to repair nerves following spinal cord injury,including peripheral nerve transplantation, Schwann cell transplantation, olfactory ensheathing cell transplantation, and embryonic neural tissue transplantation. However, there is a need for improved outcomes.OBJECTIVE: To investigate the repair feasibility for rat spinal cord injury using human neural stem cells (hNSCs) genetically modified by lentivirus to express neurotrophin-3.DESIGN, TIME AND SETTING: In vitro cell biological experiment and in vivo randomized, controlled,genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People's Hospital of Yibin, China from March 2006 to December 2007.MATERIALS: A total of 64 adult, female, Wistar rats were used for the in vivo study. Of them, 48 rats were used to establish models of spinal cord hemisection, and were subsequently equally and randomly assigned to model, genetically modified hNSC, and normal hNSC groups. The remaining 16 rats served as normal controls.METHODS: hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3. Neurotrophin-3 expression was measured by Westem blot.Genetically modified hNSC or normal hNSC suspension (5×105) was injected into the rat spinal cord following T10 spinal cord hemisection. A total of 5μL Dulbecco's-modified Eagle's medium was infused into the rat spinal cord in the model group. Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry. Motor function was evaluatedusing the Basso, Beattie, and Bresnahan (BBB) scale.MAIN OUTCOME MEASURES: The following parameters were measured: expression ofneurotrophin-3 produced by genetically modified hNSCs, transgene expression and survival ofhNSCs in rats, motor function in rats.RESULTS: hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3. The

  8. High-resolution MRI of intact and transected rat spinal cord.

    Science.gov (United States)

    Fraidakis, M; Klason, T; Cheng, H; Olson, L; Spenger, C

    1998-10-01

    Spinal cord transection at midthoracic level leads to an immediate loss of hindlimb motor function as well as to a progressive degeneration of descending and ascending spinal cord pathways. Thoracic spinal cord in unlesioned control rats and in rats 2 to 6 months after complete midthoracic transection were imaged in vivo using an ultrahigh-field (4.7 T) magnetic resonance spectrometer. High-resolution spin-echo and inversion-recovery pulse sequences were employed. In addition, the apparent diffusion coefficients (ADCs) in longitudinal and transverse directions of the spinal cord were determined. Anatomical MRI findings were confirmed in histological spinal cord tissue preparations. In healthy spinal cord, gray and white matter were easily discerned in proton density-weighted images. An infield resolution of max. 76 micrometers per pixel was achieved. In animals with chronic spinal cord transection changes in gray-white matter structure and contrast were observed toward the cut end. The spinal cord stumps showed a tapering off. This coincided with changes in the longitudinal/transverse ADC ratio. Fluid-filled cysts were found in most cases at the distal end of the rostral stump. The gap between the stumps contained richly vascularized scar tissue. Additional pathologic changes included intramedullary microcysts, vertebral dislocations, and in one animal compression of the spinal cord. In conclusion, MRI was found to be a useful method for in vivo investigation of anatomical and physiological changes following spinal cord transection and to estimate the degree of neural degeneration. In addition, MRI allows the description of the accurate extension of fluid spaces (e.g., cysts) and of water diffusion characteristics which cannot be achieved by other means in vivo.

  9. 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.

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

    DEFF Research Database (Denmark)

    Jensen, Troels 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. Spinal autofluorescent flavoprotein imaging in a rat model of nerve injury-induced pain and the effect of spinal cord stimulation.

    Directory of Open Access Journals (Sweden)

    Joost L M Jongen

    Full Text Available Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS, an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level.

  12. Apoptosis of lumbar spinal cord neurons in cauda equina syndrome rats

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To explore the law of apoptosis of lumbar spinal cord neurons in cauda equina syndrome (CES). Methods Cauda equina of rats was compressed by a piece of silica gel stick. From day 1 to day 28,the lumbar spinal cord specimens were harvested and assessed by Nissl's staining and TUNEL staining. Results Compression of cauda equina caused lesion and apoptosis of neurons in lumbar spinal cord,and the extent of apoptosis reached the peak on 7th day after compression. Conclusion Apoptosis of neurons in lum...

  13. Involvement of GABA and opioid peptide receptors in sevoflurane-induced antinociception in rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    Ying-wei WANG; Xiao-ming DENG; Xin-min YOU; Shu-xiao LIU; Zhi-qi ZHAO

    2005-01-01

    Aim: The spinal cord is pivotal in immobility induced by volatile anesthetics because the anesthetics depress the activity of motor neurons in the spinal cord.The aim of this study was to observe the effects of sevoflurane on pain processing at the spinal level. Methods: The firing of the gastrocnemius muscle was evoked by electrical stimulation to the ipsilateral hindpaw in rats. The nociceptive C response of electromyography (EMG)was selected to study. The GABAA receptor antagonist bicuculline (0.1 mg/kg) and opioid receptor antagonist naloxone (0.4 mg/kg) were administered intravenously, either in the presence or in the absence of 1.0% sevoflurane. Results: In rats with transected spinal cord,sevoflurane produced a profound reduction in the C response in a dose- and timedependent manner. In the presence of 1.0% sevoflurane, the C responses were increased after injections of bicuculline and naloxone. Conclusion: Sevoflurane is a volatile anesthetic that acts directly on the spinal cord to suppress the nociceptive reflex. The sevoflurane-induced suppression of the C response is antagonized by either bicuculline or naloxone. The results suggest that spinal GABAA receptors and opioid peptide receptors are involved in the sevoflurane-induced suppression of spinal nociception.

  14. Expression of Slit2 and Robo1 after traumatic lesions of the rat spinal cord.

    Science.gov (United States)

    Liu, Jin-Bo; Jiang, Yu-Qin; Gong, Ai-Hua; Zhang, Zhi-Jian; Jiang, Qian; Chu, Xiang-Ping

    2011-01-01

    We have used semi-quantitative RT-PCR, Western blot, and immunofluorescence imaging approaches to detect the expression levels of Slit2 and its receptor Robo1 in the rat spinal cord after traumatic lesions. Our results revealed that both the mRNA and protein levels of Slit2 were up-regulated in the injured spinal cord. The Slit2 expression level was increased at day 7 until day 14, and then returned to normal level at day 21 after injury. A double-immunolabelling study showed that Slit2 and neurofilament (NF) proteins were both localized in neurons of spinal corda cinerea. Slit2 immunopositivity was detected in neuronal plasma membranes but not in the axonal fibers. In contrast, the immunolabelling of Robo1 in the normal spinal cord was at a low level, mostly in the neurons of spinal corda cinerea, and remained unchanged at all time points following spinal cord injury (SCI). The regulation levels of Slit2 and Robo1 after traumatic lesions in the rat spinal cord are different. Our results indicate that Slit2-Robo1 might not be involved in the inhibitory environment after SCI.

  15. Allodynia and hyperalgesia in diabetic rats are mediated by GABA and depletion of spinal potassium-chloride co-transporters

    OpenAIRE

    2008-01-01

    Diabetic rats show behavioral indices of painful neuropathy that may model the human condition. Hyperalgesia during the formalin test in diabetic rats is accompanied by the apparently paradoxical decrease in spinal release of excitatory neurotransmitters and increase in the inhibitory neurotransmitter GABA. Decreased expression of the potassium-chloride co-transporter, KCC2, in the spinal cord promotes excitatory properties of GABA. We therefore measured spinal KCC2 expression and explored th...

  16. Major vault protein promotes locomotor recovery and regeneration after spinal cord injury in adult zebrafish.

    Science.gov (United States)

    Pan, Hong-Chao; Lin, Jin-Fei; Ma, Li-Ping; Shen, Yan-Qin; Schachner, Melitta

    2013-01-01

    In contrast to mammals, adult zebrafish recover locomotor functions after spinal cord injury (SCI), in part due to axonal regrowth and regeneration permissivity of the central nervous system. Upregulation of major vault protein (MVP) expression after spinal cord injury in the brainstem of the adult zebrafish prompted us to probe for its contribution to recovery after SCI. MVP is a multifunctional protein expressed not only in many types of tumours but also in the nervous system, where its importance for regeneration is, however, unclear. Using an established zebrafish SCI model, we found that MVP mRNA and protein expression levels were increased in ependymal cells in the spinal cord caudal to the lesion site at 6 and 11 days after SCI. Double immunolabelling showed that MVP was co-localised with Islet-1 or tyrosine hydroxylase around the central canal of the spinal cord in sham-injured control fish and injured fish 11 days after surgery. MVP co-localised with the neural stem cell marker nestin in ependymal cells after injury. By using an in vivo morpholino-based knock-down approach, we found that the distance moved by MVP morpholino-treated fish was reduced at 4, 5 and 6 weeks after SCI when compared to fish treated with standard control morpholino. Knock-down of MVP resulted in reduced regrowth of axons from brainstem neurons into the spinal cord caudal to the lesion site. These results indicate that MVP supports locomotor recovery and axonal regrowth after SCI in adult zebrafish.

  17. Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

    Institute of Scientific and Technical Information of China (English)

    GuGONG; Li-bang YUAN; Ling HU; Wei WL; Liang YIN; Jing-li HOU; Ying-hai LIU; Le-shun ZHOU

    2012-01-01

    To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process.Methods:Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia.The motor functions of the animals were assessed according to the modified Tarlov scale.The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2-L4) was taken out for histopathological examination and Western blotting analysis.Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA.Results:Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores,and reduced the number of apoptotic neurons,which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the plasma and injured spinal cord.Moreover,the serum HMGB1 level correlated well with the serum TNF-α,IL-1β and IL-6 levels during the time period of reperfusion.Conclusion:The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1.

  18. Investigation of the protective effect of erythropoietin on spinal cord injury in rats.

    Science.gov (United States)

    Hong, Zhenghua; Hong, Huaxing; Chen, Haixiao; Wang, Zhangfu; Hong, Dun

    2011-09-01

    Erythropoietin (EPO) is a promising therapeutic agent used in a variety of spinal cord injuries. Therefore, identifying the specific molecular pathway mediating the neuronal protective effect of EPO after spinal cord injury (SCI) is of great value to the patients concerned. Platelet-derived growth factor (PDGF)-B is an important factor in the recovery of neurological function. We explored changes in the expression of PDGF-B in spinal cord injury rats after receiving EPO treatment. We used a weight-drop contusion SCI model, and EPO treatment group rats received single doses of EPO (1,000 U/kg i.p.) immediately after the operation. Seven days after the operation, the results revealed a more rapid recovery as noted by the higher BBB scores, less disruption and more neuronal regeneration of the spinal cord in the EPO treatment group than that in the SCI group. PDGF-B expression also increased in the EPO treatment group compared to that in the SCI group (PEPO on spinal cord injury in rats, which may help to explain the quick recovery after EPO treatment of spinal cord injury.

  19. Expression and effect of Caspase-3 in neurons after tractive spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Lei; PEI Fu-xing; TANG Kang-lai; XU Jian-zhong; LI Qi-hong

    2005-01-01

    Objective: To investigate Caspase-3 expression and its role in neuronal apoptosis.Methods: The T13-L2 spinal cord of rats was injured by traction after the amplitude of P1-N1 wave, monitored by a cortical somatosensory evoked potential (CSEP) monitor, decreased to seventy percent of that before operation. Then rats were killed in 6 h, 1 d, 4 d, 7 d, 14 d and 21 d respectively after operation. Flow cytometer terminal deoxynucleotldyl transferease-mediated biotinylated deoxynuridine triphosphate nick end labeling (TUNEL), Caspase-3 activity assay and immunohistochemical method were applied to investigate Caspase-3 expression in the spinal cord tissue and to study neuronal apoptosis in rats. Results: After spinal cord injury, apoptotic cells detected by flow cytometry and TUNEL-positive cells were significantly more, and positive immunohistochemical staining of Caspase-3 and Caspase-3 activity were significantly higher in Group injury than in Groups control and laminectomy, respectively (P>0.05, P>0.01). Similar trend of changes was noticed in apoptotic cells, TUNEL-positive cells and positive immunohistochemical staining of Caspase-3, all of which reached their respective peak 7 days after operation. Caspase-3 activity reached its peak, however, 4 days postoperatively. Conclusions: Increased expression and activity of Caspase-3 protein in neurons after tractive spinal cord injury is the biochemical signal of early spinal cell apoptosis. It is of great significance for understanding the mechanism of spinal cord injury.

  20. Clinical features of adult spinal muscular atrophy:46 cases

    Institute of Scientific and Technical Information of China (English)

    Xiaojun He; Ping Zhang; Guanghui Chen

    2006-01-01

    BACKGROUND: Spinal muscular atrophy (SMA) is a kind of degenerative disease of nervous system. There are 4 types in clinic, especially types Ⅰ, Ⅱ and Ⅲ are common, and the researches on those 3 types are relative mature. Type Ⅳ is a kind of adult spinal muscular atrophy (ASMA), which has low incidence rate and is often misdiagnosed as amyotrophic lateral sclerosis, muscular dystrophy, cervical syndrome, or others.OBJECTIVE: To observe the clinical features of 46 ASMA patients and analyze the relationship between course and activity of daily living.DESIGN: Case analysis.SETTING: Departments of Neurology of the 81 Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA.PARTICIPANTS: A total of 46 ASMA patients were selected from the Departments of Neurology of the 81Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA between April 1998 and January 2002. All patients were consentient. Among 46 cases, there were 37 males and 9 females with the mean age of 42 years. The patients' courses in all ranged from 6 months to 23 years, concretely, courses of 37 cases were less than or equal to 5 years, and those of 9 cases were more than or equal to 6 years.METHODS : ① All the 46 ASMA patients were asked to check blood sedimentation, anti O, serum creatinine,creatine, blood creatine phosphokinase (CPK) and muscular biopsy as early as possible. ② X-ray was used to measure plain film of cervical vertebra borderline film of cranium and neck at proximal end of upper limb of 25 cases and plain film of abdominal vertebra at proximal end of lower limb of 17 cases.③ Cerebrospinal fluid of lumbar puncture was checked on 42 cases, for routine examination, biochemical examination, and immunoglobulin examination. Electromyogram (EMG) was also examined to 42 cases. ④ Barthel index

  1. 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

    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...... results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. METHODS: Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post...... hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated...

  2. Plateau potentials in sacrocaudal motoneurons of chronic spinal rats, recorded in vitro.

    Science.gov (United States)

    Bennett, D J; Li, Y; Siu, M

    2001-10-01

    Intracellular recordings were made from sacrocaudal tail motoneurons of acute and chronic spinal rats to examine whether plateau potentials contribute to spasticity associated with chronic injury. The spinal cord was transected at the S2 level, causing, over time, exaggerated long-lasting reflexes (hyperreflexia) associated with a general spasticity syndrome in the tail muscles of chronic spinal rats (1-5 mo postinjury). The whole sacrocaudal spinal cord of chronic or acute spinal rats was removed and maintained in vitro in normal artificial cerebral spinal fluid (ACSF). Hyperreflexia in chronic spinal rats was verified by recording the long-lasting ventral root responses to dorsal root stimulation in vitro. The intrinsic properties of sacrocaudal motoneurons were studied using intracellular injections of slow triangular current ramps or graded current pulses. In chronic spinal rats, the current injection triggered sustained firing and an associated sustained depolarization (plateau potential; 34/35 cells; mean, 5.5 mV; duration >5 s; normal ACSF). The threshold for plateau initiation was low and usually corresponded to an acceleration in the membrane potential just before recruitment. After recruitment and plateau activation, the firing rate changed linearly with current during the slow ramps [63% of cells had a linear frequency-current (F-I) relation] despite the presence of the plateau. The persistent inward current (I(PIC)) producing the plateau and sustained firing was estimated to be on average 0.8 nA as determined by the reduction in injected current needed to stop the sustained firing [DeltaI = -0.8 +/- 0.6 (SD) nA], compared with the current needed to start firing (I = 1.7 +/- 1.5 nA; 47% reduction). In motoneurons of acute spinal rats, plateaus were rarely seen (3/22), although they could be made to occur with bath application of serotonin. In motoneurons of chronic spinal rats there were no significant changes in the mean passive input resistance

  3. pSVPoMcat modifying Schwann cell to protect injured spinal neurons in rats

    Institute of Scientific and Technical Information of China (English)

    陈礼刚; 高立达; 朴永旭; 毛伯镛; 曾凡俊

    2002-01-01

    Objective: To investigate the protective effect of pSVPoMcat (myelin basic protein microgene)modifying Schwann cell on injured spinal neurons.Methods: A model of rat spinal cord injured by hemisection was used. One hundred and twenty healthy SD rats of both sexes weighing 250-300 g were divided into three groups: Group A (n=40, treated with implantation of pSVPoMcat modifying Schwann cell), Group B (n= 40, treated with implantation of Schwann cell only) and Group C (n=400, treated with sham operation as the control). One week after operation the rat functional recovery was observed dynamically by using combined behavioral score (CBS) and cortical somatasensory evoked potentials, the spinal cord sections were stained by Nissl, acid phosphatase enzyme histochemistry and cell apoptosis was examined by methye green, terminal deoxynucleotidyl and the dUTP Nick end labeling technique. Quantitative analysis was done by computer image analysis system.Results: In Group A the injured neurons recovered well morphologically. The imaging analysis showed a result of Group A>Group B>Group C in the size of the neurons (P<0.01). The percentage of ACP (acid phosphatase) stained area and the rate of apoptosis sequence were groups Aspinal neurons and promotes recovery of injured spinal cord function in rats.

  4. Distal spinal muscular atrophy as a major feature in adult-onset ataxia telangiectasia.

    NARCIS (Netherlands)

    Hiel, J.A.P.; Engelen, B.G.M. van; Weemaes, C.M.R.; Broeks, A.; Verrips, A.; Laak, H.J. ter; Vingerhoets, H.M.; Heuvel, L.P.W.J. van den; Lammens, M.M.Y.; Gabreëls, F.J.M.; Last, J.I.; Taylor, A.M.R.

    2006-01-01

    The authors report four adult-onset ataxia telangiectasia (AT) patients belonging to two families lacking pronounced cerebellar ataxia but displaying distal spinal muscular atrophy. AT was proven by genetic studies showing ATM mutations and a reduced level of ATM. ATM activity, as measured by phosph

  5. 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.

  6. 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.

  7. Long-term changes in spinal cord evoked potentials after compression spinal cord injury in the rat.

    Science.gov (United States)

    Vanický, Ivo; Ondrejcák, Tomás; Ondrejcáková, Miriam; Sulla, Igor; Gálik, Ján

    2006-01-01

    1. After traumatic spinal cord injury (SCI), histological and neurological consequences are developing for several days and even weeks. However, little is known about the dynamics of changes in spinal axonal conductivity. The aim of this study was to record and compare repeated spinal cord evoked potentials (SCEP) after SCI in the rat during a 4 weeks' interval. These recordings were used: (i) for studying the dynamics of functional changes in spinal axons after SCI, and (ii) to define the value of SCEP as an independent outcome parameter in SCI studies. 2. We have used two pairs of chronically implanted epidural electrodes for stimulation/recording. The electrodes were placed below and above the site of injury, respectively. Animals with implanted electrodes underwent spinal cord compression injury induced by epidural balloon inflation at Th8-Th9 level. There were five experimental groups of animals, including one control group (sham-operated, no injury), and four injury groups (different degrees of SCI). 3. After SCI, SCEP waveform was either significantly reduced or completely lost. Partial recovery of SCEPs was observed in all groups. The onset and extent of recovery clearly correlated with the severity of injury. There was good correlation between quantitated SCEP variables and the volumes of the compressing balloon. However, sensitivity of electropohysiological parameters was inferior compared to neurological and morphometric outcomes. 4. Our study shows for the first time, that the dynamics of axonal recovery depends on the degree of injury. After mild injury, recovery of signal is rapid. However, after severe injury, axonal conductivity can re-appear after as long as 2 weeks postinjury. In conclusion, SCEPs can be used as an independent parameter of outcome after SCI, but in general, the sensitivity of electrophysiological data were worse than standard morphological and neurological evaluations.

  8. Influence of neurotrophin-3 on Bcl-2 and Bax expressions in spinal cord injury of rats

    Institute of Scientific and Technical Information of China (English)

    GUO Shu-zhang; JIANG Tao; REN Xian-jun

    2007-01-01

    Objective:To study the protective mechanisms of neurotrophin-3 (NT-3) on the spinal cord injury.Methods:Totally 105 SD rats were randomly divided into 3 groups:control group,experimental group and sham operation group.Rats from the former 2 groups were inflicted to animal model of acute spinal cord injury according to Allen's (WD) by situating a thin plastic tube in the subarachnoid space below the injury level for perfusion.Rats in experimental group received 20μl NT-3 (200 ng) from the tube at 0,4,8,12,24 h and 3,7 d after injury,and those in control group got an equal volume of normal saline at the same time.The animals in sham operation group only received opening vertebral plate and tube was put in subarachnoid space.The rats were sacrificed at 4,8,12,24 h and 3,7,14 d post injury (n=5).The expression levels of Bcl-2 and Bax proteins in spinal cord of rats were detected by immunohistochemistry assay.Results:The level of Bax protein in control group significantly increased as compared with those in sham operation group, and the peak reached at 8 h after spinal cord injury.The Bcl-2 proteins were always weakly positive.The Bax proteins in NT-3 group significantly decreased but the Bcl-2 proteins obviously increased as compared with those in control group.Conclusion:NT-3 can protect spinal cord from injury in vivo.One of the mechanisms is that NT-3 can inhibit abnormal expression of Bax protein,and increase the expression of Bcl-2 protein,then inhibit apoptosis after spinal cord injury.

  9. Observation and establishment of an animal model of tractive spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    刘雷; 池雷庭; 屠重棋; 沈彬; 周宗科; 裴福兴

    2004-01-01

    Objective: To establish an animal model of tractive spinal cord injury in rats in order to investigate its pathophysiological changes and clinical significance.Methods: T12-L3 spines were tracted longitudinally with a special spinal retractor that was put on the proccessus transverses of T12-L3 vertebrae of the rat after exposing T13-L2 spinal cord via dual laminectomy.At the same tine, the spinal cord function was monitored by cortical somatosensory evoked potential (CSEP). Rats were randomly divided into four groups according to the amplitude of CSEP P1-N1 wave, the amount of the decreasing P1-N1 wave was 30% (the 30% group), 50% (the 50% group) and 70% (the 70% group), respectively. After traction, the changes of the neural behavioral function in rats were observed and the morphological structure of the spinal cord was analyzed quantitaltively with image analysis system of computer.Results: With traction of spine, compared with the control group, the 30% group had no marked difference in combined behavioral score (CBS), neuron count, section area of neuron and Nissl body density, but the 50% and 70% groups had marked differece (P<0.01). Light microscope showed that the neuron volume was slightly small and the Nissl body was reduced lightly in the 30% group; the neuron space was enlarged and the neuron was degenerative, reductive, and dissolved, and the spinal cord structure was destroyed in the 50% and 70% groups.Conclusions: The animal model of tractive spial cord injury in rats is a reproducible, graded and clinic mimic. The model in this article provides a valuable assistance in further understanding etiopathology and screening effective miasures of therapy and prophylaxis of the injury.

  10. Spatiotemporal Patterns of RING1 Expression after Rat Spinal Cord Injury.

    Science.gov (United States)

    Liu, Hanzhang; Ji, Wei; Gong, Peipei; Liu, Chun; Duan, Chengwei; Gao, Yilu; Liu, Xiaojuan; Zhang, Dongmei; Zhu, Shunxing; Gong, Leilei

    2016-12-28

    Ring finger protein 1 (RING1) is a RING domain characterized protein belonging to the RING finger family. It is an E3 ubiquitin-protein ligase that mediated monoubiquitination of histone H2A and the core component of PRC1 complex, which is the repressive multiprotein complex of Polycomb group (PcG). Previous studies showed the important tumorigenic role of RING1 via promoting cell proliferation and the crucial function in maintaining transcriptional program stability during development. However, its mechanism for spinal cord injury (SCI) is still unknown. In our research, we established an acute SCI model in adult rats and studied the expression and function profiles of RING1. RING1 protein level detected by western blot peaked at day 3 after trauma and then decreased gradually. Immunohistochemistry showed the increase of RING1 expression displayed in the white matter more obviously than in the gray matter. Furthermore, increased co-expression of RING1 and GFAP confirmed activated astrocytes in injured spinal cord via double immunofluorescence staining. Meanwhile, we also found the co-localization of PCNA, a famous marker of proliferative cells, with RING1 and GFAP, which indicated RING1 might play a role in astrocyte proliferation after SCI. In vitro studies, RING1 protein level in C6 cells increased after LPS challenge and RING1 was required for astrocyte proliferation and activation induced by LPS. In summary, we took a new insight into the function of RING1 in the cellular and molecular mechanism underlying the pathophysiology of SCI.

  11. Sleep patterns over 15-day period in rats with spinal cord injury

    OpenAIRE

    A.M. Esteves; de Mello, Marco Tulio; Squarcini, C. F. R.; Lancellotti, Carmen Lucia Penteado; Comparoni, Aniella [UNIFESP; Tufik,Sergio

    2007-01-01

    Study design: Experimental, controlled trial.Objectives: the purpose of this study was to evaluate over a 15-day period alterations in sleep pattern of rats after spinal cord injury (SCI).Setting: Federal University of São Paulo, Department of Psychobiology.Methods: in total, 20 male Wistar rats were used. the rats were divided in two groups: SHAM and SCI. the rats were submitted to the following procedures: electrode insertion surgery, 24 h duration baseline sleep recording, SCI (level T9) a...

  12. Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

    Institute of Scientific and Technical Information of China (English)

    Fang Huang; Hongwen He; Wenguo Fan; Yongliang Liu; Hongyu Zhou; Bin Cheng

    2013-01-01

    Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin re-ceptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal minal nucleus and trigeminal ganglion was determined with immunohistochemistry and mistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings sug-gest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin’s regulatory effect on pain is attenuated.

  13. Decreased cerebrospinal fluid flow through the central canal of the spinal cord of rats immunologically deprived of Reissner's fibre.

    Science.gov (United States)

    Cifuentes, M; Rodríguez, S; Pérez, J; Grondona, J M; Rodríguez, E M; Fernández-Llebrez, P

    1994-01-01

    The subcommissural organ is an ependymal brain gland that secretes glycoproteins to the cerebrospinal fluid (CSF) of the third ventricle. They condense to form a fibre, Reissner's fibre (RF), that runs along the aqueduct and fourth ventricle and the central canal of the spinal cord. A single injection of an antibody against the secretory glycoproteins of RF into a lateral ventricle of adult rats results in animals permanently deprived of RF in the central canal and bearing a "short" RF extending only along the aqueduct and the fourth ventricle. These animals, together with untreated control animals were used to investigate the probable influence of RF in the circulation of CSF in the central canal of the spinal cord. For this purpose, two tracers, (horseradish peroxidase and rabbit immunoglobulin) were injected into the ventricular CSF. The animals were killed 13, 20, 60, 120 and 240 min after the injection, and the amount of the tracers was estimated in tissue sections obtained at proximal, medial and distal levels of the spinal cord. In rats deprived of RF, a significant decrease in the amount of tracers present in the central canal was observed at all experimental intervals, being more evident at 20 min after the injection of the tracers. This suggests that lacking a RF in the central canal decreases the bulk flow of CSF along the central canal. Turbulences of the CSF at the entrance of the central canal of RF-deprived rats might explain the inability of the regenerating RF to progress along the central canal, as well as the reduced flow of CSF in the central canal of these animals.

  14. Effects of Nerve Growth Factor on Bcl-2 Protein after Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    汤长华; 曹晓建; 王道新

    2002-01-01

    Objective To explore the protective mechanisms of nerve growth factor( NGF) ou spinal cord injury(SCI) and provide theoretical basis for its clinical application. MethodsThe SCI of Wistar rats was done by Allens weight dropping way by a 10 g × 2.5 cm impact on theposterior of spinal cord T8 NGF ( 3 g/L, 20d) or normal saline was injected to treatment group ratsthrough catheter into subarachnoid space at 0,2,4,8,12 and 24 h after SCI. The expression of bcl-2 protein levels in rat spinal cord was detected by immunohistoclemistry. Results The strong expres-sion sequence of bcl-2 protein was found in spinal cord of normal rat group. The levels of bcl-2 pro-tein after SCI in NGF treatment group increased more significantly than those in normal saline treatmentgroup (P<0. 01). Conclusion NGF could protect injured spinal cord by stimulating bcl-2 pro-tein expression and suppressing apoptosis after SCI.

  15. Quantitative analysis of the toxicity of human amniotic fluid to cultured rat spinal cord.

    Science.gov (United States)

    Drewek, M J; Bruner, J P; Whetsell, W O; Tulipan, N

    1997-10-01

    It has been proposed that the myelodysplastic components of a myelomeningocele are secondarily damaged as the result of exposure to amniotic fluid, the so-called 'two-hit' hypothesis. The critical time at which this secondary insult might occur has not been clearly defined. The present study addresses this issue by quantitatively assessing the toxic effects of human amniotic fluid of various gestational ages upon organotypic cultures of rat spinal cord. Using an assay for lactate dehydrogenase efflux to evaluate toxicity in such spinal cord cultures, we found that the amniotic fluid became toxic at approximately 34 weeks' gestation. This toxic effect of amniotic fluid appears to emerge rather suddenly. Accordingly, it seems reasonable to suggest that prevention of exposure of vulnerable spinal cord tissue to this toxicity by surgical closure of a myelomeningocele defect prior to the emergence of toxicity in amniotic fluid may prevent injury to vulnerable myelodysplastic spinal cord tissue.

  16. EFFECTS OF NERVE GROWTH FACTOR ON ENDOTHELIN AFTER SPINAL CORD INJURY IN RATS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the protective mechanisms of nerve growth factor (NGF) on spinal cord injury.Methods The spinal cord injury (SCI) of Wistar rats was performed by a 10g×2.5cm impact on the posterior T12 spinal cord.The experimental animals received NGF liquid by subarachnoid space tube.The radioimmunological techniques were applied to examine the level of endothelin.Results The level of endothelin was significantly increased after the injury as compared with that in control group(P<0.01).The level of endothelin in NGF group as obviously lowered as compared with that in normal saline group 4 h after injury (P<0.01).Conclusion NGF can protect spinal cord against injury in vivo.One of the mechanisms is that NGF could inhibit endothelin-induced vicious circle.

  17. Sensory feedback synchronizes motor and sensory neuronal networks in the neonatal rat spinal cord.

    Science.gov (United States)

    Inácio, Ana R; Nasretdinov, Azat; Lebedeva, Julia; Khazipov, Roustem

    2016-10-07

    Early stages of sensorimotor system development in mammals are characterized by the occurrence of spontaneous movements. Whether and how these movements support correlated activity in developing sensorimotor spinal cord circuits remains unknown. Here we show highly correlated activity in sensory and motor zones in the spinal cord of neonatal rats in vivo. Both during twitches and complex movements, movement-generating bursts in motor zones are followed by bursts in sensory zones. Deafferentation does not affect activity in motor zones and movements, but profoundly suppresses activity bursts in sensory laminae and results in sensorimotor uncoupling, implying a primary role of sensory feedback in sensorimotor synchronization. This is further supported by largely dissociated activity in sensory and motor zones observed in the isolated spinal cord in vitro. Thus, sensory feedback resulting from spontaneous movements is instrumental for coordination of activity in developing sensorimotor spinal cord circuits.

