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

Science.gov (United States)

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

2018-02-01

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

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

Science.gov (United States)

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

2018-01-01

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

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

DEFF Research Database (Denmark)

Lin, X; Liu, W; Ding, Ming

2016-01-01

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

Zinc-enriched (ZEN) terminals in mouse spinal cord

DEFF Research Database (Denmark)

Jo, S M; Danscher, G; Schrøder, H D

2000-01-01

The general distribution of zinc-enriched (ZEN) terminals in mouse spinal cord was investigated at light microscopic level by means of zinc transporter-3 immunohistochemistry (ZnT3(IHC)) and zinc selenium autometallography (ZnSe(AMG)). Staining for ZnT3(IHC) corresponded closely to the Zn...... dendrites. These ZEN terminals in the ventral horn were in general larger than those in the dorsal horn. This is the first description of the pattern of ZEN terminals in mouse spinal cord....

Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

Science.gov (United States)

Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

2012-05-01

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.

MR diffusion tensor imaging in the evaluation of neural progenitor cells transplantation to acute injured canine spinal cord

International Nuclear Information System (INIS)

Wang Xiaoying; Tan Ke; Ni Shilei; Bao Shengde; Jiang Xuexiang

2006-01-01

Objective: To observe the effect of transplantation of telomerase immortalized human neural progenitor cells to acute injured canine spinal cord by using MR diffusion tensor imaging (DTI). Methods: Telomerase immortalized human neural progenitor cells with expression of green fluorescent protein were prepared for transplantation. Eight adult canines with left spinal cord hemisection at the level of T13 were examined by MR diffusion tensor imaging four times sequentially: prior to injury, one week after injury, one week after transplantation (two weeks after injury), and four weeks after transplantation. Results: The ADC values of the injured spinal cord were (1.00 ± 0.15) x 10 -3 mm 2 /s, (1.65 ± 0.45) x 10 -3 mm 2 /s, (1.44 ± 0.48) xl0 -3 mm 2 /s, and (1.43 ± 0.26) x 10 -3 mm 2 /s, respectively. There was statistically significant difference between the data obtained at different times (F= 6.038, P=0.005). The FA values of the injured spinal cord were 0.59±0.11, 0.30±0.17, 0.36±0.25, and 0.34±0.11, respectively. There was also statistically significant difference between the data obtained at different times (F=5.221, P=0.009). The ADC values of the intact spinal cord were (1.01±0.17) x 10 -3 mm 2 /s, (1.32±0.06) x 10 -3 mm 2 /s, (1.10±0.24) x 10 -3 mm 2 /s, and (1.14±0.22) x 10 -3 mm 2 /s, respectively. There was no statistically significant difference between the data obtained at different times (F=1.303, P=0.306). The FA values of the intact spinal cord were 0.60 ± 0.09, 0.38 ± 0.25, 0.46 ± 0.15, and 0.50 ± 0.21, respectively. There was also no statistically significant difference between the data obtained at different times (F=2.797, P=0.072). Conclusion: DTI can provide useful information for spinal cord injury and regeneration in experimental spinal cord injury. (authors)

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

International Nuclear Information System (INIS)

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

1994-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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.)

Body temperature responses in spinal cord injured individuals during exercise in the cold and heat.

NARCIS (Netherlands)

Boot, C.R.L.; Binkhorst, R.A.; Hopman, M.T.E.

2006-01-01

The aim of this study was to assess the effect of arm exercise on the heat balance in spinal cord-injured (SCI) individuals with complete lesions at ambient temperatures of 10 and 35 degrees C. Four SCI with a high lesion (> or = T6) (SCI-H), seven with a low lesion (< T6) (SCI-L), and ten

Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

Science.gov (United States)

Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

2010-01-01

Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

Glycoconjugates distribution during developing mouse spinal cord motor organizers.

Science.gov (United States)

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

2015-01-01

The aim of this research was to study the distribution and changes of glycoconjugates particularly their terminal sugars by using lectin histochemistry during mouse spinal cord development. Formalin-fixed sections of mouse embryo (10-16 fetal days) were processed for lectin histochemical method. In this study, two groups of horseradish peroxidase-labeled specific lectins were used: N-acetylgalactosamine, including Dolichos biflorus, Wisteria floribunda agglutinin (WFA), Vicia villosa, Glycine max as well as focuse-binding lectins, including tetragonolobus, Ulex europaeus, and Orange peel fungus (OFA). All sections were counterstained with alcian blue (pH 2.5). Our results showed that only WFA and OFA reacted strongly with the floor plate cells from early to late embryonic period of developing spinal cord. The strongest reactions were related to the 14, 15, and 16 days of tissue sections incubated with OFA and WFA lectins. The present study demonstrated that cellular and molecular differentiation of the spinal cord organizers is a wholly regulated process, and α-L-fucose, α-D-GalNAc, and α/β-D-GalNAc terminal sugars play a significant role during the prenatal spinal cord development.

Inhibitory zinc-enriched terminals in mouse spinal cord

DEFF Research Database (Denmark)

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

2001-01-01

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

Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.

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Abel Torres-Espín

Full Text Available Transplantation of bone marrow derived mesenchymal stromal cells (MSC or olfactory ensheathing cells (OEC have demonstrated beneficial effects after spinal cord injury (SCI, providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI.

Artificial gait in complete spinal cord injured subjects: how to assess clinical performance

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Karla Rocha Pithon

2015-02-01

Full Text Available Objective Adapt the 6 minutes walking test (6MWT to artificial gait in complete spinal cord injured (SCI patients aided by neuromuscular electrical stimulation. Method Nine male individuals with paraplegia (AIS A participated in this study. Lesion levels varied between T4 and T12 and time post injured from 4 to 13 years. Patients performed 6MWT 1 and 6MWT 2. They used neuromuscular electrical stimulation, and were aided by a walker. The differences between two 6MWT were assessed by using a paired t test. Multiple r-squared was also calculated. Results The 6MWT 1 and 6MWT 2 were not statistically different for heart rate, distance, mean speed and blood pressure. Multiple r-squared (r2 = 0.96 explained 96% of the variation in the distance walked. Conclusion The use of 6MWT in artificial gait towards assessing exercise walking capacity is reproducible and easy to apply. It can be used to assess SCI artificial gait clinical performance.

Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

Science.gov (United States)

Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

2014-01-01

Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord. PMID:25374590

Locomotor recovery after spinal cord hemisection/contusion injures in bonnet monkeys: footprint testing--a minireview.

Science.gov (United States)

Rangasamy, Suresh Babu

2013-07-01

Spinal cord injuries usually produce loss or impairment of sensory, motor and reflex function below the level of damage. In the absence of functional regeneration or manipulations that promote regeneration, spontaneous improvements in motor functions occur due to the activation of multiple compensatory mechanisms in animals and humans following the partial spinal cord injury. Many studies were performed on quantitative evaluation of locomotor recovery after induced spinal cord injury in animals using behavioral tests and scoring techniques. Although few studies on rodents have led to clinical trials, it would appear imperative to use nonhuman primates such as macaque monkeys in order to relate the research outcomes to recovery of functions in humans. In this review, we will discuss some of our research evidences concerning the degree of spontaneous recovery in bipedal locomotor functions of bonnet monkeys that underwent spinal cord hemisection/contusion lesions. To our knowledge, this is the first report to discuss on the extent of spontaneous recovery in bipedal locomotion of macaque monkeys through the application of footprint analyzing technique. In addition, the results obtained were compared with the published data on recovery of quadrupedal locomotion of spinally injured rodents. We propose that the mechanisms underlying spontaneous recovery of functions in spinal cord lesioned monkeys may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Moreover, based on analysis of motor functions observed in locomotion in these subjected monkeys, we understand that spinal automatism and development of responses by afferent stimuli from outside the cord could possibly contribute to recovery of paralyzed hindlimbs. This report also emphasizes the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed

Decerebrate mouse model for studies of the spinal cord circuits

DEFF Research Database (Denmark)

Meehan, Claire Francesca; Mayr, Kyle A; Manuel, Marin

2017-01-01

The adult decerebrate mouse model (a mouse with the cerebrum removed) enables the study of sensory-motor integration and motor output from the spinal cord for several hours without compromising these functions with anesthesia. For example, the decerebrate mouse is ideal for examining locomotor be......, which is ample time to perform most short-term procedures. These protocols can be modified for those interested in cardiovascular or respiratory function in addition to motor function and can be performed by trainees with some previous experience in animal surgery....

Protein composition and synthesis in the adult mouse spinal cord

International Nuclear Information System (INIS)

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

1983-01-01

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

Management of Sexual Disorders in Spinal Cord Injured Patients

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Alexander R Vaccaro

2012-05-01

Full Text Available Spinal cord injured (SCI patients have sexual disorders including erectile dysfunction (ED, impotence, priapism, ejaculatory dysfunction and infertility. Treatments for erectile dysfunction include four steps. Step 1 involves smoking cessation, weight loss, and increasing physical activity. Step 2 is phosphodiesterase type 5 inhibitors (PDE5I such as Sildenafil (Viagra, intracavernous injections of Papaverine or prostaglandins, and vacuum constriction devices. Step 3 is a penile prosthesis, and Step 4 is sacral neuromodulation (SNM. Priapism can be resolved spontaneously if there is no ischemia found on blood gas measurement or by Phenylephrine. For anejaculatory dysfunction, massage, vibrator, electrical stimulation and direct surgical biopsy can be used to obtain sperm which can then be used for intra-uterine or in-vitro fertilization. Infertility treatment in male SCI patients involves a combination of the above treatments for erectile and anejaculatory dysfunctions. The basic approach to and management of sexual dysfunction in female SCI patients are similar as for men but do not require treatment for erectile or ejaculatory problems.

Distributed plasticity of locomotor pattern generators in spinal cord injured patients.

Science.gov (United States)

Grasso, Renato; Ivanenko, Yuri P; Zago, Myrka; Molinari, Marco; Scivoletto, Giorgio; Castellano, Vincenzo; Macellari, Velio; Lacquaniti, Francesco

2004-05-01

Recent progress with spinal cord injured (SCI) patients indicates that with training they can recover some locomotor ability. Here we addressed the question of whether locomotor responses developed with training depend on re-activation of the normal motor patterns or whether they depend on learning new motor patterns. To this end we recorded detailed kinematic and EMG data in SCI patients trained to step on a treadmill with body-weight support (BWST), and in healthy subjects. We found that all patients could be trained to step with BWST in the laboratory conditions, but they used new coordinative strategies. Patients with more severe lesions used their arms and body to assist the leg movements via the biomechanical coupling of limb and body segments. In all patients, the phase-relationship of the angular motion of the different lower limb segments was very different from the control, as was the pattern of activity of most recorded muscles. Surprisingly, however, the new motor strategies were quite effective in generating foot motion that closely matched the normal in the laboratory conditions. With training, foot motion recovered the shape, the step-by-step reproducibility, and the two-thirds power relationship between curvature and velocity that characterize normal gait. We mapped the recorded patterns of muscle activity onto the approximate rostrocaudal location of motor neuron pools in the human spinal cord. The reconstructed spatiotemporal maps of motor neuron activity in SCI patients were quite different from those of healthy subjects. At the end of training, the locomotor network reorganized at both supralesional and sublesional levels, from the cervical to the sacral cord segments. We conclude that locomotor responses in SCI patients may not be subserved by changes localized to limited regions of the spinal cord, but may depend on a plastic redistribution of activity across most of the rostrocaudal extent of the spinal cord. Distributed plasticity underlies

Spinal Cord Diseases

Science.gov (United States)

Your spinal cord is a bundle of nerves that runs down the middle of your back. It carries signals back ... of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such ...

Spatial and temporal expression levels of specific microRNAs in a spinal cord injury mouse model and their relationship to the duration of compression.

Science.gov (United States)

Ziu, Mateo; Fletcher, Lauren; Savage, Jennifer G; Jimenez, David F; Digicaylioglu, Murat; Bartanusz, Viktor

2014-02-01

MicroRNAs, a class of small nonprotein-coding RNAs, are thought to control gene translation into proteins. The latter are the ultimate effectors of the biochemical cascade occurring in any physiological and pathological process. MicroRNAs have been shown to change their expression levels during injury of spinal cord in contusion rodent models. Compression is the most frequent mode of damage of neural elements in spinal cord injury. The cellular and molecular changes occurring in the spinal cord during prolonged compression are not very well elucidated. Understanding the underlying molecular events that occur during sustained compression is paramount in building new therapeutic strategies. The purpose of our study was to probe the relationship between the expression level changes of different miRNAs and the timing of spinal cord decompression in a mouse model. A compression spinal cord injury mouse model was used for the study. A laminectomy was performed in the thoracic spine of C57BL/6 mice. Then, the thecal sac was compressed to create the injury. Decompression was performed early for one group and it was delayed in the second group. The spinal cord at the epicenter of the injury and one level rostral to it were removed at 3, 6, and 24 hours after trauma, and RNA was extracted. Expression levels of six different microRNAs and the relationship to the duration of compression were analyzed. This work was supported in part by the University Research Council Grants Program at the University of Texas Health Science Center San Antonio (Grant 130267). There are no specific conflicts of interest to be disclosed for this work. Expression levels of microRNAs in the prolonged compression of spinal cord model were significantly different compared with the expression levels in the short duration of compression spinal cord injury model. Furthermore, microRNAs show a different expression pattern in different regions of the injured spinal cord. Our findings demonstrate that

Guillain-Barre syndrome: A possibility in a spinal cord injured patient

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Jagatsinh Yogendrasinh

2007-01-01

Full Text Available A 28-year-old male had paraplegia as a result of fracture dislocation of T12/L1 six years ago. He was functioning independently until four weeks ago, when he started complaining of trunkal paraesthesia which later progressed to include the upper extremities. The initial diagnosis was that of posttraumatic syringomyelia (PTS. While awaiting the MRI scan he developed weakness of upper limbs. The weakness restricted his self-care activities including transfers. The MRI did not show any evidence of syringomyelia. Neurological consultation and assessment yielded provisional diagnosis of Guillain-Barre syndrome (GBS. The patient was treated with immunoglobulins and regained 90% of his previous neurological status. This case is reported to raise awareness among clinicians to include the possibility of the GBS in the differential diagnosis of progressive neurological loss on top of existing neurological deficiency in spinal cord injured patients.

Use of a special airbed for transporting injured persons

Energy Technology Data Exchange (ETDEWEB)

Hacker, R

1981-04-01

A description is given of a special airbed for the purpose of transporting injured persons, especially those with injuries to the spinal column. This special airbed moulds itself to the shape of the injured party. (In German)

Correlation of sequential MR imaging of the injured spinal cord with prognosis

International Nuclear Information System (INIS)

Takahashi, Mutsumasa; Izunaga, Hiroshi; Sato, Ryuichiro; Shinzato, Jintetsu; Korogi, Yukunori; Yamashita, Yasuyuki; Sakae, Terumi

1993-01-01

Forty-nine patients with acute spinal cord injuries were studied sequentially with MR imaging by using 0.5 Tesla superconductive units, and sequential MR changes were correlated with the prognosis of the patients. MR images were obtained within one week of the injury and then every two to six months when possible. The Frankel classification of neurologic function was correlated with MR findings. The most frequently observed types of signal intensity patterns on MR imaging were type 0 (isointensity on both T 1 - and T 2 -weighted images) and type I (isointensity on T 1 - and hyperintensity on T 2 -weighted images). In subsequent subacute and chronic stages, type II (hypointensity on T 1 and hyperintensity on T 2 ) was most frequently observed. The evolution of type 0 was to types I and II, whereas type I usually turned into type II or remained as type I. Type III (hyperintensity on T 1 and hyper-, iso- or hypointensity on T 2 images) patients were few in number. There was a good correlation between MR imaging patterns and neurologic recovery for initial and subsequent MR patterns, in that type 0 showed good recovery, whereas types I and II revealed good improvement or no recovery. In addition, the extent of the high signal intensity area on initial as well as on subsequent T 2 -weighted images was proportionally correlated to neurologic recovery. The degree of cord compression was also important for predicting recovery of neurologic function. Findings of MR imaging of acutely injured spinal cord suggested the prognosis of spinal cord injury, especially when sequential studies were obtained. (author)

The Comparison of Traditional Exercises & Body Weight Supported Training (BWST Exercises on Sensory-Motor Function, Quality and Quantity of Walking in Paraplegic Spinal Cord Injured Persons

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Mehdi Raeisi-dehkordi

2015-01-01

Full Text Available Objective: The aim of this study was the comparison of traditional exercises & body weight supported training (BWST exercises on sensory-motor function, quality and quantity of walking in paraplegic spinal cord injured persons. Materials & Methods: 17 voluntary paraplegic spinal cord injured persons (Asia B,C, age 32.53±1.793 years, height 175.71±1.658 cm, weight 71.59±2.442 kg, and body mass index (BMI 23.18 ± 0.828 kg/m2 availability. The subjects were randomly assigned to BWSTT group (N=10 and Traditional exercises group (N=7 according to sensory and motor score. The subjects trained for 12 weeks, four times per week and 60 min per session. BWSTT include 15 min warm-up on fixed gear bike, 45 min BWSTT with 50% body weight and 10 min cold-down finally. 10% load was added each week. Traditional exercises included 15 min warm-up plus 45 min stretch exercise and resistance training. Results: The data showed that there were significant differences in changes of sensory function Pin score (P=0.002 and Light Score (P=0.002 sensory function, motor function (P=0.000, Walking index Spinal cord injury (WISCI (P=0.002, 6 min walking test (P=0.001 and 10 meter walking (P=0.001 between BWSTT and traditional exercise. Conclusion: BWSTT in comparison with traditional exercise can improve sensory-motor function and quality and quantity of walking in paraplegic spinal cord injured persons.

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

Science.gov (United States)

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

2007-10-01

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

Suicide in a spinal cord injured population

DEFF Research Database (Denmark)

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

1998-01-01

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

Remyelination of the injured spinal cord

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Sasaki, Masanori; Li, Bingcang; Lankford, Karen L.; Radtke, Christine; Kocsis, Jeffery D.

2008-01-01

Contusive spinal cord injury (SCI) can result in necrosis of the spinal cord, but often long white matter tracts outside of the central necrotic core are demyelinated. One experimental strategy to improve functional outcome following SCI is to transplant myelin-forming cells to remyelinate these axons and improve conduction. This review focuses on transplantation studies using olfactory ensheathing cell (OEC) to improve functional outcome in experimental models of SCI and demyelination. The biology of the OEC, and recent experimental research and clinical studies using OECs as a potential cell therapy candidate are discussed. PMID:17618995

An oscillating extracellular voltage gradient reduces the density and influences the orientation of astrocytes in injured mammalian spinal cord.

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Moriarty, L J; Borgens, R B

2001-01-01

We have studied the cellular basis for recovery from acute spinal cord injury induced by applied electric fields. We have emphasized this recovery is due to the regeneration of spinal axons around and through the lesion, and have begun to evaluate the contribution of other cells to the recovery process. We have imposed a voltage gradient of about 320 microV/mm across puncture wounds to the adult rat spinal cord in order to study the accumulation and orientation of GFAP+ astrocytes within and adjacent to the lesion. This electric field was imposed by a miniaturized electronic implant designed to alternate the polarity of the field every 15 minutes. Astrocytes are known to undergo hyperplastic transformation within injured mammalian cords forming a major component of the scar that forms in response to injury. We have made three observations using a new computer based morphometry technique: First, we note a slight shift in the orientation of astrocytes parallel to the long axis of the spinal cord towards an imaginary reference perpendicular to this axis by approximately 10 degrees--but only in undamaged white matter near the lesion. Second, the relative number of astrocytes was markedly, and statistically significantly, reduced within electrically--treated spinal cords, particularly in the lesion. Third, the imposed voltage gradient statistically reduced the numbers of astrocytes possessing oriented cell processes within the injury site compared to adjacent undamaged regions of spinal cord.

Differential gene expression in the EphA4 knockout spinal cord and analysis of the inflammatory response following spinal cord injury.

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Kathryn M Munro

Full Text Available Mice lacking the axon guidance molecule EphA4 have been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips™. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wildtype spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage/microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages/activated microglia in injured EphA4 knockout compared to wild-type spinal cords at 2, 4 or 14 days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages/activated microglia was observed in EphA4 knockout spinal cords at 4 days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury.

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

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

2015-05-15

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

Spinal Cord Independence Measure, version III: applicability to the UK spinal cord injured population.

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Glass, Clive A; Tesio, Luigi; Itzkovich, Malka; Soni, Bakul M; Silva, Pedro; Mecci, Munawar; Chadwick, Raymond; el Masry, Waghi; Osman, Aheed; Savic, Gordana; Gardner, Brian; Bergström, Ebba; Catz, Amiram

2009-09-01

To examine the validity, reliability and usefulness of the Spinal Cord Independence Measure for the UK spinal cord injury population. Multi-centre cohort study. Four UK regional spinal cord injury centres. Eighty-six people with spinal cord injury. Spinal Cord Independence Measure and Functional Independence Measure on admission analysed using inferential statistics, and Rasch analysis of Spinal Cord Independence Measure. Internal consistency, inter-rater reliability, discriminant validity; Spinal Cord Independence Measure subscale match between distribution of item difficulty and patient ability measurements; reliability of patient ability measures; fit of data to Rasch model; unidimensionality of subscales; hierarchical ordering of categories within items; differential item functioning across patient groups. Scale reliability (kappa coefficients range 0.491-0.835; (p Spinal Cord Independence Measure subscales compatible with stringent Rasch requirements; mean infit indices high; distinct strata of abilities identified; most thresholds ordered; item hierarchy stable across clinical groups and centres. Misfit and differences in item hierarchy identified. Difficulties assessing central cord injuries highlighted. Conventional statistical and Rasch analyses justify the use of the Spinal Cord Independence Measure in clinical practice and research in the UK. Cross-cultural validity may be further improved.

Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

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Pierre eGuertin

2014-05-01

Full Text Available Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs - from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS networks that are involved in the control of ambulation and other stereotyped motor patterns - specifically Central Pattern Generators (CPGs that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of SCI should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic spinal cord-injured patients.

Maladaptation of cerebral perfusion in the spinal cord injured individuals

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Cho, Ihn Ho; Chun, Kyung A.; Lee, Hyoung Woo; Ahn, Sang Ho; Hayashida, Kohei [National Cardiovascular Center, Osaka (Korea, Republic of)

2001-07-01

The aim of this study was to evaluate the tilt-induced alteration of cerebral perfusion of spinal cord injured individuals. Supine and upright sitting brain SPECT was performed using a 1-day protocol with {sup 99m}Tc-ethylcysteinate dimer (ECD) in 11 SCI individuals (mean age, 32.6 y), with lesions between C3 and T4, ad 5 AB individuals (mean age, 31.4 y). The patients rested on a wheelchair in the supine position. Then, they sat up and, at the same time 555MBq of ECD was injected. The upright SPECT was done. Finally, 740MBq of ECD was injected and supine SPECT was performed again. The SPECT data were acquired with dual head gamma camera (E-cam, Siemens). For semiquantitative analysis, 14 ROIs were drawn on the brain. In the SCI individuals, the radiotracer uptake in the frontal, temporal and parietal areas were significantly decreased in the upright SPECT. No postural changes was evident in the occipital lobe, basal ganglia and thalamus in the SCI individuals. In the AB individuals, there were no such changes on the upright SPECT. Postural cerebral hypoperfusion in the frontal, temporal and parietal areas in the SCI individuals might relate to maladaptation of the vascular response during the upright position.

CENTRAL SENSITIZATION AND MEDICATION IN SPINAL CORD INJURED IN-PATIENTS. A CROSS-SECTIONAL CLINICAL STUDY

DEFF Research Database (Denmark)

Rosendahl, A; Kasch, Helge

Background and aims: A major proportion of spinal cord injured subjects (SCIS) suffers from chronic pain. A majority with neuropathic pain, being: shooting, burning and stabbing. Neurological examination reveals signs of central sensitization (CS) e.g. allodynia and hyperalgesia. CS plays...... an important role in maintained neuropathic pain conditions and may lead to or be induced by analgesics. Medication-overuse-headaches (MOH) alter CNS pain processing systems, and the situation is reversed after discontinuation of headache medication. Aim: To determine the occurrence of CS and conditions...... pressure algometry, Von Frey filaments and pinprick test. Patients fulfill McGill Pain Questionnaire and the International SCI pain data-set. All participants undergo examination of the Pressure Pain Detection Threshold, Pressure Pain Tolerance Threshold, Mechanical Detection Threshold, and Wind...

Magnetic resonance imaging of acute spinal-cord injury

International Nuclear Information System (INIS)

Yamamoto, Hideki; Nakagawa, Hiroshi; Yamada, Takahisa; Iwata, Kinjiro; Okumura, Terufumi; Hoshino, Daisaku.

1992-01-01

Magnetic resonance imaging (MRI) provides a noninvasive and very important method of investigating spinal-cord injuries. By means of MRI we examined 36 patients with spinal injuries, 34 of them in the acute stage. 19 cases had complete spinal-cord injury with paraplegia, while 17 cases had incomplete spinal-cord injury. MRI showed the injured spinal-cord in the acute stage to be partially swollen, with a high signal intensity in the T 2 -weighted images. In the chronic stage, the injured cord may show atrophic changes with a post-traumatic cavity or myelomalacia, which appears as a high-signal-intensity lesion in the T 2 -weighted images and as a low-signal intensity in the T 1 -weighted images. The cases with complete spinal injuries showed a high signal intensity at the wide level, and these prognoses were poor. The cases with incomplete injuries showed normal findings or a high-signal-intensity spot. In the Gd-DTPA enhanced images, the injured cords were enhanced very well in the subchronic stage. MRI is thus found to be useful in the diagnosis of spinal injuries; it also demonstrates a potential for predicting the neurological prognosis. (author)

Seminal plasma PSA in spinal cord injured men

DEFF Research Database (Denmark)

Brasso, K; Sønksen, J; Sommer, P

1998-01-01

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

The Smn-independent beneficial effects of trichostatin A on an intermediate mouse model of spinal muscular atrophy.

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Hong Liu

Full Text Available Spinal muscular atrophy is an autosomal recessive neuromuscular disease characterized by the progressive loss of alpha motor neurons in the spinal cord. Trichostatin A (TSA is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. It is currently unclear whether TSA specifically targets the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-SMN mediated pathway. TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. As well, there was a significant attenuation of weight loss and improved motor behavior. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/- mice were protected from degeneration. Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Of interest, TSA treatment did not increase the levels of Smn protein in mouse embryonic fibroblasts or myoblasts obtained from the Smn2B/- mice. In addition, no change in the level of Smn transcripts or protein in the brain or spinal cord of TSA-treated SMA model mice was observed. Furthermore, TSA did not increase Smn protein levels in the hind limb muscle, heart, or liver of Smn2B/- mice. We therefore conclude that TSA likely exerts its effects independent of the endogenous mouse Smn gene. As such, identification of the pathways regulated by TSA in the Smn2B/- mice could lead to the development of novel therapeutics for treating SMA.

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

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

2015-01-01

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

Evaluation of the occurrence and diagnose definitions for Nocturnal Polyuria in Spinal Cord Injured patients during rehabilitation.

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Viaene, Annick; Denys, Marie-Astrid; Goessaert, An-Sofie; Claeys, Jana; Raes, Ann; Roggeman, Saskia; Everaert, Karel

2017-11-03

Little is known about the occurrence of nocturnal polyuria in spinal cord injured (SCI) patients and the definitions which are preferable in this population. To determine the occurrence of nocturnal polyuria (NP) in spinal cord injured patients during in-patient rehabilitation in the Ghent University Hospital. To study the influence of different time periods (daytime, bed rest and sleep) on the accuracy of the existing diagnose definitions for NP specifically for this type of patients. Retrospective study using patient records. SCI patients during hospital based rehabilitation between 2011 and 2014. Seventy-four SCI patients were selected and their records of frequency-volume charts were examined, after exclusion of unreliable data, forty-seven patients were retained for the current study. Retrospective study using data from frequency-volume charts of either two or three days from patients with SCI. Nocturnal urine production (NUP) and nocturnal polyuria index (NPi) were calculated. There was a significant increase in diuresis, calculated as urine production, between day time and bed rest (p=0.008) and between day time and sleep (p=0.001). All patients showed nocturnal polyuria during a 12-hour night time period (including both bed rest and sleep) and 39 patients showed nocturnal polyuria during the 8 hour period of sleep. There was no significant difference in mean urine production between bed rest and sleep. Prevalence of NP did not significantly differ between the complete or incomplete SCI patients or between patients with higher and lower SCI levels. This study showed that the occurrence of nocturnal polyuria in patients with SCI is high and that it is important to consider which definitions of NP are used for diagnosis. Increase in diuresis is observed during bed rest and sleep and the diagnose is correctly estimated when nocturnal urine production definitions are used in both time periods. In accordance with what was expected, diagnose of NP was

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

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

2017-05-01

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

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

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

2017-11-01

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

Spinal Accessory Motor Neurons in the Mouse: A Special Type of Branchial Motor Neuron?

Science.gov (United States)

Watson, Charles; Tvrdik, Petr

2018-04-16

The spinal accessory nerve arises from motor neurons in the upper cervical spinal cord. The axons of these motor neurons exit dorsal to the ligamentum denticulatum and form the spinal accessory nerve. The nerve ascends in the spinal subarachnoid space to enter the posterior cranial fossa through the foramen magnum. The spinal accessory nerve then turns caudally to exit through the jugular foramen alongside the vagus and glossopharyngeal nerves, and then travels to supply the sternomastoid and trapezius muscles in the neck. The unusual course of the spinal accessory nerve has long prompted speculation that it is not a typical spinal motor nerve and that it might represent a caudal remnant of the branchial motor system. Our cell lineage tracing data, combined with images from public databases, show that the spinal accessory motor neurons in the mouse transiently express Phox2b, a transcription factor that is required for development of brain stem branchial motor nuclei. While this is strong prima facie evidence that the spinal accessory motor neurons should be classified as branchial motor, the evolutionary history of these motor neurons in anamniote vertebrates suggests that they may be considered to be an atypical branchial group that possesses both branchial and somatic characteristics. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Segmental, synaptic actions of commissural interneurons in the mouse spinal cord

DEFF Research Database (Denmark)

Quinlan, Katharina A.; Kiehn, Ole

2007-01-01

outlines the basic connectivity pattern of CINs in the mouse spinal cord on a segmental level. Our study suggests that, based on observed synaptic connectivity, both short- and long-range CINs are likely involved in segmental left-right coordination and that the CIN system is organized into a dual......-inhibitory and single-excitatory system. These systems are organized in a way that they could provide appropriate coordination during locomotion....

Characterization and therapeutic evaluation of a Nestin⁺ CNP⁺ NG2⁺ cell population on mouse spinal cord injury.

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Liu, Rui; Zhang, Si; Yang, Haijie; Ju, Peijun; Xia, Yinyan; Shi, Yu; Lim, Tse Hui; Lim, Alvin St; Liang, Fengyi; Feng, Zhiwei

2015-07-01

The NG2 chondroitin sulfate proteoglycan-expressing neural cells (NG2 cells) have originally been considered as oligodendrocyte progenitor cells (OPCs). However, recent findings on their diverse functions and lineage heterogeneity demonstrated that the NG2 cells contain various sub-populations whose concrete features and therapeutic potential yet remained elucidated. In the present study, we characterized a Nestin(+) 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)(+) NG2(+) subpopulation from embryonic rat cerebral cortex. The Nestin(+) CNP(+) NG2(+) cells exhibited remarkable progenitor characteristics. Having been immortalized by human telomerase reverse transcriptase (hTERT), the life span of Nestin(+) CNP(+) NG2(+) cells was extended to 230 population doublings (PDs). With immortalized NG2 cells, we demonstrated their differentiation capacities to oligodendrocytes, astrocytes and neurons. Furthermore, transplanted into injured spinal cord of a mouse model, they were able to promote remyelination and neuronal regeneration, thereby enhancing the functional recovery. Our findings suggest that the Nestin(+) CNP(+) NG2(+) progenitor cells could be a good alternative cell source of cell therapy for neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurogenesis in spinal cord of mouse: an autoradiographic analysis

International Nuclear Information System (INIS)

Nornes, H.O.; Carry, M.

1978-01-01

An autoradiographic analysis of the time and sites of origin, and the migration and setting patterns of neurons was made in the spinal cord of the mouse. The neurons originated on days 10-15 of gestation with temporal gradients along the ventrodorsal and rostrocaudal axes. The motor neurons originated on days 10-11 of gestation; the neurons in the intermediate gray region originated on days 11-14 of gestation; the neurons of the head of the dorsal horn originated on days 12-14 of gestation. The neurons that originated on days 10 and 11 originated and migrated primarily from the basal plate, and they settled in the adjacent regions of the intermediate zone; those neurons formed on days 12-14 originated and migrated primarily from the alar plate, and it was concluded that these neuroblasts similarly settled in the adjacent regions of the intermediate zone. Extraventricular proliferation, which presumably signaled the initial stages of gliogenesis, was first observed on day 12 of gestation. This study supports the classical idea of the mosaic pattern of neurogenesis in the embryonic spinal cord. (Auth.)