  18. Spinal blockades of class I antiarrythmic drugs with bupivacaine by isobolographic analysis in rats.

    Science.gov (United States)

    Chen, Yu-Wen; Chu, Chin-Chen; Chen, Yu-Chung; Leung, Yuk-Man; Wang, Jhi-Joung

    2012-10-18

    Flecainide, quinidine, and mexiletine have been shown to be sodium channel blockers and local anesthetics. The purpose of this study was to examine the interaction of the traditional local anesthetic bupivacaine with flecainide, quinidine, or mexiletine on spinal blockades. To obtain the 50% effective dose (ED(50)) of drugs, dose-dependent responses of spinal blockades of motor and sensory functions with intrathecal flecainide, quinidine, mexiletine, and bupivacaine in rats were constructed. Using a continuum of different fixed drug dose ratios, the interactions of bupivacaine with drugs (flecainide, quinidine, or mexiletine) were evaluated by an isobolographic analysis. Our resulting data showed that flecainide, quinidine, and mexiletine, as well as local anesthetic bupivacaine produced dose-dependent spinal blockades in motor function and nociception. Flecainide had the most potent spinal antinociceptive effect (P<0.01) among these three class I antiarrhythmic drugs. Co-administration of bupivacaine with flecainide, quinidine, or mexiletine displayed an additive effect on spinal blockades of motor function and nociception. We concluded that bupivacaine combined with flecainide, quinidine, or mexiletine exhibited an additive effect on spinal blockades of motor function and nociception. Using such a combination strategy to produce antinociception may potentially provide an improved therapeutic separation from myocardial toxicity occurred after spinal bupivacaine.

  19. Novel observations on the origin of ependymal cells in the ventricular zone of the rat spinal cord.

    Science.gov (United States)

    Sevc, Juraj; Daxnerová, Zuzana; Haňová, Viera; Koval', Ján

    2011-02-01

    Despite extensive investigations of gliogenesis, the time of origin of ependymal cells in the spinal cord has not yet been fully elucidated. Using a single dose of 5-bromo-2-deoxyuridine combined with various survival times we monitored: mitotic activity (short survival time), the presence of newly formed cells in the ventricular zone (intermediate survival time) and the formation of ependymal cells (long survival time) during the late embryonic and early postnatal development in the ventricular zone of the spinal cord of rats. In the period of study it was found that the ependymal cells populated this region in two waves. Most of the ependymal cells originated around embryonic day 18 and then between postnatal days 8 and 15. In addition, it was observed that in the ventricular zone of the spinal cord, proliferation and production of ependymal cells continues at the slower rate at least until day 36 of postnatal development. Elucidation of the relationship between progenitors in the embryonic ventricular zone and the relative quiescent ependymal lining of the central canal in adulthood could be important in the search for the adult neural stem cell niche.

  20. Effect of Electroacupuncture on Chronic Visceral Pain and Involvement of Spinal NMDA Receptor in IBS Rats

    Institute of Scientific and Technical Information of China (English)

    王智君; 李为民; 周娟; 陈颖波

    2009-01-01

    Objective:To clarify effect of electroacupuncture (EA) on relieving chronic visceral pain and the underlying neurobiological mechanism for such an effect,we observed the effect of EA on the Irritable bowel syndrome (IBS) rat and then examined spinal expression of N-methyl-D-aspartate (NMDA)receptor-1 in rats.Methods:Daily mechanical colon distention was performed on male Sprague-Dawley neonatal rats to produce IBS model.EA was applied at acupoints of Zusanli (ST 36) and Shangjuxu (ST 37)in each hind leg.Abdominal withdrawal reflex (AWR) assessment or rectus abdominis electromyograms (AEMG) recordings were then performed after EA treatment.The mRNA expression of the NMDA subtype of glutamate receptors in the spinal dorsal horn (L4-5) before and after EA was investigated by RT-PCR analysis in IBS rats.Results:The results demonstrated that EA could significantly decreased both AWR scores from behavioral test and AEMG discharges from electrophysiological recording in IBS model rats elicited by colorectal distension (CRD) stimuli with strengths of 20,40,60 and 80 mmHg,respectively (P<0.05).Meanwhile there was a significant decrease in mRNA expression of NMDA receptor-1 in the spinal dorsal horn of IBS rats treated by EA (P<0.05),but no such effect was observed in IBS rats treated by sham EA (inserting needles without electrical stimulation).Conclusion:These results indicate that EA can relieve chronic visceral hyperalgesia in IBS rats and this effect might be correlated with the down-regulation of NMDA receptor-1 in the dorsal hom of the spinal cord.

  1. Effect of Electroacupuncture on Chronic Visceral Pain and Involvement of Spinal NMDA Receptor in IBS Rats

    Institute of Scientific and Technical Information of China (English)

    王智君; 李为民; 周娟; 陈颖波

    2008-01-01

    Objective: To clarify effect of electroacupuncture (EA) on relieving chronic visceral pain and the underlying neurobiological mechanism for such an effect, we observed the effect of EA on the Irritable bowel syndrome (IBS) rat and then examined spinal expression of N-methyl-D-aspartate (NMDA) receptor-1 in rats. Methods: Daily mechanical colon distention was performed on male Sprague-Dawley neonatal rats to produce IBS model. EA was applied at acupoints of Zusanli (ST 36) and Shangjuxu (ST 37) in each hind leg. Abdominal withdrawal reflex (AWR) assessment or rectus abdominis electromyograms (AEMG) recordings were then performed after EA treatment. The mRNA expression of the NMDA subtype of glutamate receptors in the spinal dorsal horn (L4-5) before and after EA was investigated by RT-PCR analysis in IBS rats. Results: The results demonstrated that EA could significantly decreased both AWR scores from behavioral test and AEMG discharges from electrophysiological recording in IBS model rats elicited by colorectal distension (CRD) stimuli with strengths of 20, 40, 60 and 80 mmHg, respectively (P<0.05). Meanwhile there was a significant decrease in mRNA expression of NMDA receptor-1 in the spinal dorsal horn of IBS rats treated by EA (P<0.05), but no such effect was observed in IBS rats treated by sham EA (inserting needles without electrical stimulation). Conclusion: These results indicate that EA can relieve chronic visceral hyperalgesia in IBS rats and this effect might be correlated with the down-regulation of NMDA receptor- 1 in the dorsal horn of the spinal cord.

  2. Deferoxamine improves neurological function in a rat model of experimental spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yanting Wang; Shaoji Yuan; Fachen Wang; Rong Hu; Jiangkai Lin; Zisheng Liu; Hua Feng

    2011-01-01

    A rat model of spinal cord injury was established using modified Allen's method and treated with the ferric iron-chelating agent, deferoxamine. Hematoxylin-eosin, Nissl and Perl's Prussian blue staining, at 7-14 days following spinal cord injury, showed that following deferoxamine treatment, glial cells proliferation increased significantly, nerve cell morphology was improved and hemosiderin was significantly reduced in the injury region. At 1-56 days following injury, Basso, Beattie, and Bres nahan Locomotor Rating Scale scores were increased, while latencies of somatosensory-evoked potentials and motor-evoked potentials were decreased. Results demonstrate that deferoxamine can promote neurological functional recovery after experi-mental spinal cord injury in rats.

  3. Influence of Sexuality in Functional Recovery after Spinal Cord Injury in rats

    Directory of Open Access Journals (Sweden)

    Mohammadreza Emamhadi

    2016-01-01

    Full Text Available Background: Spinal cord injury (SCI is a major clinical condition and research is commonly done to find suitable treatment options. However, there are some degrees of spontaneous recovery after SCI and gender is said to be a contributing factor in recovery, but this is controversial. This study was done to compare the effects of sexual dimorphism on spontaneous recovery after spinal cord injury in Wistar Rats. Methods: Spinal cord lesions were made by compressing the cord at T9 level and making a spinal cord contusion. Routine care of each rat was done daily. The LSS scoring system was used to measure the locomotion of these rats and to compare the recovery rate between male and female rats. Results: The results suggested that there was no significant difference between the two sex in recovery. Conclusions: To be female does not seem to be a prognostic factor for recovery after SCI. However, this preliminary study should be repeated in other animals and in larger cohorts.

  4. 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.

  5. RELATIONSHIP BETWEEN ANALGESIA AND EXTRACELLULAR MORPHINE IN BRAIN AND SPINAL-CORD IN AWAKE RATS

    NARCIS (Netherlands)

    MATES, FF; ROLLEMA, H; TAIWO, YO; LEVINE, JD; BASBAUM, AI

    1995-01-01

    Extracellular concentrations of morphine from the dorsal spinal cord, the periaqueductal gray (FAG) including the dorsal raphe, and the lateral hypothalamus were measured by microdialysis in awake rats after intraperitoneal (i.p.) administration of 2.5, 5.0 and 10 mg/kg morphine. Morphine concentrat

  6. Effects of Strontium Ranelate on Spinal Interbody Fusion Surgery in an Osteoporotic Rat Model

    Science.gov (United States)

    Tsai, Tsung-Ting; Ho, Natalie Yi-Ju; Lai, Po-Liang; Fu, Tsai-Sheng; Niu, Chi-Chien; Chen, Lih-Huei; Chen, Wen-Jer

    2017-01-01

    Osteoporosis is a bone disease that afflicts millions of people around the world, and a variety of spinal integrity issues, such as degenerative spinal stenosis and spondylolisthesis, are frequently concomitant with osteoporosis and are sometimes treated with spinal interbody fusion surgery. Previous studies have demonstrated the efficacy of strontium ranelate (SrR) treatment of osteoporosis in improving bone strength, promoting bone remodeling, and reducing the risk of fractures, but its effects on interbody fusion surgery have not been adequately investigated. SrR-treated rats subjected to interbody fusion surgery exhibited significantly higher lumbar vertebral bone mineral density after 12 weeks of treatment than rats subjected to the same surgery but not treated with SrR. Furthermore, histological and radiographic assessments showed that a greater amount of newly formed bone tissue was present and that better fusion union occurred in the SrR-treated rats than in the untreated rats. Taken together, these results show significant differences in bone mineral density, PINP level, histological score, SrR content and mechanical testing, which demonstrate a relatively moderate effect of SrR treatment on bone strength and remodeling in the specific context of recovery after an interbody fusion surgery, and suggest the potential of SrR treatment as an effective adjunct to spinal interbody fusion surgery for human patients. PMID:28052066

  7. ATF3 is a novel nuclear marker for migrating ependymal stem cells in the rat spinal cord.

    Science.gov (United States)

    Mladinic, Miranda; Bianchetti, Elena; Dekanic, Ana; Mazzone, Graciela L; Nistri, Andrea

    2014-05-01

    The present study identified ATF3 as a novel dynamic marker for ependymal stem/progenitor cells (nestin, vimentin and SOX2 positive) around the central canal of the neonatal or adult rat spinal cord. While quiescent ependymal cells showed cytoplasmic ATF3 expression, during 6-24h in vitro these cells mobilized and acquired intense nuclear ATF3 staining. Their migratory pattern followed a centrifugal pathway toward the dorsal and ventral funiculi, reminiscent of the rostral migratory stream of the brain subventricular stem cells. Thus, the chain cell formation was, by analogy, termed funicular migratory stream (FMS). The FMS process preceded the strong proliferation of ependymal cells occurring only after 24h in vitro. Pharmacological inhibition of MAPK-p38 and JNK/c-Jun (upstream effectors of ATF3 activation) prevented the FMS mobilization of ATF3 nuclear-positive cells. Excitotoxicity or ischemia-like conditions, reported to evoke neuronal and glial injury, did not further enhance migration of ependymal cells at 24h, suggesting that, at this early stage of damage, the FMS phenomenon had peaked and that more extensive repair processes are delayed beyond this time point. ATF3 is, therefore, useful to identify activation and migration of endogenous stem cells of the rat spinal cord in vitro.

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

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    Subhra Prakash Hui

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

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

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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.

  10. Effects of L-lysine monohydrochloride on insulin and blood glucose levels in spinal cord injured rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tian-ling; ZHAO Yu-wu; LIU Xue-yuan; DING Su-ju

    2010-01-01

    Background Hyperglycemia in brain and spinal cord could aggravate neurologic impairment. Recent studies showed that L-lysine monohydrochlonde (LMH) could increase the insulin secretion and regulate the blood glucose level. The aim of the present study was to investigate the effects of LMH on pancreatic islet B cells, the levels of endogenous insulin and blood glucose in spinal cord injured rats.Methods Forty male Wistar rats were divided into four groups, namely, normal control group, model group, high-dose LMH group (621.5 mg/kg equal to LMH 1/8 LD50), and low-dose LMH group (310.8 mg/kg equal to LMH 1/16 LD50). The model of spinal cord injured rat was established by hemi-transection at the lower right thoracic spinal cord. LMH was administered via intraperitoneal injection once spinal cord injury was produced in rats. All rats were sacrificed 48 hours after spinal cord injured. The effects of LMH on pancreatic islet B cells, the content of endogenous insulin, end the level of blood glucose were observed with immunohistochemical method, radioimmunoassay method, end biochemical analyzer, respectively. Results The insulin immunohistochemical intensities of islet B cells were significantly weaker in model group then those in normal control group (P 0.05). Conclusion LMH, but dose-dependent, might participate in the regulation of pancreatic islet B cells, and then reduce the blood glucose levels in the spinal cord injured rats.

  11. Efficient delivery of small interfering RNA into injured spinal cords in rats by photomechanical waves

    Science.gov (United States)

    Ando, Takahiro; Sato, Shunichi; Toyooka, Terushige; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Obara, Minoru

    2011-03-01

    In the central nervous system, lack of axonal regeneration leads to permanent functional disabilities. In spinal cord injury (SCI), the over-expressions of intermediate filament (IF) proteins, such as glial fibrillary acidic protein (GFAP) and vimentin, are mainly involved in glial scar formation; these proteins work as both physical and biochemical barriers to axonal regeneration. Thus, silencing of these IF proteins would be an attractive strategy to treat SCI. In this study, we first attempted to deliver fluorescent probe-labeled siRNAs into injured spinal cords in rats by applying photomechanical waves (PMWs) to examine the capability of PMWs as a tool for siRNA delivery. Intense fluorescence from siRNAs was observed in much broader regions in the spinal cords with PMW application when compared with those with siRNA injection alone. Based on this result, we delivered siRNAs for GFAP and vimentin into injured spinal tissues in rats by applying PMWs. The treatment resulted in efficient silencing of the proteins at five days after SCI and a decrease of the cavity area in the injured tissue at three weeks after SCI when compared with those with siRNA injection alone. These results demonstrate the capability of PMWs for efficient delivery of siRNAs into injured spinal cords and treatment of SCIs.

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

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    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.

  13. Anatomical mechanism of spontaneous recovery in regions caudal to thoracic spinal cord injury lesions in rats

    Science.gov (United States)

    Li, Lu-sheng; Yu, Hao; Raynald, Raynald; Wang, Xiao-dong; Dai, Guang-hui; Cheng, Hong-bin; Liu, Xue-bin

    2017-01-01

    Background The nerve fibre circuits around a lesion play a major role in the spontaneous recovery process after spinal cord hemisection in rats. The aim of the present study was to answer the following question: in the re-control process, do all spinal cord nerves below the lesion site participate, or do the spinal cord nerves of only one vertebral segment have a role in repair? Methods First we made a T7 spinal cord hemisection in 50 rats. Eight weeks later, they were divided into three groups based on distinct second operations at T7: ipsilateral hemisection operation, contralateral hemisection, or transection. We then tested recovery of hindlimbs for another eight weeks. The first step was to confirm the lesion had role or not in the spontaneous recovery process. Secondly, we performed T7 spinal cord hemisections in 125 rats. Eight weeks later, we performed a second single hemisection on the ipsilateral side at T8–T12 and then tested hindlimb recovery for another six weeks. Results In the first part, the Basso, Beattie, Bresnahan (BBB) scores and the electrophysiology tests of both hindlimbs weren’t significantly different after the second hemisection of the ipsilateral side. In the second part, the closer the second hemisection was to T12, the more substantial the resulting impairment in BBB score tests and prolonged latency periods. Conclusions The nerve regeneration from the lesion area after hemisection has no effect on spontaneous recovery of the spinal cord. Repair is carried out by all vertebrae caudal and ipsilateral to the lesion, with T12 being most important. PMID:28097067

  14. Up-regulation of -opioid receptors in the spinal cord of morphine-tolerant rats

    Indian Academy of Sciences (India)

    Subrata Basu Ray; Himanshu Gupta; Yogendra Kumar Gupta

    2004-03-01

    Though morphine remains the most powerful drug for treating pain, its effectiveness is limited by the development of tolerance and dependence. The mechanism underlying development of tolerance to morphine is still poorly understood. One of the factors could be an alteration in the number of m-receptors within specific parts of the nervous system. However, reports on changes in the -opioid receptor density in the spinal cord after chronic morphine administration are conflicting. Most of the studies have used subcutaneously implanted morphine pellets to produce tolerance. However, it does not simulate clinical conditions, where it is more common to administer morphine at intervals, either by injections or orally. In the present study, rats were made tolerant to morphine by injecting increasing doses of morphine (10–50 mg/kg, subcutaneously) for five days. In vitro tissue autoradiography for localization of -receptor in the spinal cord was done using [3H]-DAMGO. As compared to the spinal cord of control rats, the spinal cord of tolerant rats showed an 18.8% increase or up-regulation in the density of -receptors in the superficial layers of the dorsal horn. This up-regulation of -receptors after morphine tolerance suggests that a fraction of the receptors have been rendered desensitized, which in turn could lead to tolerance.

  15. Behavioral and Histopathological Study of Changes in Spinal Cord Injured Rats Supplemented with Spirulina platensis

    Science.gov (United States)

    Che Ramli, Muhammad Danial

    2014-01-01

    Spinal cord injury (SCI) is a devastating disease that leads to permanent disability and causes great suffering. The resulting neurological dysfunction and paralysis is proportional to the severity of the trauma itself. Spirulina is widely used as a nutritional supplement due to its high protein and antioxidant content. In the present study, the protective effect of the Spirulina treatment on locomotor function and morphological damage after SCI was investigated. Seventy Sprague-Dawley (SD) rats were divided into three groups: Sham (laminectomy alone), Control (laminectomy with SCI), and Experimental (laminectomy with SCI +180 mg/kg per day Spirulina platensis). A laminectomy was performed at T12 and an Inox No.2 modified forceps was used to perform a partial crush injury on the spinal cord. The rats were then perfused at 3, 7, 14, 21, and 28 days after injury for morphological investigations. The injured rat spinal cord indicated a presence of hemorrhage, cavity, and necrosis. Pretreatment with Spirulina significantly improved the locomotor function and showed a significant reduction on the histological changes. The experimental results observed in this study suggest that treatment with Spirulina platensis possesses potential benefits in improving hind limb locomotor function and reducing morphological damage to the spinal cord. PMID:25152764

  16. Behavioral and Histopathological Study of Changes in Spinal Cord Injured Rats Supplemented with Spirulina platensis

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    Izzuddin Aziz

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a devastating disease that leads to permanent disability and causes great suffering. The resulting neurological dysfunction and paralysis is proportional to the severity of the trauma itself. Spirulina is widely used as a nutritional supplement due to its high protein and antioxidant content. In the present study, the protective effect of the Spirulina treatment on locomotor function and morphological damage after SCI was investigated. Seventy Sprague-Dawley (SD rats were divided into three groups: Sham (laminectomy alone, Control (laminectomy with SCI, and Experimental (laminectomy with SCI +180 mg/kg per day Spirulina platensis. A laminectomy was performed at T12 and an Inox No.2 modified forceps was used to perform a partial crush injury on the spinal cord. The rats were then perfused at 3, 7, 14, 21, and 28 days after injury for morphological investigations. The injured rat spinal cord indicated a presence of hemorrhage, cavity, and necrosis. Pretreatment with Spirulina significantly improved the locomotor function and showed a significant reduction on the histological changes. The experimental results observed in this study suggest that treatment with Spirulina platensis possesses potential benefits in improving hind limb locomotor function and reducing morphological damage to the spinal cord.

  17. Noradrenergic modulation of intrinsic and synaptic properties of lumbar motoneurons in the neonatal rat spinal cord

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    Maylis Tartas

    2010-03-01

    Full Text Available Although it is known that noradrenaline powerfully controls spinal motor networks, few data are available regarding the noradrenergic modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of noradrenergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of noradrenaline and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. Noradrenaline increases the motoneuron excitability partly via the inhibition of a KIR like current. Methoxamine (α1, clonidine (α2 and isoproterenol (β differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (α1, yohimbine (α2 and propranolol (β. We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by noradrenaline, methoxamine and isoproterenol. On the other hand, noradrenaline, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic α1 and β receptor activation. Our data thus show that the noradrenergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord.

  18. Intrathecal Amylin and Salmon Calcitonin Affect Formalin Induced c-Fos Expression in the Spinal Cord of Rats

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    Zahra Khoshdel

    2014-11-01

    Full Text Available Background:Amylin and Salmon Calcitonin belong to the calcitonin family of peptides and have high affinity binding sites in the rat spinal cord. The aim of this study was to characterize receptors for Amylin and Salmon Calcitonin functionally in the spinal cord of rats. We assessed the expression of c-Fos in response to intraplantar formalin in the lumbar regions of the spinal cord in conscious rats. Methods:Amylin (0.05 nmoles or Salmon Calcitonin (0.005 nmoles was administered intrathecally (i.t. 10 minutes before the start of the formalin test. Antagonists were injected intrathecally 10 minutes before the administration of either of the peptides. Results: Two hours after formalin stimulation, rats pretreated intrathecally by either Amylin or Salmon Calcitonin, showed lower numbers of c-Fos immunoreactive nuclei in their lumbar spinal cord as compared to rats pretreated with saline. These effects were reversed upon co-administration of either of the Amylin antagonists AC187 or rat amylin8-37, but not rat α-CGRP8-37. A few cells with c-Fos immunoreactivity were found in the lumbar spinal cord of rats two hours after i.t. injection of saline, Amylin and/or Salmon Calcitonin. However, Fos-like immunoreactivity was increased in the lumbar spinal cord two hours after i.t. treatment of either of the antagonists AC187 and rat amylin8-37,when compared to saline treated rats. Conclusion:Both Amylin and Salmon Calcitonin inhibit formalin induced c-Fos expression in the rat lumbar spinal cord when administered intrathecally. Effects of the two peptides were possibly produced by undefined receptors.

  19. Reactions of the rat musculoskeletal system to compressive spinal cord injury (SCI) and whole body vibration (WBV) therapy.

    Science.gov (United States)

    Schwarz, A; Pick, C; Harrach, R; Stein, G; Bendella, H; Ozsoy, O; Ozsoy, U; Schoenau, E; Jaminet, P; Sarikcioglu, L; Dunlop, S; Angelov, D N

    2015-06-01

    Traumatic spinal cord injury (SCI) causes a loss of locomotor function with associated compromise of the musculo-skeletal system. Whole body vibration (WBV) is a potential therapy following SCI, but little is known about its effects on the musculo-skeletal system. Here, we examined locomotor recovery and the musculo-skeletal system after thoracic (T7-9) compression SCI in adult rats. Daily WBV was started at 1, 7, 14 and 28 days after injury (WBV1-WBV28 respectively) and continued over a 12-week post-injury period. Intact rats, rats with SCI but no WBV (sham-treated) and a group that received passive flexion and extension (PFE) of their hind limbs served as controls. Compared to sham-treated rats, neither WBV nor PFE improved motor function. Only WBV14 and PFE improved body support. In line with earlier studies we failed to detect signs of soleus muscle atrophy (weight, cross sectional diameter, total amount of fibers, mean fiber diameter) or bone loss in the femur (length, weight, bone mineral density). One possible explanation is that, despite of injury extent, the preservation of some axons in the white matter, in combination with quadripedal locomotion, may provide sufficient trophic and neuronal support for the musculoskeletal system.

  20. Telomerase expression in the glial scar of rats with spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Mingkun Yang; Weibin Sheng; Tao Xu; Kai Huang; Yanjiao Wang

    2012-01-01

    A rat model of spinal cord injury was established using the weight drop method. A cavity formed 14 days following spinal cord injury, and compact scar tissue formed by 56 days. Enzyme-linked immunosorbent assay and polymerase chain reaction enzyme-linked immunosorbent assay results demonstrated that glial fibrillary acidic protein and telomerase expression increased gradually after injury, peaked at 28 days, and then gradually decreased. Spearman rank correlation showed a positive correlation between glial fibrillary acidic protein expression and telomerase expression in the glial scar. These results suggest that telomerase promotes glial scar formation.

  1. Effects of nerve growth factor on N-methyI-D-asparate receptor 1 after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    曹晓建; 汤长华; 罗永湘

    2002-01-01

    To explore the effects of the nerve growth factor ( NGF ) on N-methyI-D-asparate receptor 1(NMDAR 1 ) after spinal cord injury. Methods: Spinal cord injury of Wistar rats was performed with Allen's method by a 10 g x 2.5 cm impact on the posterior T8 spinal cord. NGF was given to the rats of the treatment group via subarachnoid space tube at once,2, 4, 8, 12 and 24 hours after spinal cord injury,respectively. The expression of NMDAR1 mRNA in spinal cord was detected by in situ hybridization. Results: Rare expression sequence of NMDAR1 mRNA was found in rat spinal cord of the normal group. A strong expression sequence of NMDAR1 mRNA was found in rat spinal cord of the normal saline group. The expression of NMDAR1 mRNA in the NGF group was significantly decreased as compared with that in the normal saline group ( P = 0.01 ). Conclusions: NGF can relieve damage of injured spinal cord by prohibiting the expression of NMDAR1 mRNA.

  2. pSVPoMcat modifying Schwann cell to protect injured spinal neurons in rats

    Institute of Scientific and Technical Information of China (English)

    陈礼刚; 高立达; 等

    2002-01-01

    Objective:To investigate the protective effect of pSVPoMcat(myelin basic protein microgene)modifying Schwann cell on injured spinal neurons.Methods;A model of rat spinal cord injured by hemisection was used.One hundred and twenty healthy SD rats of both sexes weighing 250-300g were divided into three groups:GroupA(n=40,treated with implantation of pSPVoMcat modifying Schwann cell),GroupB(n=40,treated with implantation of Schwann cell only)and GroupC(n=400,treated with sham operation as the control).One week after operation the rat functional recovery was observed dynamically by using combined behavioral score(CBS)and cortical somatasensory evoked potentials,the spinal cord sections were stained by Nissl,acid phosphatase enzyme histochemistry and cell apoptosis was examined by metye green,terminal deoxynucleotidyl and the dUTP Nick end labeling technique.Quantitative analysis was done by computer image analysis system.Results:In Group A the injured neurons recovered well morphologically.The imaging analysis showed a result of GroupA>GroupB>Group Cin the size of the neurons (P<0.01),The percentage of ACP(acid phosphatase) stained area and the rate of apoptosis sequence were groupsAspinal neurons and promotes recovery of injured spinal cord function in rats.

  3. Effect of nerve growth factor on neuronal apoptosis after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    曹晓建; 汤长华; 罗永湘

    2002-01-01

    To explore the molecular mechanism of the protective effect of nerve growth factor (NGF) on injured spinal cord. Methods: The posterior T8 (the 8th thoracic segment) spinal cords of 60 Wistar rats were injured by impacts caused by objects (weighing 10 g) falling from a height of 2.5 cm with Allens way. Solution with nerve growth factors (NGF) was given to 30 rats (the NGF group) through a microtubule inserted into the subarachnoid cavity immediately, and at 2, 4, 8, 12 and 24 hours after spinal cord injury (SCI) respectively. Normal saline (NS) with same volume was given to the other 30 rats (the NS group) with the same method. And 5 normal rats were taken as the normal controls. The expression of bcl-2 and bax proteins in spinal cord was detected with immunohistochemistry. The apoptotic neurons in spinal cord were measured with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) staining. Results: The positive expression of bcl-2 protein was strong in the normal controls, but decreased in the NS group, and increased significantly in the NGF group as compared with that of the NS group (P<0.01). The positive expression of bax protein was also strong in the normal controls, but increased in the NS group, and decreased significantly in the NGF group as compared with that of the NS group (P<0.01). Apoptotic neurons were found in the NS group, and they decreased significantly in the NGF group as compared with that of the NS group (P<0.01). Conclusions: NGF can protect the injured nerve tissues through stimulating the expression of bcl-2 protein, inhibiting the expression of bax protein and inhibiting the neuronal apoptosis after SCI.

  4. SPONTANEOUS SPINAL EPIDURAL ABSCESS FOLLOWING TRAUMA TO BACK IN A HEALTHY ADULT WITHOUT PREDISPOSING FACTORS - A RARE CASE REPORT

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    Shanmuga Sundaram

    2014-02-01

    Full Text Available Spinal epidural abscess due to its varied presentation , poses a great challenge, more so in a healthy adult, without any predisposing factors. Early diagnosis and treatment is paramount, as late diagnosis and delayed treatment result in increased mortality and morbidity. In this case report, we are presenting a case of spinal extradural abscess in a healthy young adult without predisposing factors, provisionally diagnosed as extradural hematoma and early surgical intervention confirmed the diagnosis of spinal epidural abscess and prevented any devastating consequence

  5. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

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    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  6. Involvement of spinal monocyte chemoattractant protein-1 (MCP-1) in cancer-induced bone pain in rats.

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    Hu, Ji-Hua; Zheng, Xiao-Yan; Yang, Jian-Ping; Wang, Li-Na; Ji, Fu-Hai

    2012-05-23

    In this study, we examined the involvement of chemokine monocyte chemoattractant protein-1 (MCP-1) in the spinal cord of a rat model of cancer-induced bone pain (CIBP). In this model, CIBP was established by an intramedullary injection of Walker 256 cells into the tibia of rats. We observed a significant increase in expression levels of MCP-1 and its receptor CCR2 in the spinal cord of CIBP rats. Furthermore, the intrathecal administration of an anti-MCP-1 neutralizing antibody attenuated the mechanical allodynia established in CIBP rats. Likewise, an intrathecal injection of exogenous recombinant MCP-1 induced a striking mechanical allodynia in naïve rats. These results suggest that increases in spinal MCP-1 and CCR2 expression are involved in the development of mechanical allodynia associated with bone cancer rats.

  7. Posterior spinal decompression, stabilization and arthrodesis in Nigerian adults: Profile and outcome

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    O E Idowu

    2012-01-01

    Full Text Available Background: The availability of intraoperative fluoroscopy and improved access to varieties of spinal titanium implants has revived posterior spinal stabilization techniques with their distinct advantages. Our aim is to describe the profile of various spine pathologies requiring subaxial posterior spinal decompression, stabilization (using titanium implants, and arthrodesis, and to determine the rate of postoperative complications and factors affecting outcome. Materials and Methods: This is a prospective single institution study of consecutive adult patients seen during the study period. Data collected included the patients′ demographics, radiological findings, indication for surgery, surgical procedure, operation time, intraoperative blood loss, and postoperative complications. Results: There were 26 patients (15 males and 11 females. Their ages ranged between 24 and 78 years (median = 42 years. The most common indications for surgery were spinal trauma and degenerative spine disease (24 patients. The region that was most commonly stabilized was the lumbar- 12 cases (46.2%. No patients experienced neural or vascular injury as a result of screw position; likewise no patient had screw loosening. There was a case each of superficial surgical site infection and transient cerebrospinal fluid leak but no case of implant failure was encountered. The outcome was significantly associated with the etiology (0.030 of the indication for surgery and preoperative power grade (0.000. Conclusion: Spinal trauma and degenerative spine disease are the two most common indications for posterior spinal decompression, stabilization and fusion in our center. It is associated with acceptable postoperative complication rate when done under fluoroscopic guidance. Outcome is related more to the preoperative neurological deficit and etiology of the indication for surgical stabilization.