GHSR deficiency suppresses neointimal formation in injured mouse arteries

International Nuclear Information System (INIS)

Li, Jing; Zhang, Man; Wang, Mo; Wang, Zhipeng; Liu, Yahan; Zhang, Weizhen; Wang, Nanping

2016-01-01

Growth hormone secretagogue receptor (GHSR) is involved in appetite regulation and energy homeostasis. In the present study, we examined the role of GHSR in neointimal formation following vascular injury. In the mouse model of femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in GHSR deficiency (GHSR −/− ) mice compared with that in wild-type mice. Immunohistochemical staining showed that the smooth muscle cell (SMCs) in the neointima were significantly decreased in the injured arteries of GHSR −/− mice which was associated with decreased SMC proliferation and migration. Furthermore, immunoblotting demonstrated that, in cultured rat aortic SMCs, small interfering RNA-mediated GHSR knockdown suppressed the activation of Akt and ERK1/2 signaling pathway. These findings suggested a novel role of GHSR in neointimal formation likely via promoting the proliferation and migration of SMCs involving Akt and ERK1/2 signaling. Therefore, GHSR may be a potential therapeutic target in restenosis and vascular remodeling. - Highlights: • GHSR deficiency inhibits neointimal formation after vascular injury. • GHSR deficiency suppresses SMCs numbers in vivo. • Knockdown GHSR represses SMCs proliferation and migration in vitro. • Knockdown GHSR inhibited Akt and ERK1/2 phosphorylation in SMCs.

Computed tomography of the spinal canal for the cervical spine and spinal cord injury

International Nuclear Information System (INIS)

Kimura, Isao; Niimiya, Hikosuke; Nasu, Kichiro; Shioya, Akihide; Ohhama, Mitsuru

1983-01-01

The cervical spinal canal and cervical spinal cord were measured in normal cases and 34 cases of spinal or spinal cord injury. The anteroposterior diameter and area of the normal cervical spinal canal showed a high correlation. The area ratio of the normal cervical spinal canal to the cervical spinal cord showed that the proportion of the cervical spinal cord in the spinal canal was 1/3 - 1/5, Csub(4,5) showing a particularly large proportion. In acute and subacute spinal or spinal cord injury, CT visualized in more details of the spinal canal in cases that x-ray showed definite bone injuries. Computer assisted myelography visualized more clearly the condition of the spinal cord in cases without definite findings bone injuries on x-ray. Demonstrating the morphology of spinal injury in more details, CT is useful for selection of therapy for injured spines. (Chiba, N.)

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

Science.gov (United States)

Huie, J. Russell

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Sandra M. Garraway

2016-01-01

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

Effect of BCNU on mouse skin and spinal cord in single drug and radiation exposures

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Lelieveld, P.; Brown, J.M.; Goffinet, D.R.; Schoeppel, S.L.; Scoles, M.

1979-01-01

We set out to determine whether any interaction occurs between BCNU and radiation for the mouse skin and spinal cord. Single doses of BCNU of 10, 20, or 30 mg/kg were injected intraperitoneally as a function of time before or after irradiation of the foot or spinal cord of anesthesized C3H mice. Enhancement of the radiation skin reaction (dose enhancement factor = 1.3) was seen when BCNU (30 mg/kg) was given 1 day, 6 hr, and 2 hr prior to irradiation of the foot with 2,500 rad, and a larger DEF of 1.6 was observed when BCNU was given immediately before the radiation dose. However, with a different mouse strain (BALB/c) not anesthetized at the time of irradiation, no significant enhancement following a dose of 20 mg/kg BCNU was observed. Experiments are in progress to determine the cause of these differences. BCNU (10 mg/kg) was given 24 hr or immediately prior to various single doses of radiation to a 12 mm segment of the mouse spinal cord (T/sub 11-12/ to L/sub 1-2/), and the subsequent myelitis was scored monthly. The addition of BCNU to irradiation did not accelerate the development of myelitis, not the ultimate proportion of animals developing hind limb paralysis: the 50% myelitis dose at 10 months (MD/sub 50/10/sub mo/) values for irradiation alone, BCNU at the time of irradiation and 24 hr before were 3,722, 3,795 and 3,853 rad, respectively

Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury

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Zhijian Cheng

2016-08-01

Full Text Available Neural stem cell (NSC transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6 and interleukin-12 (IL-12. Furthermore, bone marrow-derived macrophages (BMDMs were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS, TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA. Transplanted NSCs had significantly increased BMS scores (p < 0.05. Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05. Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05. These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.

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

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

2014-11-04

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

The cellular and subcellular localization of zinc transporter 7 in the mouse spinal cord

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The present work addresses the cellular and subcellular localization of the zinc transporter 7 (ZNT7, SLC30a7) protein and the distribution of zinc ions (Zn2+) in the mouse spinal cord. Our results indicated that the ZNT7 immunoreactive neurons were widely distributed in the Rexed’s laminae of the g...

Rapid recovery and altered neurochemical dependence of locomotor central pattern generation following lumbar neonatal spinal cord injury.

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Züchner, Mark; Kondratskaya, Elena; Sylte, Camilla B; Glover, Joel C; Boulland, Jean-Luc

2018-01-15

Spinal compression injury targeted to the neonatal upper lumbar spinal cord, the region of highest hindlimb locomotor rhythmogenicity, leads to an initial paralysis of the hindlimbs. Behavioural recovery is evident within a few days and approaches normal function within about 3 weeks. Fictive locomotion in the isolated injured spinal cord cannot be elicited by a neurochemical cocktail containing NMDA, dopamine and serotonin 1 day post-injury, but can 3 days post-injury as readily as in the uninjured spinal cord. Low frequency coordinated rhythmic activity can be elicited in the isolated uninjured spinal cord by NMDA + dopamine (without serotonin), but not in the isolated injured spinal cord. In both the injured and uninjured spinal cord, eliciting bona fide fictive locomotion requires the additional presence of serotonin. Following incomplete compression injury in the thoracic spinal cord of neonatal mice 1 day after birth (P1), we previously reported that virtually normal hindlimb locomotor function is recovered within about 3 weeks despite substantial permanent thoracic tissue loss. Here, we asked whether similar recovery occurs following lumbar injury that impacts more directly on the locomotor central pattern generator (CPG). As in thoracic injuries, lumbar injuries caused about 90% neuronal loss at the injury site and increased serotonergic innervation below the injury. Motor recovery was slower after lumbar than thoracic injury, but virtually normal function was attained by P25 in both cases. Locomotor CPG status was tested by eliciting fictive locomotion in isolated spinal cords using a widely used neurochemical cocktail (NMDA, dopamine, serotonin). No fictive locomotion could be elicited 1 day post-injury, but could within 3 days post-injury as readily as in age-matched uninjured control spinal cords. Burst patterning and coordination were largely similar in injured and control spinal cords but there were differences. Notably, in both groups there

Recovery of forward stepping in spinal cord injured patients does not transfer to untrained backward stepping.

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Grasso, Renato; Ivanenko, Yuri P; Zago, Myrka; Molinari, Marco; Scivoletto, Giorgio; Lacquaniti, Francesco

2004-08-01

Six spinal cord injured (SCI) patients were trained to step on a treadmill with body-weight support for 1.5-3 months. At the end of training, foot motion recovered the shape and the step-by-step reproducibility that characterize normal gait. They were then asked to step backward on the treadmill belt that moved in the opposite direction relative to standard forward training. In contrast to healthy subjects, who can immediately reverse the direction of walking by time-reversing the kinematic waveforms, patients were unable to step backward. Similarly patients were unable to perform another untrained locomotor task, namely stepping in place on the idle treadmill. Two patients who were trained to step backward for 2-3 weeks were able to develop control of foot motion appropriate for this task. The results show that locomotor improvement does not transfer to untrained tasks, thus supporting the idea of task-dependent plasticity in human locomotor networks.

Robot-assisted arm assessments in spinal cord injured patients: a consideration of concept study.

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Urs Keller

Full Text Available Robotic assistance is increasingly used in neurological rehabilitation for enhanced training. Furthermore, therapy robots have the potential for accurate assessment of motor function in order to diagnose the patient status, to measure therapy progress or to feedback the movement performance to the patient and therapist in real time. We investigated whether a set of robot-based assessments that encompasses kinematic, kinetic and timing metrics is applicable, safe, reliable and comparable to clinical metrics for measurement of arm motor function. Twenty-four healthy subjects and five patients after spinal cord injury underwent robot-based assessments using the exoskeleton robot ARMin. Five different tasks were performed with aid of a visual display. Ten kinematic, kinetic and timing assessment parameters were extracted on joint- and end-effector level (active and passive range of motion, cubic reaching volume, movement time, distance-path ratio, precision, smoothness, reaction time, joint torques and joint stiffness. For cubic volume, joint torques and the range of motion for most joints, good inter- and intra-rater reliability were found whereas precision, movement time, distance-path ratio and smoothness showed weak to moderate reliability. A comparison with clinical scores revealed good correlations between robot-based joint torques and the Manual Muscle Test. Reaction time and distance-path ratio showed good correlation with the "Graded and Redefined Assessment of Strength, Sensibility and Prehension" (GRASSP and the Van Lieshout Test (VLT for movements towards a predefined position in the center of the frontal plane. In conclusion, the therapy robot ARMin provides a comprehensive set of assessments that are applicable and safe. The first results with spinal cord injured patients and healthy subjects suggest that the measurements are widely reliable and comparable to clinical scales for arm motor function. The methods applied and results can

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

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Jian Hao

2017-01-01

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

Care of post-traumatic spinal cord injury patients in India: An analysis

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Pandey V

2007-01-01

Full Text Available Background: The spinal cord injured patients if congregated early in spinal units where better facilities and dedicated expert care exist the outcome of treatment and rehabilitation, can be improved. The objective of this study is to find out the various factors responsible for a delay in the presentation of spinal injury patients to the specialized spinal trauma units and to suggest steps to improve the quality of care of the spinal trauma patients in the Indian setup. Materials and Methods: Sixty patients of traumatic spinal cord injury admitted for rehabilitation between August 2005 and May 2006 were enrolled into the study and their data was analyzed. Results: Eighty-five per cent of the spinal cord injured patients were males and the mean age was 34 years (range 13-56 years. Twenty-nine (48.33% of the spinal injuries occurred due to fall from height. There was an average of 45 days (range 0-188 days of delay in presentation to a specialized spinal unit and most of the time the cause for the delay was unawareness on the part of patients and/or doctors regarding specialized spinal units. In 38 (62.5% cases the mode of transportation of the spinal cord injured patient to the first visited hospital was by their own conveyance and the attendants of the patients did not have any idea about precautions essential to prevent neurological deterioration. Seventeen (28.33% patients were given injection solumedrol with conservative treatment, 35 (60% patients were given only conservative treatment and seven patients were operated (11.66% upon at initially visited hospital. Of the seven patients operated five were fixed with posterior Harrington instrumentation (71.42% and two (28.57% were operated by short segment posterior pedicle screw fixation. None of the patients were subjected to physiotherapy-assisted transfers or wheel chair skills or even basic postural training, proper bladder/ bowel training program and sitting balance. Conclusion: Awareness

MRI of the injured spinal cord of the thoracic and lumber spin

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Shimizu, Kenji; Satoh, Tetsurou; Hyodo, Hironori; Ohira, Nobuhiro; Moriai, Norio

1991-01-01

Magnetic resonance studies using a 1.5 Tesla superconductive magnet were performed on 23 patients with spinal cord injury of the thoracic and lumbar regions in their chronic stages. Our results were as follows. The MR images were found to well represent the spinal cord lesions except several cases of complex displacement of the spinal cord. The size and the degree of penetration of the MRI abnormalities well correlated with the spinal cord injury; those cases of large and penetrating MRI abnormalities were represented by complete paraplegia and those of small and non-penetrating abnormalities were those of imcomplete paraplegia. However, the neurological levels of the spinal cord injury in cases of complete paraplegia appeared higher than the spinal segments indicated by the MRI. This discrepancy was thought to be explained by a concomitant, additional nerve roots involvement along with the spinal cord injury. Incidentally, the MRI of the cone lesions did not seem to be reproducible presumably as the result of its too small sensitive volume. We also discussed the problem of MRI artifacts and effects from gross anatomical displacement of traumatic origin. (author)

Macrophage activation and its role in repair and pathology after spinal cord injury.

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Gensel, John C; Zhang, Bei

2015-09-04

The injured spinal cord does not heal properly. In contrast, tissue repair and functional recovery occur after skin or muscle injuries. The reason for this dichotomy in wound repair is unclear but inflammation, and specifically macrophage activation, likely plays a key role. Macrophages have the ability to promote the repair of injured tissue by regulating transitions through different phase of the healing response. In the current review we compare and contrast the healing and inflammatory responses between spinal cord injuries and tissues that undergo complete wound resolution. Through this comparison, we identify key macrophage phenotypes that are inaptly triggered or absent after spinal cord injury and discuss spinal cord stimuli that contribute to this maladaptive response. Sequential activation of classic, pro-inflammatory, M1 macrophages and alternatively activated, M2a, M2b, and M2c macrophages occurs during normal healing and facilitates transitions through the inflammatory, proliferative, and remodeling phases of repair. In contrast, in the injured spinal cord, pro-inflammatory macrophages potentiate a prolonged inflammatory phase and remodeling is not properly initiated. The desynchronized macrophage activation after spinal cord injury is reminiscent of the inflammation present in chronic, non-healing wounds. By refining the role macrophages play in spinal cord injury repair we bring to light important areas for future neuroinflammation and neurotrauma research. This article is part of a Special Issue entitled SI: Spinal cord injury. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Treatment of spinal fractures with paraplegia.

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Riska, E B; Myllynen, P

1981-01-01

Of 206 patients with vertebral fractures in the thoraco-lumbar spine with spinal cord injuries, an antero-lateral decompression with stabilization of the injured segment of the vertebral column was undertaken in 56 cases. In all these cases there was a compression of the spinal cord from the front. 8 patients made a complete recovery, 31 a good recovery, and 6 were improved. In 8 patients no improvement was noted. 2 patients developed pressure sores later and 1 patient died one year after the operation of uraemia. 22 patients out of 55 got a normal function of the bladder and 25 patients out of 54 a normal function of the anal sphincter. 16 patients out of 17 made a complete or good recovery after removal of a displaced rotated vertebral bony fragment from the spinal canal, and 7 patients out of 9 with wedge shaped fractures. In our clinic today, in cases of vertebral fractures with neural involvement, reduction and internal fixation with Harrington rods and fusion of the injured segment is undertaken as soon as possible, also during the night. If narrowing of the neural canal and compression of the spinal cord are verified, a decompression operation with interbody fusion is undertaken during the next days.

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells

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Sandeep Gupta

2018-02-01

Full Text Available Summary: Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC- or induced pluripotent stem cell (hiPSC-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs, which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients. : In this article, Gupta and colleagues describe a robust protocol to derive spinal dorsal sensory interneurons from human pluripotent stem cells using the sequential addition of RA and BMP4. They find that neural progenitors must be in the correct competence state to respond to RA/BMP4 as dorsalizing signals. This competence state changes over time and determines the efficiency of the protocol. Keywords: spinal cord, neurons, sensory interneurons, proprioception, mechanosensation, human embryonic stem cells, induced pluripotent stem cells, directed differentiation, primate spinal cord, mouse spinal cord

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

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

2018-05-01

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

Spinal cord regeneration by modulating bone marrow with neurotransmitters and Citicholine: Analysis at micromolecular level.

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Paulose, Cheramadathukudiyil Skaria; John, Ponnezhathu Sebastian; Chinthu, Romeo; Akhilraj, Puthenveetil Raju; Anju, Thoppil Raveendran

2017-04-01

Spinal cord injury results in disruption of brain-spinal cord fibre connectivity, leading to progressive tissue damage at the site of injury and resultant paralysis of varying degrees. The current study investigated the role of autologous bone marrow modulated with neurotransmitters and neurotransmitter stimulating agent, Citicholine, in spinal cord of spinal cord injured rats. Radioreceptor assay using [3H] ligand was carried out to quantify muscarinic receptor. Gene expression studies were done using Real Time PCR analysis. Scatchard analysis of muscarinic M1 receptor showed significantly decreased B max (p neurotransmitters combination along with bone marrow or Citicholine with bone marrow can reverse the muscarinic receptor alterations in the spinal cord of spinal cord injured rats, which is a promising step towards a better therapeutic intervention for spinal cord injury because of the positive role of cholinergic system in regulation of both locomotor activity and synaptic plasticity. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

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

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

2015-11-01

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

Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: A focus on lamina X.

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Gotts, Jittima; Atkinson, Lucy; Yanagawa, Yuchio; Deuchars, Jim; Deuchars, Susan A

2016-09-01

Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However, the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurons were observed in lamina X of both adult and juvenile mice and in both age groups a population of cells containing both ChAT-IR and GAD67-GFP were observed in lumbar, thoracic and cervical spinal cord. Such dual labelled cells were predominantly located ventral to the central canal. Immunohistochemistry for vesicular acetylcholine transporter (VAChT) and GAD67 revealed a small number of double labelled terminals located lateral, dorsolateral and ventrolateral to the central canal. This study therefore describes in detail a population of ChAT-IR/GAD67-GFP neurons predominantly ventral to the central canal of the cervical, thoracic and lumbar spinal cord of adult and juvenile mice. These cells potentially correspond to a sub-population of the cholinergic central canal cluster cells which may play a unique role in controlling spinal cord circuitry. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Follow-up CT myelography of severe cervical spinal cord injury

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Okada, Keiichi; Onoda, Kimio; Kawashima, Yasuhiro; Muto, Atsushi; Kobayashi, Yoichi

1987-11-01

There are many reports describing gross anatomical and microscopical findings of severely injured cervical cords in autopsy of the acute and chronic state, but no morphological findings of a severe cervical spinal cord injury in a chronic state by follow-up CT myelography have been found in the literature so far. The sagittal and transverse diameters of the cervical spinal cord and subarachnoid space of 9 out of 14 severe cervical spinal cord injury patients were measured with CT myelography within 7.5 years after the tranuma and their size compared with a control group which was made up of 29 patients with slight radiculopathy due to cervical spondylosis and whiplash injuries. Injured cord levels were C4 4 cases, C5 4 cases and C6 1 case. Remarkable spinal cord atrophy was recogniged in the sagittal diameter from C1 to C7 and in the transverse diameter below C4 and narrowing of the cervical subarachnoid space in the sagittal diameter from C2 to C5. The significance level was set at 1 - 5 %. From these fingings, we have concluded that atrophy appeared not only in the injured segment but also the whole cervical cord after the trauma. There was less cord atrophy in a good functional prognosis than in a poor prognosis.

Follow-up CT myelography of severe cervical spinal cord injury

International Nuclear Information System (INIS)

Okada, Keiichi; Onoda, Kimio; Kawashima, Yasuhiro; Muto, Atsushi; Kobayashi, Yoichi

1987-01-01

There are many reports describing gross anatomical and microscopical findings of severely injured cervical cords in autopsy of the acute and chronic state, but no morphological findings of a severe cervical spinal cord injury in a chronic state by follow-up CT myelography have been found in the literature so far. The sagittal and transverse diameters of the cervical spinal cord and subarachnoid space of 9 out of 14 severe cervical spinal cord injury patients were measured with CT myelography within 7.5 years after the tranuma and their size compared with a control group which was made up of 29 patients with slight radiculopathy due to cervical spondylosis and whiplash injuries. Injured cord levels were C4 4 cases, C5 4 cases and C6 1 case. Remarkable spinal cord atrophy was recogniged in the sagittal diameter from C1 to C7 and in the transverse diameter below C4 and narrowing of the cervical subarachnoid space in the sagittal diameter from C2 to C5. The significance level was set at 1 - 5 %. From these fingings, we have concluded that atrophy appeared not only in the injured segment but also the whole cervical cord after the trauma. There was less cord atrophy in a good functional prognosis than in a poor prognosis. (author)

Evaluation of blood and serum markers in spinal cord injured patients with pressure sores.

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Gurcay, Eda; Bal, Ajda; Gurcay, Ahmet G; Cakci, Aytul

2009-03-01

To evaluate blood and serum markers in traumatic spinal cord injured (SCI) patients, with and without pressure sores. This cross-sectional study was performed at the Ministry of Health Diskapi Yildirim Beyazit, and Numune Education and Research Hospitals, Ankara, Turkey, from 2006-2008. A total of 23 SCI patients with pressure sores (group I) and a control group of 25 SCI patients without pressure sores (group II) were evaluated. Characteristics of sores were examined with respect to duration, location, grade, tissue types, surface area, and exudate amount. Recorded laboratory parameters included erythrocyte sedimentation rates (ESR), C-reactive protein (CRP), hemoglobin (Hb), hematocrit (Htc), lymphocytes, white blood cells (WBC), red blood cells (RBC), serum iron, transferrin, total iron-binding capacity (TIBC), ferritin, total protein, albumin, vitamin B12, and zinc. The most common pressure sore location was the sacrum (38%). Compared to the control group, the patients with pressure sores showed anemia with reduced serum iron, transferrin, TIBC, and increased ferritin. They also had increased ESR, CRP, and WBC and reduced lymphocytes, total protein, albumin and zinc. Statistically significant correlations were found between CRP, Hb, Htc, lymphocytes, RBC, WBC, and serum protein levels, and grade of pressure sores. Clinicians should regularly screen patients with respect to blood and serum markers, in order to determine any risks for pressure sores, and they should perform immediate preventive measures based on the patient's condition.

Symptom-Based Treatment of Neuropathic Pain in Spinal Cord-Injured Patients: A Randomized Crossover Clinical Trial.

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Min, Kyunghoon; Oh, Yoongul; Lee, Sang-Hyuk; Ryu, Ju Seok

2016-05-01

The objective of this study was to identify the differences in medication effect according to pain characteristics in spinal cord-injured patients. This study is a prospective, randomized, crossover study. Fifty-five patients and 66 locations of neuropathic pain were included. Pain was classified into four spontaneous characteristics and three evoked pain characteristics. Oxcarbazepine (Na channel blocker) and pregabalin (calcium channel α2-δ ligand medication) were tried. Patients were divided into two groups: evoked pain present and evoked pain absent. Overall average visual analog scale was obtained. Oxcarbazepine was significantly more effective for patients without evoked pain than in those with it for electrical, burning, and pricking pain. The effect of pregabalin was not different regarding the presence or absence of evoked pain for all pain categories, except burning pain. In patients with evoked pain, pregabalin was shown to be significantly more effective for electrical pain, allodynia, and heat hyperalgesia than oxcarbazepine. In the evoked pain absent group, oxcarbazepine showed greater improvement than pregabalin but was not significant. In summary, the phenotype of neuropathic pain was associated with the efficacy of different pharmacologic treatments. Symptom-based treatment, therefore, can lead to more efficient analgesia.

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

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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.

Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

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Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

2012-01-01

The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

Astrocytes from the Contused Spinal Cord Inhibit Oligodendrocyte Differentiation of Adult Oligodendrocyte Precursor Cells by Increasing the Expression of Bone Morphogenetic Proteins

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

2011-01-01

Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cor...

Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

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Charlotte Debaud

Full Text Available We previously reported the development of a new acquired neurogenic HO (NHO mouse model, combining spinal cord transection (SCI and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7, bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5 compared to contralateral sides (0.56 mm3 +/-0.4, p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6, bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI. Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro

Pericytes Make Spinal Cord Breathless after Injury.

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Almeida, Viviani M; Paiva, Ana E; Sena, Isadora F G; Mintz, Akiva; Magno, Luiz Alexandre V; Birbrair, Alexander

2017-09-01

Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.

Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization

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Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A; Harris-Warrick, Ronald M

2012-01-01

We explored the organization of the spinal central pattern generator (CPG) for locomotion by analysing the activity of spinal interneurons and motoneurons during spontaneous deletions occurring during fictive locomotion in the isolated neonatal mouse spinal cord, following earlier work on locomotor deletions in the cat. In the isolated mouse spinal cord, most spontaneous deletions were non-resetting, with rhythmic activity resuming after an integer number of cycles. Flexor and extensor deletions showed marked asymmetry: flexor deletions were accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor bursting was not perturbed during extensor deletions. Rhythmic activity on one side of the cord was not perturbed during non-resetting spontaneous deletions on the other side, and these deletions could occur with no input from the other side of the cord. These results suggest that the locomotor CPG has a two-level organization with rhythm-generating (RG) and pattern-forming (PF) networks, in which only the flexor RG network is intrinsically rhythmic. To further explore the neuronal organization of the CPG, we monitored activity of motoneurons and selected identified interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the

eGFP expression under the Uchl1 promoter labels corticospinal motor neurons and a subpopulation of degeneration resistant spinal motor neurons in ALS mouse models

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Yasvoina, Marina V.

Current understanding of basic cellular and molecular mechanisms for motor neuron vulnerability during motor neuron disease initiation and progression is incomplete. The complex cytoarchitecture and cellular heterogeneity of the cortex and spinal cord greatly impedes our ability to visualize, isolate, and study specific neuron populations in both healthy and diseased states. We generated a novel reporter line, the Uchl1-eGFP mouse, in which cortical and spinal components of motor neuron circuitry are genetically labeled with eGFP under the Uchl1 promoter. A series of cellular and anatomical analyses combined with retrograde labeling, molecular marker expression, and electrophysiology were employed to determine identity of eGFP expressing cells in the motor cortex and the spinal cord of novel Uchl1-eGFP reporter mice. We conclude that eGFP is expressed in corticospinal motor neurons (CSMN) in the motor cortex and a subset of S-type alpha and gamma spinal motor neurons (SMN) in the spinal cord. hSOD1G93A and Alsin-/- mice, mouse models for amyotrophic lateral sclerosis (ALS), were bred to Uchl1-eGFP reporter mouse line to investigate the pathophysiology and underlying mechanisms of CSMN degeneration in vivo. Evidence suggests early and progressive degeneration of CSMN and SMN in the hSOD1G93A transgenic mice. We show an early increase of autophagosome formation in the apical dendrites of vulnerable CSMN in hSOD1G93A-UeGFP mice, which is localized to the apical dendrites. In addition, labeling S-type alpha and gamma SMN in the hSOD1G93A-UeGFP mice provide a unique opportunity to study basis of their resistance to degeneration. Mice lacking alsin show moderate clinical phenotype and mild CSMN axon degeneration in the spinal cord, which suggests vulnerability of CSMN. Therefore, we investigated the CSMN cellular and axon defects in aged Alsin-/- mice bred to Uchl1-eGFP reporter mouse line. We show that while CSMN are preserved and lack signs of degeneration, CSMN axons

Spinal cord injury reveals multilineage differentiation of ependymal cells.

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Konstantinos Meletis

2008-07-01

Full Text Available Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury.

Salvianolic acid B protects the myelin sheath around injured spinal cord axons

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Zhe Zhu

2016-01-01

Full Text Available Salvianolic acid B, an active pharmaceutical compound present in Salvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study, in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose was 20 μg/mL. For in vivo investigation, rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks. The amount of myelin sheath and the number of regenerating axons increased, neurological function recovered, and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats. These results indicate that salvianolic acid B can protect axons and the myelin sheath, and can promote the recovery of neurological function. Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

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

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

2007-01-01

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

Protective Effects of Butyrate-based Compounds on a Mouse Model for Spinal Muscular Atrophy

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Butchbach, Matthew E. R.; Lumpkin, Casey J.; Harris, Ashlee W.; Saieva, Luciano; Edwards, Jonathan D.; Workman, Eileen; Simard, Louise R.; Pellizzoni, Livio; Burghes, Arthur H. M.

2016-01-01

Proximal spinal muscular atrophy (SMA) is a childhood-onset degenerative disease resulting from the selective loss of motor neurons in the spinal cord. SMA is caused by the loss of SMN1 (survival motor neuron 1) but retention of SMN2. The number of copies of SMN2 modifies disease severity in SMA patients as well as in mouse models, making SMN2 a target for therapeutics development. Sodium butyrate (BA) and its analogue (4PBA) have been shown to increase SMN2 expression in SMA cultured cells. In this study, we examined the effects of BA, 4PBA as well as two BA prodrugs—glyceryl tributyrate (BA3G) and VX563—on the phenotype of SMNΔ7 SMA mice. Treatment with 4PBA, BA3G and VX563 but not BA beginning at PND04 significantly improved the lifespan and delayed disease end stage, with administration of VX563 also improving the growth rate of these mice. 4PBA and VX563 improved the motor phenotype of SMNΔ7 SMA mice and prevented spinal motor neuron loss. Interestingly, neither 4PBA nor VX563 had an effect on SMN expression in the spinal cords of treated SMNΔ7 SMA mice; however, they inhibited histone deacetylase (HDAC) activity and restored the normal phosphorylation states of Akt and glycogen synthase kinase 3β, both of which are altered by SMN deficiency in vivo. These observations show that BA-based compounds with favourable pharmacokinetics ameliorate SMA pathology possibly by modulating HDAC and Akt signaling. PMID:26892876

High-speed video analysis improves the accuracy of spinal cord compression measurement in a mouse contusion model.

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Fournely, Marion; Petit, Yvan; Wagnac, Éric; Laurin, Jérôme; Callot, Virginie; Arnoux, Pierre-Jean

2018-01-01

Animal models of spinal cord injuries aim to utilize controlled and reproducible conditions. However, a literature review reveals that mouse contusion studies using equivalent protocols may show large disparities in the observed impact force vs. cord compression relationship. The overall purpose of this study was to investigate possible sources of bias in these measurements. The specific objective was to improve spinal cord compression measurements using a video-based setup to detect the impactor-spinal cord time-to-contact. A force-controlled 30kDyn unilateral contusion at C4 vertebral level was performed in six mice with the Infinite Horizon impactor (IH). High-speed video was used to determine the time-to-contact between the impactor tip and the spinal cord and to compute the related displacement of the tip into the tissue: the spinal cord compression and the compression ratio. Delayed time-to-contact detection with the IH device led to an underestimation of the cord compression. Compression values indicated by the IH were 64% lower than those based on video analysis (0.33mm vs. 0.88mm). Consequently, the mean compression ratio derived from the device was underestimated when compared to the value derived from video analysis (22% vs. 61%). Default time-to-contact detection from the IH led to significant errors in spinal cord compression assessment. Accordingly, this may explain some of the reported data discrepancies in the literature. The proposed setup could be implemented by users of contusion devices to improve the quantative description of the primary injury inflicted to the spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel first aid stretcher for immobilization and transportation of spine injured patients.

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Liu, Yan-Sheng; Feng, Ya-Ping; Xie, Jia-Xin; Luo, Zhuo-Jing; Shen, Cai-Hong; Niu, Fang; Zou, Jian; Tang, Shao-Feng; Hao, Jiang; Xu, Jia-Xiang; Xiao, Li-Ping; Xu, Xiao-Ming; Zhu, Hui

2012-01-01

Effective immobilization and transportation are vital to the life-saving acute medical care needed when treating critically injured people. However, the most common types of stretchers used today are wrought with problems that can lead to further medical complications, difficulty in employment and rescue, and ineffective transitions to hospital treatment. Here we report a novel first aid stretcher called the "emergency carpet", which solves these problems with a unique design for spine injured patients. Polyurethane composite material, obtained by a novel process of manually mixing isocyanate and additives, can be poured into a specially designed fabric bag and allowed to harden to form a rigid human-shaped stretcher. The effectiveness of the emergency carpet was examined in the pre-hospital management of victims with spinal fractures. Additionally, it was tested on flat ground and complex terrain as well as in the sea and air. We demonstrated that the emergency carpet can be assembled and solidified on the scene in 5 minutes, providing effective immobilization to the entire injured body. With the protection of the emergency carpet, none of the 20 patients, who were finally confirmed to have spinal column fracture or dislocation, had any neurological deterioration during transportation. Furthermore, the carpet can be handled and transported by multiple means under differing conditions, without compromising immobilization. Finally, the emergency carpet allows the critically injured patient to receive multiple examinations such as X-ray, CT, and MRI without being removed from the carpet. Our results demonstrate that the emergency carpet has ideal capabilities for immobilization, extrication, and transportation of the spine injured patients. Compared with other stretchers, it allows for better mobility, effective immobilization, remarkable conformity to the body, and various means for transportation. The emergency carpet is promising for its intrinsic advantages in

A novel first aid stretcher for immobilization and transportation of spine injured patients.

Directory of Open Access Journals (Sweden)

Yan-Sheng Liu

Full Text Available Effective immobilization and transportation are vital to the life-saving acute medical care needed when treating critically injured people. However, the most common types of stretchers used today are wrought with problems that can lead to further medical complications, difficulty in employment and rescue, and ineffective transitions to hospital treatment. Here we report a novel first aid stretcher called the "emergency carpet", which solves these problems with a unique design for spine injured patients. Polyurethane composite material, obtained by a novel process of manually mixing isocyanate and additives, can be poured into a specially designed fabric bag and allowed to harden to form a rigid human-shaped stretcher. The effectiveness of the emergency carpet was examined in the pre-hospital management of victims with spinal fractures. Additionally, it was tested on flat ground and complex terrain as well as in the sea and air. We demonstrated that the emergency carpet can be assembled and solidified on the scene in 5 minutes, providing effective immobilization to the entire injured body. With the protection of the emergency carpet, none of the 20 patients, who were finally confirmed to have spinal column fracture or dislocation, had any neurological deterioration during transportation. Furthermore, the carpet can be handled and transported by multiple means under differing conditions, without compromising immobilization. Finally, the emergency carpet allows the critically injured patient to receive multiple examinations such as X-ray, CT, and MRI without being removed from the carpet. Our results demonstrate that the emergency carpet has ideal capabilities for immobilization, extrication, and transportation of the spine injured patients. Compared with other stretchers, it allows for better mobility, effective immobilization, remarkable conformity to the body, and various means for transportation. The emergency carpet is promising for its

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

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

2013-12-01

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

Early development of the circumferential axonal pathway in mouse and chick spinal cord.