  8. Combined spinal epidural anesthesia for laparoscopic appendectomy in adults: A case series

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    Rajesh S Mane

    2012-01-01

    Full Text Available Background: Laparoscopy is one of the most common surgical procedures and is the procedure of choice for most of the elective abdominal surgeries performed preferably under endotracheal general anesthesia. Technical advances in the field of laparoscopy have helped to reduce surgical trauma and discomfort, reduce anesthetic requirement resulting in shortened hospital stay. Recently, regional anaesthetic techniques have been found beneficial, especially in patients at a high risk to receive general anesthesia. Herewith we present a case series of laparoscopic appendectomy in eight American Society of Anaesthesiologists (ASA I and II patients performed under spinal-epidural anaesthesia. Methods: Eight ASA Grade I and II adult patients undergoing elective Laparoscopic appendectomy received Combined Spinal Epidural Anaesthesia. Spinal Anaesthesia was performed at L 2 -L 3 interspace using 2 ml of 0.5% (10 mg hyperbaric Bupivacaine mixed with 0.5ml (25 micrograms of Fentanyl. Epidural catheter was inserted at T 10 -T 11 interspace for inadequate spinal anaesthesia and postoperative pain relief. Perioperative events and operative difficulty were studied. Systemic drugs were administered if patients complained of shoulder pain, abdominal discomfort, nausea or hypotension. Results: Spinal anaesthesia was adequate for surgery with no operative difficulty in all the patients. Intraoperatively, two patients experienced right shoulder pain and received Fentanyl, one patient was given Midazolam for anxiety and two were given Ephedrine for hypotension. The postoperative period was uneventful. Conclusion: Spinal anaesthesia with Hyperbaric Bupivacaine and Fentanyl is adequate and safe for elective laparoscopic appendectomy in healthy patients but careful evaluation of the method is needed particularly in compromised cardio respiratory conditions.

  9. Activation of peroxisome proliferator-activated receptor alpha in rat spinal cord after peripheral noxious stimulation.

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    Benani, A; Heurtaux, T; Netter, P; Minn, A

    2004-10-07

    Following recurrent noxious stimulation, both functional modification and structural reorganization such as activation of the arachidonate cascade or axon sprouting occur in the central nervous system (CNS). It has been recently proposed that these alterations observed during chronic pain state were supported by an intensification of the lipid metabolism. In this regard, it has been shown that mRNA coding for several fatty acid metabolizing enzymes are up-regulated in the rat lumbar spinal cord in response to persistent nociception induced by a peripheral inflammation. As peroxisome proliferators-activated receptor (PPAR) could mediate such effects, we therefore investigated the activation of this transcription factor in the rat spinal cord following subcutaneous injection of complete Freund's adjuvant (CFA) into a hind paw. In this study, we compared the DNA-binding activity of nuclear proteins extracted from healthy and inflamed rats toward a PPAR response element. Using electrophoretic mobility-shift assay (EMSA), we found that only the PPARalpha isoform was activated in the rat spinal cord after CFA injection. This activation occurred rapidly, as early as 30 min post-CFA injection, and was persistent up to 10 h, reaching a maximum at 6h after CFA injection. In view of the consequences of PPARalpha activation in other tissues, these results suggest that fatty acid utilization is enhanced in the CNS during chronic pain state. Although the physiopathological relevance of PPARalpha activation during hyperalgesia needs further investigation, we provided here a new player in the molecular modeling of pain pathways.

  10. Effect of Electroacupuncture at Acupoints of the Governor Vessel on Aquaporin-4 in Rat with Experimental Spinal Cord Injury

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    Xie Jie; Fang Jian; Feng Xinsong; Liu Qingsi

    2006-01-01

    This study is to investigate the effects of electroacupuncture at acupoints of the Governor Vessel(GV) on aquaporin-4 (AQP-4) expression and on functions of the hind limbs in the rat of spinal cord injury. The functions of the hind limbs were detected with BBB scale on the 1d, 3d, 7d and 21d after the spinal cord injury, respectively, and AQP-4 expression in the spinal cord was determined with immunohistochemical method and analyzed quantitatively with image analyzer. The results indicated that on the 1d after the spinal cord injury, increased AQP-4 expression can be seen significantly in both the gray matter and the white matter of the injured spinal cord, and it reached the peaks on the 3d after the spinal cord injury in both the electroacupuncture group and the spinal cord injury group. However, AQP-4 express was significantly decreased in the electroacupuncture group as compared with that in the control group on 7d, 14d and 21d (P<0.05 or P<0.01). The decrease of AQP-4 expression almost went with the improvement of the neurological function, which suggested that electroacupuncture at the acupoints of the Governor Vessel can inhibit edema of the spinal cord to alleviate the secondary spinal cord injury by means of decreasing the AQP-4 expression after the spinal cord injury, so as to protect the residual normal spinal cord tissues and promote the rebuilding of nervous tissues.

  11. Role of telomerase reverse transcriptase in glial scar formation after spinal cord injury in rats.

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    Tao, Xu; Ming-Kun, Yang; Wei-Bin, Sheng; Hai-Long, Guo; Rui, Kan; Lai-Yong, Tu

    2013-09-01

    The study aims to determine the expression of telomerase reverse transcriptase (TERT) in the glial scar following spinal cord injury in the rat, and to explore its relationship with glial scar formation. A total of 120 Sprague-Dawley rats were randomly divided into three groups: SCI only group (without TERT interference), TERT siRNA group (with TERT interference), and sham group. The TERT siRNA and SCI only groups received spinal cord injury induced by the modified Allen's weight drop method. In the sham group, the vertebral plate was opened to expose the spinal cord, but no injury was modeled. Five rats from each group were sacrificed under anesthesia at days 1, 3, 5, 7, 14, 28, 42, and 56 after spinal cord injury. Specimens were removed for observation of glial scar formation using hematoxylin-eosin staining and immunofluorescence detection. mRNA and protein expressions of TERT and glial fibrillary acidic protein (GFAP) were detected by reverse-transcription (RT)-PCR and western blotting, respectively. Hematoxylin-eosin staining showed evidence of gliosis and glial scarring in the spinal cord injury zone of the TERT siRNA and SCI only groups, but not in the sham group. Immunofluorescence detection showed a significant increase in GFAP expression at all time points after spinal cord injury in the SCI only group (81 %) compared with the TERT siRNA group (67 %) and sham group (2 %). In contrast, the expression of neurofilament protein 200 (NF-200) was gradually reduced and remained at a stable level until 28 days in the SCI only group. There were no NF-200-labeled cells in the spinal cord glial scar and cavity at day 56 after spinal cord injury. NF-200 expression at each time point was significantly lower in the SCI only group than the TERT siRNA group, while there was no change in the sham group. Western blotting showed that TERT and GFAP protein expressions changed dynamically and showed a linear relationship in the SCI only group (r = 0.765, P scar, which

  12. 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

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    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.

  13. Cervical Spinal Cord Atrophy Profile in Adult SMN1-Linked SMA.

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    Mohamed-Mounir El Mendili

    Full Text Available The mechanisms underlying the topography of motor deficits in spinal muscular atrophy (SMA remain unknown. We investigated the profile of spinal cord atrophy (SCA in SMN1-linked SMA, and its correlation with the topography of muscle weakness.Eighteen SMN1-linked SMA patients type III/V and 18 age/gender-matched healthy volunteers were included. Patients were scored on manual muscle testing and functional scales. Spinal cord was imaged using 3T MRI system. Radial distance (RD and cord cross-sectional area (CSA measurements in SMA patients were compared to those in controls and correlated with strength and disability scores.CSA measurements revealed a significant cord atrophy gradient mainly located between C3 and C6 vertebral levels with a SCA rate ranging from 5.4% to 23% in SMA patients compared to controls. RD was significantly lower in SMA patients compared to controls in the anterior-posterior direction with a maximum along C4 and C5 vertebral levels (p-values < 10-5. There were no correlations between atrophy measurements, strength and disability scores.Spinal cord atrophy in adult SMN1-linked SMA predominates in the segments innervating the proximal muscles. Additional factors such as neuromuscular junction or intrinsic skeletal muscle defects may play a role in more complex mechanisms underlying weakness in these patients.

  14. Adult spinal V2a interneurons show increased excitability and serotonin-dependent bistability.

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    Husch, Andreas; Dietz, Shelby B; Hong, Diana N; Harris-Warrick, Ronald M

    2015-02-15

    In mice, most studies of the organization of the spinal central pattern generator (CPG) for locomotion, and its component neuron classes, have been performed on neonatal [postnatal day (P)2-P4] animals. While the neonatal spinal cord can generate a basic locomotor pattern, it is often argued that the CPG network is in an immature form whose detailed properties mature with postnatal development. Here, we compare intrinsic properties and serotonergic modulation of the V2a class of excitatory spinal interneurons in behaviorally mature (older than P43) mice to those in neonatal mice. Using perforated patch recordings from genetically tagged V2a interneurons, we revealed an age-dependent increase in excitability. The input resistance increased, the rheobase values decreased, and the relation between injected current and firing frequency (F/I plot) showed higher excitability in the adult neurons, with almost all neurons firing tonically during a current step. The adult action potential (AP) properties became narrower and taller, and the AP threshold hyperpolarized. While in neonates the AP afterhyperpolarization was monophasic, most adult V2a interneurons showed a biphasic afterhyperpolarization. Serotonin increased excitability and depolarized most neonatal and adult V2a interneurons. However, in ∼30% of adult V2a interneurons, serotonin additionally elicited spontaneous intrinsic membrane potential bistability, resulting in alternations between hyperpolarized and depolarized states with a dramatically decreased membrane input resistance and facilitation of evoked plateau potentials. This was never seen in younger animals. Our findings indicate a significant postnatal development of the properties of locomotor-related V2a interneurons, which could alter their interpretation of synaptic inputs in the locomotor CPG.

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

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    Oza, Chintan S; Giszter, Simon F

    2015-05-01

    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.

  16. Effect of amiloride on endoplasmic reticulum stress response in the injured spinal cord of rats.

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    Kuroiwa, Masahiro; Watanabe, Masahiko; Katoh, Hiroyuki; Suyama, Kaori; Matsuyama, Daisuke; Imai, Takeshi; Mochida, Joji

    2014-10-01

    After traumatic spinal cord injury (SCI), endoplasmic reticulum (ER) stress exacerbates secondary injury, leading to expansion of demyelination and reduced remyelination due to oligodendrocyte precursor cell (OPC) apoptosis. Although recent studies have revealed that amiloride controls ER stress and leads to improvement in several neurological disorders including SCI, its mechanism is not completely understood. Here, we used a rat SCI model to assess the effects of amiloride on functional recovery, secondary damage expansion, ER stress-induced cell death and OPC survival. Hindlimb function in rats with spinal cord contusion significantly improved after amiloride administration. Amiloride significantly decreased the expression of the pro-apoptotic transcription factor CHOP in the injured spinal cord and significantly increased the expression of the ER chaperone GRP78, which protects cells against ER stress. In addition, amiloride treatment led to a significant decrease in ER stress-induced apoptosis and a significant increase of NG2-positive OPCs in the injured spinal cord. Furthermore, in vitro experiments performed to investigate the direct effect of amiloride on OPCs revealed that amiloride reduced CHOP expression in OPCs cultured under ER stress. These results suggest that amiloride controls ER stress in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present study suggests that amiloride may be an effective treatment to reduce ER stress-induced cell death in the acute phase of SCI.

  17. 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.

  18. Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats.

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    Mao-Ying, Qi-Liang; Wang, Xiao-Wei; Yang, Chang-Jiang; Li, Xiu; Mi, Wen-Li; Wu, Gen-Cheng; Wang, Yan-Qing

    2012-05-20

    It has been reported that remarkable and sustained activation of astrocytes and/or microglia occurs in cancer induced pain (CIP), which is different from neuropathic and inflammatory pain. The present study was designed to investigate the role of spinal Toll-like receptor 4 (TLR4) induced glial neuroinflammation in cancer induced pain using a modified rat model of bone cancer. The rat model of CIP consisted of unilateral intra-tibial injection with Walker 256 mammary gland carcinoma. Nine days after Walker 256 inoculation, a robust activation of both astrocytes and microglia in bilateral spinal dorsal horn was observed together with significant bilateral mechanical allodynia. This neuroinflammation was characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker), and an elevated level of IL-1β, IL-6 and TNF-α mRNA. I.t. administration of fluorocitrate (an inhibitor of glial metabolism, 1 nmol) or minocycline (an inhibitor of microglia, 100 μg) has significant anti-allodynic effects on day 12 after Walker 256 inoculation. Naloxone (a nonstereoselective TLR4 signaling blocker, 60 μg, i.t.) also significantly alleviated mechanical allodynia and simultaneously blocked the increased inflammatory cytokine mRNA. The results suggested that spinal TLR4 might play an important role in the sustained glial activation that critically contributed to the robust and sustained spinal neuroinflammation in CIP. This result could potentially help clinicians and researchers to better understand the mechanism of complicated cancer pain.

  19. Raman spectroscopic investigation of spinal cord injury in a rat model

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    Saxena, Tarun; Deng, Bin; Stelzner, Dennis; Hasenwinkel, Julie; Chaiken, Joseph

    2011-02-01

    Raman spectroscopy was used to study temporal molecular changes associated with spinal cord injury (SCI) in a rat model. Raman spectra of saline-perfused, injured, and healthy rat spinal cords were obtained and compared. Two injury models, a lateral hemisection and a moderate contusion were investigated. The net fluorescence and the Raman spectra showed clear differences between the injured and healthy spinal cords. Based on extensive histological and biochemical characterization of SCI available in the literature, these differences were hypothesized to be due to cell death, demyelination, and changes in the extracellular matrix composition, such as increased expression of proteoglycans and hyaluronic acid, at the site of injury where the glial scar forms. Further, analysis of difference spectra indicated the presence of carbonyl containing compounds, hypothesized to be products of lipid peroxidation and acid catalyzed hydrolysis of glycosaminoglycan moieties. These results compared well with in vitro experiments conducted on chondroitin sulfate sugars. Since the glial scar is thought to be a potent biochemical barrier to nerve regeneration, this observation suggests the possibility of using near infrared Raman spectroscopy to study injury progression and explore potential treatments ex vivo, and ultimately monitor potential remedial treatments within the spinal cord in vivo.

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

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    Guasti, Leonardo; Richardson, Denise; Jhaveri, Maulik; Eldeeb, Khalil; Barrett, David; Elphick, Maurice R; Alexander, Stephen P H; Kendall, David; Michael, Gregory J; Chapman, Victoria

    2009-07-01

    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 pain states.

  1. 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

  2. Label-free imaging of rat spinal cords based on multiphoton microscopy

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    Liao, Chenxi; Wang, Zhenyu; Zhou, Linquan; Zhu, Xiaoqin; Liu, Wenge; Chen, Jianxin

    2016-10-01

    As an integral part of the central nervous system, the spinal cord is a communication cable between the body and the brain. It mainly contains neurons, glial cells, nerve fibers and fiber tracts. The recent development of the optical imaging technique allows high-resolution imaging of biological tissues with the great potential for non-invasively looking inside the body. In this work, we evaluate the imaging capacity of multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) for the cells and extracellular matrix in the spinal cord at molecular level. Rat spinal cord tissues were sectioned and imaged by MPM to demonstrate that MPM is able to show the microstructure including white matter, gray matter, ventral horns, dorsal horns, and axons based on the distinct intrinsic sources in each region of spinal cord. In the high-resolution and high-contrast MPM images, the cell profile can be clearly identified as dark shadows caused by nuclei and encircled by cytoplasm. The nerve fibers in white matter region emitted both SHG and TPEF signals. The multiphoton microscopic imaging technique proves to be a fast and effective tool for label-free imaging spinal cord tissues, based on endogenous signals in biological tissue. It has the potential to extend this optical technique to clinical study, where the rapid and damage-free imaging is needed.

  3. Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.

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    Chen, Yu-Wen; Chiu, Chong-Chi; Liu, Kuo-Sheng; Hung, Ching-Hsia; Wang, Jhi-Joung

    2015-12-01

    Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade.

  4. Selective retrograde transport of D-aspartate in spinal interneurons and cortical neurons of rats

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    Rustioni, A.; Cuenod, M. (Zurich Univ. (Switzerland))

    1982-03-18

    Retrograde labeling of neuronal elements in the brain and spinal cord has been investigated by autoradiographic techniques following injections of D-(/sup 3/H)aspartate (asp), (/sup 3/H)..gamma..-aminobutyric acid (GABA) or horseradish peroxidase (HRP) in the medulla and spinal cord of rats. Twenty-four hours after D-(/sup 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 (/sup 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-(/sup 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-(/sup 3/H)asp although autoradiographic grains overlie pyramidal tract fibers on the side contralateral to the injection.

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

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    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.

  6. Neuroprotective effect of exogenous vascular endothelial growth factor on rat spinal cord neurons in vitro hypoxia

    Institute of Scientific and Technical Information of China (English)

    DING Xin-min; MAO Bo-yong; JIANG Shu; LI Sheng-fu; DENG Yi-ling

    2005-01-01

    Background Vascular endothelial growth factor (VEGF) is well known as a hypoxia-induced protein. That it markedly increased expression of VEGF and improvement of rat motor function after spinal cord injury suggested that VEGF could play a neuroprotective role in ischaemic tolerance. This study investigated whether vascular endothelial growth factor has direct neuroprotective effects on rat spinal cord neurons. Methods We employed primary cultures of embryonic rat spinal cord neurons, then administrated different concentrations of VEGF164 in the culture medium before hypoxia when the number of neurons was counted and the cell viability was detected by MTT. The neuronal apoptosis and expression of VEGF and its receptor genes were evaluated by terminal deoxynucleotidyl transferase mediated dUTP nick-end labelling (TUNEL) and immunohistochemistry. The VEGFR2/FLK-1 inhibitor, SU1498, was used to confirm whether the neuroprotective effect of VEGF was mediated through VEGFR2/Flk-1 receptors. Result In hypoxic conditions,the number and viability of neurons decreased progressively, while the number of TUNEL-positive cells increased along with the prolongation of hypoxic exposure. When the concentration of VEGF in cell culture medium reached 25 ng/ml, the cell viability increased 11% and neuronal apoptosis reduced to half, this effect was dose dependent and led to an approximately 25% increase in cell viability and about threefold decrease in TUNEL-positive cells at a maximally effective concentration of 100 ng/ml. In normal conditions, VEGF/Flk-1 but not VEGF/Flt-1 gene expressed at a low level: after hypoxia, the expression of VEGF/Flk-1, but not VEGF/Flt-1 was significantly increased. The protective effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor, SU1498. Conclusions VEGF has direct neuroprotective effects on rat spinal cord neurons, which may be mediated in vitro through VEGFR2/Flk-1 receptors.

  7. Bladder response to acute sacral neuromodulation while treating rats in different phases of complete spinal cord injury: a preliminary study

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    Ping Shi

    2015-12-01

    Full Text Available Background: Compared to conventional therapies, sacral neuromodulation (SNM may offer an alternative, non-destructive treatment for SCI patients with bladder dysfunction. Understanding bladder response to SNM treatment for SCI in different phases may yield new insights for innovative use of this promising technique. Materials and Methods: Female Sprague-Dawley rats were used in this study to examine the effects of acute SNM on bladder reflex in complete SCI rats. All rats were anesthetized and set up for continuous saline infusion. Acute SNM treatment was implemented for about 6 hours for each rat. Cystometric parameters, including time between contractions, contraction duration, bladder peak pressure, and number of uninhibited contractions, were analyzed and compared within rats before and after SNM treatment. Results: For the spinally transected rats during early phase (less than two weeks post spinalization, the time between contractions and contraction duration both increased after SNM treatments, yet the increased amplitude was about or less than 20%. For the spinally transected rats with a longer days survival (about two to four weeks post spinalization, the time between contractions and contraction duration substantially increased after SNM treatment and the changes for their average values were more than 90%. For the spinally transected rats with a much longer days survival (more than five weeks post spinalization, the time between contractions and contraction duration increased after SNM treatments, yet the magnitude of changes were less than 30%. Conclusion: The present study suggested that the significant effectiveness of SNM for complete SCI played its role after the spinal shock phase and prior to the development of detrusor overactivity. It indicated that the time point of SNM treatment is necessary to be paid attention.

  8. Presence of neuropeptide FF receptors on primary afferent fibres of the rat spinal cord

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    Zajac, J.-M. [Laboratoire de Pharmacologie et de Toxicologie Fondamentales, C.N.R.S., 205 Route de Narbonne, 31077 Toulouse Cedex (France); Kar, S. [Douglas Hospital Research Centre and Department of Psychiatry, McGill University, 6875 LaSalle Blvd, Verdun, Quebec H4H1R3 (Canada); Gouarderes, C. [Laboratoire de Pharmacologie et de Toxicologie Fondamentales, C.N.R.S., 205 Route de Narbonne, 31077 Toulouse Cedex (France)

    1996-09-01

    A radioiodinated analogue of neuropeptide FF, [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF, was used as a selective probe to label neuropeptide FF receptors in the rat spinal cord. Following neonatal capsaicin treatment, dorsal rhizotomy or sciatic nerve section, the distribution and possible alterations of spinal cord specific [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF binding sites were evaluated using in vitro quantitative receptor autoradiography. In normal rats, the highest densities of sites were observed in the superficial layers of the dorsal horn (laminae I-II) whereas moderate to low amounts of labelling were seen in the deeper (III-VI) laminae, around the central canal, and in the ventral horn. Capsaicin-treated rats showed a bilateral decrease (47%) in [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF binding in all spinal areas. Unilateral sciatic nerve section and unilateral dorsal rhizotomy induced significant depletions (15-27%) in [{sup 125}I][d.Tyr{sup 1},(NMe)Phe{sup 3}]neuropeptide FF labelling in the ipsilateral dorsal horn.These results suggest that a proportion of neuropeptide FF receptors is located on primary afferent terminals of the dorsal horn and could thus play a role in the modulation of nociceptive transmission. (Copyright (c) 1996 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. Survival and migration of Schwann cells after the vascularized peripheral nerve grafted into spinal cord in rats

    Institute of Scientific and Technical Information of China (English)

    GUO Qing-shan; WANG Ai-min; WANG Xiao-jun; SUN Hong-zhen; DU Quan-yin

    2005-01-01

    Objective:To study the survival and ability of inducing axonal regeneration of the Schwann cells after the peripheral nerve being grafted into spinal cord. Methods:A total of 30 adult female Wistar rats were randomly divided into the VN (vascularized peripheral nerve) and PN (peripheral nerve) groups. A 5-mm spinal cord defect of the left posterior column was made at the T1-3 vertebral level. The defect was grafted with the vascularized or isolated peripheral nerve respectively. The survival and proliferation of the Schwann cells were assessed by histological and morphometric analysis 8 weeks after the operation. Results:In the VN group, the peripheral nerve grew into the cord with lots of Schwann cells survived and proliferated, and had more NF and S-100 positive fibers than in the PN group. Conclusion:The vascularized peripheral nerve enhances the survival and proliferation of the Schwann cells and prompts the regeneration of injured axon of the central nerve system to certain degree.

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

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    Wojciech Dabrowski

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

  11. Effect of glial cell line-derived neurotrophic factor on peripheral nerve regeneration in adult rat

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; LI Jian-hong; ZHENG Xing-dong; LU Chang-lin; HE Cheng

    2001-01-01

    Objective: To study the effect of glial cell line-derived neurotrophic (GDNF) on adult peripheral nerve regeneration. Methods: Transectioned sciatic nerve in adult rats was sutured into silicone channel. GDNF or SAL solution was injected into the silicone channels during operation. Four weeks later, the effect of GDNF on axonal regeneration was evaluated by degenerative neurofiber staining and HRP retrograde tracing. Results: Compared with SAL group, the percentage of degenerative neurofiber areas decreased from 17.3% to 1.9% ( P<0.01 ) and the ratio of labeled spinal somas number was significantly increased from 43.5% to 68.3% ( P<0.01 ) in GDNF group. Conclusion: The results suggest that exogenous GDNF can obviously enhance adult peripheral nerve regeneration.

  12. Presynaptic facilitation by tetracaine of glutamatergic spontaneous excitatory transmission in the rat spinal substantia gelatinosa - Involvement of TRPA1 channels.

    Science.gov (United States)

    Piao, Lian-Hua; Fujita, Tsugumi; Yu, Ting; Kumamoto, Eiichi

    2017-02-15

    The amide-type local anesthetic (LA) lidocaine activates transient receptor potential (TRP) ankyrin-1 (TRPA1) channels to facilitate spontaneous l-glutamate release onto spinal substantia gelatinosa (SG) neurons, which play a crucial role in regulating nociceptive transmission. In contrast, the ester-type LA procaine reduces the spontaneous release of l-glutamate in SG neurons. In order to determine whether TRPA1 activation by LAs is specific to amide-types, we examined the actions of tetracaine, another ester-type LA, and other amide-type LAs on glutamatergic spontaneous excitatory transmission in SG neurons by focusing on TRP activation. Whole-cell patch-clamp recordings were performed on SG neurons of adult rat spinal cord slices at a holding potential of -70mV. Bath-applied tetracaine increased spontaneous excitatory postsynaptic current (sEPSC) frequency in a concentration-dependent manner. Tetracaine activity was resistant to the voltage-gated Na(+)-channel blocker tetrodotoxin, the TRP vanilloid-1 antagonist capsazepine, and the TRP melastatin-8 antagonist BCTC, but was inhibited by the non-selective TRP antagonist ruthenium red and the TRPA1 antagonist HC-030031. With respect to amide-type LAs, prilocaine had a tendency to increase sEPSC frequency, while ropivacaine and levobupivacaine reduced the frequency. In conclusion, tetracaine facilitated spontaneous l-glutamate release from nerve terminals by activating TRPA1 channels in the SG, resulting in an increase in the excitability of SG neurons. TRPA1 activation was not specific to amide-type or ester-type LAs. The facilitatory action of LAs may be involved in pain occurring after recovery from spinal anesthesia.

  13. Spinal anandamide produces analgesia in neuropathic rats: possible CB(1)- and TRPV1-mediated mechanisms.

    Science.gov (United States)

    Starowicz, K; Makuch, W; Osikowicz, M; Piscitelli, F; Petrosino, S; Di Marzo, V; Przewlocka, B

    2012-03-01

    The endocannabinoid anandamide (AEA) activates also transient receptor potential vanilloid-1 (TRPV1) channels. However, no data exist on the potential role of spinal TRPV1 activation by AEA in neuropathic pain. We tested the effect of: 1) AEA (5-100 μg), alone or in the presence of an inhibitor of its hydrolysis, and 2) elevated levels of endogenous AEA (following inhibition of AEA hydrolysis), in CCI rats, and the involvement of TRPV1 or cannabinoid CB(1) receptors in the observed effects. Levels of AEA in the spinal cord of CCI rats were measured following all treatments. AEA (50 μg) displayed anti-allodynic and anti-hyperalgesic effects which were abolished by previous antagonism of TRPV1, but not CB(1), receptors. Depending on the administered dose, the selective inhibitor of AEA enzymatic hydrolysis, URB597 (10-100 μg), reduced thermal and tactile nociception via CB(1) or CB(1)/TRPV1 receptors. The anti-nociceptive effects of co-administered per se ineffective doses of AEA (5 μg) and URB597 (5 μg) was abolished by antagonism of CB(1), but not TRPV1, receptors. Spinal AEA levels were increased after CCI, slightly increased further by URB597, 10 μg i.t., and strongly elevated by URB597, 100 μg. Injection of AEA (50 μg) into the lumbar spinal cord led to its dramatic elevation in this tissue, whereas, when a lower dose was used (5 μg) AEA endogenous levels were elevated only in the presence of URB597 (5 μg). We suggest that spinal AEA reduces neuropathic pain via CB(1) or TRPV1, depending on its local concentration.

  14. The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain

    Science.gov (United States)

    Kim, Do Yun; Chae, Joo Wung; Lim, Chang Hun; Heo, Bong Ha; Park, Keun Suk; Lee, Hyung Gon; Choi, Jeong Il; Yoon, Myung Ha

    2016-01-01

    Background Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level. PMID:27413481

  15. Passive immunization with LINGO-1 polyclonal antiserum afforded neuroprotection and promoted functional recovery in a rat model of spinal cord injury.

    Science.gov (United States)

    Lv, Jun; Xu, Ru-xiang; Jiang, Xiao-dan; Lu, Xin; Ke, Yi-quan; Cai, Ying-qian; Du, Mou-xuan; Hu, Changchen; Zou, Yu-xi; Qin, Ling-sha; Zeng, Yan-jun

    2010-01-01

    LINGO-1 (leucine-rich repeat and Ig domain-containing, Nogo receptor-interacting protein) is an important component of the NgR receptor complex involved in RhoA activation and axon regeneration. The authors report on passive immunization with LINGO-1 polyclonal antiserum, a therapeutic approach to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). The intrathecally administered high-titer rabbit-derived antiserum can be detected around the injury site within a wide time window; it blocks LINGO-1 in vivo with high molecular specificity. In this animal model, passive immunization with LINGO-1 antiserum significantly decreased RhoA activation and increased neuronal survival. Adult rats immunized in this manner show recovery of certain hindlimb motor functions after dorsal hemisection of the spinal cord. Thus, passive immunotherapy with LINGO-1 polyclonal antiserum may represent a promising repair strategy following acute SCI.

  16. Spontaneous axonal regeneration in rodent spinal cord after ischemic injury

    DEFF Research Database (Denmark)

    von Euler, Mia; Janson, A M; Larsen, Jytte Overgaard;

    2002-01-01

    Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total l...

  17. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human.