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Holley, J A

1982-03-10

The early development of the circumferential axonal pathway in the brachial and lumbar spinal cord of mouse and chick embryos was studied by scanning and transmission electron microscopy. The cellular processes which comprise this pathway grow in the transverse plane and along the lateral margin of the marginal zone (i.e., circumferentially oriented), as typified by the early embryonic commissural axons. The first formative event observed was in the ventrolateral margin of the primitive spinal cord ventricular zone. Cellular processes were found near the external limiting membrane that appeared to grow a variable distance either dorsally or ventrally. Later in development, presumptive motor column neurons migrated into the ventrolateral region, distal to these early circumferentially oriented processes. Concurrently, other circumferentially oriented perikarya and processes appeared along the dorsolateral margin. Due to their aligned sites of origin and parallel growth, the circumferential processes formed a more or less continuous line or pathway, which in about 10% of the scanned specimens could be followed along the entire lateral margin of the embryonic spinal cord. Several specimens later in development had two sets of aligned circumferential processes in the ventral region. Large numbers of circumferential axons were then found to follow the preformed pathway by fasciculation, after the primitive motor column had become established. Since the earliest circumferential processes appeared to differentiate into axons and were found nearly 24 hours prior to growth of most circumferential axons, their role in guidance as pioneering axons was suggested.

Self-Assembling Peptide Nanofiber Scaffold Enhanced with RhoA Inhibitor CT04 Improves Axonal Regrowth in the Transected Spinal Cord

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Weiwei Zhang

2012-01-01

Full Text Available The present study was designed to explore the therapeutic potential of self-assembling peptide nanofiber scaffold (SAPNS delivered RhoA inhibitor to ameliorate the hostile microenvironment of injured spinal cord for axonal regeneration. After a transection was applied to the thoracic spinal cord of mice, the combination of SAPNS and CT04 (a cell permeable RhoA inhibitor, single SAPNS with vehicle, or saline was transplanted into the lesion cavity. Results showed that SAPNS+CT04 implants achieved the best therapeutic outcomes among treatment groups. The novel combination not only reconstructed the injured nerve gap but also elicited significant axonal regeneration and motor functional recovery. Additionally, the combination also effectively reduced the apoptosis and infiltration of activated macrophages in the injured spinal cord. Collectively, the present study demonstrated that SAPNS-based delivery of RhoA inhibitor CT04 presented a highly potential therapeutic strategy for spinal cord injury with reknitting lesion gap, attenuating secondary injury, and improving axonal regrowth.

Self-Assembling Peptide Nanofiber Scaffold Enhanced with RhoA Inhibitor CT04 Improves Axonal Regrowth in the Transected Spinal Cord

International Nuclear Information System (INIS)

Weiwei, Z.; Xiaoduo, Z.; Zhongying, L.

2012-01-01

The present study was designed to explore the therapeutic potential of self-assembling peptide nano fiber scaffold (SAPNS) delivered RhoA inhibitor to ameliorate the hostile microenvironment of injured spinal cord for axonal regeneration. After a transection was applied to the thoracic spinal cord of mice, the combination of SAPNS and CT04 (a cell permeable RhoA inhibitor), single SAPNS with vehicle, or saline was transplanted into the lesion cavity. Results showed that SAPNS+CT04 implants achieved the best therapeutic outcomes among treatment groups. The novel combination not only reconstructed the injured nerve gap but also elicited significant axonal regeneration and motor functional recovery. Additionally, the combination also effectively reduced the apoptosis and infiltration of activated macrophages in the injured spinal cord. Collectively, the present study demonstrated that SAPNS-based delivery of RhoA inhibitor CT04 presented a highly potential therapeutic strategy for spinal cord injury with reknitting lesion gap, attenuating secondary injury, and improving axonal regrowth.

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

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

2015-11-01

Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that affects males, results from a CAG triplet repeat/polyglutamine expansions in the androgen receptor (AR) gene. Patients develop progressive muscular weakness and atrophy, and no effective therapy is currently available. The tissue-specific pathogenesis, especially relative pathological contributions between degenerative motor neurons and muscles, remains inconclusive. Though peripheral pathology in skeletal muscle caused by toxic AR protein has been recently reported to play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degeneration in SBMA has not been rigorously investigated. Here, we exploited synthetic antisense oligonucleotides to inhibit the RNA levels of mutant AR in the central nervous system (CNS) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes. A single intracerebroventricular administration of the antisense oligonucleotides in the presymptomatic phase efficiently suppressed the mutant gene expression in the CNS, and delayed the onset and progression of motor dysfunction, improved body weight gain and survival with the amelioration of neuronal histopathology in motor units such as spinal motor neurons, neuromuscular junctions and skeletal muscle. These findings highlight the importance of the neurotoxicity of mutant AR protein in motor neurons as a therapeutic target. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury.

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Falnikar, Aditi; Hala, Tamara J; Poulsen, David J; Lepore, Angelo C

2016-03-01

Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. In our unilateral cervical contusion model of mouse SCI that is associated with ipsilateral forepaw heat hypersensitivity (a form of chronic at-level neuropathic pain-related behavior), we previously reported significant and long-lasting reductions in GLT1 expression and functional GLT1-mediated glutamate uptake in cervical spinal cord dorsal horn. To therapeutically address GLT1 dysfunction following cervical contusion SCI, we injected an adeno-associated virus type 8 (AAV8)-Gfa2 vector into the superficial dorsal horn to increase GLT1 expression selectively in astrocytes. Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI. © 2015 Wiley Periodicals, Inc.

Adaptation of a ladder beam walking task to assess locomotor recovery in mice following spinal cord injury

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Cummings, Brian J.; Engesser-Cesar, Christie; Anderson, Aileen J.

2007-01-01

Locomotor impairments after spinal cord injury (SCI) are often assessed using open-field rating scales. These tasks have the advantage of spanning the range from complete paralysis to normal walking; however, they lack sensitivity at specific levels of recovery. Additionally, most supplemental assessments were developed in rats, not mice. For example, the horizontal ladder beam has been used to measure recovery in the rat after SCI. This parametric task results in a videotaped archival record of the event, is easily administered, and is unambiguously scored. Although a ladder beam apparatus for mice is available, its use in the assessment of recovery in SCI mice is rare, possibly because normative data for uninjured mice and the type of step misplacements injured mice exhibit is lacking. We report the development of a modified ladder beam instrument and scoring system to measure hindlimb recovery in vertebral T9 contusion spinal cord injured mice. The mouse ladder beam allows for the use of standard parametric statistical tests to assess locomotor recovery. Ladder beam performance is consistent across four strains of mice, there are no sex differences, and inter-rater reliability between observers is high. The ladder beam score is proportional to injury severity and can be used to easily separate mice capable of weight-supported stance up to mice with consistent forelimb to hindlimb coordination. Critically, horizontal ladder beam testing discriminates between mice that score identically in terms of stepping frequency in open-field testing. PMID:17197044

Adaptation of a ladder beam walking task to assess locomotor recovery in mice following spinal cord injury.

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Cummings, Brian J; Engesser-Cesar, Christie; Cadena, Gilbert; Anderson, Aileen J

2007-02-27

Locomotor impairments after spinal cord injury (SCI) are often assessed using open-field rating scales. These tasks have the advantage of spanning the range from complete paralysis to normal walking; however, they lack sensitivity at specific levels of recovery. Additionally, most supplemental assessments were developed in rats, not mice. For example, the horizontal ladder beam has been used to measure recovery in the rat after SCI. This parametric task results in a videotaped archival record of the event, is easily administered, and is unambiguously scored. Although a ladder beam apparatus for mice is available, its use in the assessment of recovery in SCI mice is rare, possibly because normative data for uninjured mice and the type of step misplacements injured mice exhibit is lacking. We report the development of a modified ladder beam instrument and scoring system to measure hindlimb recovery in vertebral T9 contusion spinal cord injured mice. The mouse ladder beam allows for the use of standard parametric statistical tests to assess locomotor recovery. Ladder beam performance is consistent across four strains of mice, there are no sex differences, and inter-rater reliability between observers is high. The ladder beam score is proportional to injury severity and can be used to easily separate mice capable of weight-supported stance up to mice with consistent forelimb to hindlimb coordination. Critically, horizontal ladder beam testing discriminates between mice that score identically in terms of stepping frequency in open-field testing.

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

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

2016-03-01

Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. © 2016. Published by The Company of Biologists Ltd.

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

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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.

Noncontiguous double-level unstable spinal injuries.

Science.gov (United States)

Takami, Masanari; Okada, Motohiro; Enyo, Yoshio; Iwasaki, Hiroshi; Yamada, Hiroshi; Yoshida, Munehito

2017-01-01

Noncontiguous double-level unstable spinal injuries (NDUSI) are uncommon and have not been well described. In this study, we aimed to better understand the patterns of NDUSI, in order to recommend proper diagnostic and treatment methods, as well as to raise awareness among traumatologists about the possibility of these uncommon injuries. A total of 710 consecutive patients with spine fractures were treated for >9 years since 2007 at a single regional trauma center. Of them, 18 patients with NDUSI were reviewed retrospectively. The incidence of NDUSI was 2.5 % of all spine fractures. In 17 of 18 patients (94.7 %), NDUSI was caused by a high-energy trauma. Nine patients (50.0 %) exhibited complete neurological deficit. Spinal cord injury occurred in the cranial injured region in all American Spinal Injury Association grade A cases. In one case, a second fracture was overlooked at the initial examination. NDUSI are common in cases of high-energy trauma and should be taken into consideration at the initial examination. A second fracture may be easily overlooked because of the high frequency of concomitant severe spinal cord injury in the cranial injured region and/or loss of consciousness due to associated injuries. To avoid overlooking injuries, full spine computed tomography is useful at the initial examination. Operative reduction and internal fixation with instrumentation through a posterior approach is recommendable for cases of NDUSI. In elderly patients, a very rapid stabilizing surgery should be planned before aspiration pneumonia occurs or the pulmonary condition worsens.

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

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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.

Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway

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Kai Gao

2015-01-01

Full Text Available The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, ca-spase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental findings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

The Impact of Smoking and Smoking Cessation on Wound Healing in Spinal Cord-Injured Patients With Pressure Injuries: A Retrospective Comparison Cohort Study.

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Lane, Cheryl A; Selleck, Cynthia; Chen, Yuying; Tang, Ying

2016-01-01

The purpose of this study was to evaluate the impact of implementing evidence-based guidelines on smoking cessation in persons with spinal cord injuries and pressure injuries. We also evaluated the impact of smoking on pressure injury healing in this population. The sample population included 158 spinal cord-injured patients with pressure injuries (29 females and 129 males). There were 83 in the control group and 75 in the intervention group, with a mean age of 44 years in both groups. The research setting was an outpatient wound clinic located in a large medical center in the southeastern United States. A retrospective chart review was completed. Data were reviewed 6 months before and 6 months after implementation of the US Department of Health and Human Services Clinical Practice Guidelines for Treating Tobacco Use and Dependence. We evaluated the number and size of wounds, achievement of smoking cessation, and demographic information. Forty-eight percent of the control group participants and 57% of the intervention group participants smoked cigarettes at baseline. Smoking cessation doubled with the use of the clinical practice guidelines (P = .03). Smokers presented with a greater number of pressure injuries than nonsmokers. They experienced a mean increase rather than reduction in wound size. Nearly half (45.5%) of the intervention group participants who desired to have surgery had it performed, compared with only 34.9% of the control group participants (P = .35). Our findings demonstrate a positive influence with use of clinical practice guidelines to help individuals stop smoking. Results also confirm findings of previous studies supporting the negative impact of smoking on pressure injury healing in persons with spinal cord injuries.

Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation

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Wang Feng-Chao

2010-10-01

Full Text Available Abstract Background Transplantation of oligodendrocyte precursor cells (OPCs is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored. Results We transplanted green fluorescent protein (GFP expressed OPCs (GFP-OPCs into injured spinal cords of rats treated with or without CsA (10 mg/kg. Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI. Conclusions These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

Bladder stones in catheterized spinal cord-injured patients in Nigeria

African Journals Online (AJOL)

Objective: The objective was to determine the incidence of bladder stones in patients with spinal cord injury (SCI) and to assess if catheter encrustation or positive urinary culture of Proteus mirabilis is predictive of bladder stones. Background: Bladder stones are common urological complication in those with SCI managed ...

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

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Nan-Fu Chen

2018-04-01

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

Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord Injury PRINCIPAL...TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After Cervical Spinal Cord...care. However, despite these drastic interventions, the cervical injured patient is still susceptible to death due to respiratory complications

Viral vector-mediated gene expression in olfactory ensheathing glia implants in the lesioned rat spinal cord

NARCIS (Netherlands)

Ruitenberg, Marc J; Plant, Giles W; Christensen, C L; Blits, B; Niclou, Simone P; Harvey, Alan R; Boer, G J; Verhaagen, J

Implantation of olfactory ensheathing glia (OEG) is a promising strategy to augment long-distance regeneration in the injured spinal cord. In this study, implantation of OEG following unilateral hemisection of the dorsal cervical spinal cord was combined with ex vivo gene transfer techniques. We

Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling.

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Nagendran, Tharkika; Larsen, Rylan S; Bigler, Rebecca L; Frost, Shawn B; Philpot, Benjamin D; Nudo, Randolph J; Taylor, Anne Marion

2017-09-20

Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.Spinal cord injury can induce synaptic reorganization and remodeling in the brain. Here the authors study how severed distal axons signal back to the cell body to induce hyperexcitability, loss of inhibition and enhanced presynaptic release through netrin-1.

Gender differences in psychological adjustment among spinal cord ...

African Journals Online (AJOL)

In the present study gender differences in psychological adjustment of Spinal Cord Injured (SCI) patients was studied. The sample of 70 SCI patients (35 male and 35 female) was selected from the National Institute of Rehabilitation Medicine (NIRM) Islamabad, Bagh and Muzafrabad, (Azad & Jammu Kashmir AJK).

Spinal-cord injuries in Australian footballers, 1960-1985.

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Taylor, T K; Coolican, M R

1987-08-03

A review of 107 footballers who suffered a spinal-cord injury between 1960 and 1985 has been undertaken. Since 1977, the number of such injuries in Rugby Union, Rugby League and Australian Rules has increased, from an average of about two injuries a year before 1977 to over eight injuries a year since then. Rugby Union is clearly the most dangerous game, particularly for schoolboys; all of the injuries in schoolboy games for this code have occurred since 1977. This study has shown that collision at scrum engagement, and not at scrum collapse, is the way in which the majority of scrum injuries are sustained. These injuries are largely preventable, and suggestions for rule changes are made. Half the injured players recovered to Frankel grades D or E. The financial entitlements of those injured were grossly inadequate; this warrants action. A national register for spinal-cord injuries from football should be established to monitor the effects of desirable rule changes in Rugby Union and Rugby League.

Pregnancy in spinal cord-injured women, a cohort study of 37 pregnancies in 25 women.

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Le Liepvre, H; Dinh, A; Idiard-Chamois, B; Chartier-Kastler, E; Phé, V; Even, A; Robain, G; Denys, P

2017-02-01

A retrospective observational study. To describe specificities of pregnancy in a traumatic spinal cord-injured (SCI) population managed by a coordinated medical care team involving physical medicine and rehabilitation (PMR) physicians, urologists, infectious diseases' physicians, obstetricians and anaesthesiologists. NeuroUrology Department in a University Hospital, France. All consecutive SCI pregnant women managed between 2001 and 2014 were included. A preconceptional consultation was proposed whenever possible. Obstetrical and urological outcomes, delivery mode and complications were reported. Overall, thirty-seven pregnancies in 25 women, of a mean age of 32±4 years, were included. Thirty-five children were born alive (three miscarriages, a twin pregnancy) without complications except for a case of neonatal respiratory distress in premature twins born at 33 weeks. The mean birth weight was 2979±599 g. Twenty-one (57%) pregnancies benefited from preconceptional care. A weekly oral cyclic antibiotic programme was prescribed in 28 (75%) pregnancies. The main complications during pregnancy included pyelonephritis (30%), lower urinary tract infections (UTI) (32%), pressure sores (8.8%) and prematurity (12% deliveries before 37 weeks, with only one delivery before 36 weeks). Two patients suffered from autonomic dysreflexia, one with serious complication (brain haematoma). Caesarean sections were performed for 68% of deliveries (23/34) to prevent syringomyelia deterioration (n=10), stress urinary incontinence aggravation (n=3) or for obstetrical reasons (n=7). Mothers' and infants' outcomes were satisfying after pregnancy in SCI women, but required many adjustments. Pregnancy must be prepared by a preconceptional consultation, and managed by a multidisciplinary team involving specialists of neurological disability and pregnancy.

Hypobaric spinal anesthesia in the operative management of orthopedic emergencies in geriatric patients.

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Sidi, A; Pollak, D; Floman, Y; Davidson, J T

1984-07-01

Hypobaric spinal anesthesia was administered to 40 patients undergoing lower limb surgery. Twenty-nine of the patients were debilitated geriatric patients who presented with orthopedic emergencies, in most cases a fractured hip. Hypobaric spinal anesthesia was found to be a simple and safe procedure that provided adequate analgesia. Due to its inherent nature, hypobaric spinal anesthesia does not necessitate positioning of the patient on the injured, painful side (unlike hyperbaric spinal or epidural anesthesia) and, therefore, facilitates a smooth and painless transfer of the patient to the operating table. Complications encountered were similar to those following hyperbaric anesthesia.

Standardization of a spinal cord lesion model and neurologic evaluation using mice

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Borges, Paulo Alvim; Cristante, Alexandre Fogaça; de Barros-Filho, Tarcísio Eloy Pessoa; Natalino, Renato Jose Mendonça; dos Santos, Gustavo Bispo; Marcon, Raphael Marcus

2018-01-01

OBJECTIVE: To standardize a spinal cord lesion mouse model. METHODS: Thirty BALB/c mice were divided into five groups: four experimental groups and one control group (sham). The experimental groups were subjected to spinal cord lesion by a weight drop from different heights after laminectomy whereas the sham group only underwent laminectomy. Mice were observed for six weeks, and functional behavior scales were applied. The mice were then euthanized, and histological investigations were performed to confirm and score spinal cord lesion. The findings were evaluated to prove whether the method of administering spinal cord lesion was effective and different among the groups. Additionally, we correlated the results of the functional scales with the results from the histology evaluations to identify which scale is more reliable. RESULTS: One mouse presented autophagia, and six mice died during the experiment. Because four of the mice that died were in Group 5, Group 5 was excluded from the study. All the functional scales assessed proved to be significantly different from each other, and mice presented functional evolution during the experiment. Spinal cord lesion was confirmed by histology, and the results showed a high correlation between the Basso, Beattie, Bresnahan Locomotor Rating Scale and the Basso Mouse Scale. The mouse function scale showed a moderate to high correlation with the histological findings, and the horizontal ladder test had a high correlation with neurologic degeneration but no correlation with the other histological parameters evaluated. CONCLUSION: This spinal cord lesion mouse model proved to be effective and reliable with exception of lesions caused by a 10-g drop from 50 mm, which resulted in unacceptable mortality. The Basso, Beattie, Bresnahan Locomotor Rating Scale and Basso Mouse Scale are the most reliable functional assessments, and but the horizontal ladder test is not recommended. PMID:29561931

Anatomical and electrophysiological characterization of a population of dI6 interneurons in the neonatal mouse spinal cord.

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Griener, Anna; Zhang, Wei; Kao, Henry; Haque, Farhia; Gosgnach, Simon

2017-10-24

The locomotor central pattern generator is a neural network located in the ventral aspect of the caudal spinal cord that underlies stepping in mammals. While many genetically defined interneurons that are thought to comprise this neural network have been identified and characterized, the dI6 cells- which express the transcription factors WT1 and/or DMRT3- are one population that settle in this region, are active during locomotion, whose function is poorly understood. These cells were originally hypothesized to be commissural premotor interneurons, however evidence in support of this is sparse. Here we characterize this population of cells using the TgDbx1 Cre ;R26 EFP ;Dbx1 LacZ transgenic mouse line, which has been shown to be an effective marker of dI6 interneurons. We show dI6 cells to be abundant in laminae VII and VIII along the entire spinal cord and provide evidence that subtypes outside the WT1/DMRT3 expressing dI6 cells may exist. Retrograde tracing experiments indicate that the majority of dI6 cells project descending axons, and some make monosynaptic or disynaptic contacts onto motoneurons on either side of the spinal cord. Analysis of their activity during non-resetting deletions, which occur during bouts of fictive locomotion, suggests that these cells are involved in both locomotor rhythm generation and pattern formation. This study provides a thorough characterization of the dI6 cells labeled in the TgDbx1 Cre ;R26 EFP ;Dbx1 LacZ transgenic mouse, and supports previous work suggesting that these cells play multiple roles during locomotor activity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Ergonomics intervention on an alternative design of a spinal board.

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Zadry, Hilma Raimona; Susanti, Lusi; Rahmayanti, Dina

2017-09-01

A spinal board is the evacuation tool of first aid to help the injured spinal cord. The existing spinal board has several weaknesses, both in terms of user comfort and the effectiveness and efficiency of the evacuation process. This study designs an ergonomic spinal board using the quality function deployment approach. A preliminary survey was conducted through direct observation and interviews with volunteers from the Indonesian Red Cross. Data gathered were translated into a questionnaire and answered by 47 participants in West Sumatra. The results indicate that the selection of materials, the application of strap systems as well as the addition of features are very important in designing an ergonomic spinal board. The data were used in designing an ergonomic spinal board. The use of anthropometric data ensures that this product can accommodate safety and comfort when immobilized, as well as the flexibility and speed of the rescue evacuation process.

Spinal-Cord-Injured Individual's Experiences of Having a Partner

DEFF Research Database (Denmark)

Angel, Sanne

2015-01-01

Having a partner is a strong factor in adaptation to the new life situation with a spinal cord injury (SCI). Still, more knowledge in detail about the partner's influences according to the experiences of individuals with SCI could contribute to the understanding of the situation after an injury. ...... and allowed SCI individuals the ability to self-realize. This promoted feelings of profound gratitude but also dependency. Thus, the SCI individual benefitted from the partner's support mentally and physically, which enabled a life that would not otherwise be possible....

Local vascular adaptations after hybrid training in spinal cord-injured subjects.

NARCIS (Netherlands)

Thijssen, D.H.J.; Heesterbeek, P.J.C.; Kuppevelt, D. van; Duysens, J.E.J.; Hopman, M.T.E.

2005-01-01

PURPOSE: Studies investigating vascular adaptations in non-exercised areas during whole body exercise training show conflicting results. Individuals with spinal cord injury (SCI) provide a unique model to examine vascular adaptations in active tissue vs adjacent inactive areas. The purpose of this

Bladder cancer mortality after spinal cord injury over 4 decades.

Science.gov (United States)

Nahm, Laura S; Chen, Yuying; DeVivo, Michael J; Lloyd, L Keith

2015-06-01

We estimate bladder cancer mortality in people with spinal cord injury compared to the general population. Data and statistics were retrieved from the National Spinal Cord Injury Statistical Center and the National Center for Health Statistics. The mortality experience of the 45,486 patients with traumatic spinal cord injury treated at a Spinal Cord Injury Model System or Shriners Hospital was compared to the general population using a standardized mortality ratio. The standardized mortality ratio data were further stratified by age, gender, race, time since injury and injury severity. Our study included 566,532 person-years of followup between 1960 and 2009, identified 10,575 deaths and categorized 99 deaths from bladder cancer. The expected number of deaths from bladder cancer would have been 14.8 if patients with spinal cord injury had the same bladder cancer mortality as the general population. Thus, the standardized mortality ratio is 6.7 (95% CI 5.4-8.1). Increased mortality risk from bladder cancer was observed for various ages, races and genders, as well as for those injured for 10 or more years and with motor complete injuries. Bladder cancer mortality was not significantly increased for ventilator users, those with motor incomplete injuries or those injured less than 10 years. Individuals with a spinal cord injury can potentially live healthier and longer by reducing the incidence and mortality of bladder cancer. Study findings highlight the need to identify at risk groups and contributing factors for bladder cancer death, leading to the development of prevention, screening and management strategies. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Weight-bearing locomotion in the developing opossum, Monodelphis domestica following spinal transection: remodeling of neuronal circuits caudal to lesion.

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Wheaton, Benjamin J; Noor, Natassya M; Whish, Sophie C; Truettner, Jessie S; Dietrich, W Dalton; Zhang, Moses; Crack, Peter J; Dziegielewska, Katarzyna M; Saunders, Norman R

2013-01-01

Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming) P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors' gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating that although

Weight-bearing locomotion in the developing opossum, Monodelphis domestica following spinal transection: remodeling of neuronal circuits caudal to lesion.

Directory of Open Access Journals (Sweden)

Benjamin J Wheaton

Full Text Available Complete spinal transection in the mature nervous system is typically followed by minimal axonal repair, extensive motor paralysis and loss of sensory functions caudal to the injury. In contrast, the immature nervous system has greater capacity for repair, a phenomenon sometimes called the infant lesion effect. This study investigates spinal injuries early in development using the marsupial opossum Monodelphis domestica whose young are born very immature, allowing access to developmental stages only accessible in utero in eutherian mammals. Spinal cords of Monodelphis pups were completely transected in the lower thoracic region, T10, on postnatal-day (P7 or P28 and the animals grew to adulthood. In P7-injured animals regrown supraspinal and propriospinal axons through the injury site were demonstrated using retrograde axonal labelling. These animals recovered near-normal coordinated overground locomotion, but with altered gait characteristics including foot placement phase lags. In P28-injured animals no axonal regrowth through the injury site could be demonstrated yet they were able to perform weight-supporting hindlimb stepping overground and on the treadmill. When placed in an environment of reduced sensory feedback (swimming P7-injured animals swam using their hindlimbs, suggesting that the axons that grew across the lesion made functional connections; P28-injured animals swam using their forelimbs only, suggesting that their overground hindlimb movements were reflex-dependent and thus likely to be generated locally in the lumbar spinal cord. Modifications to propriospinal circuitry in P7- and P28-injured opossums were demonstrated by changes in the number of fluorescently labelled neurons detected in the lumbar cord following tracer studies and changes in the balance of excitatory, inhibitory and neuromodulatory neurotransmitter receptors' gene expression shown by qRT-PCR. These results are discussed in the context of studies indicating

Patient-focused goal planning process and outcome after spinal cord injury rehabilitation: quantitative and qualitative audit.

Science.gov (United States)

Byrnes, Michelle; Beilby, Janet; Ray, Patricia; McLennan, Renee; Ker, John; Schug, Stephan

2012-12-01

To evaluate the process and outcome of a multidisciplinary inpatient goal planning rehabilitation programme on physical, social and psychological functioning for patients with spinal cord injury. Clinical audit: quantitative and qualitative analyses. Specialist spinal injury unit, Perth, Australia. Consecutive series of 100 newly injured spinal cord injury inpatients. MAIN MEASURE(S): The Needs Assessment Checklist (NAC), patient-focused goal planning questionnaire and goal planning progress form. The clinical audit of 100 spinal cord injured patients revealed that 547 goal planning meetings were held with 8531 goals stipulated in total. Seventy-five per cent of the goals set at the first goal planning meeting were achieved by the second meeting and the rate of goal achievements at subsequent goal planning meetings dropped to 56%. Based on quantitative analysis of physical, social and psychological functioning, the 100 spinal cord injury patients improved significantly from baseline to discharge. Furthermore, qualitative analysis revealed benefits consistently reported by spinal cord injury patients of the goal planning rehabilitation programme in improvements to their physical, social and psychological adjustment to injury. The findings of this clinical audit underpin the need for patient-focused goal planning rehabilitation programmes which are tailored to the individual's needs and involve a comprehensive multidisciplinary team.

Spinal cord regeneration: moving tentatively towards new perspectives.

Science.gov (United States)

Jones, D G; Anderson, E R; Galvin, K A

2003-01-01

The failure of the adult human spinal cord to regenerate following injury is not absolute, but appears to be amenable to therapeutic manipulation. Recent work has shown that the provision of a growth permissive environment by the neutralization of inhibitory influences, or the grafting of fetal tissue, peripheral nerve, Schwann cells, or olfactory ensheathing cells can enhance regeneration in animal models of spinal cord injury. Stem cells are gaining ever-increasing favour as a treatment option for spinal cord injury. The potential of neural stem cells, embryonic stem cells, and bone marrow stromal cells is discussed. Additional treatment options such as pharmacological interventions, functional electrical stimulation and physiotherapy approaches are also explored. Basic science insights are used as a foundation for a discussion of a variety of clinical perspectives including repair of the chronically injured spinal cord, animal models of human spinal cord injuries and clinical trials. A more holistic approach towards spinal cord injury is suggested, one where a hierarchy of needs is recognised and quality of life is paramount. Finally, this review cautions against overly grandiose claims of an imminent miracle cure for human spinal cord injury.

Cerebral activation is correlated to regional atrophy of the spinal cord and functional motor disability in spinal cord injured individuals

DEFF Research Database (Denmark)

Lundell, Henrik; Christensen, Mark Schram; Barthélemy, Dorothy

2011-01-01

Recovery of function following lesions in the nervous system requires adaptive changes in surviving circuitries. Here we investigate whether changes in cerebral activation are correlated to spinal cord atrophy and recovery of functionality in individuals with incomplete spinal cord injury (SCI). 19...... hand and the functional ability of the SCI participants measured by the clinical motor score on the other. There was no significant correlation between activation in any other cerebral area and the motor score. Activation in ipsilateral somatosensory cortex (S1), M1 and PMC was negatively correlated...... to the width of the spinal cord in the left-right direction, where the corticospinal tract is located, but not in the antero-posterior direction. There was a tendency for a negative correlation between cerebral activation in ipsilateral S1, M1 and PMC and the amplitude of motor evoked potentials...

Spinal endoscopy combined with selective CT myelography for dural closure of the spinal dural defect with superficial siderosis: technical note.

Science.gov (United States)

Arishima, Hidetaka; Higashino, Yoshifumi; Yamada, Shinsuke; Akazawa, Ayumi; Arai, Hiroshi; Tsunetoshi, Kenzo; Matsuda, Ken; Kodera, Toshiaki; Kitai, Ryuhei; Awara, Kousuke; Kikuta, Ken-Ichiro

2018-01-01

The authors describe a new procedure to detect the tiny dural hole in patients with superficial siderosis (SS) and CSF leakage using a coronary angioscope system for spinal endoscopy and selective CT myelography using a spinal drainage tube. Under fluoroscopy, surgeons inserted the coronary angioscope into the spinal subarachnoid space, similar to the procedure of spinal drainage, and slowly advanced it to the cervical spine. The angioscope clearly showed the small dural hole and injured arachnoid membrane. One week later, the spinal drainage tube was inserted, and the tip of the drainage tube was located just below the level of the dural defect found by the spinal endoscopic examination. This selective CT myelography clarifies the location of the dural defect. During surgery, the small dural hole could be easily located, and it was securely sutured. It is sometimes difficult to detect the actual location of the small dural hole even with thin-slice MRI or dynamic CT myelography in patients with SS. The use of a coronary angioscope for the spinal endoscopy combined with selective CT myelography may provide an effective examination to assess dural closure of the spinal dural defect with SS in cases without obvious dural defects on conventional imaging.

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

Directory of Open Access Journals (Sweden)

Karen K Y Ling

2010-11-01

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

Challenges in comprehensive management of spinal cord injury in India and in the Asian Spinal Cord network region: findings of a survey of experts, patients and consumers.

Science.gov (United States)

Chhabra, H S; Sharma, S; Arora, M

2018-01-01

Online survey. To understand the prevailing scenario of the comprehensive management of spinal cord injuries (SCI) in India and in the Asian Spinal Cord Network (ASCoN) region, especially with a view to document the challenges faced and its impact. Indian Spinal Injuries Centre. A questionnaire was designed which covered various aspects of SCI management. Patients, consumers (spinal injured patients discharged since at least 1 year) and experts in SCI management from different parts of India and the ASCoN region were approached to complete the survey. Sixty patients, 66 consumers and 34 experts completed the survey. Difference of opinion was noticed among the three groups. Disposable Nelaton catheters were used by 57% consumers and 47% patients. For reusable catheter, 31% experts recommended processing with soap and running water and 45% recommended clean cotton cloth bag for storage. Pre-hospital care and community inclusion pose the biggest challenges in management of SCI. More than 75% of SCI faced problems of access and mobility in the community. Awareness about SCI, illiteracy and inadequate patient education are the most important factors hindering pre- and in-hospital care. Inadequate physical as well as vocational rehabilitation and financial barriers are thought to be the major factors hindering integration of spinal injured into mainstream society. Strong family support helped in rehabilitation. Our study brought out that SCI in India and ASCoN region face numerous challenges that affect access to almost all aspects of comprehensive management of SCI.

Necrosulfonamide Attenuates Spinal Cord Injury via Necroptosis Inhibition.