    Science.gov (United States)

    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel

    2014-06-01

    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  18. Application of Luxol Fast Blue staining in locating the corticospinal tract in adult rats

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    Su Liu; Guangyu Shen; Guangming Lü; Xiaosong Gu

    2006-01-01

    BACKGROUND: There are many methods for myelin staining,mordant,or the special reaction of osmic acid with lipoid is used according to different principles.The commonly used methods are classic Well staining ,classic lithium carbonate-haematine staining,fast green staining,silver staining ,etc.Luxol Fast Blue can brightly stain myelin sheath,and has certain specificity .The background can be very clean if there is proper differentiation,whereas Luxol Fast Blue is cheap and convenient to operate,thus it is an ideal staining reagent for routine myelin sheath.OBJECTIVE: To show the coricospinal tract of normal adult rats with Luxol Fast Blue shaining method.DESIGN:A repetitive measurement design.SETTINGS: Institute of Nuerobiology,Nantong University;Department of Rehabilitation Medicine,Affiliated Hospital of Nantong University.MATERIALS: Six healthy adult male SD rats of clean dergree,weighing averagely 300 g.were provided by the experimental animal center of Nantong University.1 g/L Luxol Fast Blue solution was provided by Sigma Company;Leica CM1900 cryostat microtome by Leica Company;Leica DMR microscope by Leica Company.METHODS:The experiment was carried out in the Staff Room of Human Anatomy,Nantong University in May 2005.The rats were given intraperitoneal injection of combined anesthetic(2 mL/kg),then the chest was open for perfusing saline and phosphate buffer containing formamint via heart. Brain and spinal cord were removed after 1 hour then fixed,then changed to phosphate buffer(pH 7.4)containing 300 g/L saccharu at 4 ℃.and stayed overnight,tissue blocks at pyramid,decussation of pyramid and cervical,thoracic,lumbar and sacral segments of spinal cord were removed to prepare continuous horizontal frozen sections(30 μm) after sedimentation,the sections were dried at room temperature.The corticospinal tract of normal adult rats were shown with Luxol Fast Blue staining method,and observed under Leica DMR microscope.MAIN OUTCOME MEASURES:Positive fibers in

  19. ω-conotoxin MVIIA intralesional injection in spinal cord injury in rats

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    Karen Maciel de Oliveira

    2016-01-01

    Full Text Available This study aimed to investigate the neuroprotective effect of ω-conotoxin MVIIA (MVIIA intralesional application in rats submitted to spinal cord injury. Male Wistar rats, weighing 300g±23.4, were distributed in five groups: negative control (SHAM, placebo (PLA, 5μM MVIIA, 10μM MVIIA and 20μM MVIIA MVIIA. After laminectomy of the 12th thoracic vertebra (SHAM, the PLA, 5μM MVIIA, 10μM MVIIA and 20μM MVIIA groups were subjected to acute compressive spinal cord trauma for five minutes, and then five minutes later, the animals received specific treatment in a standard total volume of 2µL, by intralesional route, using sterile PBS as placebo. Locomotor activity was assayed using Basso Beattie Bresnahan (BBB scale to show the patterning of SCI. With 48 hours of injury, the animals were euthanized, the liquor sample was collected in atlantooccipital space, and also the spinal segment, including the epicenter and caudal region to injury. Assays were performed for mitochondrial viability, serum glutamate, production of reactive oxygen species (ROS and lipid peroxidation (LP were performed. The study design was randomized and the data submitted to ANOVA and comparison of means by SNK test, and data from BBB scale were evaluated using Kruskal-Wallis test (P<0.05. There was no significant difference between groups in BBB scores. The MVIIA did not promote decrease in the levels of glutamate, ROS, LP, and did not preserve the mitochondria in the intralesional application five minutes after spinal cord injury in rats.

  20. Electrical stimulation modulates injury potentials in rats after spinal cord injury*

    Institute of Scientific and Technical Information of China (English)

    Guanghao Zhang; Xiaolin Huo; Aihua Wang; Changzhe Wu; Cheng Zhang; Jinzhu Bai

    2013-01-01

    An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as wel as injury current, can be modulated by direct current field stimulation;however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around-70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon il ustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cel membrane and the reduction of cation influx.

  1. 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

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    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

  2. Hemisection spinal cord injury in rat: The value of intraoperative somatosensory evoked potential monitoring

    Science.gov (United States)

    Cloud, Beth A.; Ball, Bret G.; Chen, Bingkun; Knight, Andrew M.; Hakim, Jeffrey S.; Ortiz, Ana M.; Windebank, Anthony J.

    2012-01-01

    Techniques used to produce partial spinal cord injuries in animal models have the potential for creating variability in lesions. The amount of tissue affected may influence the functional outcomes assessed in the animals. The recording of somatosensory evoked potentials (SSEPs) may be a valuable tool for assessing the extent of lesion applied in animal models of traumatic spinal cord injury (SCI). Intraoperative tibial SSEP recordings were assessed during surgically induced lateral thoracic hemisection SCI in Sprague-Dawley rats. The transmission of SSEPs, or lack thereof, was determined and compared against the integrity of the dosal funiculi on each side of the spinal cord upon histological sectioning. An association was found between the presence of an SSEP signal and presence of intact dorsal funiculus tissue. The relative risk is 4.50 (95% confidence interval: 1.83 to 11.08) for having an intact dorsal funiculus when the ipsilateral SSEP was present compared to when it was absent. Additionally, the amount of spared spinal cord tissue correlates with final functional assessments at nine weeks post injury: BBB (linear regression, R2 = 0.618, p <0.001) and treadmill test (linear regression, R2 = 0.369, p = 0.016). Therefore, we propose intraoperative SSEP monitoring as a valuable tool to assess extent of lesion and reduce variability between animals in experimental studies of SCI. PMID:22960163

  3. Phosphoproteomics and bioinformatics analyses of spinal cord proteins in rats with morphine tolerance.

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    Wen-Jinn Liaw

    Full Text Available INTRODUCTION: Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. METHODS: To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. RESULTS: Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. CONCLUSIONS: Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance.

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

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    Yan Sun

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

  5. 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.

  6. Neuroprotective effect of epigallocatechin-3-gallate on hemisection-induced spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fengjun Deng; Rubing Li; Yingbao Yang; Dan Zhou; Qian Wang; Jiangping Xu

    2011-01-01

    Epigallocatechin-3-gallate (EGCG), a naturally occurring compound in green tea, has been widely used as an antioxidant agent. In the present study, model rats with acute spinal cord injury were intraperitoneally injected with 25, 50, and 100 mg/kg EGCG, and spinal cord ultrastructure, oxidative stress reaction, inflammatory factors, and apoptosis-associated gene expression were observed. Results showed that EGCG attenuated neuronal and axonal injury 24 hours post injury. It also decreased serum interleukin-1β, tumor necrosis factor-α, and intercellular adhesion molecule-1 release, and decreased apoptosis-associated gene expression. Furthermore, it increased the level of the superoxide anion (O2-), superoxide dismutase, and B-cell lymphoma/leukemia-2, and reduced malondialdehyde levels. Furthermore, it reduced the expression of the pro-apoptotic protein Bax. Noticeably, EGCG at the 100 mg/kg dosage exhibited similar effects as methylprednisolone sodium succinate, which has been frequently used for clinical acute spinal cord injury. The results demonstrated that EGCG can significantly inhibit inflammation, suppress oxidation, and reduce apoptosis in acute spinal cord injury.

  7. Role of spinal GABAA receptor reduction induced by stress in rat thermal hyperalgesia.

    Science.gov (United States)

    Ma, Xuelian; Bao, Weiying; Wang, Xiujun; Wang, Zhilong; Liu, Qiaoran; Yao, Zhenyu; Zhang, Di; Jiang, Hong; Cui, Shuang

    2014-11-01

    The mechanisms underlying stress-induced hyperalgesia (SIH) remain poorly understood. Recent findings have provided strong evidence indicating that SIH could be related, at least in part, to alterations in spinal cord GABA activity. In the present study, we first investigated how acute restraint stress impacted pain responses as assessed using the tail flick immersion test. These results showed that rats developed hyperalgesia at 6 h after being subjected to 1-h acute restraint stress. Second, we measured the activation of spinal neurons and alterations in expression of GABAA receptor β2 and β3 subunits as related to stress-induced hyperalgesia. Results from Western blot and immunofluorescence assays showed that c-fos protein increased in the dorsal horn of the lumbar spinal cord and GABAA receptor β2 and β3 subunit proteins decreased significantly at 6 h after exposure to 1 h of acute restraint stress. Finally, the effects of spinal GABAA receptor alteration on SIH were evaluated. These results showed that intrathecal administration of muscimol inhibited hyperalgesia induced by stress while bicuculline enhanced hyperalgesia in the control groups. Taken together, the present data reveal that GABAA receptor β2 and β3 decrease following 1 h of acute restraint stress and may play a critical role in SIH.

  8. Paclitaxel-induced peripheral neuropathy increases substance P release in rat spinal cord.

    Science.gov (United States)

    Chiba, Terumasa; Oka, Yusuke; Kambe, Toshie; Koizumi, Naoya; Abe, Kenji; Kawakami, Kazuyoshi; Utsunomiya, Iku; Taguchi, Kyoji

    2016-01-05

    Peripheral neuropathy is a common adverse effect of paclitaxel treatment. The major dose-limiting side effect of paclitaxel is peripheral sensory neuropathy, which is characterized by painful paresthesia of the hands and feet. To analyze the contribution of substance P to the development of paclitaxel-induced mechanical hyperalgesia, substance P expression in the superficial layers of the rat spinal dorsal horn was analyzed after paclitaxel treatment. Behavioral assessment using the von Frey test and the paw thermal test showed that intraperitoneal administration of 2 and 4mg/kg paclitaxel induced mechanical allodynia/hyperalgesia and thermal hyperalgesia 7 and 14 days after treatment. Immunohistochemistry showed that paclitaxel (4mg/kg) treatment significantly increased substance P expression (37.6±3.7% on day 7, 43.6±4.6% on day 14) in the superficial layers of the spinal dorsal horn, whereas calcitonin gene-related peptide (CGRP) expression was unchanged. Moreover, paclitaxel (2 and 4mg/kg) treatment significantly increased substance P release in the spinal cord on day 14. These results suggest that paclitaxel treatment increases release of substance P, but not CGRP in the superficial layers of the spinal dorsal horn and may contribute to paclitaxel-induced painful peripheral neuropathy.

  9. 大鼠脊髓损伤后死亡原因分析%Analysis of death cause in rats with spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    南国新; 覃佳强; 廖维宏

    2010-01-01

    Objective To investigate the causes for death in rats after spinal cord injury.Methods A total of 120 adult Wister rats were selected for the study. The animal model with acute spinal injury at T10 was established by using Allen' s combat (25 g · cm). The dissection analysis was performed in death rats. Results Of all, 25 patients died, with mortality rate of 21%. Of death rats, five rats were died before awakening, with no abnormal anatomy; 12 rats died within three days after injury and three died of injuries 3-7days injury. Anatomy found pulmonary bleeding and edema, even hematocele bladder in some rats. There were three rats died within 1-2 weeks, one died of injury only after 2-3 weeks, with lung infection and urinary tract infection. There was no death after three weeks. Conclusions The early causes for death of rats with spinal cord injury is mainly due to lung congestion and pulmonary edema, whereas the leading cause of late death of rats is pulmonary and urinary tract infection.%目的 探讨大鼠Allen脊髓损伤模型动物死亡的原因.方法 选用120只Wistar成年大鼠,采用Allen打击模型(25 g·cm),在T10段造成急性脊髓损伤,对损伤后死亡动物进行统计和解剖.结果 死亡25例,死亡率为21%,其中5只死于苏醒前,解剖未发现异常;12只死于损伤后3 d内,3只死于损伤后3~7 d,解剖发现肺部均有出血、水肿.部分动物有膀胱积血;3只死于8~14 d,1只死于损伤后15~21 d,解剖发现分别有肺部感染和泌尿系感染.3周后无死亡.结论大鼠Allen脊髓损伤模型动物早期死亡的主要原因是肺淤血和肺水肿,晚期死亡的主要原因是肺部和泌尿系感染.

  10. Developmental Changes in Pain and Spinal Immune Gene Expression after Radicular Trauma in the Rat.

    Science.gov (United States)

    Barr, Gordon A; Wang, Shaoning; Weisshaar, Christine L; Winkelstein, Beth A

    2016-01-01

    Neuropathic pain is 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 days 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 1 day after compression injury when performed at PN14, 21, or 28. Thermal withdrawal latencies returned to near baseline by 7 days postsurgery when the injuries were at PN14, and lasted up to 14 days when the injury was imposed at PN28. There was mechanical allodynia following injury at 1 day postinjury and at 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7, and 14 days postinjury 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. This may be due to the use of a

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

    Directory of Open Access Journals (Sweden)

    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

  12. Developmental Changes in Pain and Spinal Immune Gene Expression after Radicular Trauma in the Rat

    Science.gov (United States)

    Barr, Gordon A.; Wang, Shaoning; Weisshaar, Christine L.; Winkelstein, Beth A.

    2016-01-01

    Neuropathic pain is 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 days 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 1 day after compression injury when performed at PN14, 21, or 28. Thermal withdrawal latencies returned to near baseline by 7 days postsurgery when the injuries were at PN14, and lasted up to 14 days when the injury was imposed at PN28. There was mechanical allodynia following injury at 1 day postinjury and at 14 days after injury at PN14. Measurements of mRNA from spinal cord at 1, 7, and 14 days postinjury 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. This may be due to the use of

  13. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection

    Science.gov (United States)

    Buzoianu-Anguiano, Vinnitsa; Orozco-Suárez, Sandra; García-Vences, Elisa; Caballero-Chacón, Sara; Guizar-Sahagún, Gabriel; Chavez-Sanchez, Luis; Grijalva, Israel

    2015-01-01

    Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model. PMID:26634157

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

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    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.

  15. Contribution of spinal glia activation to mechanical hyperalgesia induced by spared nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    FENG Si-zhe; WEI Xue-zhong; ZHANG Xiang

    2004-01-01

    Objective: To investigate the role of spinal glial cells activation in neuropathic pain in a recently developed spared nerve injury (SNI) animal model by Decosterd and Woolf. Methods: A lesion was made to two of the three terminal branches of the sciatic nerve of rats (tibial and common peroneal nerves) leaving the sural nerve intact. Continuous intrathecai administration of propentofyliine, a glial modulating agent, 1 d before and 5 d after operation, was performed to disrupt spinal cord glia function. The vehicle was intrathecally administrated as control. The paw withdrawal threshold to mechanical stimulation (paw withdrawal mechaical threshold PWMT), body mass and motor function were determined pre- and post-surgery. Results: It produced a prolonged mechanical allodynia in the medial and lateral part of the ipsilateral hind paw in SNL models. The treatment with propentofylline significantly prevented the development of mechanical allodynia located in either medial or lateral plantar surface. Rats in two groups showed normal motor function and body weight increase. Conclusion:SNI model can be applied as a useful method with little variance in searching the mechanism of neuropathic pain. These study suggest that spinal glia activation may contribute to mechanical allodynia induced by SNI.

  16. 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

  17. Extract of Cornus officinalis SIEB ameliorates osteoporosis in Spinal Cord-Injured Rats

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    Qingxi Meng; Baolong Wang; Peng Yu; Qunqun Shan; Zhaohu Mao; Fan Zhang; Jian Li; Tinbao Zhao

    2015-01-01

    目的:观察山茱萸的提取物对脊髓损伤大鼠的骨质疏松的治疗作用。方法40只Wistar雄性大鼠分成四组:标准对照组、脊髓损伤组、脊髓损伤高剂量提取物治疗组、脊髓损伤低剂量提取物治疗组。除标准对照组外,建立脊髓损伤引起的骨质疏松大鼠模型,然后进行相关生物化学、骨密度及形态的分析和比较。结果与标准对照组相比,脊髓损伤组的大鼠显示骨量、生物化学指标和形态学参数的显著下降。山茱萸提取物高剂量组治疗大鼠胫骨骨干内、外部区域骨质疏松显示剂量依赖性。结论山茱萸提取物治疗可能通过刺激成骨细胞引骨组织反应,从而导致形态学的变化。%This study investigated the effects of extract of Cornus officinalis CO) on bone loss in spinal cord-injured rats.Forty male Wistar rats were used to establish osteoporosis induced by spinal cord injury, subsequently divided into four groups: standard control group (CG);spinal cord-injured control (SC); spinal cord-injured treated with low-dose extract (L group); and spinal cord-injured treated with high-dose extract ( H group) .Biomechanical, densitometric, and morphometric analyses were performed. SC rats showed a significant decrease in bone mass, biomechanical properties, and morphometric parameters (versus CG).CO-treated rats showed significantly higher values of inner diameter and internal and external areas of tibia diaphysis in a dose-dependent manner.We conclude that the extract of Cornus officinalis SIEB et.ZUCC treatment was able to initiate a positive bone-tissue response, might through stimulation of osteoblasts, which was able to determine the observed morphometric modifications.

  18. 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

  19. Olfactory ensheathing cells (OECs) degrade neurocan in injured spinal cord by secreting matrix metalloproteinase-2 in a rat contusion model.

    Science.gov (United States)

    Yui, Sho; Fujita, Naoki; Chung, Cheng-Shu; Morita, Maresuke; Nishimura, Ryohei

    2014-11-01

    The mechanism by which olfactory ensheathing cells (OECs) exert their potential to promote functional recovery after transplantation into spinal cord injury (SCI) tissue is not fully understood, but the relevance of matrix metalloproteinases (MMPs) has been suggested. We evaluated the expression of MMPs in OECs in vitro and the MMP secretion by OECs transplanted in injured spinal cord in vivo using a rat SCI model. We also evaluated the degradation of neurocan, which is one of the axon-inhibitory chondroitin sulfate proteoglycans, using SCI model rats. The in vitro results showed that MMP-2 was the dominant MMP expressed by OECs. The in vivo results revealed that transplanted OECs secreted MMP-2 in injured spinal cord and that the expression of neurocan was significantly decreased by the transplantation of OECs. These results suggest that OECs transplanted into injured spinal cord degraded neurocan by secreting MMP-2.

  20. Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    Shuang-quan YU; Donna H WANG

    2011-01-01

    Aim: To investigate the effects of selective knockdown of TRPV1 channels in the lower thoracic and upper lumbar segments of spinal cord, dorsal root ganglia (DRG) and me senteric arteries on rat blood pressure responses to high salt intake.Methods: TRPV1 short-hairpin RNA (shRNA) was delivered using intrathecal injection (6 μg.kg1-d-1, for 3 d). Levels of TRPV1 and tyrosine hydroxylase expression were determined by Western blot analysis. Systolic blood pressure and mean arterial pressure (MAP) were examined using tail-cuff and direct arterial measurement, respectively.Results: In rats injected with control shRNA, high-salt diet (HS) caused higher systolic blood pressure compared with normal-salt diet(NS) (HS:149±4 mmHg; NS:126±2 mmHg, P<0.05). Intrathecal injection of TRPV1 shRNA significantly increased the systolic blood pressure in both HS rats and NS rats (HS:169±3 mmHg; NS:139±2 mmHg). The increases was greater in HS rats than in NS rats (HS:13.9%±1.8%; NS: 9.8±0.7, P<0.05). After TRPV1 shRNA treatment, TRPV1 expression in the dorsal horn and DRG of T8-L3 segments and in mesenteric arteries was knocked down to a greater extent in HS rats compared with NS rats. Blockade of α1-adrenoceptors abolished the TRPV1 shRNA-induced pressor effects. In rats injected with TRPV1 shRNA, level of tyrosine hydroxylase in mesenteric arteries was increased to a greater extent in HS rats compared with NS rats.Conclusion: Selective knockdown of TRPV1 expression in the lower thoracic and upper lumbar segments of spinal cord, DRG, and mesenteric arteries enhanced the prohypertensive effects of high salt intake, suggesting that TRPV1 channels in these sites protect against increased salt sensitivity, possibly via suppression of sympatho-excitatory responses.

  1. Effects of Jisuikang on hemorheology and inflammatory factors in rats following spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yong Ma; Jianzhong Zhou; Wengui Yanga; Wenjian Sun; Shaojian Yin; Shijie Sun

    2008-01-01

    BACKGROUND: Trauma can damage the spinal cord or cauda equina to different degrees. Previous studies have verified that traditional Chinese medicine has effects on spinal cord injury via a variety of pathways. OBJECTIVE: To observe changes in hemorheology and inflammatory factors in spinal cord injury rats following treatment with the Chinese medicine Jisuikang, to verify the dose-dependent effect of Jisuikang, and to compare its effects with the effects of prednisone. DESIGN, TIME AND SETTING: A randomized study was performed at the Research Institute of Orthopedics, and Experimental Center of First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, China from September 2007 to March 2008. MATERIALS: Jisuikang powdered extract, composed of milkvetch root (30 g), Chinese angelica (12 g), red peony root (12 g), earthworm (10 g), szechwan lovage rhizome (10 g), peach seed (10 g) and safflower (10 g), was provided by the Experimental Center, First Clinical Medical College, Nanjing University of Traditional Chinese medicine. Each gram of powdered extract was equivalent to 6.47 g crude drug. METHODS: A total of 72 Sprague Dawley rats were randomly assigned into 6 groups (n = 12). Rat models of spinal cord injury were established using the occlusion method. Rats in the model group were treated with distilled water. Rats in the 25 g/kg, 12.5 g/kg, and 6.25 g/kg Jisuikang groups were given 25 g/kg, 12.5 g/kg, or 6.25 g/kg Jisuikang by gavage, for 14 days. Rats in the prednisone group received 0.06 g/kg prednisone by gavage, for 7 days. Rats in the normal group were given the same volume of distilled water. The volume of administration was 15 mL/kg.MAIN OUTCOME MEASURES: Rat serum interleukin-10, tumor necrosis factor-α (TNF-α), nitric oxide, nitric oxide synthase levels, malondialdehyde content, superoxide dismutase activity and whole blood viscosity were measured in each group. Spinal cord around the site of the model was collected. Half the

  2. Effect of erhuangfang on cerebral and spinal demyelination and regeneration as well as expression of glial fibrillary acidic protein in rats with experimental allergic encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: It demonstrates that erhuangfang can improve clinical symptoms of multiple sclerosis and relieve side effects of hormone. However, whether erhuangfang can improve experimental allergic encephalomyelitis (EAE) or not needs a further study.OBJECTIVE: To observe the effect of erhuangfang on neuro-pathology and astrocyte in EAE rats and compare with the effect of hormone.DESIGN: Randomized controlled animal study.SETTINGS: Department of Traditional Chinese Medicine, Beijing Tiantan Hospital, Capital Medical University; College of Traditional Chinese Medicine, Capital Medical University.MATERIALS: The experiment was carried out in the Laboratory Center of Capital Medical University from August to October 2005. Ten adult guinea pigs (SPF grade, weighing 400 - 450 g) and 70 adult Lewis rats (SPF grade, weighing 200- 220 g) were selected in this study. Erhuangfang consisted of jiudahuang,shengdi, shuizhi, dabeimu, etc.METHODS: ① Experimental intervention: Rats were randomly divided into normal group (n=10), model group (n=20), western medicine group (n=20) and Chinese herb group (n=20). Mixed emulsion, which was consisted of Freund's adjuvant and spinal cord homogenate of guinea pigs, was subcutaneously injected into palms of the two hindfeet of rats in the latter three groups to establish EAE models. Foot pads were injected with saline and then rats were perfused with saline in the normal group. In the model group, models were established as the same as those mentioned above, and rats were also perfused with saline. Rats in the western medicine group were perfused with saline and then 5 mg/kg prednisone acetate suspension. Rats in the Chinese herb group were perfused with erhuangfang decoction (15 g raw materials per kilogram) at 5 days before model establishment. The dosage in the four groups was 3 mL/day per rat. ② Experimental evaluation: At 28 days after model establishment, rats were randomly selected for cerebral (mainly surrounding cerebral

  3. Fluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury

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    Scali, Manuela; Begenisic, Tatjana; Mainardi, Marco; Milanese, Marco; Bonifacino, Tiziana; Bonanno, Giambattista; Sale, Alessandro; Maffei, Lamberto

    2013-01-01

    Spinal cord injury (SCI) is a severe condition leading to enduring motor deficits. When lesions are incomplete, promoting spinal cord plasticity might be a useful strategy to elicit functional recovery. Here we investigated whether long-term fluoxetine administration in the drinking water, a treatment recently demonstrated to optimize brain plasticity in several pathological conditions, promotes motor recovery in rats that received a C4 dorsal funiculus crush. We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms. The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance. Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies. PMID:23860568

  4. Alteration of Excitatory Amino Acid in Experimental Spinal Cord Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    张宁; 罗永湘

    2002-01-01

    Objective To detect the effect of excitatory amino acid (EAA) in the sec-ondary damage following spinal cord injury (SCI). Methods Glutamate (Glu) and Aspartate(Asp) on the injury site (T8) were studied using a rat SCI model induced by Allen's weight drop method(10g×2.5cm). The result suggested that Asp and Glu were significantly increased in 10 min. Re-sults Glu was significantly decreased from 2 h to 24 h,while Asp was a little reduced in 2 h,andslightly rose in 4 h as compared with Control Group. Though elevated in 8 h, it dropped again in 24 h ascompared with Control Group. Conclusion The result indicates that the rise of EAA following SCIcould be the cause of the secondary spinal cord damage.

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

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    Hayley R Inglis

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

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

    Institute of Scientific and Technical Information of China (English)

    Peng Xie; Wen-Hui Ruan

    2016-01-01

    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.

  8. Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats

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    Mao-Ying Qi-Liang

    2012-05-01

    Full Text Available Abstract It has been reported that remarkable and sustained activation of astrocytes and/or microglia occurs in cancer induced pain (CIP, which is different from neuropathic and inflammatory pain. The present study was designed to investigate the role of spinal Toll-like receptor 4 (TLR4 induced glial neuroinflammation in cancer induced pain using a modified rat model of bone cancer. The rat model of CIP consisted of unilateral intra-tibial injection with Walker 256 mammary gland carcinoma. Nine days after Walker 256 inoculation, a robust activation of both astrocytes and microglia in bilateral spinal dorsal horn was observed together with significant bilateral mechanical allodynia. This neuroinflammation was characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker and OX-42 (microglia marker, and an elevated level of IL-1β, IL-6 and TNF-α mRNA. I.t. administration of fluorocitrate (an inhibitor of glial metabolism, 1 nmol or minocycline (an inhibitor of microglia, 100 μg has significant anti-allodynic effects on day 12 after Walker 256 inoculation. Naloxone (a nonstereoselective TLR4 signaling blocker, 60 μg, i.t. also significantly alleviated mechanical allodynia and simultaneously blocked the increased inflammatory cytokine mRNA. The results suggested that spinal TLR4 might play an important role in the sustained glial activation that critically contributed to the robust and sustained spinal neuroinflammation in CIP. This result could potentially help clinicians and researchers to better understand the mechanism of complicated cancer pain.

  9. Purinergic signalling in a latent stem cell niche of the rat spinal cord.

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    Marichal, Nicolás; Fabbiani, Gabriela; Trujillo-Cenóz, Omar; Russo, Raúl E

    2016-06-01

    The ependyma of the spinal cord harbours stem cells which are activated by traumatic spinal cord injury. Progenitor-like cells in the central canal (CC) are organized in spatial domains. The cells lining the lateral aspects combine characteristics of ependymocytes and radial glia (RG) whereas in the dorsal and ventral poles, CC-contacting cells have the morphological phenotype of RG and display complex electrophysiological phenotypes. The signals that may affect these progenitors are little understood. Because ATP is massively released after spinal cord injury, we hypothesized that purinergic signalling plays a part in this spinal stem cell niche. We combined immunohistochemistry, in vitro patch-clamp whole-cell recordings and Ca(2+) imaging to explore the effects of purinergic agonists on ependymal progenitor-like cells in the neonatal (P1-P6) rat spinal cord. Prolonged focal application of a high concentration of ATP (1 mM) induced a slow inward current. Equimolar concentrations of BzATP generated larger currents that reversed close to 0 mV, had a linear current-voltage relationship and were blocked by Brilliant Blue G, suggesting the presence of functional P2X7 receptors. Immunohistochemistry showed that P2X7 receptors were expressed around the CC and the processes of RG. BzATP also generated Ca(2+) waves in RG that were triggered by Ca(2+) influx and propagated via Ca(2+) release from internal stores through activation of ryanodine receptors. We speculate that the intracellular Ca(2+) signalling triggered by P2X7 receptor activation may be an epigenetic mechanism to modulate the behaviour of progenitors in response to ATP released after injury.

  10. Effects of morphine and endomorphins on the polysynaptic reflex in the isolated rat spinal cord.

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    Tao, Pao-Luh; Lai, Yong-Shang; Chow, Lok-Hi; Huang, Eagle Yi-Kung

    2005-01-01

    At the spinal level, mu-opioids exert their actions on nociceptive primary afferent neurons both pre- and postsynaptically. In the present study, we used an in vitro isolated neonatal rat (11-15 days old) spinal cord preparation to examine the effects of morphine and the endogenous mu-opioid ligands endomorphin-1 (EM-1) and endomorphin-2 (EM-2) on the polysynaptic reflex (PSR) of dorsal root-ventral root (DR-VR) reflex. The actions of mu-opioids on spinal nociception were investigated by quantification of the firing frequency and the mean amplitude of the PSR evoked by stimuli with 20 x threshold intensity. EM-1 decreased the mean amplitude of PSR, whereas EM-2 and morphine decreased the firing frequency. The pattern of the effects elicited by morphine was the same as that for EM-2, except at high concentration. Naloxonazine, a selective mu(1) opioid receptor antagonist, had no significant effect on PSR by itself, but blocked the inhibition of PSR firing frequency or amplitude induced by EM-1, -2 and morphine. This may suggest that EM-1, EM-2 and morphine modulate spinal nociception differently and act mainly at the mu(1)-opioid receptors. Although they all act via mu(1)-opioid receptors, their different effects on the PSR may suggest the existence of different subtypes of the mu(1)-opioid receptor. The present data is also consistent with a further hypothesis, namely, that morphine and EM-2 activate a subtype of mu(1)-opioid receptor presynaptically, while EM-1 acts mainly through another subtype postsynaptically. However, since other reports indicate that EM-2, but not EM-1, could stimulate the release of enkephalins or dynorphin, presynaptic delta and kappa receptors may be also involved indirectly in the different regulation by mu-opioids at the spinal level.

  11. Protective effect of Crocus sativus L. (Saffron extract on spinal cord ischemia-reperfusion injury in rats

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    Gholam Hossein Farjah

    2017-03-01

    Full Text Available Objective(s: Ischemia/reperfusion (I/R injury of spinal cord is leading to the paraplegia observed. In this study, we investigated the protective effect of the saffron extract on spinal cord I/R injury. Materials and Methods: Thirty five male Sprague-Dawley rats were divided into 5 groups: intact, sham surgery, normal saline (NS, low dose saffron aqua extract, high dose saffron aqua extract. Results: The mean motor deficit index (MDI scores were significantly lower in the saffron extract groups than in the NS group at 48 hr after spinal cord ischemia (P

  12. Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats.

    Science.gov (United States)

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

    2016-03-01

    We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.

  13. Long-distance axonal regeneration in the filum terminale of adult rats is regulated by ependymal cells.

    Science.gov (United States)

    Kwiecien, Jacek M; Avram, Ronen

    2008-03-01

    Studies of regeneration of transected adult central nervous system (CNS) axons are difficult due to lack of appropriate in vivo models. In adult rats, we described filum terminale (FT), a caudal slender extension of the sacral spinal cord and an integral part of the central nervous system (CNS), to use it as a model of spinal cord injury. FT is more than 3 cm long, encompasses a central canal lined with ependymal cells surrounded by a narrow band of axons interspersed with oligodendrocytes and astrocytes but not neurons. Two weeks after the crush of FT, histological, ultrastructural, and axonal tracing studies revealed long distance descending axonal regeneration uniquely in close proximity of the ependymal cells of the central canal. Ependymal cells extended basal processes to form channels encompassing axons apparently regenerating at a rate of more than 2 mm a day. Remarkable increase of axonal sprouting was observed in the sacral spinal cord of Long Evans Shaker (LES) rats with crushed FT. FT offers an excellent model to study mechanisms of axonal regeneration regulated by ependymal cells in the adult CNS.

  14. 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.

  15. Curcumin exerts antinociceptive effects by inhibiting the activation of astrocytes in spinal dorsal horn and the intracellular extracellular signal-regulated kinase signaling pathway in rat model of chronic constriction injury

    Institute of Scientific and Technical Information of China (English)

    JI Feng-tao; LIANG Jiang-jun; LIU Ling; CAO Ming-hui; LI Feng

    2013-01-01

    Background Activation of glial cells and the extracellular signal-regulated kinase (ERK) signaling pathway play an important role in the development and maintenance of neuropathic pain.Curcumin can alleviate the symptom of inflammatory pain by inhibiting the production and release of interleukin and tumor necrosis factor.However,whether curcumin affects neuropathic pain induced by nerve injury and the possible mechanism involved are still unknown.This study investigated the effects of tolerable doses of curcumin on the activation of astrocytes and ERK signaling in the spinal dorsal horn in rat model of neuropathic pain.Methods Adult male Sprague-Dawley rats were randomly divided into three groups:a control (sham operated) group,and chronic constriction injury groups (to induce neuropathic pain) that were either untreated or treated with curcumin.Thermal and mechanical hyperalgesia thresholds were measured.The distribution and morphological changes of astrocytes were observed by immunofluorescence.Western blotting was used to detect changes in the expression of glial flbrillary acid protein (GFAP) and phosphorylated ERK.Results Injured rats showed obvious mechanical allodynia and thermal hyperalgesia.The number of GFAP-positive astrocytes,and the fluorescence intensity of GFAP were significantly increased in the spinal dorsal horn of injured compared with control rats.The soma of astrocytes also appeared hypertrophied in injured animals.Expression of GFAP and phosphorylated ERK was also significantly increased in the spinal dorsal hom of injured compared with control rats.Curcumin reduced the injury-induced thermal and mechanical hyperalgesia,the increase in the fluorescence intensity of GFAP and the hypertrophy of astrocytic soma,activation of GFAP and phosphorylation of ERK in the spinal dorsal horn.Conclusions Curcumin can markedly alleviate nerve injury-induced neuropathic pain in rats.The analgesic effect of curcumin may be attributed to its inhibition of

  16. Protective effect of liposome-mediated glial cell line-derived neurotrophic factor gene transfer in vivo on motoneurons following spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    鲁凯伍; 陈哲宇; 侯铁胜

    2004-01-01

    Objective:To investigate the effect of liposomemediated glial cell line-derived neurotrophic factor (GDNF) gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats.Methods: Sixty male Sprague-Dawley rats were divided equally into two groups: GDNF group and control group. The SCI model was established according to the method of Nystrom, and then the DC-Chol liposomes and recombinant plasmid pEGFP-GDNF cDNA complexes were injected into the injured spinal cord. The expression of GDNF cDNA 1 week after injection was detected by RTPCR and fluorescence microscope. We observed the remaining motoneurons in the anterior horn and the changes of cholinesterase (CHE) and acid phosphatase (ACP) activity using Nissl and enzyme histochemistry staining. The locomotion function of hind limbs of rats was evaluated using inclined plane test and BBB locomotor scale.Results: RT-PCR and fluorescence observation confirmed the presence of expression of GDNF cDNA 1week and 4 weeks after injection. At 1, 2, 4 weeks after SCI, the number of motoneurons in the anterior horn in GDNF group (20.4±3.2, 21.7±3.6, 22.5±3.4) was more than that in control group ( 16.8±2.8, 17.3 ± 2.7,18.2±3.2, P<0.05). At 1, 2 weeks after SCI, the mean gray of the CHE-stained spinal motoneurons in GDNF group (74.2± 25.8, 98.7± 31.6 was less than that in control group (98.5 ±32.2, 134.6 ±45.2, P<0.01), and the mean gray of ACP in GDNF group (84.5±32.6, 79.5±28.4) was more than that in control group (61.2±24.9,52.6±19.9, P<0.01). The locomotion functional scales in GDNF group were higher than that in control group within 1 to 4 weeks after SCI (P<0.05).Conclusions: GDNF gene transfer in vivo can protect motoneurons from death and degeneration induced by incompleted spinal cord injury as well as enhance locomotion functional restoration of hind limbs. These results suggest that liposome-mediated delivery of GDNF cDNA might be a practical method for treating

  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.

  18. Differential protein levels and post-translational modifications in spinal cord injury of the rat.

    Science.gov (United States)

    Afjehi-Sadat, Leila; Brejnikow, Mika; Kang, Sung Ung; Vishwanath, Vinay; Walder, Nadja; Herkner, Kurt; Redl, Heinz; Lubec, Gert

    2010-03-05

    Although changes in protein expression in spinal cord injury (SCI) would be of pivotal interest, information so far is limited. It was therefore the aim of the study to determine protein levels and post-translational modifications in the early phase following SCI in the rat. SCI was induced in Sprague-Dawley rats and sham operated rats served as controls. A gel-based proteomic approach using two-dimensional gel electrophoresis followed by quantification with specific software and subsequent identification of differentially expressed proteins by nano-ESI-LC-MS/MS was applied. Proteins of several pathways and cascades were dysregulated in SCI: 14-3-3 epsilon protein, dynein light chain 1, and tubulin beta-5 chain showed higher levels in SCI, whereas adenylyl cyclase associated protein 1, dihydropyrimidinase-related protein 2, F-actin capping protein subunit beta, glyceraldehyde-3-phosphate dehydrogenase, stress-induced phosphoprotein 1 and transthyretin showed lower levels in the injured tissue. Post-translational modifications indicated free oxygen radical attack on proteins in SCI. The occurrence of stress is indicated by deranged stress-induced phosphoprotein 1 and signaling abnormalities are reflected by adenylyl cyclase-associated protein 1 and 14-3-3 epsilon protein. The findings propose the involvement of the corresponding cascades and challenge further work into aberrant signaling and oxidative stress in SCI, which may form the basis for experimental intervention for spinal cord trauma.

  19. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain

    Science.gov (United States)

    Hama, Aldric T.; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-01-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggests that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. PMID:20732348

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

    Institute of Scientific and Technical Information of China (English)

    Shaoqiang Chen; Bilian Wu; Jianhua Lin

    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.

  1. Therapy of acute and delayed spinal infections after spinal surgery treated with negative pressure wound therapy in adult patients

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    Pawel Zwolak

    2013-11-01

    Full Text Available We present the results of the treatment of infected primary or delayed spine wounds after spinal surgery using negative pressure wound therapy. In our institution (University Hospital Zurich, Switzerland nine patients (three women and six men; mean age 68.6, range 43- 87 years were treated in the period between January to December 2011 for non-healing spinal wounds. The treatment consisted of repeated debridements, irrigation and temporary closure with negative pressure wound therapy system. Three patients were admitted with a spinal epidural abscess; two with osteoporotic lumbar fracture; two with pathologic vertebra fracture and spinal cord compression, and two with vertebra fracture after trauma. All nine patients have been treated with antibiotic therapy. In one case the hardware has been removed, in three patients laminectomy was performed without instrumentation, in five patients there was no need to remove the hardware. The average hospital stay was 16.6 days (range 11-30. The average follow-up was 3.8, range 0.5-14 months. The average number of negative pressure wound therapy procedures was three, with the range 1-11. Our retrospective study focuses on the clinical problems faced by the spinal surgeon, clinical outcomes after spinal surgery followed by wound infection, and negative pressure wound therapy. Moreover, we would like to emphasize the importance for the patients and their relatives to be fully informed about the increased complications of surgery and about the limitations of treatment of these wounds with negative pressure wound therapy.

  2. Expression of NF-кB in Schwann cells and its effect on motor neuron apoptosis in spinal cord following sciatic nerves injury in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-tang; LU Xiu-min; YU Ying; YANG Yan-hong; GAO Jie

    2007-01-01

    Objective:To explore the expression of nuclear factor-kappa B (NF-кB) in Schwann cells (SCs) and its effect on motor neuron apoptosis in spinal cord following sciatic nerves injury in adult rats. Methods:Thirty-six adult Sprague-Dawley (SD) rats were divided randomly into normal control group (n=6),and sciatic nerves crushing group (n=30),and the later was further equally randomized into 5 nerves were examined by immunohistochemistry staining,and the apoptosis of motor neurons in spinalcord of lumbar 4 to lumbar 6(L4-L6)was investigated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay.Both were quantitated by image analysis.Results:In the normal control group (P<0.05,P<0.01).At 1 d after sciatic nerves crushing,the expression of served in the time-course on motor neuron apoptosis after sciatic nerves injury.Correlation analyses refollowing sciatic nerves injury(r=0.976 0,P<0.01).Conclusion:After injury of sciatic nerves,the presence and up-regulation of NF-κB in SCs may be involved in motor neuron apoptosis in L4-L6 spinal cord.

  3. Proteomic analysis of PKCγ-related proteins in the spinal cord of morphine-tolerant rats.

    Directory of Open Access Journals (Sweden)

    Zongbin Song

    Full Text Available BACKGROUND: Morphine tolerance is a common drawback of chronic morphine exposure, hindering use of this drug. Studies have shown that PKCã may play a key role in the development of morphine tolerance, although the mechanisms are not fully known. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of morphine tolerance, PKCã knockdown in the spinal cord was successfully carried out using RNA interference (RNAi with lentiviral vector-mediated short hairpin RNA of PKCã (LV-shPKCã. Spinal cords (L4-L5 were obtained surgically from morphine-tolerant (MT rats with and without PKCã knockdown, for comparative proteomic analysis. Total proteins from the spinal cords (L4-L5 were extracted and separated using two-dimensional gel electrophoresis (2DGE; 2D gel images were analyzed with PDQuest software. Seven differential gel-spots were observed with increased spot volume, and 18 spots observed with decreased spot volume. Among these, 13 differentially expressed proteins (DEPs were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS, comparing between MT rats with and without PKCã knockdown. The DEPs identified have roles in the cytoskeleton, as neurotrophic factors, in oxidative stress, in ion metabolism, in cell signaling, and as chaperones. Three DEPs (GFAP, FSCN and GDNF were validated with Western blot analysis, confirming the DEP data. Furthermore, using immunohistochemical analysis, we reveal for the first time that FSCN is involved in the development of morphine tolerance. CONCLUSIONS/SIGNIFICANCE: These data cast light on the proteins associated with the PKCã activity during morphine tolerance, and hence may contribute to clarification of the mechanisms by which PKCã influences MT.

  4. Kinematics of wheelchair propulsion in adults and children with spinal cord injury.

    Science.gov (United States)

    Bednarczyk, J H; Sanderson, D J

    1994-12-01

    This study examined the kinematic features of wheelchair propulsion in two neurologically matched groups of adults and children with uncomplicated spinal cord injury. The average mass and age of the pediatric group was much smaller than the adult group (37.4kg and 11.3 years vs 68.5kg and 33.5 years). Each subject propelled his/her own chairs and new, low-mass wheelchairs at a steady, nominal speed of 2 m/sec across a level surface. Three dimensional video analysis determined the movement of upper body angles (elbow, shoulder, trunk, and shoulder abduction) based on reflective markers placed on the subjects' shoulder, elbow, wrist, and hip joints. Analysis of the temporal factors showed that although the average group overground velocities of the adult group (2.4m/sec) were significantly greater than the pediatric group (2.3 m/sec), the two groups spent comparable proportions of the wheeling cycle in propulsion (24%). Analysis of the angular kinematics (elbow, shoulder, and shoulder abduction angular changes over a time normalized wheeling cycle) showed that whereas the pediatric group did show significant absolute angular differences from the adult group, the angular changes over time were the same in both groups. The implications of this work are that, for the first time, it can be said that children propel their wheelchairs in the same manner as adults. In addition, these data were similar to those previously reported in athletic adult populations. We conclude that published data from adult wheelchair users may be applied to pediatric wheelchair users, thus providing a basis for pediatric wheelchair prescription.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone

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    Xiao-lin Hou

    2015-01-01

    Full Text Available Resistance mechanisms of rho-associated kinase (ROCK inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2. The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T 11 . Rat models were orally administrated with celecoxib (20 mg/kg and/or intramuscularly with fasudil (10 mg/kg for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.

  6. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone.

    Science.gov (United States)

    Hou, Xiao-Lin; Chen, Yan; Yin, Hua; Duan, Wei-Gang

    2015-11-01

    Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.

  7. Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Edvinsson, Lars

    2011-01-01

    was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal...... to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal...... trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level...

  8. Experiment K307: Vertebral body strength of rat spinal columns

    Science.gov (United States)

    Kazarian, L. E.

    1981-01-01

    The effects of space flight on vertebral body bone strength excised were investigated. Comparative biomechanical investigations of vertebral body strength for flight, synchronous, and vivarium rats following spacecraft recovery (R+0), at R+6 and R+29 days post flight recovery are presented. Statistical analyses are presented for the mechanical properties of stiffness, ultimate load, displacement to ultimate load, and energy to ultimate load. At R+0 all of the above properties show that the vertebral body exhibits an increasing susceptibility to fracture. The reduction of bone strength is inhomogeneous and dependent on vertebral level. The R+6 recovery data was inconclusive since it varied above and below the R+0 data. At R+29 ultimate load values showed a statistically significant increase in bone strength approaching that of the vivarium or control group.

  9. Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model

    Science.gov (United States)

    Biardeau, Xavier; Przydacz, Mikolaj; Aharony, Shachar; Loutochin, George; Campeau, Lysanne; Kyheng, Maeva; Corcos, Jacques

    2017-01-01

    Background In spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques. Purpose To assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model. Methods 33 Sprague-Dawley rats were allocated to 6 groups–Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn’s tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05. Results Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls. Conclusion Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols. PMID:28060912

  10. Effects of methyl prednisolone, dimethyl sulphoxide and naloxone in experimental spinal cord injuries in rats.

    Science.gov (United States)

    Zileli, M; Ovül, I; Dalbasti, T

    1988-12-01

    The effects of methyl prednisolone (MPD), dimethyl sulphoxide (DMSO), and naloxone were examined in 38 albino rats after making an impact spinal cord injury on the midthoracic segments with a modified Allen's weight dropping trauma method. Somatosensorial evoked potentials (SEPs) were recorded before and 12 h and 14 d after the injury from epidurally inserted electrodes on the parietal cortex with sciatic nerve stimulations. Lower extremity motor functions of the animals were also examined. It may be concluded that in this study model, DMSO has a moderate effect which can be demonstrated clinically and through SEPs. Naloxone has no effect on the clinical outcome but causes reasonable improvement electrophysiologically.

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

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    Juan D. Robles

    2000-04-01

    Full Text Available 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 branches with hind limb function. 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 funci

  12. Assessing Function and Endurance in Adults with Spinal and Bulbar Muscular Atrophy: Validity of the Adult Myopathy Assessment Tool

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    Michael O. Harris-Love

    2014-01-01

    Full Text Available Purpose. The adult myopathy assessment tool (AMAT is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA. Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years. The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer disease duration (r=-0.29; P<0.03 and lower serum androgen levels (r=0.49–0.59; P<0.001. The AMAT was significantly correlated with strength and functional status (r=0.82–0.88; P<0.001. The domains of the AMAT exhibited good internal consistency (Cronbach’s α = 0.77–0.89; P<0.001. Conclusions. The AMAT is a standardized, performance-based tool that may be used to assess functional limitations and muscle endurance. The AMAT has good internal consistency, and the construct validity of the AMAT is supported by its significant associations with hormonal, strength, and functional characteristics of adults with SBMA. This trial is registered with Clinicaltrials.gov identifier NCT00303446.

  13. iNOS participates in apoptosis of spinal cord neurons via p-BAD dephosphorylation following ischemia/reperfusion (I/R) injury in rat spinal cord.

    Science.gov (United States)

    Li, Yiming; Gu, Jun; Liu, Yuwen; Long, Hao; Wang, Guannan; Yin, Guoyong; Fan, Jin

    2013-06-17

    The pro-apoptotic effect of nitric oxide (NO) has been reported both in vivo and in vitro. Previous studies have revealed that NO, especially which produced by inducible nitric oxide synthase (iNOS), has an important effect on apoptosis of neurons in spinal cord ischemia/reperfusion (I/R) injury. To investigate the role of iNOS in this process, a randomized, controlled study was designed using a classical rat model of ischemic spinal cord injury. Fifty-four male Sprague-Dawley rats were randomly divided into three different groups: a sham-operated group (n=6), a vehicle group (I/R, n=24), and an iNOS inhibitor (aminoguanidine: AG) group (I/R+AG, n=24). Rats were sacrificed 6, 12, 24 and 72 h after reperfusion. We examined neurological motor function evaluated by 'Tarlov's score', assessed alterations in the morphology of spinal cord neurons by transmission electron microscopy (TEM), analyzed expression of iNOS at the levels of mRNA and protein, evaluated local concentrations and cellular locations of other key regulatory proteins, and investigated protein-protein interactions. In the vehicle group, iNOS expression, dephosphorylation of p-BAD (Ser 136), disassociation of BAD from p-BAD/14-3-3 dimers, and release of cytochrome c were all increased compared with the sham group. But in the AG group, all the performances above were decreased compared with the vehicle group. Similarly, rats in the sham group got a maximum score of 5 by Tarlov's motor scores evaluation. While the scores were higher in the AG group compared to the vehicle group because iNOS was inhibited. These results indicate that the activity of iNOS plays a critical role in the apoptosis of spinal cord neurons by influencing the dephosphorylation of p-BAD (Ser 136) and the interaction between BAD and 14-3-3.

  14. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    Science.gov (United States)

    Fabbro, Alessandra; Sucapane, Antonietta; Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  15. Subacute Tissue Response to 3D Graphene Oxide Scaffolds Implanted in the Injured Rat Spinal Cord.

    Science.gov (United States)

    López-Dolado, Elisa; González-Mayorga, Ankor; Portolés, María Teresa; Feito, María José; Ferrer, María Luisa; Del Monte, Francisco; Gutiérrez, María Concepción; Serrano, María Concepción

    2015-08-26

    The increasing prevalence and high sanitary costs of lesions affecting the central nervous system (CNS) at the spinal cord are encouraging experts in different fields to explore new avenues for neural repair. In this context, graphene and its derivatives are attracting significant attention, although their toxicity and performance in the CNS in vivo remains unclear. Here, the subacute tissue response to 3D flexible and porous scaffolds composed of partially reduced graphene oxide is investigated when implanted in the injured rat spinal cord. The interest of these structures as potentially useful platforms for CNS regeneration mainly relies on their mechanical compliance with neural tissues, adequate biocompatibility with neural cells in vitro and versatility to carry topographical and biological guidance cues. Early tissue responses are thoroughly investigated locally (spinal cord at C6 level) and in the major organs (i.e., kidney, liver, lung, and spleen). The absence of local and systemic toxic responses, along with the positive signs found at the lesion site (e.g., filler effect, soft interface for no additional scaring, preservation of cell populations at the perilesional area, presence of M2 macrophages), encourages further investigation of these materials as promising components of more efficient material-based platforms for CNS repair.

  16. Effects of moxibustion on heat-shock protein 70 expression in the spinal cord and colonic mucosa in a rat model of ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Li Qi; Yin Shi; Luyi Wu; Jingping Mu; Linying Tan; Xiaopeng Ma; Huirong Liu; Shifen Xu; Huangan Wu

    2010-01-01

    Pathological changes in the colon are closely associated with the spinal cord, and innervation of spinal cord can regulate cellular functions. Our previous studies verified that moxibustion protects and restores the colonic mucosa, but the mechanisms of action remain unknown. The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70 (HSP70) and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats. Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats. The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats. Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.

  17. Dynamic "Range of Motion" Hindlimb Stretching Disrupts Locomotor Function in Rats with Moderate Subacute Spinal Cord Injuries.

    Science.gov (United States)

    Keller, Anastasia; Rees, Kathlene; Prince, Daniella; Morehouse, Johnny; Shum-Siu, Alice; Magnuson, David

    2017-04-12

    Joint contractures and spasticity are two common secondary complications of a severe spinal cord injury (SCI), which can significantly reduce quality of life, and stretching is one of the top strategies for rehabilitation of these complications. We have previously shown that a daily static stretching protocol administered to rats at either acute or chronic time points after a moderate or moderate-severe T10 SCI significantly disrupts their hindlimb locomotor function. The objective of the current study was to examine the effects of dynamic range of motion (ROM) stretching on the locomotor function of rats with SCI as an alternative to static stretching. Starting at 6 weeks post-injury (T10 moderate contusion) eight adult Sprague-Dawley rats were subjected to hindlimb stretching for 4 weeks. Our standard stretching protocol (six maneuvers to stretch the major hindlimb muscle groups) was modified from 1 min static stretch-and-hold at the end ROM of each stretch position to a dynamic 2 sec hold, 1 sec release rhythm repeated for a duration of 1 min. Four weeks of daily (5 days/week) dynamic stretching led to significant disruption of locomotor function as assessed by the Basso, Beattie, Bresnahan (BBB) Open Field Locomotor Scale and three-dimensional (3D) kinematic and gait analyses. In addition, we identified and analyzed an apparently novel hindlimb response to dynamic stretch that resembles human clonus. The results of the current study extend the observation of the stretching phenomenon to a new modality of stretching that is also commonly used in SCI rehabilitation. Although mechanisms and clinical relevance still need to be established, our findings continue to raise concerns that stretching as a therapy can potentially hinder aspects of locomotor recovery.

  18. Serotonin differentially modulates the intrinsic properties of spinal motoneurons from the adult turtle

    Science.gov (United States)

    Perrier, Jean-François; Cotel, Florence

    2008-01-01

    This report considers serotonergic (5-HT) effects on spinal motoneurons, reviewing previous data and presenting a new study showing distinct effects of two 5-HT receptor subtypes. We previously investigated the effects of 5-HT on motoneurons in a slice preparation from the spinal cord of the adult turtle. In agreement with previous studies, we had found that 5-HT applied to the extracellular medium promoted a voltage sensitive plateau potential. However, we also reported that this effect was only observed in half of the motoneurons; 5-HT inhibited the firing of the other half of the motoneurons recorded from. To investigate the reasons for this, we applied 5-HT focally by means of the microiontophoresis technique. Facilitation of plateau potentials was observed when 5-HT was released at sites throughout the somatodendritic region. However, motoneurons were inhibited by 5-HT when selectively applied in the perisomatic region. These two effects could be induced in the same motoneuron. With pharmacological tools, we demonstrate here that the facilitation of plateau potentials is mediated by 5-HT2 receptors and the inhibitory effect is due to the activation of 5-HT1A/7 receptors. PMID:18096602

  19. Comparative analysis of NADPH-diaphorase positive neurons in the rat, rabbit and pheasant thoracic spinal cord. A histochemical study

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    D Kluchová

    2009-12-01

    Full Text Available The distribution of NADPH-diaphorase (NADPHd activity was investigated and compared in the rat, rabbit and pheasant thoracic spinal cord. The investigation of all spinal cord regions (laminae in three experimental species revealed marked differences in the distribution of NADPH-d activity. Cross sectional analysis of the spinal cord of the rat, rabbit and pheasant confirmed differences in the shape of the gray matter in all examined species. More detailed investigation of Rexed´s laminas showed similar distribution of NADPH-d activity in the spinal cord of the rat and rabbit, which were different when compared with the spinal cord of the pheasant. Ventral horn of the rat and rabbit showed no labelling whereas in pheasant this area possessed a number of scattered, intensively stained neurons. In the location of autonomic preganglionic neurons, differences were found as well. In the rat there was seen a number of densely packed, clearly dark blue coloured neurons. Similarly, these neurons were present in the rabbit spinal cord but they were less numerous. No staining was found in this region of pheasant. Pericentral area (lamina X and intermediate zone (laminaVII revealed the presence of NADPH-d positive neurons in all examined species although they differed in number and shape of their bodies. The dorsal horn showed the presence of NADPH-d staining in all three animals but its distribution was different in medio - lateral direction. It can be suggested that observed differencies in the presence and distribution of NADPH-d activity across the examined species may reflect different fylogenetic development

  20. Effects of poly lactic-co-glycolic acid-Nogo A antibody delayed-release microspheres on regeneration of injured spinal cord in rats

    Institute of Scientific and Technical Information of China (English)

    Hai Lan; Yueming Song

    2009-01-01

    BACKGROUND: Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE: To compare the therapeutic effects of poly lactic-co-glycolic acid (PLGA)-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord.DESIGN, TIME AND SETTING: A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008.MATERIALS: Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University.METHODS: A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups (n=12): model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μL normal saline solution, 50 μL normal saline solution containing 50 μ g Nogo A antibody, and 50 μ L normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES: The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale.RESULTS: Four weeks after injury, expression of Nogo A in

  1. Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

    Science.gov (United States)

    Ersen, Ali; Elkabes, Stella; Freedman, David S.; Sahin, Mesut

    2015-02-01

    Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

  2. Acquired lumbar spinal stenosis.

    Science.gov (United States)

    Deasy, JoAnn

    2015-04-01

    Lumbar spinal stenosis is the most frequent reason for spinal surgery in patients over age 65 years. In this condition, narrowing of the lumbar spinal canal and nerve root canals leads to painful, debilitating compression of spinal nerves and blood vessels. As the population ages, an increasing number of patients will be diagnosed and treated for lumbar spinal stenosis by primary care providers. This article reviews the pathophysiology, diagnosis, and management of lumbar spinal stenosis in adults over age 50 years.

  3. [Quality of life of adults with spinal cord injury: a study using the WHOQOL-bref].

    Science.gov (United States)

    de França, Inacia Sátiro Xavier; Coura, Alexsandro Silva; de França, Eurípedes Gil; Basílio, Narjara Neumann Vieira; Souto, Rafaela Queiroga

    2011-12-01

    The objective of this study was to evaluate the quality of life (QOL) of adults with spinal cord injury and to identify the domains that may influence QOL. Data was collected using the WHOQOL-bref and a questionnaire with sociodemographic variables. Participants were 47 subjects, with a mean age of 42.95 years, 91.5% males and 8.5% females. The domains obtained the following scores: physical (58.59), psychological (63.82), social (68.79), and environmental (55.20). Through multiple linear regression, it was verified the correlation between domain scores and the perception of QOL: physical (p <0.187), psychological (p <0.399), social (p <0.000), and environmental (p <0.008). In conclusion, most participants (55.3%) are unsatisfied with their QOL, and the social and environmental domains showed a higher correlation with QOL.

  4. 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.

  5. Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat

    Directory of Open Access Journals (Sweden)

    Feng Quan-Xing

    2011-02-01

    Full Text Available Abstract Background Mechanisms underlying pain in chronic pancreatitis (CP are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs were involved in astrocytic activation and pain behavior in CP-induced pain. Results To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS. Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1β, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1 were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1β and MCP-1. Conclusions These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.

  6. Surgical Treatment for Adult Spinal Deformity: Projected Cost Effectiveness at 5-Year Follow-Up

    Science.gov (United States)

    Terran, Jamie; McHugh, Brian J.; Fischer, Charla R.; Lonner, Baron; Warren, Daniel; Glassman, Steven; Bridwell, Keith; Schwab, Frank; Lafage, Virginie

    2014-01-01

    Background In the United States, expenditures related to spine care are estimated to account for $86 billion annually. Policy makers have set a cost-effectiveness benchmark of less than $100,000/quality adjusted life year (QALY), forcing surgeons to defend their choices economically. This study projects the cost/QALY for surgical treatment of adult spinal deformity at 5-year follow-up based on 2-year cost- and health-related quality-of-life (HRQOL) data. Methods In a review of 541 patients with adult spinal deformity, the patients who underwent revision or were likely to undergo revision were identified and cost of surgery was doubled to account for the second procedure; all other patients maintained the cost of the initial surgery. Oswestry Disability Index (ODI) was modeled by revision status based on literature findings. Total surgical cost was based on Medicare reimbursement. Chi square and student t tests were utilized to compare cost-effective and non–cost-effective patients. Results The average cost/QALY at 5-year follow-up was $120,311.73. A total of 40.7% of patients fell under the threshold of a cost/QALY <$100,000. Cost-effective patients had higher baseline ODI scores (45% vs 34% [P=0.001]), lower baseline total Scoliosis Research Society scores (2.89 vs 3.00 [P=0.04]), and shorter fusions (8.23 vs 9.87 [P=0.0001]). Conclusion We found 40.7% of patients to be below the threshold of cost effectiveness. Factors associated with reaching the threshold <$100,000/QALY were greater preoperative disability, diagnosis of idiopathic scoliosis, poor preoperative HRQOL scores, and fewer fusion levels. PMID:24688328

  7. The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features.

    Science.gov (United States)

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Florensa-Vila, José; Ferrer, Isidro; Grassner, Lukas; Molina-Holgado, Eduardo

    2015-06-01

    Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution.

  8. 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.

  9. Peripheral nerve injury increases glutamate-evoked calcium mobilization in adult spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Doolen Suzanne

    2012-07-01

    Full Text Available Abstract Background Central sensitization in the spinal cord requires glutamate receptor activation and intracellular Ca2+ mobilization. We used Fura-2 AM bulk loading of mouse slices together with wide-field Ca2+ imaging to measure glutamate-evoked increases in extracellular Ca2+ to test the hypotheses that: 1. Exogenous application of glutamate causes Ca2+ mobilization in a preponderance of dorsal horn neurons within spinal cord slices taken from adult mice; 2. Glutamate-evoked Ca2+ mobilization is associated with spontaneous and/or evoked action potentials; 3. Glutamate acts at glutamate receptor subtypes to evoked Ca2+ transients; and 4. The magnitude of glutamate-evoked Ca2+ responses increases in the setting of peripheral neuropathic pain. Results Bath-applied glutamate robustly increased [Ca2+]i in 14.4 ± 2.6 cells per dorsal horn within a 440 x 330 um field-of-view, with an average time-to-peak of 27 s and decay of 112 s. Repeated application produced sequential responses of similar magnitude, indicating the absence of sensitization, desensitization or tachyphylaxis. Ca2+ transients were glutamate concentration-dependent with a Kd = 0.64 mM. Ca2+ responses predominantly occurred on neurons since: 1 Over 95% of glutamate-responsive cells did not label with the astrocyte marker, SR-101; 2 62% of fura-2 AM loaded cells exhibited spontaneous action potentials; 3 75% of cells that responded to locally-applied glutamate with a rise in [Ca2+]i also showed a significant increase in AP frequency upon a subsequent glutamate exposure; 4 In experiments using simultaneous on-cell recordings and Ca2+ imaging, glutamate elicited a Ca2+ response and an increase in AP frequency. AMPA/kainate (CNQX- and AMPA (GYKI 52466-selective receptor antagonists significantly attenuated glutamate-evoked increases in [Ca2+]i, while NMDA (AP-5, kainate (UBP-301 and class I mGluRs (AIDA did not. Compared to sham controls, peripheral nerve injury

  10. 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.

  11. Changes in brain-derived neurotrophic factor expression after transplanting microencapsulated sciatic nerve cells of rabbits into injured spinal cord of rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Changes of brain-derived neurotrophic factor (BDNF) expression reflect function of nerve cells; meanwhile, they play a significant role in researching interventions on plerosis of nerve injury.OBJECTIVE: To observe and compare the effects on changes of BDNF expression in rats with spinal cord injury between microencapsulated sciatic nerve cells of rabbits and only transplanting sciatic nerve cells of rabbits.DESIGN: Randomized controlled animal study.SETTING: Medical School of Jiujiang College.MATERIALS: The experiment was carried out in the Medical Science Researching Center, Jiujiang College from May 2004 to May 2006. A total of 90 healthy adult SD rats, weighing 250 - 300 g, of either gender; and 10 rabbits, weighing 2.0 - 2.5 kg, of either gender, were provided by Jiangxi Experimental Animal Center.METHODS: Sciatic nerve tissue of rabbits was separated to make cell suspension. After centrifugation,suspension was mixed with 15 g/L alginate saline solution and ejaculated to 20 mmol/L barium chloride saline solution by double-cavity ejaculator. The obtained cell microcapsules were suspended in saline. Rats were randomly divided into microencapsulated group, only suspension group, and only injured group with 30 animals in each group. After anesthesia, T10 spinous process and vertebra lamina of rats in the former two groups were exposed. Spinal cord tissue in 2-mm length was removed from rats by spinal cord right hemi-section. The gelatin sponges with the size of 2 mm × 2 mm × 2 mm were grafted as filing cage,and absorbed 10 μμ L microencapsulated sciatic nerve cells of rabbit in the microencapsulated group and 10 μ L sciatic nerve cells of rabbits in the only suspension group; respectively. No graft was placed in the only injured group.MAIN OUTCOME MEASURES: On the 1st, 3rd, 7th, 14th and 28th days after operation,immunohistochemistry (SABC technique) was used to detect distribution and amount of positive-reactive neurons in BDNF of spinal cord

  12. 成年大鼠脊髓全横断损伤后酪氨酸激酶受体C在脊髓和大脑皮层的表达%Expression of tyrosine kinase receptor C in the segments of the spinal cord and the cerebral cortex after cord transection in adult rats

    Institute of Scientific and Technical Information of China (English)

    钱东翔; 张洪钿; 蔡颖谦; 罗鹏; 徐如祥

    2011-01-01

    目的 研究神经营养因子3(neurotrophin-3,NT-3)的受体-酪氨酸激酶受体C(tyrosine kinase receptor C,TrkC)在脊髓损伤(spinal cord injury,SCI)后神经重塑中的作用.方法 研究脊髓全横断损伤大鼠手术后第1、3、7和14 d时,低位胸髓节段和大脑中央前回TrkC的表达.结果 损伤节段(T10-T11)双侧和临近节段(T9和T12)的TrkC蛋白水平在术后1-7 d显著下调,而在术后14 d快速增强.此外,TrkC mRNA表达水平的暂时性变化与TrkC蛋白的变化模式相似.TrkC蛋白和mRNA在损伤节段(T10-T11)的水平显著高于在临近节段(T9和T12)的水平.此外,TrkC蛋白和mRNA在吻侧节段的水平高于在尾侧节段的水平.与脊髓不同的是,运动皮层中并未检测到TrkC蛋白,并且TrkC mRNA的表达水平也很低.结论 TrkC可能与脊髓损伤后的神经功能重塑有关.%Objective To investigate the role of tyrosine kinase receptor C (TrkC), the receptor of neurotrophin-3 (NT-3), in neuroplasticity following spinal cord injury (SCI). Methods Rats with cord transection were allowed to survive for 1, 3, 7 and 14 d post operation (dpo). TrkC expressions at lower thoracic levels of the spinal cord and in precentral gyrus of cerebral cortex were investigated. Results TrkC protein levels at both the site of injury (T10-T11) and the neighboring segments (T9 and T12) in the spinal cord decreased significantly at 1-7 dpo, followed by a rapid increase at 14 dpo. The temporal changes in TrkC mRNA expression level showed a similar pattern with that of TrkC protein. In addition, the levels of TrkC protein and mRNA at the site of injury (T10-T11) were significantly higher than those at the neighboring spinal segments (T9 and T12). Besides, the levels of TrkC protein and mRNA were higher at the rostral segment than at the caudal segment. However, in the motor cortex, TrkC protein was not detected and TrkC mRNA was expressed at a very low level. Conclusion These results suggest that TrkC may be

  13. Endomorphins suppress nociception-induced c-Fos and Zif/268 expression in the rat spinal dorsal horn.

    Science.gov (United States)

    Tateyama, Shingo; Ikeda, Tetsuya; Kosai, Kazuko; Nakamura, Tadashi; Kasaba, Toshiharu; Takasaki, Mayumi; Nishimori, Toshikazu

    2002-09-06

    We evaluated the potency of endomorphin-1 and -2 as endogenous ligands on c-Fos and Zif/268 expression in the spinal dorsal horn by formalin injection to the rat hind paw. Endomorphin-1, -2, or morphine was administered intrathecally or intracerebroventricularly 5 min before formalin injection (5%, 100 microl). All drugs produced marked reductions of formalin-induced c-Fos and Zif/268 immunoreactivity in laminae I and II, and laminae V and VI in the rat lumbar spinal cord. The reductions of Zif/268 expression by endomorphins were greater than those by morphine, while the reductions of c-Fos expression by endomorphins were smaller than those by morphine. These effects of endomorphins were attenuated by pretreatment with naloxone. These results indicate that endomorphin-1 and -2 act as endogenous ligands of mu-opioid receptor in neurons of the spinal dorsal horn and suppress the processing of nociceptive information in the central nervous system.

  14. Adolescent social isolation influences cognitive function in adult rats

    Institute of Scientific and Technical Information of China (English)

    Feng Shao; Xiao Han; Shuang Shao; Weiwen Wang

    2013-01-01

    Adolescence is a critical period for neurodevelopment. Evidence from animal studies suggests that isolated rearing can exert negative effects on behavioral and brain development. The present study aimed to investigate the effects of adolescent social isolation on latent inhibition and brain-derived neurotrophic factor levels in the forebrain of adult rats. Male Wistar rats were randomly divided into adolescent isolation (isolated housing, 38–51 days of age) and social groups. Latent inhibition was tested at adulthood. Brain-derived neurotrophic factor levels were measured in the medial prefrontal cortex and nucleus accumbens by an enzyme-linked immunosorbent assay. Adolescent social isolation impaired latent inhibition and increased brain-derived neurotrophic factor levels in the medial prefrontal cortex of young adult rats. These data suggest that adolescent social isolation has a profound effect on cognitive function and neurotrophin levels in adult rats and may be used as an animal model of neurodevelopmental disorders.

  15. Exercise Training after Spinal Cord Injury Selectively Alters Synaptic Properties in Neurons in Adult Mouse Spinal Cord

    Science.gov (United States)

    Flynn, Jamie R.; Dunn, Lynda R.; Galea, Mary P.; Callister, Robin; Rank, Michelle M.

    2013-01-01

    Abstract Following spinal cord injury (SCI), anatomical changes such as axonal sprouting occur within weeks in the vicinity of the injury. Exercise training enhances axon sprouting; however, the exact mechanisms that mediate exercised-induced plasticity are unknown. We studied the effects of exercise training after SCI on the intrinsic and synaptic properties of spinal neurons in the immediate vicinity (<2 segments) of the SCI. Male mice (C57BL/6, 9–10 weeks old) received a spinal hemisection (T10) and after 1 week of recovery, they were randomized to trained (treadmill exercise for 3 weeks) and untrained (no exercise) groups. After 3 weeks, mice were killed and horizontal spinal cord slices (T6–L1, 250 μm thick) were prepared for visually guided whole cell patch clamp recording. Intrinsic properties, including resting membrane potential, input resistance, rheobase current, action potential (AP) threshold and after-hyperpolarization (AHP) amplitude were similar in neurons from trained and untrained mice (n=67 and 70 neurons, respectively). Neurons could be grouped into four categories based on their AP discharge during depolarizing current injection; the proportions of tonic firing, initial bursting, single spiking, and delayed firing neurons were similar in trained and untrained mice. The properties of spontaneous excitatory synaptic currents (sEPSCs) did not differ in trained and untrained animals. In contrast, evoked excitatory synaptic currents recorded after dorsal column stimulation were markedly increased in trained animals (peak amplitude 78.9±17.5 vs. 42.2±6.8 pA; charge 1054±376 vs. 348±75 pA·ms). These data suggest that 3 weeks of treadmill exercise does not affect the intrinsic properties of spinal neurons after SCI; however, excitatory synaptic drive from dorsal column pathways, such as the corticospinal tract, is enhanced. PMID:23320512

  16. Data on dose-volume effects in the rat spinal cord do not support existing NTCP models

    NARCIS (Netherlands)

    Van Luijk, P; Bijl, HP; Konings, AWT; Van Der Kogel, AJ; Schippers, JM

    2005-01-01

    Purpose: To evaluate several existing dose-volume effect models for their ability to describe the occurrence of white matter necrosis in rat spinal cord after irradiation with small proton beams. Methods and Materials: A large number of dose-volume effect models has been fitted to data on the occurr

  17. Influence of adjacent low-dose fields on tolerance to high doses of protons in rat cervical spinal cord

    NARCIS (Netherlands)

    Bijl, HP; van Luijk, P; Coppes, RP; Schippers, JM; Konings, AWT; van der Kogel, AJ

    2006-01-01

    Purpose: The dose-response relationship for a relatively short length (4 mm) of rat spinal cord has been shown to be significantly modified by adjacent low-dose fields. In an additional series of experiments, we have now established the dose-volume dependence of this effect. Methods and Materials: W

  18. Quantitative study of neurofilament-positive fiber length in rat spinal cord lesions using isotropic virtual planes

    DEFF Research Database (Denmark)

    von Euler, Mia; Larsen, Jytte Overgaard; Janson, A M

    1998-01-01

    Spontaneous reocurrence of neurofilament (NF)-positive fibers has been described after spinal cord lesions in rats. However, previously introduced methods to evaluate the lesion and the regenerative fiber outgrowth suffer from several biases, why a new concept of quantitative, morphological analy...

  19. A methd for simultaneous measurement of intragastric, intraduodenal, and intracolonic pressures in the bilaterally vagotomized spinal rat

    NARCIS (Netherlands)

    Y.N. Zhu (Y.); K.M. Dhasmana (K.); W. Erdmann (Wilhelm)

    1994-01-01

    textabstractA method has been developed where quantitative evaluation of intragastric (IGP), intraduodenal (IDP), and intracolonic (ICP) pressures (cm H2O) can be obtained in the bilaterally vagotomized spinal rat. The preparation is very sensitive to 5-hydroxytryptamine (5-HT) and 5-HT-agonists, ca

  20. A novel thermoelectric cooling device using Peltier modules for inducing local hypothermia of the spinal cord: the effect of local electrically controlled cooling for the treatment of spinal cord injuries in conscious rats.

    Science.gov (United States)

    Morizane, Kei; Ogata, Tadanori; Morino, Tadao; Horiuchi, Hideki; Yamaoka, Gotaro; Hino, Masayuki; Miura, Hiromasa

    2012-03-01

    We developed a novel thermoelectric cooling device using Peltier modules for the treatment of spinal cord injury in rats. The extracorporeal electrically cooling component was attached to the aluminum arched plate which was placed on the surface of the spinal cord after the contusion injury in the 11th thoracic spinal cord. During the hypothermic treatment, rats were awake and could move in the cage. Hind limb motor function, evaluated using a BBB scale, in the hypothermic animals (33°C for 48 h) was significantly higher than that in the normothermic animals from 2 weeks to 8 weeks after the injury.

  1. The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat

    Directory of Open Access Journals (Sweden)

    Shaohui Zong

    2014-01-01

    Full Text Available Study Design. In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI. Objective. The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat. Methods. Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23. Results. Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages. Conclusion. IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.

  2. Spinal analgesic action of endomorphins in acute, inflammatory and neuropathic pain in rats.

    Science.gov (United States)

    Przewłocka, B; Mika, J; Labuz, D; Toth, G; Przewłocki, R

    1999-02-19

    We studied spinal analgesic and antiallodynic effects of endomorphin-1 and endomorphin-2 administered i.t. in comparison with Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO) or morphine, during acute, inflammatory and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin-1 and endomorphin-2 (2.5, 5, 10 microg i.t.) increased the tail-flick latency and, to the lesser extent, the paw pressure latency. The range of potencies in both those models of acute pain was as follows: DAMGO > morphine = endomorphin-1 > endomorphin-2. In a model of inflammatory pain, the number of formalin-induced flinching episodes was decreased by endomorphin-1. The effect of endomorphin-2 was much less pronounced. Both DAMGO and morphine significantly inhibited the pain-related behavior evoked by formalin. In a neuropathic pain model (sciatic nerve crushing in rats), endomorphin-1 and -2 (5 microg i.t.) had a statistically significant effect on the tail-flick latency and on the cold-water tail flick latency. Morphine, 5 microg, was found to be ineffective. Endomorphin-1 and -2 (2.5 and 5 microg i.t.) dose-dependently antagonized allodynia. Those effects of endomorphins were antagonized in acute (30 microg), inflammatory (30 microg) and neuropathic pain models (60 microg) by cyprodime, a selective mu-opioid receptor antagonist. In conclusion, our results show a strong analgesic action of endomorphins at the spinal cord level. The most interesting finding is a strong, stronger than in the case of morphine, antiallodynic effect of endomorphins in rats subjected to sciatic nerve crushing, which suggests a possible use of these compounds in a very difficult therapy of neuropathic pain.

  3. Incidence of surgical site infection following adult spinal deformity surgery: an analysis of patient risk.

    NARCIS (Netherlands)

    Pull ter Gunne, A.F.; Laarhoven, C.J.H.M. van; Cohen, D.B.

    2010-01-01

    Surgical site infection (SSI) following spinal surgery is a frequent complication and results in higher morbidity, mortality and healthcare costs. Patients undergoing surgery for spinal deformity (scoliosis/kyphosis) have longer surgeries, involving more spinal levels and larger blood losses than ty

  4. Repair effect of Schwann cells modified by microgene pSVPoMcat on injured spinal cord in rats

    Institute of Scientific and Technical Information of China (English)

    陈礼刚; 高立达; 卢敏; 毛伯镛; 曾凡俊; 李开慧; 朴永旭

    2002-01-01

    To observe the repair effect of Schwann cells (SCs) modified by microgene pSVPoMcat on injured spinal cord in rats. Methods: Semi-transection injury at the level of T8 of spinal cord was made with cutting method on 120 Sprague Dawley (SD) rats. Then 40 rats implanted with SCs modified by microgene pSVPoMcat were taken as Group A,40 rats implanted with simple SCs as Group B and the other 40 rats were taken as the control group (Group C ). The functional recovery of the rats was observed through combined behavioral score ( CBS ) and cortical somatosensory evoked potential ( CSEP ), and the expression of the glial fibrillary acidic protein (GFAP) was measured with in situ hybridization and immunocytochemistry. At 3 months after operation, the rats were examined with magnetic resonance image (MRI), and the neurofilaments (NF) of the axons were stained with immunohistochemical method. Results: GFAP expression in Group A was significantly lower than that of the other 2 groups. MRI showed that the spinal signals in the injured area recovered fundamentally in Group A, didn't recover in Group B and malacia focus was found in Group C, which was same as the results of NF staining. Wave amplitudes in incubation periods in Group A and Group B tended to recover. It recovered to the normal level in Group A, which was similar to the results of CBS. Conclusions: SCs modified by microgene pSVPoMcat can inhibit GFAP expression, improve the growth of the axons and the functional recovery of neurons after spinal cord injury.

  5. Chronic infusion of SOD1(G93A) astrocyte-secreted factors induces spinal motoneuron degeneration and neuromuscular dysfunction in healthy rats.

    Science.gov (United States)

    Ramírez-Jarquín, Uri N; Rojas, Fabiola; van Zundert, Brigitte; Tapia, Ricardo

    2017-01-27

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and studies in vitro show that motoneuron degeneration is triggered by non-cell-autonomous mechanisms. However, whether soluble toxic factor(s) released by mutant superoxide dismutase 1 (SOD1) expressing astrocytes induces death of motoneurons and leads to motor dysfunction in vivo is not known. To directly test this, healthy adult rats were treated with conditioned media derived from primary mouse astrocytes (ACM) that express human (h) SOD1(G93A) (ACM-hG93A) via chronic osmotic pump infusion in the lumbar spinal cord. Controls included ACM derived from transgenic mice expressing hSOD1(WT) (ACM-hWT) or non-transgenic mouse SOD1(WT) (ACM-WT) astrocytes. Rats chronically infused with ACM-hG93A started to develop motor dysfunction at 8 days, as measured by rotarod performance. Additionally, immunohistochemical analyses at day 16 revealed reactive astrogliosis and significant loss of motoneurons in the ventral horn of the infused region. Controls did not show significant motor behavior alterations or neuronal damage. Thus, we demonstrate that factors released in vitro from astrocytes derived from ALS mice cause spinal motoneuron death and consequent neuromuscular dysfunction in vivo.

  6. {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

  7. Spinal infections.

    Science.gov (United States)

    Tay, Bobby K-B; Deckey, Jeffrey; Hu, Serena S

    2002-01-01

    Spinal infections can occur in a variety of clinical situations. Their presentation ranges from the infant with diskitis who is unwilling to crawl or walk to the adult who develops an infection after a spinal procedure. The most common types of spinal infections are hematogenous bacterial or fungal infections, pediatric diskitis, epidural abscess, and postoperative infections. Prompt and accurate diagnosis of spinal infections, the cornerstone of treatment, requires a high index of suspicion in at-risk patients and the appropriate evaluation to identify the organism and determine the extent of infection. Neurologic function and spinal stability also should be carefully evaluated. The goals of therapy should include eradicating the infection, relieving pain, preserving or restoring neurologic function, improving nutrition, and maintaining spinal stability.

  8. In vivo longitudinal Myelin Water Imaging in rat spinal cord following dorsal column transection injury.

    Science.gov (United States)

    Kozlowski, Piotr; Rosicka, Paulina; Liu, Jie; Yung, Andrew C; Tetzlaff, Wolfram

    2014-04-01

    Longitudinal Myelin Water Imaging was carried out in vivo to characterize white matter damage following dorsal column transection (DC Tx) injury at the lumbar level L1 of rat spinal cords. A transmit-receive implantable coil system was used to acquire multiple spin-echo (MSE) quantitative T2 data from the lumbar spinal cords of 16 rats at one week pre-injury as well as 3 and 8weeks post-injury (117 microns in-plane resolution and 1.5mm slice thickness). In addition, ex vivo MSE and DTI data were acquired from cords fixed and excised at 3 or 8weeks post injury using a solenoid coil. The MSE data were used to generate Myelin Water Fractions (MWFs) as a surrogate measure of myelin content, while DTI data were acquired to study damage to the axons. Myelin damage was assessed histologically with Eriochrome cyanine (EC) and Myelin Basic Protein in degenerated myelin (dgen-MBP) staining, and axonal damage was assessed by neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining. These MRI and histological measures of injury were studied in the dorsal column at 5mm cranial and 5mm caudal to injury epicenter. MWF increased significantly at 3weeks post-injury at both the cranial and caudal sites, relative to baseline. The values on the cranial side of injury returned to baseline at 8weeks post-injury but remained elevated on the caudal side. This trend was found in both in vivo and ex vivo data. This MWF increase was likely due to the presence of myelin debris, which were cleared by 8 weeks on the cranial, but not the caudal, side. Both EC and dgen-MBP stains displayed similar trends. MWF showed significant correlation with EC staining (R=0.63, p=0.005 in vivo and R=0.74, p=0.0001 ex vivo). MWF also correlated strongly with the dgen-MBP stain, but only on the cranial side (R=0.64, p=0.05 in vivo; R=0.63, p=0.038 ex vivo). This study demonstrates that longitudinal MWI in vivo can accurately characterize white matter damage in DC Tx model of injury

  9. Granulocyte colony-stimulating factor (G-CSF protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats.

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    Ryo Kadota

    Full Text Available BACKGROUND: Granulocyte colony-stimulating factor (G-CSF is a protein that stimulates differentiation, proliferation, and survival of cells in the granulocytic lineage. Recently, a neuroprotective effect of G-CSF was reported in a model of cerebral infarction and we previously reported the same effect in studies of murine spinal cord injury (SCI. The aim of the present study was to elucidate the potential therapeutic effect of G-CSF for SCI in rats. METHODS: Adult female Sprague-Dawley rats were used in the present study. Contusive SCI was introduced using the Infinite Horizon Impactor (magnitude: 200 kilodyne. Recombinant human G-CSF (15.0 µg/kg was administered by tail vein injection at 1 h after surgery and daily the next four days. The vehicle control rats received equal volumes of normal saline at the same time points. RESULTS: Using a contusive SCI model to examine the neuroprotective potential of G-CSF, we found that G-CSF suppressed the expression of pro-inflammatory cytokine (IL-1 beta and TNF- alpha in mRNA and protein levels. Histological assessment with luxol fast blue staining revealed that the area of white matter spared in the injured spinal cord was significantly larger in G-CSF-treated rats. Immunohistochemical analysis showed that G-CSF promoted up-regulation of anti-apoptotic protein Bcl-Xl on oligpodendrocytes and suppressed apoptosis of oligodendrocytes after SCI. Moreover, administration of G-CSF promoted better functional recovery of hind limbs. CONCLUSIONS: G-CSF protects oligodendrocyte from SCI-induced cell death via the suppression of inflammatory cytokines and up-regulation of anti-apoptotic protein. As a result, G-CSF attenuates white matter loss and promotes hindlimb functional recovery.

  10. Effects of transplantation of microencapsulated rabbit sciatic nerve on nuclear factor-kappa B expression after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xiaolian Wang; Jianmin Ma; Hui Chen; Deming Liu

    2009-01-01

    BACKGROUND: It has been reported that nuclear factor-kappa B (NF- k B), activated after spinal cord injury in rats, plays a key role in inflammatory responses in the central nervous system.OBJECTIVE: To investigate the effects of transplantation of microencapsulated rabbit sciatic nerve on NF- k B expression and motor function after spinal cord injury in rats, and to compare the results with the transplantation of rabbit sciatic nerve alone.DESIGN, TIME AND SETTING: This completely randomized, controlled study was performed at the Department of Neurobiology, Medical College of Nanchang University between December 2007 and July 2008.MATERIALS: A rabbit anti-NF- k B P65 monoclonal antibody was made by the Santa Cruz Company, USA and a streptavidin peroxidase immunohistochemical kit was provided by the Sequoia Company, China.METHODS: Eight rabbits were used to prepare a sciatic nerve cell suspension that was divided into two parts: one stored for transplantation, and the other mixed with a 1.5% sodium alginate solution. One hundred and twenty adult Sprague Dawley rats weighing 220-250 g were randomly divided into four groups: the microencapsulated cell group (n = 36), the non-encapsulated cell group (n = 36), the saline group (n = 36) and the sham operation group (n = 12). The first three groups underwent a right hemisection injury of the spinal cord at the T level, into which was transplanted a gelatin sponge soaked with 10 μ L of a microencapsulated nerve tissue/cell suspension (microencapsulated cell group), a tissue/cell suspension (non-encapsulated cell group) or physiological saline (saline group). In the sham operation group the vertebrae were exposed, but the spinal cord was not injured, and no implantation was given.MAIN OUTCOME MEASURES: Pathological changes were detected using hematoxylin-eosin staining; NF- K B expression was quantified using immunohistochemical staining; motor function was assessed using the Basso, Beattie and Bresnahan (BBB) scale

  11. Over-expression of PUMA correlates with the apoptosis of spinal cord cells in rat neuropathic intermittent claudication model.

    Directory of Open Access Journals (Sweden)

    Bin Ma

    Full Text Available BACKGROUND: Neuropathic intermittent claudication (NIC is a typical clinical symptom of lumbar spinal stenosis and the apoptosis of neurons caused by cauda equina compression (CEC has been proposed as an important reason. Whereas, the factors and the mechanism involved in the process of apoptosis induced by CEC remain unclear. METHODOLOGY AND RESULTS: In our modified rat model of NIC, a trapezoid-shaped silicon rubber was inserted into the epidural space under the L5 and L6 vertebral plate. Obvious apoptosis was observed in spinal cord cells after compression by TUNEL assay. Simultaneously, qRT-PCR and immunohistochemistry showed that the expression levels of PUMA (p53 up-regulated modulator of apoptosis and p53 were upregulated significantly in spinal cord under compression, while the expression of p53 inhibitor MDM2 and SirT2 decreased in the same region. Furthermore, CEC also resulted in the upregulation of Bcl-2 pro-apoptotic genes expression and caspase-3 activation. With the protection of Methylprednisolone, the upregulation of PUMA and p53 expression as well as the decrease of MDM2 and SirT2 in spinal cord were partially rescued in western bolt analysis. CONCLUSIONS: These results suggest that over-expression of PUMA correlates with CEC caused apoptosis of spinal cord cells, which is characterized by the increase of p53, Bax and Bad expression. PUMA upregulation might be crucial to induce apoptosis of spinal cord cells through p53-dependent pathway in CEC.

  12. Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats.

    Science.gov (United States)

    Gwak, Young S; Kang, Jonghoon; Unabia, Geda C; Hulsebosch, Claire E

    2012-04-01

    In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to 1 month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not simple events, rather they are the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinflammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neuron and glial cells via their own receptors

  13. Hyperprolactinemia affects spermiogenesis in adult male rats.

    Science.gov (United States)

    Aleem, M; Choudhari, J; Padwal, V; Balasinor, N; Parte, P; Gill-Sharma, M K

    2005-01-01

    The mechanisms underlying the antifertility effects of hyperprolactinemia have yet to be established in an appropriate experimental model. Hyperprolactinemia is a known side effect of fluphenazine, a broad spectrum, long-acting phenothiazine known to be dopamine type-D2 receptor antagonist. In our earlier study in adult male rats, we reported that fluphenazine at a dose of 3 mg/kg/day suppressed serum FSH but not testosterone (T) through increasing dopamine (DA) metabolism in the pituitary gland, within 60 days. Fluphenazine treatment affected sperm quality and male rats treated with fluphenazine sired fewer litters. The effects of fluphenazine-induced hyperprolactinemia on sperm quality appeared to be related to reduced FSH. We now report that FSH suppression enhanced the uptake of acridine orange (AO), a DNA intercalating, fluorescent dye by the fluphenazine-treated caput epididymal sperms with concomitant reduction in the uptake of thiol-specific monobromobimane (mBBr) fluorescent dye in vitro, suggesting greater accessibility of DNA intercalating dye to sperm chromatin and reduction in free sperm protein thiols. The concomitant increase in AO and decrease in mBBr fluorescence was suggestive of loose chromatin packaging in caput epididymal sperms after treatment with fluphenazine at 3 mg/kg/day for 60 days. The suppression in levels of protamine (P1) in caput epididymal sperms suggested that chromatin hypocompaction was due to reduced deposition of protamines in sperm chromatin. Reduction in testicular levels of cyclic adenosyl 3', 5' monophosphate response element modulator (CREMtau) and P1 further suggested that reduced deposition was indeed due to reduced synthesis. The concomitant reduction in testicular levels of transition protein 1 (TP1) and transition protein 2 (TP2) also suggested that hypoprotamination was due to reduced synthesis of these proteins crucial for facilitating P1 deposition. The effect appeared to have occurred at the level of translation

  14. Effect ofFerula sinkiangensis K.M. Shen on pain threshold and Fos protein expression and astrocyte activation in the spinal cord of neuropathic pain rats

    Institute of Scientific and Technical Information of China (English)

    Huang Yi-fei; Hu Wei; Li Lei; Liu Yan-lu

    2015-01-01

    BACKGROUND:Ferula sinkiangensis K.M. Shen is composed of volatile oil, resin and gum that have the anti-inflammatory, anti-alergic, antispasmodic and analgesic effects. But its analgesic mechanism is unclear. OBJECTIVE: To observe the effect ofFerula sinkiangensis K.M. Shen on heat pain, mechanical pain, Fos protein expression and astrocyte activation in spinal cord of rats with neuropathic pain. METHODS: Eighty adult Sprague-Dawley rat models of chronic sciatic nerve injury were randomly divided into five groups and then intragasticaly administeredFerula sinkiangensis K.M. Shen at low, moderate and high doses (0.075, 0.15, 0.30 g/kg), celecoxib or physiological saline. Heat pain and mechanical pain were measured at 1 day before operation and at 1, 2, 3, 5, 7, 14 days after operation. The spinal cord tissue at S4-5 segments was harvested and Fos protein expression and astrocyte activation in the spinal cord of rats were observed by immunohistochemical staining method. RESULTS AND CONCLUSION: After 1 and 5 days of medication, behavioral pain scores of rats in the low-, moderate-, and high-doseFerula sinkiangensis K.M. Shen groups were significantly higher than that in the physiological saline group (P < 0.01). The largest reduction in heat pain threshold was measured in the moderate-doseFerula sinkiangensis K.M. Shen group compared to the other groups (P < 0.01). The most significant reduction in rat mechanical pain threshold was measured in the high-doseFerula sinkiangensis K.M. Shen group than in the other groups (P < 0.01). At each time point post-operation, the number of Fos protein-positive cels in the low-, moderate- and high-doseFerula sinkiangensis K.M. Shen and celecoxib groups was significantly lower than that in the physiological saline group (P < 0.05); the number of Fos protein-positive cels in the moderate- and high-doseFerula sinkiangensis K.M Shen groups was significantly higher than that in the celecoxib group (P< 0.05). At each time point post

  15. Effects of acute millimeter wave exposure on the expression of substance P and c-fos in rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yan-wen ZHANG

    2013-04-01

    Full Text Available Objective  To observe the expression changes in substance P (SP and c-fos in rat spinal cord after acute millimeter-wave (MMW exposure, and explore the mechanism of thermal hyperalgesia at the spinal level. Methods  The back skin of SD rats was exposed to 35 GHz MMW (40W/cm2 for 0s (control group, 30s, 1min, or 3min. The corresponding segment of the spinal cord was taken at 0min, 5min, 10min, 1h and 3h after MMW irradiation for total RNA and protein extraction. The expressions of SP and c-fos mRNA were measured by real-time RT-PCR, and the expression of c-fos protein was detected by Western blotting. Results  No significant difference was found between the control group and irradiation groups in SP and c-fos mRNA expression in the corresponding segment of spinal cord after MMW irradiation for 30s. After MMW irradiation for 1min, the SP and c-fos mRNA expressions in the corresponding segment of spinal cord increased significantly at 10min time point, and then decreased to the level of control group. After MMW irradiation for 3min, the SP and c-fos mRNA expression in the corresponding segment of spinal cord increased significantly at 5min, 10min and 1h time points, and decreased to the level of control group at 3h. No significant change was found in c-fos protein expression in the corresponding segment of spinal cord after MMW irradiation for 30s and 1min. After MMW irradiation for 3min, the c-fos protein expression in the corresponding segment of spinal cord increased significantly at 5min and 10min time point, and then decreased to the level of control group. Conclusion  The increase of SP expression in rat skin after MMW irradiation may be related to the increase of SP and c-fos expressions in the corresponding segment of the spinal cord induced by thermal pain stimulation.

  16. Rabbit IgG distribution in skin, spinal cord and DRG following systemic injection in rat.

    Science.gov (United States)

    Tonra, J R; Mendell, L M

    1997-12-01

    In order to determine the distribution of antibodies such as anti-NGF following systemic injection in neonates, immunocytochemical techniques were used to examine the localization of rabbit IgG in rat skin, DRG, and spinal cord after treatments with normal rabbit serum or purified rabbit IgG. Daily subcutaneous injections beginning on postnatal day 2 or on day 15 were given for three days. On the fourth day the animals were sacrificed and tissues were processed for rabbit IgG-IR. In the dorsal and ventral spinal cord, staining intensities suggest a substantial increase in the blood-brain barrier during the first two weeks after birth. Staining intensity in the epidermis of the glabrous skin from the hindpaw was substantially lower than in the adjacent dermis. In addition, IgG infrequently accumulated intracellularly in intensely stained patches in the epidermis. IgG was also able to reach relatively high intracellular concentrations in a small number of sensory neurons. The IgG staining pattern in the skin was similar when anti-NGF itself was administered to the animals. The results are discussed in the context of the effects of anti-NGF on the development of nociceptive afferents.

  17. Decoding intravesical pressure from local field potentials in rat lumbosacral spinal cord

    Science.gov (United States)

    Im, Changkyun; Park, Hae Yong; Koh, Chin Su; Ryu, Sang Baek; Seo, In Seok; Kim, Yong Jung; Kim, Kyung Hwan; Shin, Hyung-Cheul

    2016-10-01

    Chronic monitoring of intravesical pressure is required to detect the onset of intravesical hypertension and the progression of a more severe condition. Recent reports demonstrate the bladder state can be monitored from the spiking activity of the dorsal root ganglia or lumbosacral spinal cord. However, one of the most serious challenges for these methods is the difficulty of sustained spike signal acquisition due to the high-electrode-location-sensitivity of spikes or neuro-degeneration. Alternatively, it has been demonstrated that local field potential recordings are less affected by encapsulation reactions or electrode location changes. Here, we hypothesized that local field potential (LFP) from the lumbosacral dorsal horn may provide information concerning the intravesical pressure. LFP and spike activities were simultaneously recorded from the lumbosacral spinal cord of anesthetized rats during bladder filling. The results show that the LFP activities carry significant information about intravesical pressure along with spiking activities. Importantly, the intravesical pressure is decoded from the power in high-frequency bands (83.9-256 Hz) with a substantial performance similar to that of the spike train decoding. These findings demonstrate that high-frequency LFP activity can be an alternative intravesical pressure monitoring signal, which could lead to a proper closed loop system for urinary control.

  18. Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in male rats.

    Science.gov (United States)

    Juif, Pierre-Eric; Poisbeau, Pierrick

    2013-08-01

    Oxytocin (OT) and arginine vasopressin (AVP) are 2 neuropeptides that display well-known effects on the reproductive system. Although still controversial, oxytocin and vasopressin were demonstrated to exert potent effects on the nociceptive system when administered directly in various central nervous structures. On the other hand, little is known about their peripheral (hormonal) actions on nociception and pain responses. The aim of the present work was to characterize the effects of physiological blood concentrations of OT and AVP on spinal nociception and on pain responses. To do so, growing doses of OT or AVP were administered intravenously and the nociceptive processing by spinal cord neurons was analyzed in anesthetized male rats in vivo. We observed that the action potentials mediated by C-type nociceptive fibers was strongly reduced (antinociception) after intravenous injections of low doses of OT (effects were fully abolished in the presence of the OT receptor antagonist and the AVP receptor antagonist type 1A (V1A), respectively. We confirmed this result with a behavioral model of forced swim stress-induced analgesia associated with plasmatic release of OT (and not vasopressin). Stress-induced analgesia was transiently lost after i.v. administration of OTR antagonist. Together, the present work provides straightforward evidence that blood levels of OT and AVP modulate nociception, windup plasticity and pain responses. The final target structures explaining these effects remains to be identified but are likely to be C-type nociceptors.

  19. Electrophysiological properties of lumbosacral preganglionic neurons in the neonatal rat spinal cord.

    Science.gov (United States)

    Miura, A; Kawatani, M; Araki, I; de Groat, W C

    2000-07-28

    The electrophysiological properties of parasympathetic preganglionic neurons (PGN) in L6 and S1 spinal cord slices from neonatal rats were studied using the patch clamp techniques. PGN were identified by retrograde axonal transport of a fluorescent dye (Fast Blue) injected intraperitoneally before the experiment. PGN in the intermediolateral region of the spinal cord were divided into two classes (tonic PGN and phasic PGN) on the basis of firing properties during prolonged (300 ms) depolarizing current pulses. Tonic neurons exhibited a prolonged discharge (average maximum: 5.6); whereas phasic PGN fired on average only 1.4 spikes during depolarizing pulses. PGN were usually oval in shape. The mean long axis of tonic PGN (20.7+/-0.5 microm) was significantly (PAHP) in tonic PGN (200.5+/-11.9 ms) was longer than in phasic PGN (137.6+/-9.8 ms). 4-aminopyridine (4-AP, 0. 5 mM) reduced the threshold for spike activation in tonic and phasic PGN. 4-AP also unmasked tonic firing in phasic PGN (average maximum: 5.5 spikes during 300 ms depolarizing current pulses) and increased firing frequency by 19% in tonic PGN. These data indicate that the different discharge patterns of parasympathetic PGN are dependent in part on differences in the expression of 4-AP-sensitive K(+) channels. The two types of PGN may provide an innervation to different targets in the pelvic viscera.

  20. Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated Glial-derived neurotrophic factor combined with early rehabilitation training

    Institute of Scientific and Technical Information of China (English)

    Han Qingquan; Xiang Jingjing; Zhang Yun; Qiao Hujun; Shen Yongwei; Zhang Chun

    2014-01-01

    Background Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims.The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats.Then besides the sham operation group,the SCI rats were randomly divided into four groups:natural healing group,gene therapy group,rehabilitation training group,and combination therapy group (gene therapy in combination with rehabilitation training).Motor dysfunction,protein expression of GDNF,edema formation,and cell injury were examined 7,14,and 21 days after trauma.Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF,especially after the 14th day,and could protect the motor neuron ceils.Early rehabilitative treatment resulted in significantly improved motor function,reduced edema formation,and protected the cells from injury,especially after the 7th and 14th days,and increased the GDNF expression in the damaged area,which was most evident after Day 14.The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.

  1. 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.

  2. Effects of noradrenaline on locomotor rhythm-generating networks in the isolated neonatal rat spinal cord

    DEFF Research Database (Denmark)

    Kiehn, O; Sillar, K T; Kjaerulff, O;

    1999-01-01

    We have studied the effects of the biogenic amine noradrenaline (NA) on motor activity in the isolated neonatal rat spinal cord. The motor output was recorded with suction electrodes from the lumbar ventral roots. When applied on its own, NA (0.5-50 microM) elicited either no measurable root...... slowing effect on the rhythm while preserving the normal coordination between flexors and extensors. The ability of NA to "rescue" rhythmic locomotor activity after its time-dependent deterioration suggests that the amine may be important in the maintenance of rhythmic motor activity.......M). NA modulated this activity by decreasing the cycle frequency and increasing the ventral root burst duration. These effects were dose dependent in the concentration range 1-5 microM. In contrast, at no concentration tested did NA have consistent effects on burst amplitudes or on the background...

  3. Retrograde tracing of zinc-enriched (ZEN) neuronal somata in rat spinal cord

    DEFF Research Database (Denmark)

    Wang, Z; Danscher, G; Mook Jo, S

    2001-01-01

    and having either inhibitory or excitatory ZEN terminals. The ZEN neurons seem to form a vast network of terminals located primarily in the gray matter, but also contacting dendrites radiating into the white matter. Important functions of this rather massive system of ZEN terminals can not be deduced from......The zinc selenide autometallographic (ZnSeAMG) technique for tracing the retrograde axonal transport of zinc ions in zinc-enriched (ZEN) neurons was used to map the distribution of ZEN neuronal somata in rat spinal cord. After a local injection of sodium selenide into the dorsal or ventral horn, Zn......SeAMG-labeled ZEN neurons appeared in Rexed's laminae V, VII and X while laminae I and II were void. A few scattered ZEN somata were observed in the remaining laminae. The labeled neurons differed in shape and size, and the relatively high level of labeled somata around the injection site suggests that many ZEN...

  4. The change of neurotrophin 3 in spinal motor neurons following sciatic nerve lesion in rats%周围神经损伤对脊髓运动神经元NT-3表达的影响

    Institute of Scientific and Technical Information of China (English)

    石向群; 范明; 陆兵勋; 杨金升; 赵友岐; 汪泳

    2001-01-01

    Objective:To study the change of neurotroph in 3(NT-3) in the spinal motor neuron and the association between it and the degree of degeneration and death in spinal motor neuron following sciatic nervele sion in the rats.Methods:The sciatic nerve lesion wa s induced with cutting and removing part of the sciatic nerve in the adult and 3 days of age rats.The rats were allowed to survive for 3,7,14,21,28 days.The ext ent of spinal motor neuron death and degeneration was examined,the level of NT- 3 in spinal motor neuron were measured with image analysis.Results :The level of NT-3 in spinal motor neuron in suckling and adultr at groap was significant reduced following sciatic nerve lesion,and it was lowest in the second week after sciatic nerve lesion.The level of NT-3 in spinal mot or neuron in the 28th day following sciatic nerve lesion did not increase to it of the control.The change of spin al motor neuron death and degeneration was similar to the change of the level of NT-3.The level of NT-3 in spinal motor neuron in suckling rat was highter than it in adult rat. Conclusion:The level of NT-3 in spinal motor neurons would take change following sciatic nerve lesion,and the de ath and degeneration of spinal motor neuron may be induced by the peripheral ner ve lesion,The level of NT-3 in spinal motor neuron was negative with the extent of spinal motor neuron death and degeneration.%目的:探讨周围神经损伤后脊髓运动神经元神经营养因子-3(NT-3)水平变化规律及与神经元病理变化的相关性。方法:切断大鼠坐骨神经复制周围神经损伤模型,免疫组织化学染色NT-3阳性脊髓运 动神经元、图像分析计算其吸光度以反映NT-3的水平。结果:成鼠或乳鼠坐骨神经损伤后运动神经元NT-3水平均很快下降,至伤后第2周降至最低 水平,随后逐渐恢复,至4周仍未恢复到对照组水平;神经元病理改变过程与此相似。但乳 鼠NT-3基

  5. Immunohistochemical distribution of Plexin A4 in the adult rat central nervous system

    Directory of Open Access Journals (Sweden)

    Claire-Anne Gutekunst

    2010-07-01

    Full Text Available PlexinA4 is the latest member to be identified of the plexin A subfamily, critical transducers of class 3 semaphorin signaling as co-receptors to neuropilins 1 and 2. Despite functional information regarding the role of PlexinA4 in development and guidance of specific neuronal pathways, little is known about its distribution in the adult central nervous system (CNS. Here we report an in depth immunohistochemical analysis of PlexinA4 expression in the adult rat CNS. PlexinA4 staining was present in neurons and fibers throughout the brain and spinal cord, including neocortex, hippocampus, lateral hypothalamus, red nucleus, facial nucleus and the mesencephalic trigeminal nucleus. PlexinA4 antibodies labeled fibers in the lateral septum, nucleus accumbens, several thalamic nuclei, substantia nigra pars reticulata, zona incerta, pontine reticular region, as well as in several cranial nerve nuclei. This constitutes the first detailed description of the topographic distribution of PlexinA4 in the adult CNS and will set the basis for future studies on the functional implications of PlexinA4 in adult brain physiology.

  6. Dobutamine stress echocardiography in healthy adult male rats

    OpenAIRE

    Couet Jacques; Roussel Élise; Drolet Marie-Claude; Lachance Dominic; Plante Eric; Arsenault Marie

    2005-01-01

    Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intra...

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

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    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.

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

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    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.

  9. Spinal orexin-1 receptors mediate anti-hyperalgesic effects of intrathecally-administered orexins in diabetic neuropathic pain model rats.

    Science.gov (United States)

    Kajiyama, Seiji; Kawamoto, Masashi; Shiraishi, Seiji; Gaus, Syafruddin; Matsunaga, Aki; Suyama, Hidemichi; Yuge, Osafumi

    2005-05-17

    Orexin-A and orexin-B are endogenous ligands of orexin receptors that contain orexin-1 and orexin-2. Activation of the orexinergic system can produce antinociceptive effects in acute inflammatory, mono-neuropathic, and postoperative pain animal models, though the effects of orexins on diabetic neuropathic pain have not been previously investigated. In this study, we studied the anti-hyperalgesic effects of intrathecally administered orexins in a streptozotocin-induced diabetic rat. First, dose-dependent effects were investigated by measuring hind paw withdrawal thresholds in response to noxious-heat and punctate stimuli, after which orexin levels in the cerebrospinal fluid of diabetic rats were measured and compared with those of normal rats using a radioimmunoassay method. The functional role of spinal orexin-1 receptors with the anti-hyperalgesic effects of orexins was also investigated using intrathecal pretreatment with SB-334867, a selective orexin-1 receptor antagonist. Intrathecally administered orexins produced an antinociceptive effect in diabetic rats, however, not in normal rats, though the orexin levels in the cerebrospinal fluid of diabetic rats were similar to those in normal rats. In addition, the anti-hyperalgesic effects of orexins were significantly inhibited by pretreatment with SB-334867. These findings demonstrate that the anti-hyperalgesic effects of orexins in diabetic rats are unlikely due to any direct effect by the supplement on decreased endogenous orexins in the cerebrospinal fluid and that orexin-1 receptors in the spinal cord may be involved in the modulation of nociceptive transmission in diabetic neuropathy. We conclude that the spinal orexinergic system may be a possible target for elucidating the mechanisms of diabetes-induced hyperalgesia.

  10. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson’s Disease

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    Lei-Fang Cao

    2016-01-01

    Full Text Available In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA into the bilateral striatum (CPu. PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4 aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE precursor droxidopa (L-DOPS or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE and 5-hydroxytryptamine (5-HT reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain.

  11. Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Jianjun Zhang

    2012-01-01

    Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours (mild hypothermia). Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells (bromodeoxyuridine-positive cells), better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.

  12. Risk factors for rod fracture after posterior correction of adult spinal deformity with osteotomy: a retrospective case-series

    OpenAIRE

    Barton, Cameron; Noshchenko, Andriy; Patel, Vikas; Cain, Christopher; Kleck, Christopher; Burger, Evalina

    2015-01-01

    Background Osteotomies including pedicle subtraction (PSO) and/or Smith-Peterson (SPO) are used to facilitate surgical correction of adult spinal deformity (ASD), but are associated with complications including instrumentation failure and rod fracture (RF). The purpose of this study was to determine incidence and risk factors for RF, including a clinically significant subset (CSRF), after osteotomy for ASD. Methods A retrospective review of clinical records was conducted on consecutive ASD pa...

  13. Hypertension after bilateral kidney irradiation in young and adult rats

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

    1987-09-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Xin Geng; Tao Sun; Jing-hui Li; Ning Zhao; Yong Wang; Hua-lin Yu

    2015-01-01

    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-Daw-ley rats was clamped for 60 seconds.Dazhui (GV14) andMingmen (GV4) acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expres-sion of serum inlfammatory 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 ifndings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem cells.

  15. 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.

  16. Mini-Open Anterior Lumbar Interbody Fusion Combined with Lateral Lumbar Interbody Fusion in Corrective Surgery for Adult Spinal Deformity

    Science.gov (United States)

    Lee, Chong-Suh; Chung, Sung-Soo; Lee, Jun-Young; Yum, Tae-Hoon; Shin, Seong-Kee

    2016-01-01

    Study Design Prospective observational study. Purpose To introduce the techniques and present the surgical outcomes of mini-open anterior lumbar interbody fusion (ALIF) at the most caudal segments of the spine combined with lateral lumbar interbody fusion (LLIF) for the correction of adult spinal deformity Overview of Literature Although LLIF is increasingly used to correct adult spinal deformity, the correction of sagittal plane deformity with LLIF alone is reportedly suboptimal. Methods Thirty-two consecutive patients with adult spinal deformity underwent LLIF combined with mini-open ALIF at the L5–S1 or L4–S1 levels followed by 2-stage posterior fixation. ALIF was performed for a mean 1.3 levels and LLIF for a mean 2.7 levels. Then, percutaneous fixation was performed in 11 patients (percutaneous group), open correction with facetectomy with or without laminectomy in 16 (open group), and additional pedicle subtraction osteotomy (PSO) in 5 (PSO group). Spinopelvic parameters were compared preoperatively and postoperatively. Hospitalization data and clinical outcomes were recorded. Results No major medical complications developed, and clinical outcomes improved postoperatively in all groups. The mean postoperative segmental lordosis was greater after ALIF (17.5°±5.5°) than after LLIF (8.1°±5.3°, p sagittal balance and reducing the necessity of more extensive surgery. PMID:27994777

  17. Tethered Spinal Cord Syndrome

    Science.gov (United States)

    ... roots may be cut to relieve pain. In adults, surgery to free (detether) the spinal cord can reduce the size ... is a neurological disorder caused by tissue attachments that limit the movement of the spinal cord ...

  18. Comparative Study on the Differentiation of Mesenchymal Stem Cells Between Fetal and Postnatal Rat Spinal Cord Niche.

    Science.gov (United States)

    Cao, Songying; Wei, Xiaowei; Li, Hui; Miao, Jianing; Zhao, Guifeng; Wu, Di; Liu, Bo; Zhang, Yi; Gu, Hui; Wang, Lili; Fan, Yang; An, Dong; Yuan, Zhengwei

    2016-01-01

    In a previous study, we established a prenatal surgical approach and transplanted mesenchymal stem cells (MSCs) into the fetal rat spinal column to treat neural tube defects (NTDs). We found that the transplanted MSCs survived and differentiated into neural lineage cells. Various cytokines and extracellular signaling systems in the spinal cord niche play an important role in cell differentiation. In this study, we observed the differentiation of transplanted MSCs in different spinal cord niches and further observed the expression of neurotrophic factors and growth factors in the spinal cord at different developmental stages to explore the mechanism of MSC differentiation in different spinal cord niches. The results showed that transplanted MSCs expressed markers of neural precursor cells (nestin), neurogliocytes (GFAP), and neurons (β-tubulin). The percentages of GFP(+)/nestin(+) double-positive cells in transplanted MSCs in E16, P1, and P21 rats were 18.31%, 12.18%, and 5.06%, respectively. The percentages of GFP(+)/GFAP(+) double-positive cells in E16, P1, and P21 rats were 32.01%, 15.35%, and 12.56%, respectively. The percentages of GFP(+)/β-tubulin(+) double-positive cells in E16, P1, and P21 were 11.76%, 7.62%, and 4.88%, respectively. The differentiation rates of MSCs in embryonic spinal cords were significantly higher than in postnatal spinal cords (p < 0.05). We found that the transplanted MSCs expressed synapsin-1 at different developmental stages. After MSC transplantation, we observed that neurotrophic factor-3 (NT-3), fibroblast growth factor-2 (FGF-2), FGF-8, transforming growth factor-α (TGF-α), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) significantly increased in the MSC transplantation group compared with the blank injection group. Furthermore, FGF-2 and VEGF expression were positively correlated with the number of surviving MSCs. In addition, we found that the expression of brain

  19. The effect of July admission on inpatient morbidity and mortality after adult spinal deformity surgery

    Science.gov (United States)

    De la Garza-Ramos, Rafael; Passias, Peter G.; Schwab, Frank J.; Lafage, Virginie

    2016-01-01

    Background Some studies have suggested patients who undergo surgery in July have worse outcomes compared to patients treated during other months. The purpose of this study is to compare inpatient morbidity and mortality among patients who underwent adult spinal deformity (ASD) surgery in July with those who underwent surgery in other months. Methods Admission data for patients who underwent ASD surgery were extracted from the Nationwide Inpatient Sample for the years 2002 to 2011. Only adult patients (over 21 years of age) and elective admissions to teaching hospitals were included. A multivariable regression analysis was performed to examine the independent effect of July admissions on overall complications, major complications, and inpatient mortality. Results A total of 27,794 patients were identified, with 2,023 (7.8%) admitted in July and 25,771 (92.2%) in other months. Overall complication rates in July (43.1%) were not different from rates in other months (44.9%, p=0.468). Similarly, major complication rates were similar; 12.9% in July and 12.4% in other months (p=0.764). Mortality was not different between groups (p=0.807). After multivariable analysis, July admissions were not found to increase the odds of developing any complication (OR 0.94; 95% CI, 0.77 - 1.12; p=0.403), major complications (OR 1.04; 95% CI, 0.76 - 1.41; p=0.788) or inpatient mortality (OR 1.35; 95% CI, 0.31 - 5.84; p=0.684). Conclusion In this study of a nationwide database, patients who underwent ASD surgery in July did not have increased odds of developing a complication or inpatient mortality compared to patients admitted in other months. PMID:26913223

  20. Transplantation of low-power laser-irradiated olfactory ensheathing cells to promote repair of spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Haoxian Chen; Xinfeng Zheng; Weibin Sheng; Qin Wei; Tao Jiang; Gele Jin

    2009-01-01

    BACKGROUND: Previous studies have demonstrated that low-power laser (LPL) irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it is thought to be a potential treatment for spinal cord injury.OBJECTIVE: Utilizing histological observations and behavioral evaluations, the aim of this study was to investigate the influence of transplanted olfactory ensheathing cells (OECs), irradiated by LPL, on functional repair of rats following transversal spinal cord injury.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the animal experimental center in the First Affiliated Hospital of Xinjiang Medical University between January 2007 and February 2008.MATERIALS: A total of 52 Sprague Dawley rats were included in this experiment. Twelve rats were used to harvest OECs, some of which were irradiated by LPL on days 3, 5, and 7 in culture.The remaining 40 rats were used to establish T12 complete spinal cord transection injury.DMEM/F12 medium was purchased from Sigma, USA, Fluorogold was provided by Chemicon,USA, and the LY/JG650-D500-16 low-power laser was produced by Xi'an Lingyue Electromechanical Science And Technology Co., Ltd., China.METHODS: The successful rat models were randomly divided into three groups: OEC transplantation, LPL-irradiated OEC transplantation, and control. These animals were microinjected with OEC suspension, LPL-irradiated OEC suspension, and DMEM/F12 medium(10 μL) respectively 4 weeks after spinal cord was completely transected at the T12 level.MAIN OUTCOME MEASURES: Spinal cord injury was observed using hematoxylin-eosin staining.Expression of nerve growth factor receptor p75 and glial fibrillary acidic protein were determined using immunohistochemical staining. Regeneration of spinal nerve fibers in rats was assayed by Fluorogold retrograde labeling method. Basso, Beattie and Bresnahan (BBB) scores were used to evaluate motor

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

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Wei [Department of Out-Patient, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Wang, Wei; Huang, Jing [Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi' an 710032 (China); Ren, Ning [Comprehensive Diagnostic and Therapeutic Center, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Wu, Sheng-Xi, E-mail: shengxi@fmmu.edu.cn [Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi' an 710032 (China); Li, Yong-Qi, E-mail: devneuro@fmmu.edu.cn [Comprehensive Diagnostic and Therapeutic Center, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2010-05-14

    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-1{beta} 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-1{beta} was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1{beta}. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1{beta} expression and thus modulating spinal excitatory synaptic transmission and pain response.

  2. Mild Hyperbaric Oxygen Improves Decreased Oxidative Capacity of Spinal Motoneurons Innervating the Soleus Muscle of Rats with Type 2 Diabetes.

    Science.gov (United States)

    Takemura, Ai; Ishihara, Akihiko

    2016-09-01

    Rats with type 2 diabetes exhibit decreased oxidative capacity, such as reduced oxidative enzyme activity, low-intensity staining for oxidative enzymes in fibers, and no high-oxidative type IIA fibers, in the skeletal muscle, especially in the soleus muscle. In contrast, there are no data available concerning the oxidative capacity of spinal motoneurons innervating skeletal muscle of rats with type 2 diabetes. This study examined the oxidative capacity of motoneurons innervating the soleus muscle of non-obese rats with type 2 diabetes. In addition, this study examined the effects of mild hyperbaric oxygen at 1.25 atmospheres absolute with 36 % oxygen for 10 weeks on the oxidative capacity of motoneurons innervating the soleus muscle because mild hyperbaric oxygen improves the decreased oxidative capacity of the soleus muscle in non-obese rats with type 2 diabetes. Spinal motoneurons innervating the soleus muscle were identified using nuclear yellow, a retrograde fluorescent neuronal tracer. Thereafter, the cell body sizes and succinate dehydrogenase activity of identified motoneurons were analyzed. Decreased succinate dehydrogenase activity of small-sized alpha motoneurons innervating the soleus muscle was observed in rats with type 2 diabetes. The decreased succinate dehydrogenase activity of these motoneurons was improved by mild hyperbaric oxygen. Therefore, we concluded that rats with type 2 diabetes have decreased oxidative capacity in motoneurons innervating the soleus muscle and this decreased oxidative capacity is improved by mild hyperbaric oxygen.

  3. 重组人促红细胞生成素对SCI大鼠Akt和p-Akt表达的影响%The effect of recombinant human erythropoietin on the expression of Akt and p-Akt in spinal cord injury rat

    Institute of Scientific and Technical Information of China (English)

    车敏; 刘颖; 王岩峰

    2012-01-01

    目的 探讨重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)对脊髓损伤(spinal cord injury,SCI)大鼠Akt与p-Akt表达的影响.方法 成年健康Wistar大鼠72只,雌雄不限,按随机数字表法分为假手术组、脊髓损伤组和重组人促红细胞生成素治疗组,参照Nystrom's压迫方法制作大鼠脊髓压迫损伤模型,按照存活时间再分为脊髓损伤6h,12h,24h,3d组.免疫组化和Western blot方法检测Akt、p-Akt在各组大鼠脊髓表达的变化.结果 免疫组化和Western blot结果发现,脊髓Akt、p-Akt蛋白阳性表达的平均光密度值SCI组低于假手术组(P <0.05),重组人促红细胞生成素治疗组显著高于SCI组(P<0.05).结论 rHuEPO可通过上调Akt、p-Akt蛋白的表达参与脊髓损伤修复.%Objective To study the effect of recombinant human erythropoietin(rHuEPO) on the expressions of Akt and p-Akt in spinal cord injury rat. Methods 72 healthy adult Wistar rats were randomly divided into the sham group(n=8), the spinal cord injury group(n=32) and rHuEPO group(n=32). The spinal cord injury was induced with Nyslrom's way. The spinal cord injury group and rHuEPO group were further randomly subdivided into four subgroups (6h, 12h, 24h, 3d) according to the postoperative survival time. The expressions of Akt and p-Akt were observed by immunochemistry and Western blot methods. Results The mean optic density(MOD) values of Akt and p—Akt products in spinal cord were decreased in spinal cord injury than in sham group( P <0.05), but increased significantly in rHuEPO treated group than in spinal cord injury( P <0.05) by immunochemistry and Western blot. Conclusion The impairment effect of rHuEPO in spinal cord injury might be related to the upregulation of the expressions of Akt and p—Akt.

  4. Effects of Sevoflurane on the discharges of wide dynamic range neurons in spinally transected rats

    Institute of Scientific and Technical Information of China (English)

    WANG Ying-wei; XIONG Yuan-chang; DENG Xiao-ming; ZHAO Zhi-qi

    2004-01-01

    Objective: To study the effects of clinical concentration of sevoflurane on activity of wide dynamic range neurons. Methods: Eight Spraque-Dawley rats(male) were selected. Their spinal cords were exposed and transected at T9- 10 level. The rate of firings of single neurons in the dorsal horn in response to electrical stimulation of skin was recorded with microelectrodes. The early and late discharges were observed when rats inhaled 0.5%, 1.0%, 1.5%, and 2.0%sevoflurane. Results: Sevoflurane suppressed the early and late discharges at the concentration of 0.5%, 1.0%, 1.5%,and 2.0%. Compared with early discharges, the extent of inhibition of late discharges was wider at the concentration of1%, 1.5 %, and 2.0% of sevoflurane. Conclusion: It is indicated that sevoflurane could suppress the transmission of nociceptive and non-nociceptive stimulation at dorsal horn. The suppression on nociceptive imput is stronger than that on nonnociceptive imput when the concentration of sevoflurane is more than 1%.

  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. Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats

    Science.gov (United States)

    Kim, C-Yoon; Sikkema, William K. A.; Hwang, In-Kyu; Oh, Hanseul; Kim, Un Jeng; Lee, Bae Hwan; Tour, James M.

    2016-01-01

    Background: The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons. Methods: Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery. Results: While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery. Conclusion: In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord. PMID:27656326

  7. Effects of brain-derived neurotrophic factor on synapsin expression in rat spinal cord anterior horn neurons cultured in vitro

    Institute of Scientific and Technical Information of China (English)

    Zhifei Wang; Daguang Liao; Changqi Li

    2010-01-01

    Brain-derived neurotrophic factor(BDNF)promotes synaptic formation and functional maturation by upregulating synapsin expression in cortical and hippocampal neurons.However,it remains controversial whether BDNF affects synapsin expression in spinal cord anterior horn neurons.Wistar rat spinal cord anterior hom neurons were cultured in serum-supplemented medium containing BDNF,BDNF antibody,and Hank's solution for 3 days,and then synapsin I and synaptophysin protein and mRNA expression was detected.Under serum-supplemented conditions,the number of surviving neurons in the spinal cord anterior horn was similar among BDNF,anti-BDNF,and control groups(P > 0.05).Synapsin I and synaptophysin protein and mRNA expressions were increased in BDNF-treated neurons,but decreased in BDNF antibody-treated neurons(P< 0.01).These results indicated that BDNF significantly promotes synapsin I and synaptophysin expression in in vitro-cultured rat spinal cord anterior horn neurons.

  8. Expression of acetylated histone 3 in the spinal cord and the effect of morphine on inflammatory pain in rats

    Institute of Scientific and Technical Information of China (English)

    Hua Li; Changqi Li; Ruping Dai; Xudan Shi; Junmei Xu; Jianyi Zhang; Xinfu Zhou; Zhiyuan Li; Xuegang Luo

    2012-01-01

    In this study, a rat model of inflammatory pain was produced by injecting complete Freund's adjuvant into the hind paw, and the expression of acetylated histone 3 in the spinal cord dorsal horn was examined using immunohistochemical staining.One day following injection, there was a dramatic decrease in acetylated histone 3 expression in spinal cord dorsal horn neurons.However, on day 7, expression recovered in adjuvant-injected rats.While acetylated histone 3 labeling was present in dorsal horn neurons, it was more abundant in astrocytes and microglial cells.The recovery of acetylated histone 3 expression was associated with a shift in expression of the protein from neurons to glial cells.Morphine injection significantly upregulated the expression of acetylated histone 3 in spinal cord dorsal horn neurons and glial cells 1 day after injection, especially in astrocytes, preventing the transient downregulation.Our results indicate that inflammatory pain induces a transient downregulation of acetylated histone 3 in the spinal cord dorsal horn at an early stage following adjuvant injection, and that this effect can be reversed by morphine.Thus, the downregulation of acetylated histone 3 may be involved in the development of inflammatory pain.

  9. 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.

  10. 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

    2016-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.18146.001 PMID:27759565

  11. 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...

  12. Protective effect of sodium valproate on motor neurons in the spinal cord following sciatic nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fei Wu; Danmou Xing; Zhengren Peng; Wusheng Kan

    2006-01-01

    BACKGROUND: Sodium valproate (VPA) is used to be an effective anti-epileptic drug. VPA possesses the characteristics of penetrating rapidly through the blood-brain barrier (BBB) and increasing levels of Bcl-2 and growth cone-associated protein (GAP) 43 in spinal cord.OBJECTIVE: To observe the effect of VPA on Bcl-2 expression and motor neuronal apoptosis in spinal cord of rats following sciatic nerve transection.DESIGN: Randomized controlled experiment.SETTING: Department of Hand Surgery and Microsurgery, Wuhan Puai Hospital.MATERIALS: A total of 30 male healthy SD rats of olean grade and with the body mass of 180-220 g were provided by Experimental Animal Center of Medical College of Wuhan University. Sodium Valproate Tablets were purchases from Hengrui Pharmaceutical Factory, Jiangsu.METHODS: The experiment was performed in the Central Laboratory of Wuhan Puai Hospital and Medical College of Wuhan University from February to May 2006. Totally 30 rats were randomly divided into two groups:treatment group (n =15) and model group (n =15). Longitudinal incision along backside of right hind limbs of rats was made to expose sciatic nerves, which were sharply transected 1 cm distal to the inferior margin of piriform muscle after nerve liberation under operation microscope to establish sciatic nerve injury rat models.Sodium Valproate Tablets were pulverized and diluted into 50 g/L suspension with saline. On the day of operation, the rats in the treatment group received 6 Ml/kg VPA suspension by gastric perfusion, once a day,whereas model group received 10 Ml/kg saline by gastric perfusion, once a day. L4-6 spinal cords were obtained at days 1, 4, 7, 14 and 28 after operation, respectively. Terminal deoxyribonucleotidyl transferase (TdT)-mediated Dutp-biotin nick end labeling (TUNEL) technique and immunohistochemical method (SP method) were used to detect absorbance (A) of neurons with positive Bcl-2 expression. Apoptotic rate of cells (number of apoptotic cells

  13. 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.

  14. The role of calcium in endotoxin-induced release of calcitonin gene-related peptide (CGRP) from rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    唐跃明; 韩启德; 王宪

    1997-01-01

    In the present study, the role of calcium in endotoxin-induced CGRP release was studied. 2 .5-50 μg/mL endotoxin and 1 -10 mmol/L caffeine caused concentration-dependent increase of CGRP release from rat spinal cord in vitro. However, no additive effect could he found when caffeine and endotoxin were concomitantly incubated. By using capsaicin, Ca2+-free medium, Omega-Conotoxin, nifedipine, W-7, ryanodine, MgCl2, Tris-ATP, rutheni-um red, the results indicate that the release of CGRP evoked by endotoxin from the sensory fibers of rat spinal cord is dependent on extracellular calcium. After entering into the cell through the N-type calcium channel, calcium binds to calmodulin, and triggers calcium release from intracellular calcium store by activating the caffeine-sensitive but ryan-odine-insensitive mechanism.

  15. [Effect of embryonic anlage allografts of the rat spinal cord on growth of regenerating fibers of the recipient nerve].

    Science.gov (United States)

    Petrova, E S; Isaeva, E N

    2014-01-01

    A comparative study of the effect of tissue and suspension allografts of an embryonic spinal cord on regeneration of nerve fibers of impaired (by application of a ligature) sciatic nerve in rats was conducted. It was demonstrated that unlike tissue grafts that reach a large volume 21 and 60 days after transplantation, suspension grafts do not inhibit the growth of axons of the recipient to the periphery. It was established that introduction of a suspension of dissociated cells of the spinal cord embryonic anlages (but not fragments of these anlages) into the impaired sciatic nerve in rats results in an increase in the amount of myelinated regenerating nerve fibers of the recipient 60 days after the operation.

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

    Institute of Scientific and Technical Information of China (English)

    Duo Zhang; Xiao-hui Li; Xu Zhai; Xi-jing He

    2015-01-01

    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 cordin vivo. Diffusion tensor imaging technology is a sensitive method to diagnose spinal cord injury; ifber tractography visualizes the white matter ifbers, and directly displays the structural integrity and resultant damage of the ifber 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 coefifcient 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 signiifcantly lower than those in normal rats (P < 0.05); the apparent diffusion coefifcient was signiifcantly increased compared with the normal group (P < 0.05). Following spinal cord transection, fractional anisotropy scores were negatively correlated with apparent diffusion coefifcient values (r = –0.856,P < 0.01), and positively correlated with the average combined scores (r= 0.943,P < 0.01), while apparent diffusion coefifcient values had a negative correlation with the average combined scores (r = –0.949,P < 0.01). Experimental ifndings suggest that, as a non-invasive examination, diffusion tensor magnetic resonance imaging can provide qualita-tive and quantitative information about spinal cord injury. The fractional anisotropy score and apparent diffusion coefifcient have a good correlation with the average combined scores, which relfect functional recovery after spinal cord injury.

  17. Peripheral and spinal 5-HT receptors participate in cholestatic itch and antinociception induced by bile duct ligation in rats

    Science.gov (United States)

    Tian, Bin; Wang, Xue-Long; Huang, Ya; Chen, Li-Hua; Cheng, Ruo-Xiao; Zhou, Feng-Ming; Guo, Ran; Li, Jun-Cheng; Liu, Tong

    2016-01-01

    Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which was induced by common bile duct ligation (BDL) in rats. 5-HT-induced enhanced scratching and antinociception to mechanical and heat stimuli were demonstrated in BDL rats. 5-HT level in the skin and spinal cord was significantly increased in BDL rats. Quantitative RT-PCR analysis showed 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3A, 5-HT5B, 5-HT6, and 5-HT7 were up-regulated in peripheral nervous system and 5-HT1A, 5-HT1F, 5-HT2B, and 5-HT3A were down-regulated in the spinal cord of BDL rats. Intradermal 5-HT2, 5-HT3, and 5-HT7 receptor agonists induced scratching in BDL rats, whereas 5-HT3 agonist did not induce scratching in sham rats. 5-HT1A, 5-HT2, 5-HT3, and 5-HT7 agonists or antagonists suppressed itch in BDL rats. 5-HT1A agonist attenuated, but 5-HT1A antagonist enhanced antinociception in BDL rats. 5-HT2 and 5-HT3 agonists or antagonists attenuated antinociception in BDL rats. Our data suggested peripheral and central 5-HT system dynamically participated in itch and antinociception under cholestasis condition and targeting 5-HT receptors may be an effective treatment for cholestatic itch. PMID:27824106

  18. Quantitative test of responses to thermal stimulation in spinally injured rats using a Peltier thermode: a new approach to study cold allodynia.

    Science.gov (United States)

    Gao, Tianle; Hao, Jing-Xia; Wiesenfeld-Hallin, Zsuzsanna; Xu, Xiao-Jun

    2013-01-30

    In this work, we described a method of testing of responses of spinally injured rats to thermal stimulation (heating and cooling) to the flank area using a Peltier thermode. With a baseline holding temperature at 32°C and the temperature change rate of 0.5°C/s, we measured vocalization thresholds of rats to thermal stimulation in the flank area. While normal rats did not vocalize to temperatures changes ranging from 6°C to 50°C, the spinally injured rats exhibited significantly increased response to cooling with average response temperature above 15°C through the 70 day observation period after spinal cord injury. The response temperature to cooling in spinally injured rats is correlated with the magnitude of responses to cold stimulation scored after ethyl chloride spray and with the response threshold to mechanical stimulation. In contrast, we did not observe an increase in response to warm/heat stimuli. The results showed that ischemic spinal cord injury produced cold, but not heat, allodynia in rats. Furthermore, we showed that it is possible to quantitatively measure response of rats to thermal stimulation on the body using temperature as end points which may aid further studies on mechanisms and treatments of thermal stimulation, particularly cold, evoked pain.

  19. Involvement of spinal somatostatin receptor SST(2A) in inflammation-induced thermal hyperalgesia: ultrastructural and behavioral studies in rats.

    Science.gov (United States)

    Zhao, Jun; Hu, Jiang-Yuan; Zhang, Yu-Qiu; Zhao, Zhi-Qi

    2008-10-01

    Our previous results have shown that somatostatin receptor subtype SST(2A) is responsible for thermal, but not mechanical nociceptive transmission in the rat spinal cord. The present study was undertaken to further examine the ultrastructural localization of SST(2A) receptor in lamina II of the spinal dorsal horn and the role of SST(2A) receptor in thermal hyperalgesia following Complete Freund's Adjuvant (CFA)-induced inflammation. We found that SST(2A) receptors in lamina II are located primarily in postsynaptic dendrites and soma, but not in axons or synaptic terminals. CFA-induced inflammation markedly increased SST(2A) receptor-like immunoreactivity in lamina II. Paw withdrawal latency (PWL) evoked by noxious heating was obviously shortened 1 h after intraplantar injection of CFA, exhibiting thermal hyperalgesia. Pre-blocking SST(2A) activity by intrathecal pre-administration of CYN154806, a broad-spectrum antagonist of SST(2) receptor, or specific antiserum against SST(2A) receptor (anti-SST(2A)) significantly attenuated thermal hyperalgesia in a dose-dependent fashion in CFA-treated rats. But, administration of anti-SST(2A) or CYN154806 after CFA treatment had no effect upon thermal hyperalgesia. Intrathecal application of SST(2A) agonist SOM-14 at different doses prior to CFA treatment did not influence thermal hyperalgesia in inflamed rats, but at a low dose shortened PWL evoked by noxious heating in normal rats. These results suggest that spinal SST(2A) receptors play a key role in triggering the generation, but not maintenance, of thermal hyperalgesia evoked by CFA-induced inflammation. The up-regulation of SST(2A) receptors in the spinal cord may be one of the mechanisms underlying inflammation-induced thermal hyperalgesia.

  20. 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.

  1. Spinal antinociceptive action of amiloride and its interaction with tizanidine in the rat formalin test

    Science.gov (United States)

    Ouyang, Handong; Wang, Peizong; Huang, Wan; Li, Qiang; Nie, Bilin; Zeng, Weian

    2015-01-01

    BACKGROUND: Amiloride has been reported to produce a wide variety of actions, thereby affecting several ionic channels and a multitude of receptors and enzymes. Intrathecal α2-adrenergic receptor agonists produce pronounced analgesia, and amiloride modulates α2-adrenergic receptor agonist binding and function, acting via the allosteric site on the α2A-adrenergic receptor. OBJECTIVES: To investigate the antinociceptive interaction of intrathecal amiloride and the α2-adrenoceptor agonist tizanidine using a rat formalin test. METHODS: Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters and were tested for paw flinching using formalin injection. Biphasic painful behaviour was recorded. Amiloride, tizanidine or an amiloride-tizanidine mixture was administered 10 min before formalin injection. To characterize any interactions, isobolographic analysis was performed. The effects of a pretreatment using intrathecally administered yohimbine was also tested. RESULTS: Intrathecally administered amiloride (12.5 μg to 100 μg) and tizanidine (0.5 μg to 5 μg), given separately, produced a significant dose-related suppression of the biphasic responses in the formalin test. Isobolographic analysis revealed that the combination of intrathecal amiloride and tizanidine synergistically reduced phase I and II activities. Intrathecally administered yohimbine antagonized or attenuated the antinociceptive effect of amiloride, tizanidine and the amiloride-tizanidine mixture. Intrathecally administered amiloride synergistically interacts with tizanidine to reduce the nociceptive response in the formalin test, most likely by activating α2-adrenoceptors in the spinal cord. CONCLUSIONS: Although intrathecal tizanidine produced pronounced analgesia, antinociceptive doses of intrathecal tizanidine also produced several side effects, including bradycardia and sedation. Amiloride produced antinociceptive action against the thermal nociceptive test without side

  2. NGF message and protein distribution in the injured rat spinal cord.

    Science.gov (United States)

    Brown, Arthur; Ricci, Mary-Jo; Weaver, Lynne C

    2004-07-01

    Nerve growth factor (NGF) content of the spinal cord is increased after cord injury. NGF can cause central sprouting of sensory fibers after spinal cord injury (SCI), leading to autonomic dysfunction and pain. NGF also can promote the death of oligodendroglia after SCI. Knowing the source of intraspinal NGF would benefit strategies for minimizing abnormal plasticity and cell death after SCI. We identified these sources, using RNA in situ hybridization to detect NGF mRNA and double-labeling immunocytochemistry for NGF and cell-marking antigens. In uninjured and sham-injured rats, we identified NGF mRNA in leptomeningeal cells and in neurons in the intermediate grey matter, whereas NGF protein was observed only in leptomeningeal cells. At 3-7 days after transection or clip-compression SCI, NGF mRNA and protein were expressed in the lesion and throughout the intermediate grey matter and white matter rostral and caudal to the injury site. Transection-SCI was used to permit comparisons to previous studies; clip-compression injury was used as a more clinically relevant model. mRNA and protein in adjacent sections were expressed in ramified microglia, astrocytes, intermediate grey neurons, pial cells, and leptomeningeal and Schwann cells in the lateral white matter and the lesion site. Rounded macrophages in the lesion were immunoreactive (Ir) for NGF, but the cells expressing NGF mRNA were not in the same areas of the lesion and were not stained by a macrophage marker. Our data demonstrate that glia, neurons, meningeal cells and Schwann cells but not macrophages contribute to the increased intraspinal NGF after SCI.

  3. Measures of bulbar and spinal motor function, muscle innervation, and mitochondrial function in ALS rats.

    Science.gov (United States)

    Smittkamp, Susan E; Spalding, Heather N; Brown, Jordan W; Gupte, Anisha A; Chen, Jie; Nishimune, Hiroshi; Geiger, Paige C; Stanford, John A

    2010-07-29

    Symptom onset in amyotrophic lateral sclerosis (ALS) may occur in the muscles of the limbs (spinal onset) or those of the head and neck (bulbar onset). Most preclinical studies have focused on spinal symptoms, despite the prevalence of and increased morbidity and mortality associated with bulbar disease. We measured lick rhythm and tongue force to evaluate bulbar disease in the SOD1-G93A rat model of familial ALS. Body weight and grip strength were measured concomitantly. Testing spanned the early (maturation), middle (pre-symptomatic), and late (symptomatic and end-stage) phases of the disease. We measured a persistent tongue motility deficit that became apparent in the early phase of the disease, providing behavioral evidence of bulbar pathology. At end-stage, however, cytochrome oxidase (CO) activity was normal in the hypoglossal nucleus, and in the tongue, neuromuscular innervation, citrate synthase (CS) protein levels and activity, and uncoupling protein 3 (UCP3) protein levels remained unchanged. Interestingly, significant denervation and atrophy were evident in the end-stage sternomastoid muscle, providing peripheral anatomical evidence of bulbar pathology. Changes in body weight and grip strength occurred in the late phase of the disease. Extensive atrophy and denervation were observed in the end-stage gastrocnemius muscle. In contrast to our findings in the tongue, CS protein levels were decreased in the extensor digitorum longus (EDL) and soleus, although CS activity was maintained or increased. UCP3 protein was decreased also in the EDL. These data provide evidence of differential effects in muscles that were more or less affected by disease.

  4. Long-term viral brain-derived neurotrophic factor delivery promotes spasticity in rats with a cervical spinal cord hemisection

    Directory of Open Access Journals (Sweden)

    Karim eFouad

    2013-11-01

    Full Text Available We have recently reported that rats with spinal cord injury (SCI that received a combinatorial treatment, including viral BDNF delivery in the spinal cord, did not only show enhanced axonal regeneration, but also deterioration of hindlimb motor function. By demonstrating that BDNF over-expression can trigger spasticity-like symptoms in another rat model of spinal cord injury (SCI, we proposed a causal relationship between the observed spasticity-like symptoms (i.e., resistance to passive range of motion and the over-expression of BDNF. The current study was originally designed to evaluate a comparable combined treatment to rats with cervical SCI to improve motor recovery. Once again we found similar signs of spasticity, involving clenching of the paws and wrist flexion. Using electromyographic measurements changed the focus of the study and explored whether this spasticity like symptom is directly related to the over-expression of BDNF by administering a BDNF antagonist. In an acute experiment this treatment gradually diminished the resistance to overcome forelimb flexion. Thus, we conclude that neuro-excitatory effects of chronic BDNF delivery together with diminished descending control after SCI can result in adverse effects.

  5. 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.

  6. GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats

    Institute of Scientific and Technical Information of China (English)

    Yi-Ning Sun; Jin-Yan Luo; Zhi-Ren Rao; Li Lan; Li Duan

    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, P<0.05). The density of GFAP in MVZ was significantly higher after 3 d of TNBS administration (34.3±2.5, P<0.05). After 28 d of TNBS administration,the density of GFAP in the spinal cord and MVZ decreased and became comparable to that of the controls (18.0±4.9,14.6±6.4, P>0.05).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.

  7. Calcitonin gene-related peptide (CGRP and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

    Directory of Open Access Journals (Sweden)

    Eftekhari Sajedeh

    2011-11-01

    Full Text Available Abstract Background Calcitonin gene-related peptide (CGRP has a key role in migraine pathophysiology and is associated with activation of the trigeminovascular system. The trigeminal ganglion, storing CGRP and its receptor components, projects peripheral to the intracranial vasculature and central to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal trigeminal nucleus (STN and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR and receptor activity modifying protein 1 (RAMP1 - in human and rat STN and at the C1-level, using a set of newly well characterized antibodies. In addition, double-stainings with CGRP and myelin basic protein (MBP, myelin, synaptophysin (synaptic vesicles or IB4 (C-fibers in general were performed. Results In the STN, the highest density of CGRP immunoreactive fibers were found in a network around fiber bundles in the superficial laminae. CLR and RAMP1 expression were predominately found in fibers in the spinal trigeminal tract region, with some fibers spanning into the superficial laminae. Co-localization between CGRP and its receptor components was not noted. In C1, CGRP was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal microscopy. Conclusions This study demonstrates the detailed expression of CGRP and its receptor components within STN in the brainstem and in the spinal cord at C1

  8. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    Science.gov (United States)

    1991-12-01

    begun. Diazepam , chlordiazepoxide , morphine, or naloxone was administered I.P. prior to placing the rat in the tailshock apparatus. Four different...by chlordiazepoxide and diazepam . Drug Dev. Res., 5, 185-193 (1985). Gardner, C.R., and Budhram, P. Effects of agents which interact with central... diazepam , and chlorpromazine, attenuate these vocalizations. Recent work by Kaltwasser (1990) examined the occurrence of vocalizations in response to

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

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    Marcus Vinicius Amaral Barreto

    2015-06-01

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

  10. Effects of electroacupuncture on c-Fos expression in the spinal cord and brain of rats with chronic visceral hypersensitivity

    Institute of Scientific and Technical Information of China (English)

    Xiaomei Wang; Huirong Liu; Guanghong Ding; Yunfei Chen; Huangan Wu; Na Li; Enhua Zhou; Xiudi Qin; Lingsong Yuan

    2009-01-01

    BACKGROUND: Visceral hypersensitivity is the main cause of irritable bowel syndrome, c-Fos is a marker of visceral hypersensitivity in the central nervous system. Electroacupuncture can relieve chronic visceral hypersensitivity in rats, but the mechanism is still unknown.OBJECTIVE: To identify c-Fos expression in the spinal cord and cerebral cortex of rats with chronic visceral hypersensitivity, and to test the effects of electroacupuncture on pain sensitivity in rats with chronic visceral hypersensitivity.DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Animal Experimental Center, Shanghai University of Traditional Chinese Medicine, from January to April, 2007.MATERIALS: A total of 24 neonatal, male, Sprague Dawley rats, aged five days old, were equally and randomly assigned into a normal group, a model group, and an electroacupuncture group. Rabbit anti-rat c-Fos antibody and Evision secondary antibody kits (Sigma, USA), diaminobenzidine kit (Dako, Denmark), and an LD202H electroacupuncture apparatus (Huawei, Beijing, China) were used in this study.METHODS: Neonatal rats from the model and electroacupuncture groups were used to establish rat models of chronic visceral hypersensitivity by the saccule stimulation method. After model establishment, 0.25 mm diameter electric needles were inserted into Tianshu (ST 25) and Shangjuxu (ST37) at a depth of approximately 0.5 cm, with an square wave (alternating current frequency at 100/20 Hz, amplitude ranged 0.2-0.6 ms, intensify at 1 mA) once for 20 minutes, once a day, for seven days. Rats in the normal and model groups were not treated.MAIN OUTCOME MEASURES: Following 7 days of treatment, c-Fos expression in the spinal cord and cerebral cortex was detected by immunohistochemistry. After the first electroacupuncture treatment, abdominal withdrawal reflex scores were investigated to evaluate the pain threshold for chronic visceral hypersensitivity in rats.RESULTS: Visceral

  11. Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats.

    Science.gov (United States)

    Li, Zhen; Lu, Yun-Fei; Li, Chun-Li; Wang, Yan; Sun, Wei; He, Ting; Chen, Xue-Feng; Wang, Xiao-Liang; Chen, Jun

    2014-07-01

    Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception.

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

    Directory of Open Access Journals (Sweden)

    L.P. Rodrigues

    2012-01-01

    Full Text Available 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.

  14. The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model.

    Science.gov (United States)

    Geis, Christian; Ritter, Christian; Ruschil, Christoph; Weishaupt, Andreas; Grünewald, Benedikt; Stoll, Guido; Holmoy, Trygve; Misu, Tatsuro; Fujihara, Kazuo; Hemmer, Bernhard; Stadelmann, Christine; Bennett, Jeffrey L; Sommer, Claudia; Toyka, Klaus V

    2015-03-01

    Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesions at the site of application of anti-AQP4 IgG. Somatosensory evoked potential amplitudes were reduced in symptomatic animals corroborating the observed functional impairment. Spinal cord histology showed specific IgG deposition in the grey and white matter in the affected areas. We did not find inflammatory cell infiltration nor activation of complement in spinal cord areas of immunoglobulin deposition. Moreover, destructive lesions showing axon or myelin damage and loss of astrocytes and oligodendrocytes were all absent. Immunoreactivity to AQP4 and to the excitatory amino acid transporter 2 (EAAT2) was markedly reduced whereas immunoreactivity to the astrocytic marker glial fibrillary acid protein (GFAP) was preserved. The expression of the NMDA-receptor NR1 subunit was downregulated in areas of IgG deposition possibly induced by sustained glutamatergic overexcitation. Disease signs and histopathology were reversible within weeks after stopping injections. We conclude that in vivo application of ABs directed at AQP 4 can induce a reversible spinal cord disease in recipient rats by inducing distinct histopathological abnormalities. These findings may be the experimental correlate of "penumbra-like" lesions recently reported in NMO patients adjacent to effector-mediated tissue damage.

  15. Identification of interneurons activated at different inclines during treadmill locomotion in adult rats.

    Science.gov (United States)

    Tillakaratne, Niranjala J K; Duru, Paul; Fujino, Hidemi; Zhong, Hui; Xiao, Mei Si; Edgerton, V Reggie; Roy, Roland R

    2014-12-01

    By using c-fos as an activity-dependent marker, we identified the cholinergic interneurons around the central canal and lumbar interneurons throughout the gray matter that were activated after a 30-min bout of quadrupedal treadmill stepping at a 0° or 25° incline in adult rats. Increased loading (elevated treadmill incline) imposed during treadmill stepping activated more cholinergic interneurons in the proximity of the central canal, i.e., central canal cluster cells and partition neurons. Since cholinergic central canal cells are thought to modulate motoneuron excitability, these data suggest that increased load during stepping may increase motoneuronal activity through activating more cholinergic central canal cells. We identified the muscle-specific motoneurons and afferent terminals in the spinal cord by injecting cholera toxin subunit B in the soleus and tibialis anterior muscles. The number of interneurons in lumbar segments L4 (tibialis anterior) and L5 (soleus) was higher in both groups that stepped on the treadmill compared with control and was highest in rats that stepped at a 25° incline. In a majority of laminae, the distribution of total and muscle-specific activated interneurons was highest in the 25° incline group and lowest in the control group for both muscles. These data could reflect increased peripheral (proprioceptive) input as well as supraspinal drive associated with stepping and demonstrate the differences in 1) the activation of cholinergic interneurons near the central canal and 2) the laminar and segmental location of interneurons throughout the gray matter that play a role in generating stepping under different loading conditions in adult rats.

  16. Mild moxibustion decreases the expression of prokineticin 2 and prokineticin receptor 2 in the colon and spinal cord of rats with irritable bowel syndrome.

    Science.gov (United States)

    Zhou, Cili; Zhao, Jimeng; Wu, Luyi; Huang, Renjia; Shi, Yin; Wang, Xiaomei; Liao, Wen; Hong, Jue; Liu, Shimin; Wu, Huangan

    2014-01-01

    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.

  17. 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.

  18. Viabilidade de células do sistema nervoso central fetal no tratamento da lesão medular em ratos Viability of fetal central nervous system cells in the treatment of spinal cord injury in rats

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    Alexandre Fogaça Cristante

    2010-01-01

    Full Text Available OBJETIVOS: Propor um modelo experimental de transplante de células do sistema nervoso fetal de ratos Wistar para o sítio de lesão medular de ratos adultos que permitisse sua sobrevivência e integração para possibilitar protocolos de pesquisa que identificarão outros fatores de regeneração e recuperação funcional pós trauma raquimedular. MÉTODOS: Vinte ratos adultos foram submetidos a laminectomia, e lesão de 5mm de hemimedula realizada com auxílio de microscópio óptico. Quinze deste ratos tiveram seu sítio de lesão medular transplantado com células do sistema nervoso central de fetos de rato; os ratos foram monitorados por 2 dias e tiveram sua coluna vertebral extraída para análise histológica. RESULTADOS: Evidenciou-se que em 60% dos casos as células transplantadas permaneciam viáveis no sítio da lesão e que a reação inflamatória no grupo transplantado era sempre maior que no grupo controle. CONCLUSÃO: O presente trabalho demonstrou a possibilidade de contar com o modelo de pesquisa para transplante de células fetais que permanecem viáveis 2 dias após seu implante.OBJECTIVE: To propose an experimental model for transplantation of fetal cells from the nervous system of Wistar rats to the site of spinal cord injury in adult rats, to enable their survival and integration for research protocols that identify other factors of regeneration and functional recovery following spinal cord trauma. METHODS: Twenty adult rats were submitted to laminectomy and a 5mm incision was made, using an optical microscope, In fifteen of these rats, the site of the spinal cord lesion was transplanted with cells from the fetal rat central nervous system; the rats were monitored for two days, then the spinal cord was removed for histological analysis. RESULTS: In 60% of cases, the transplanted cells remained viable in the site of the lesion; the inflammatory response in the transplanted group was always greater than in the control group

  19. Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Cemil, Berker; Gokce, Emre Cemal; Kahveci, Ramazan; Gokce, Aysun; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Erdogan, Bulent; Kosem, Bahadir

    2016-06-01

    Garlic has been used as a food as well as a component of traditional medicine. Aged garlic extract (AGE) is claimed to promote human health through antioxidant/anti-inflammatory activities with neuroprotective effects. We evaluated the possible beneficial effect of AGE neurologically, pathologically, ultrastructurally, and biochemically in a spinal cord ischemia-reperfusion (I/R) model of rats. Twenty-four Sprague-Dawley rats were divided into three groups: sham (no I/R), I/R, and AGE (I/R+AGE); each group consisted of eight animals. Animals were evaluated neurologically with the Basso, Beattie, and Bresnahan (BBB) scoring system. The spinal cord tissue samples were harvested for pathological and ultrastructural examinations. Oxidative products (Malondialdehyde, nitric oxide), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), inflammatory cytokines (tissue tumor necrosis factor alpha, interleukin-1), and caspase-3 activity were analyzed. The AGE group had significantly higher BBB scores than the I/R group. Pathologically, AGE group revealed reduced degree of ischemia and spinal cord edema. Ultrastructural results also showed preservation of tissue structure in the AGE group. Oxidative product levels of the I/R group were significantly higher than both the other groups, and antioxidant enzyme levels of AGE group were significantly higher than the I/R group. There was also significant difference between the sham and AGE groups in terms of total antioxidant enzyme levels. Furthermore, AGE treatment significantly reduced the inflammatory cytokines and caspase-3 activity than the I/R group. This study demonstrates the considerable neuroprotective effect of AGE on the neurological, pathological, ultrastructural, and biochemical status of rats with I/R-induced spinal cord injury.

  20. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  1. Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα.

    Science.gov (United States)

    Zhang, Yanan; Song, Chengwei; Li, Haiou; Hou, Jingdong; Li, Dongliang

    2016-06-01

    Obesity is a risk factor for several pain syndromes and is associated with increased pain sensitivity. Evidence suggests that obesity causes the downregulation of peroxisome proliferator‑activated receptor (PPAR)α in the spinal cord, contributing to augmented peripheral edema and inflammatory hyperalgesia. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, has been shown to upregulate PPARα in the peripheral tissues of obese animals. The present study hypothesized that UA prevents augmented peripheral inflammation and inflammatory hyperalgesia in obesity by restoring downregulated spinal PPARα. The present study demonstrated that Sprague‑Dawley rats fed a high‑fat diet (HFD) for 12 weeks developed obesity and metabolic disorder. Following carrageenan injection, the HFD rats exhibited increased thermal hyperalgesia and paw edema, compared with the rats fed a low‑fat diet. Molecular investigations revealed that the HFD rats exhibited decreased PPARα activity, and exaggerated expression of inflammatory mediators and nuclear factor‑kB activity in the spinal cord in response to carrageenan. Oral administration of UA ameliorated obesity and metabolic disorder, and prevented increased thermal hyperalgesia and paw edema in the HFD rats. Additionally, UA normalized PPARα activity and inhibited the exaggerated spinal cord inflammatory response to carrageenan. Although the knockdown of spinal PPARα with small interfering RNA following the administration of UA did not alter obesity or metabolic parameters, it eradicated the beneficial effects of UA on thermal hyperalgesia and paw edema, and reversed the spinal cord inflammatory response. These results suggested that the systemic administration of UA inhibited the exaggerated spinal cord inflammatory response to peripheral inflammatory stimulation in HFD‑induced obesity by restoring downregulated spinal PPARα, preventing peripheral inflammation and inflammatory hyperalgesia. UA may be a

  2. 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

  3. Is There a Role for an Ultrasonic Bone-Cutting Device in Adult Spinal Deformity: A Safety and Reproducibility Study

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    Pooria Hosseini

    2016-07-01

    Full Text Available Background Ultrasonic bone-cutting devices (UBC are new cutting tools and have low frequency ultrasonic blade. There is limited data on the safety and effectiveness of using ultrasonic bone-cutting devices in the treatment of adult spinal deformities (ASD. Objectives This Retrospective review of prospectively collected data was designed to determine if the use of an ultrasonic bone-cutting device is safe in the adult spinal deformity population and to compare its effectiveness in blood loss reduction by using a comparison group from a prospective multicenter database of adult spinal deformity patients. Methods Nineteen consecutive surgical ASD cases in which the UBC was used were compared with 19 propensity-matched cases from a prospective ASD database in which conventional bone cutting instruments were used. The two groups were matched based on age, ASA, and number of levels fused posteriorly. The need for blood transfusion, volume of blood transfusion if required, estimated blood loss (EBL, and total operating time were compared between the two groups. Data were analyzed using non-parametric Mann-Whitney U test and Spearman’s Correlation test (P < 0.05. Results There was no statistically significant difference in any measured parameter between the two groups. While the EBL difference between the two groups (925 mL in the study group vs. 1628 mL in the control group was not statistically significant (P = 0.142, the 703 mL difference is clinically relevant. In addition, no complications directly related to the use of the UBC were reported. Conclusions The use of an ultrasonic bone-cutting device was shown to be safe and effective in the surgical treatment of ASD. It resulted in a 43% reduction in EBL, which was clinically relevant and statistically non-significant, without the addition of any complications. We did not identify statistical differences in transfusion rates, EBL, or operative time, which may be due to our small sample size.

  4. Imaging corticospinal tract connectivity in injured rat spinal cord using manganese-enhanced MRI

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