Science.gov (United States)

Wang, Yongxiang; Wang, Jingcheng; Wang, Hua; Feng, Xinmin; Tao, Yuping; Yang, Jiandong; Cai, Jun

2018-03-31

Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. This study is to investigate the effects, mechanism, and potential benefit of necrosulfonamide (NSA) for SCI therapy. Pathologic condition was detected using hematoxylin-eosin staining on injured spinal cord and other major organs. Necroptosis-related factors-RIP1, RIP3, and MLKL-were detected using Western blot. Detections on mitochondrial functions such as adenosine triphosphate generation and activities of superoxide dismutase and caspase-3 were also performed. Finally, ethologic performance was detected using a 21-point open-field locomotion test. Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA using hematoxylin-eosin staining for pathologic detection. No obvious toxicity on rat liver, kidney, heart, and spleen was detected. Rather than RIP1 and RIP3, MLKL was significantly inhibited by the NSA using Western blot detection. Adenosine triphosphate generation was obviously decreased post injury but slightly increased after the NSA treatment, especially 24 hours post injury. No significant changes were found on activities of superoxide dismutase and caspase-3 after the treatment of NSA. Ethologic performance was significantly improved using a 21-point, open-field locomotion test. Our research indicates NSA attenuates the spinal cord injury via necroptosis inhibition. It might be a potential and safe chemical benefit for SCI therapy. To our knowledge, this is the first study on the effects of NSA as treatment of traumatic SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

Science.gov (United States)

Hawryluk, Gregory W.J.; Mothe, Andrea; Wang, Jian; Wang, Shelly; Tator, Charles

2012-01-01

Cellular transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant elevation of nerve growth factor (NGF), leukemia inhibitory factor (LIF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β1 (TGF-β1), and lower expression of vascular endothelial growth factor isoform A (VEGF-A) and platelet-derived growth factor-A (PDGF-A). Transplantation of NPCs led to modest changes in trophin expression, and the co-administration of intrathecal trophins resulted in significant elevation of the neurotrophins, glial-derived neurotrophic factor (GDNF), LIF, and basic fibroblast growth factor (bFGF). BMSCs transplantation upregulated NGF, LIF, and IGF-1. NPCs isolated after transplantation into the injured spinal cord expressed the neurotrophins, ciliary neurotrophic factor (CNTF), epidermal growth factor (EGF), and bFGF at higher levels than host cord. These data show that trophin expression in the spinal cord is influenced by injury and cell transplantation, particularly when combined with intrathecal trophin infusion

Prevention of urinary tract infection in six spinal cord-injured pregnant women who gave birth to seven children under a weekly oral cyclic antibiotic program.

Science.gov (United States)

Salomon, Jérôme; Schnitzler, Alexis; Ville, Yves; Laffont, Isabelle; Perronne, Christian; Denys, Pierre; Bernard, Louis

2009-05-01

Pregnancies in spinal cord-injured (SCI) patients present unique clinical challenges. Because of the neurogenic bladder and the use of intermittent catheterization, chronic bacteriuria and recurrent urinary tract infection (UTI) is common. During pregnancy the prevalence of UTI increases dramatically. Recurrent UTI requires multiple courses of antibiotics and increases the risks of abortion, prematurity, and low birth weight. A weekly oral cyclic antibiotic (WOCA) program was recently described for the prevention of UTI in SCI patients. To test the impact of WOCA in six SCI pregnant women (four paraplegic, two tetraplegic). This was a prospective observational study. WOCA consists of the alternate administration of one of two antibiotics once per week. We observed a significant reduction of UTI (6 UTI/patient/year before pregnancy to 0.4 during pregnancy and under WOCA; pUTI prophylaxis in SCI pregnant women.

Development of spinal deformities in Atlantic salmon and Arctic charr fed diets supplemented with oxytetracycline

International Nuclear Information System (INIS)

Toften, H.; Jobling, M.

1996-01-01

Some individuals within populations of Atlantic salmon Salmo salar and Arctic charr Salvelinus alpinus fed diets supplemented with oxytetracycline (OTC) developed spinal deformations. Possible differences in feed intake and growth of spinally deformed fish relative to fish without any deformities were investigated. Amongst Atlantic salmon, 17% of the fish fed OTC-supplemented feed developed spinal fractures, whereas none of the fish receiving the basic feed did so. Despite deformation of the spinal column, the injured fish continued to feed and grow, but at lower rates than unaffected individuals. In contrast to Atlantic salmon, Arctic charr showed no signs of spinal fractures at any time during the 65-day experiment

Development of spinal deformities in Atlantic salmon and Arctic charr fed diets supplemented with oxytetracycline

Energy Technology Data Exchange (ETDEWEB)

Toften, H.; Jobling, M. [Norwegian Institute of Fisheries and Aquaculture, N-9005 Tromsoe (Norway)

1996-07-01

Some individuals within populations of Atlantic salmon Salmo salar and Arctic charr Salvelinus alpinus fed diets supplemented with oxytetracycline (OTC) developed spinal deformations. Possible differences in feed intake and growth of spinally deformed fish relative to fish without any deformities were investigated. Amongst Atlantic salmon, 17% of the fish fed OTC-supplemented feed developed spinal fractures, whereas none of the fish receiving the basic feed did so. Despite deformation of the spinal column, the injured fish continued to feed and grow, but at lower rates than unaffected individuals. In contrast to Atlantic salmon, Arctic charr showed no signs of spinal fractures at any time during the 65-day experiment.

Understanding physical activity in spinal cord injury rehabilitation: translating and communicating research through stories.

Science.gov (United States)

Smith, Brett; Papathomas, Anthony; Martin Ginis, Kathleen A; Latimer-Cheung, Amy E

2013-01-01

The purpose of this article is to develop an evidence-based resource for knowing and communicating the complexities involved for both males and females in implementing and sustaining a physically active lifestyle shortly after spinal cord injury (SCI). Synthesizing a set of qualitative and quantitative studies with over 500 spinal cord injured people, the article represents research utilizing the genre of ethnographic creative non-fiction. This genre of representation holds enormous potential for researchers in terms of disseminating their findings to diverse audiences beyond the academy, and having real impact. The ethnographic creative non-fictions show together for the first time the barriers, determinants, benefits, trajectories, emotions, fears, preferred methods and messengers for delivering important physical activity information to men and women with a SCI. The article contributes to knowledge by showing the embodied complexities involved when in rehabilitation for both males and females in implementing and sustaining a physically active lifestyle shortly after SCI. It also makes a contribution to practice by providing researchers, health care professionals and disability user-groups with a theory and evidence based resource to assist in informing, teaching and enabling people living with SCI to initiate and maintain a physically active lifestyle. Stories may be a highly effective tool to communicate with and to influence spinal cord injured people's activity. The findings of this research showed the many benefits and barriers to developing and sustaining a physically active lifestyle shortly after spinal cord injury. The preferred methods and messengers for delivering physical activity information as well as the activity types, intensities and durations of physical activity for men and women were also shown. Within rehabilitation, spinal cord injured people need to be offered accessible knowledge about how to implement and sustain a physically active

Spinal Trauma is Never without Sin: A Tetraplegia Patient Presented Without any Symptoms

OpenAIRE

EFEOGLU, Melis; AKOGLU, Haldun; AKOGLU, Tayfun; EROGLU, Serkan Emre; ONUR, Ozge Ecmel; DENIZBASI, Arzu

2016-01-01

SUMMARY: Spinal cord injuries are amongst the most dangerous injuries, leading to high mortality and morbidity. Injured patients are occasionally faced with life-threatening complications and quality-of-life changing neurological deficits. Thoracic and cervical spinal segments are the most effected sites of injury and a wide range of complications including paraplegia, respiratory and cardiovascular compromise secondary to autonomic dysfunction or tetraplegia may ensue. We aim to draw attenti...

Functional electrical stimulation-assisted walking for persons with incomplete spinal injuries

DEFF Research Database (Denmark)

Ladouceur, M.; Barbeau, H.

2000-01-01

This study investigated the changes in maximal overground walking speed (MOWS) that occurred during; walking training with a functional electrical stimulation (FES) orthosis by chronic spinal cord injured persons with incomplete motor function loss. The average walking: speed over a distance of 10...

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

Science.gov (United States)

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

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

Connexin 50 Expression in Ependymal Stem Progenitor Cells after Spinal Cord Injury Activation

Directory of Open Access Journals (Sweden)

Francisco Javier Rodriguez-Jimenez

2015-11-01

Full Text Available Ion channels included in the family of Connexins (Cx help to control cell proliferation and differentiation of neuronal progenitors. Here we explored the role of Connexin 50 (Cx50 in cell fate modulation of adult spinal cord derived neural precursors located in the ependymal canal (epSPC. epSPC from non-injured animals showed high expression levels of Cx50 compared to epSPC from animals with spinal cord injury (SCI (epSPCi. When epSPC or epSPCi were induced to spontaneously differentiate in vitro we found that Cx50 favors glial cell fate, since higher expression levels, endogenous or by over-expression of Cx50, augmented the expression of the astrocyte marker GFAP and impaired the neuronal marker Tuj1. Cx50 was found in both the cytoplasm and nucleus of glial cells, astrocytes and oligodendrocyte-derived cells. Similar expression patterns were found in primary cultures of mature astrocytes. In addition, opposite expression profile for nuclear Cx50 was observed when epSPC and activated epSPCi were conducted to differentiate into mature oligodendrocytes, suggesting a different role for this ion channel in spinal cord beyond cell-to-cell communication. In vivo detection of Cx50 by immunohistochemistry showed a defined location in gray matter in non-injured tissues and at the epicenter of the injury after SCI. epSPCi transplantation, which accelerates locomotion regeneration by a neuroprotective effect after acute SCI is associated with a lower signal of Cx50 within the injured area, suggesting a minor or detrimental contribution of this ion channel in spinal cord regeneration by activated epSPCi.

Self-concept and sexuality of spinal cord injured women.

Science.gov (United States)

Fitting, M D; Salisbury, S; Davies, N H; Mayclin, D K

1978-03-01

Differences in perceived self-concept and sexual response before and after spinal cord injury were examined. Twenty-four women between the ages of 20 and 40 completed a questionnaire and participated in a brief taped interview. Most of the women viewed themselves as very or somewhat attractive and had been involved in a sexual relationship since injury. The majority viewed sexual relationships as very enjoyable, although many commented that changes in bowel and bladder function had inhibited sexual expression. The need for more effective sexual counseling was highlighted. A trend was noted for an interrelationship between sexuality and self-concept in adapting to acquired disability.

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

Science.gov (United States)

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

2012-01-01

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

X-ray phase-contrast computed tomography visualizes the microstructure and degradation profile of implanted biodegradable scaffolds after spinal cord injury

Energy Technology Data Exchange (ETDEWEB)

Takashima, Kenta, E-mail: takashima-k@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Sendai (Japan); University of Tokyo, Tokyo (Japan); Hoshino, Masato; Uesugi, Kentaro; Yagi, Naoto [SPring-8, Hyogo (Japan); Matsuda, Shojiro [Gunze Limited, Shiga (Japan); Nakahira, Atsushi [Osaka Prefecture University, Osaka (Japan); Osumi, Noriko; Kohzuki, Masahiro [Tohoku University Graduate School of Medicine, Sendai (Japan); Onodera, Hiroshi [University of Tokyo, Tokyo (Japan)

2015-01-01

X-ray phase-contrast computed tomography imaging based on the Talbot grating interferometer is described, and the way it can visualize the polyglycolic acid scaffold, including its microfibres, after implantation into the injured spinal cord is shown. Tissue engineering strategies for spinal cord repair are a primary focus of translational medicine after spinal cord injury (SCI). Many tissue engineering strategies employ three-dimensional scaffolds, which are made of biodegradable materials and have microstructure incorporated with viable cells and bioactive molecules to promote new tissue generation and functional recovery after SCI. It is therefore important to develop an imaging system that visualizes both the microstructure of three-dimensional scaffolds and their degradation process after SCI. Here, X-ray phase-contrast computed tomography imaging based on the Talbot grating interferometer is described and it is shown how it can visualize the polyglycolic acid scaffold, including its microfibres, after implantation into the injured spinal cord. Furthermore, X-ray phase-contrast computed tomography images revealed that degradation occurred from the end to the centre of the braided scaffold in the 28 days after implantation into the injured spinal cord. The present report provides the first demonstration of an imaging technique that visualizes both the microstructure and degradation of biodegradable scaffolds in SCI research. X-ray phase-contrast imaging based on the Talbot grating interferometer is a versatile technique that can be used for a broad range of preclinical applications in tissue engineering strategies.

Reaction to topical capsaicin in spinal cord injury patients with and without central pain

DEFF Research Database (Denmark)

Finnerup, Nanna Brix; Pedersen, Louise H.; Terkelsen, Astrid J.

2007-01-01

of a spinal cord injury which already is hyperexcitable, would cause enhanced responses in patients with central pain at the level of injury compared to patients without neuropathic pain and healthy controls. Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above, at, and below injury......Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence...... at the level of injury. Keywords: Spinal cord injury; Neuropathic pain; Capsaicin; Neuronal hyperexcitability; Hyperalgesia; Blood flow...

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

Directory of Open Access Journals (Sweden)

Claire Bacon

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

Sim1 is required for the migration and axonal projections of V3 interneurons in the developing mouse spinal cord.

Science.gov (United States)

Blacklaws, Jake; Deska-Gauthier, Dylan; Jones, Christopher T; Petracca, Yanina L; Liu, Mingwei; Zhang, Han; Fawcett, James P; Glover, Joel C; Lanuza, Guillermo M; Zhang, Ying

2015-09-01

V3 spinal interneurons (INs) are a group of excitatory INs that play a crucial role in producing balanced and stable gaits in vertebrate animals. In the developing mouse spinal cord, V3 INs arise from the most ventral progenitor domain and form anatomically distinctive subpopulations in adult spinal cords. They are marked by the expression of transcription factor Sim1 postmitotically, but the function of Sim1 in V3 development remains unknown. Here, we used Sim1(Cre) ;tdTomato mice to trace the fate of V3 INs in a Sim1 mutant versus control genetic background during development. In Sim1 mutants, V3 INs are produced normally and maintain a similar position and organization as in wild types before E12.5. Further temporal analysis revealed that the V3 INs in the mutants failed to migrate properly to form V3 subgroups along the dorsoventral axis of the spinal cord. At birth, in the Sim1 mutant the number of V3 INs in the ventral subgroup was normal, but they were significantly reduced in the dorsal subgroup with a concomitant increase in the intermediate subgroup. Retrograde labeling at lumbar level revealed that loss of Sim1 led to a reduction in extension of contralateral axon projections both at E14.5 and P0 without affecting ipsilateral axon projections. These results demonstrate that Sim1 is essential for proper migration and the guidance of commissural axons of the spinal V3 INs. © 2015 Wiley Periodicals, Inc.

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

Science.gov (United States)

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

2016-09-05

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

Childhood onset of spinal cord injury: self-esteem and self-perception.

Science.gov (United States)

Kennedy, P; Gorsuch, N; Marsh, N

1995-11-01

The effects of spinal cord injury in childhood upon later psychological adjustment were investigated by comparing a group of 86 people injured as children with a control group (matched for time since injury and level of injury) of people injured as adults. It was hypothesized that adolescence is a crucial period in psychological development and that the effect of spinal cord injury on body image, self-concept and social relationships during adolescence will have a long-term negative effect on psychological well-being. However, on overall measures of depression, self-esteem and self-perception, there were no significant differences between the experimental and control groups. Furthermore, there were no significant differences between paraplegics and tetraplegics, between men women, or between those who were involved in a significant intimate relationship and those who were not. These findings support previous research which has suggested that organic variables, such as age at injury and level of injury, are not predictive of long-term psychological adjustment.

Firing patterns of spontaneously active motor units in spinal cord-injured subjects

NARCIS (Netherlands)

Zijdewind, Inge; Thomas, Christine K.

Involuntary motor unit activity at low rates is common in hand muscles paralysed by spinal cord injury. Our aim was to describe these patterns of motor unit behaviour in relation to motoneurone and motor unit properties. Intramuscular electromyographic activity (EMG), surface EMG and force were

The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord injured mice.

Science.gov (United States)

Almad, Akshata; Lash, A Todd; Wei, Ping; Lovett-Racke, Amy E; McTigue, Dana M

2011-12-01

Peroxisome Proliferator Activated Receptor (PPAR)-α is a key regulator of lipid metabolism and recent studies reveal it also regulates inflammation in several different disease models. Gemfibrozil, an agonist of PPAR-α, is a FDA approved drug for hyperlipidemia and has been shown to inhibit clinical signs in a rodent model of multiple sclerosis. Since many studies have shown improved outcome from spinal cord injury (SCI) by anti-inflammatory and neuroprotective agents, we tested the efficacy of oral gemfibrozil given before or after SCI for promoting tissue preservation and behavioral recovery after spinal contusion injury in mice. Unfortunately, the results were contrary to our hypothesis; in our first attempt, gemfibrozil treatment exacerbated locomotor deficits and increased tissue pathology after SCI. In subsequent experiments, the behavioral effects were not replicated but histological outcomes again were worse. We also tested the efficacy of a different PPAR-α agonist, fenofibrate, which also modulates immune responses and is beneficial in several neurodegenerative disease models. Fenofibrate treatment did not improve recovery, although there was a slight trend for a modest increase in histological tissue sparing. Based on our results, we conclude that PPAR-α agonists yield either no effect or worsen recovery from spinal cord injury, at least at the doses and the time points of drug delivery tested here. Further, patients sustaining spinal cord injury while taking gemfibrozil might be prone to exacerbated tissue damage. Copyright © 2011 Elsevier Inc. All rights reserved.

Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

Science.gov (United States)

Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

2015-01-01

Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats. PMID:26487860

CT study in primary low spinal fluid pressure syndrome

Energy Technology Data Exchange (ETDEWEB)

Hoshino, Moritoshi; Okayama, Kenji; Kubo, Hiromasa; Watanabe, Hiromi; Endou, Riuko (Ohmiya Red Cross Hospital, Yono, Saitama (Japan))

1991-02-01

CT findings in primary low spinal fluid pressure syndrome were studied on the basis of 3 cases. Case 1 was a 43-year-old male with a complicated bilateral isodense subdural hematoma (SDH). Case 2 was a 45-year-old female with a complicated bilateral high dense SDH. Case 3 was a 36-year-old female discharged without any complications after spinal fluid pressure normalized. Slight downward displacement of the brain under low spinal fluid pressure was shown as the narrowing of a Sylvian fissures and infratentorial cisterns on CT. On the other hand, in this syndrome with a complicated bilateral isodense SDH, in addition to this finding, CT revealed distortion and narrowing of body lateral ventricles, which might be differential findings from this syndrome without complicated SDH. Under low spinal fluid pressure, bridging veins are more stretched by a downward displacement of the brain. And consequently they were easily injured and SDH was developed. (author).

Complete Spinal Accessory Nerve Palsy From Carrying Climbing Gear.

Science.gov (United States)

Coulter, Jess M; Warme, Winston J

2015-09-01

We report an unusual case of spinal accessory nerve palsy sustained while transporting climbing gear. Spinal accessory nerve injury is commonly a result of iatrogenic surgical trauma during lymph node excision. This particular nerve is less frequently injured by blunt trauma. The case reported here results from compression of the spinal accessory nerve for a sustained period-that is, carrying a load over the shoulder using a single nylon rope for 2.5 hours. This highlights the importance of using proper load-carrying equipment to distribute weight over a greater surface area to avoid nerve compression in the posterior triangle of the neck. The signs and symptoms of spinal accessory nerve palsy and its etiology are discussed. This report is particularly relevant to individuals involved in mountaineering and rock climbing but can be extended to anyone carrying a load with a strap over one shoulder and across the body. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Surgical reconstruction of spinal cord circuit provides functional return in humans

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Thomas Carlstedt

2017-01-01

Full Text Available This mini review describes the current surgical strategy for restoring function after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus injury in man. As this lesion is a spinal cord or central nervous injury functional return depends on spinal cord nerve cell growth within the central nervous system. Basic science, clinical research and human application has demonstrated good and useful motor function after ventral root avulsion followed by spinal cord reimplantation. Recently, sensory return could be demonstrated following spinal cord surgery bypassing the injured primary sensory neuron. Experimental data showed that most of the recovery depended on new growth reinnervating peripheral receptors. Restored sensory function and the return of spinal reflex was demonstrated by electrophysiology and functional magnetic resonance imaging of human cortex. This spinal cord surgery is a unique treatment of central nervous system injury resulting in useful functional return. Further improvements will not depend on surgical improvements. Adjuvant therapy aiming at ameliorating the activity in retinoic acid elements in dorsal root ganglion neurons could be a new therapeutic avenue in restoring spinal cord circuits after nerve root avulsion injury.

Dynamic oscillatory signatures of central neuropathic pain in spinal cord injury.

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Vuckovic, Aleksandra; Hasan, Muhammad A; Fraser, Matthew; Conway, Bernard A; Nasseroleslami, Bahman; Allan, David B

2014-06-01

Central neuropathic pain (CNP) is believed to be accompanied by increased activation of the sensorimotor cortex. Our knowledge of this interaction is based mainly on functional magnetic resonance imaging studies, but there is little direct evidence on how these changes manifest in terms of dynamic neuronal activity. This study reports on the presence of transient electroencephalography (EEG)-based measures of brain activity during motor imagery in spinal cord-injured patients with CNP. We analyzed dynamic EEG responses during imaginary movements of arms and legs in 3 groups of 10 volunteers each, comprising able-bodied people, paraplegic patients with CNP (lower abdomen and legs), and paraplegic patients without CNP. Paraplegic patients with CNP had increased event-related desynchronization in the theta, alpha, and beta bands (16-24 Hz) during imagination of movement of both nonpainful (arms) and painful limbs (legs). Compared to patients with CNP, paraplegics with no pain showed a much reduced power in relaxed state and reduced event-related desynchronization during imagination of movement. Understanding these complex dynamic, frequency-specific activations in CNP in the absence of nociceptive stimuli could inform the design of interventional therapies for patients with CNP and possibly further understanding of the mechanisms involved. This study compares the EEG activity of spinal cord-injured patients with CNP to that of spinal cord-injured patients with no pain and also to that of able-bodied people. The study shows that the presence of CNP itself leads to frequency-specific EEG signatures that could be used to monitor CNP and inform neuromodulatory treatments of this type of pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

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Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

2012-12-01

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

Targeted retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene prevents loss of mouse (twy/twy) anterior horn neurons in vivo sustaining mechanical compression.

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Xu, Kan; Uchida, Kenzo; Nakajima, Hideaki; Kobayashi, Shigeru; Baba, Hisatoshi

2006-08-01

Immunohistochemical analysis after adenovirus (AdV)-mediated BDNF gene transfer in and around the area of mechanical compression in the cervical spinal cord of the hyperostotic mouse (twy/twy). To investigate the neuroprotective effect of targeted AdV-BDNF gene transfection in the twy mouse with spontaneous chronic compression of the spinal cord motoneurons. Several studies reported the neuroprotective effects of neurotrophins on injured spinal cord. However, no report has described the effect of targeted retrograde neurotrophic gene delivery on motoneuron survival in chronic compression lesions of the cervical spinal cord resembling lesions of myelopathy. LacZ marker gene using adenoviral vector (AdV-LacZ) was used to evaluate retrograde delivery from the sternomastoid muscle in adult twy mice (16-week-old) and (control). Four weeks after the AdV-LacZ or AdV-BDNF injection, the compressed cervical spinal cord was removed en bloc for immunohistologic investigation of b-galactosidase activity and immunoreactivity and immunoblot analyses of BDNF. The number of anterior horn neurons was counted using Nissl, ChAT and AChE staining. Spinal accessory motoneurons between C1 and C3 segments were successfully transfected by AdV-LacZ in both twy and ICR mice after targeted intramuscular injection. Immunoreactivity to BDNF was significantly stronger in AdV-BDNF-gene transfected twy mice than in AdV-LacZ-gene transfected mice. At the cord level showing the maximum compression in AdV-BDNF-transfected twy mice, the number of anterior horn neurons was sinificantly higher in the topographic neuronal cell counting of Nissl-, ChAT-, and AChE-stained samples than in AdV-LacZ-injected twy mice. Targeted AdV-BDNF-gene delivery significantly increased Nissl-stained anterior horn neurons and enhanced cholinergic enzyme activities in the twy. Our results suggest that targeted retrograde AdV-BDNF-gene in vivo delivery may enhance neuronal survival even under chronic mechanical compression.

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

DEFF Research Database (Denmark)

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

2005-01-01

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

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

International Nuclear Information System (INIS)

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

2016-01-01

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

Abdominal pain in long-term spinal cord injury

DEFF Research Database (Denmark)

Finnerup, Nanna Brix; Faaborg, Pia Møller; Krogh, Klaus

2008-01-01

Objectives:To describe the prevalence and character of chronic abdominal pain in a group of patients with long-term spinal cord injury (SCI) and to assess predictors of abdominal pain.Study design:Postal survey.Setting:Members of the Danish Paraplegic Association.Methods:We mailed a questionnaire...... to 284 members of the Danish Paraplegic Association who met the inclusion criteria (member for at least 10 years). The questionnaire contained questions about cause and level of spinal injury, colorectal function and pain/discomfort.Results:Seventy percent returned the questionnaire (133 men and 70 women....../discomfort. There was no relation of abdominal pain to other types of pain.Conclusion:Chronic pain located in the abdomen is frequent in patients with long-term SCI. The delayed onset following SCI and the relation to constipation suggest that constipation plays an important role for this type of pain in the spinal cord injured....

Abdominal pain in long-term spinal cord injury

DEFF Research Database (Denmark)

Finnerup, Nanna Brix; Faaborg, Pia Møller; Krogh, Klaus

2008-01-01

Objectives:To describe the prevalence and character of chronic abdominal pain in a group of patients with long-term spinal cord injury (SCI) and to assess predictors of abdominal pain.Study design:Postal survey.Setting:Members of the Danish Paraplegic Association.Methods:We mailed a questionnaire....../discomfort. There was no relation of abdominal pain to other types of pain.Conclusion:Chronic pain located in the abdomen is frequent in patients with long-term SCI. The delayed onset following SCI and the relation to constipation suggest that constipation plays an important role for this type of pain in the spinal cord injured....... to 284 members of the Danish Paraplegic Association who met the inclusion criteria (member for at least 10 years). The questionnaire contained questions about cause and level of spinal injury, colorectal function and pain/discomfort.Results:Seventy percent returned the questionnaire (133 men and 70 women...

Using Mixed Methods to Build Research Capacity within the Spinal Cord Injured Population of New Zealand

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Sullivan, Martin; Derrett, Sarah; Paul, Charlotte; Beaver, Carolyn; Stace, Hilary

2014-01-01

In 2007, a 4-year longitudinal study of all people admitted to the two New Zealand spinal units commenced. It aims to (a) explore interrelationship(s) of body, self, and society for people with spinal cord injury (SCI) and (b) investigate how entitlement to rehabilitation and compensation through New Zealand's Accident Compensation Corporation…

Spinal injuries in sports in the UK.

OpenAIRE

Silver, J R

1993-01-01

An analysis was made of 150 rugby, trampolining, gymnastics and horse-riding injuries between 1952 and 1985, resulting in severe spinal injury. The individual analyses of the separate sports had been published previously. There are common factors to all these sports. Of those injured 121 had cervical injuries often as a result of participation in sport by young impetuous people, and causes included: inadequate supervision; motivation to attempt tasks beyond their abilities; a mismatch between...

The mechanism of Naringin-enhanced remyelination after spinal cord injury

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Wei Rong

2017-01-01

Full Text Available Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway.

Targeting the Full Length of the Motor End Plate Regions in the Mouse Forelimb Increases the Uptake of Fluoro-Gold into Corresponding Spinal Cord Motor Neurons

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Andrew Paul Tosolini

2013-05-01

Full Text Available Lower motor neuron dysfunction is one of the most debilitating motor conditions. In this regard, transgenic mouse models of various lower motor neuron dysfunctions provide insight into the mechanisms underlying these pathologies and can also aid the development of new therapies. Viral-mediated gene therapy can take advantage of the muscle-motor neuron topographical relationship to shuttle therapeutic genes into specific populations of motor neurons in these mouse models. In this context, motor end plates (MEPs are highly specialised regions on the skeletal musculature that offer direct access to the pre-synaptic nerve terminals, henceforth to the spinal cord motor neurons. The aim of this study was two-folded. First it was to characterise the exact position of the MEP regions for several muscles of the mouse forelimb using acetylcholinesterase histochemistry. This MEP-muscle map was then used to guide a series of intramuscular injections of Fluoro-Gold (FG in order to characterise the distribution of the innervating motor neurons. This analysis revealed that the MEPs are typically organised in an orthogonal fashion across the muscle fibres and extending throughout the full width of each muscle. Furthermore, targeting the full length of the MEP regions gave rise to a seemingly greater number of labelled motor neurons that are organised into columns spanning through more spinal cord segments than previously reported. The present analysis suggests that targeting the full width of the muscles’ MEP regions with FG increases the somatic availability of the tracer. This process ensures a greater uptake of the tracer by the pre-synaptic nerve terminals, hence maximising the labelling in spinal cord motor neurons. This investigation should have positive implications for future studies involving the somatic delivery of therapeutic genes into motor neurons for the treatment of various motor dysfunctions.

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

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

2011-04-20

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

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

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

2017-01-01

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

A bipedal mammalian model for spinal cord injury research: The tammar wallaby [version 1; referees: 2 approved

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Norman R. Saunders

2017-06-01

Full Text Available Background: Most animal studies of spinal cord injury are conducted in quadrupeds, usually rodents. It is unclear to what extent functional results from such studies can be translated to bipedal species such as humans because bipedal and quadrupedal locomotion involve very different patterns of spinal control of muscle coordination. Bipedalism requires upright trunk stability and coordinated postural muscle control; it has been suggested that peripheral sensory input is less important in humans than quadrupeds for recovery of locomotion following spinal injury. Methods: We used an Australian macropod marsupial, the tammar wallaby (Macropus eugenii, because tammars exhibit an upright trunk posture, human-like alternating hindlimb movement when swimming and bipedal over-ground locomotion. Regulation of their muscle movements is more similar to humans than quadrupeds. At different postnatal (P days (P7–60 tammars received a complete mid-thoracic spinal cord transection. Morphological repair, as well as functional use of hind limbs, was studied up to the time of their pouch exit. Results: Growth of axons across the lesion restored supraspinal innervation in animals injured up to 3 weeks of age but not in animals injured after 6 weeks of age. At initial pouch exit (P180, the young injured at P7-21 were able to hop on their hind limbs similar to age-matched controls and to swim albeit with a different stroke. Those animals injured at P40-45 appeared to be incapable of normal use of hind limbs even while still in the pouch. Conclusions: Data indicate that the characteristic over-ground locomotion of tammars provides a model in which regrowth of supraspinal connections across the site of injury can be studied in a bipedal animal. Forelimb weight-bearing motion and peripheral sensory input appear not to compensate for lack of hindlimb control, as occurs in quadrupeds. Tammars may be a more appropriate model for studies of therapeutic interventions

Mouse adenovirus type 1 infection of macrophages

NARCIS (Netherlands)

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

2009-01-01

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

Sleep disordered breathing following spinal cord injury

DEFF Research Database (Denmark)

Biering-Sørensen, Fin; Jennum, Poul; Laub, Michael

2009-01-01

Individuals with spinal cord injury (SCI) commonly complain about difficulty in sleeping. Although various sleep disordered breathing definitions and indices are used that make comparisons between studies difficult, it seems evident that the frequency of sleep disorders is higher in individuals...... with SCI, especially with regard to obstructive sleep apnea. In addition, there is a correlation between the incidence of sleep disturbances and the spinal cord level injured, age, body mass index, neck circumference, abdominal girth, and use of sedating medications. Regulation of respiration is dependent...... on wakefulness and sleep. Thus, it is important to be aware of basic mechanisms in the regulation and control of sleep and awake states. Supine position decreases the vital capacity in tetraplegic individuals, and diminished responsiveness to Pa(CO)(2) may further decrease ventilatory reserve. There also may...

Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

Science.gov (United States)

Ryu, Hak-Hyun; Kang, Byung-Jae; Park, Sung-Su; Kim, Yongsun; Sung, Gyu-Jin; Woo, Heung-Myong; Kim, Wan Hee; Kweon, Oh-Kyeong

2012-12-01

Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (Pin the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (Pin the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.

HGF mediates the anti-inflammatory effects of PRP on injured tendons.

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Jianying Zhang

Full Text Available Platelet-rich plasma (PRP containing hepatocyte growth factor (HGF and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Science.gov (United States)

Zhang, Jianying; Middleton, Kellie K.; Fu, Freddie H.; Im, Hee-Jeong; Wang, James H-C.

2013-01-01

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. PMID:23840657

Advances in the management of infertility in men with spinal cord injury

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Emad Ibrahim

2016-01-01

Full Text Available Couples with a spinal cord injured male partner require assisted ejaculation techniques to collect semen that can then be further used in various assisted reproductive technology methods to achieve a pregnancy. The majority of men sustaining a spinal cord injury regardless of the cause or the level of injury cannot ejaculate during sexual intercourse. Only a small minority can ejaculate by masturbation. Penile vibratory stimulation and electroejaculation are the two most common methods used to retrieve sperm. Other techniques such as prostatic massage and the adjunct application of other medications can be used, but the results are inconsistent. Surgical sperm retrieval should be considered as a last resort if all other methods fail. Special attention must be paid to patients with T6 and rostral levels of injury due to the risk of autonomic dysreflexia resulting from stimulation below the level of injury. Bladder preparation should be performed before stimulation if retrograde ejaculation is anticipated. Erectile dysfunction is ubiquitous in the spinal cord injured population but is usually easily managed and does not pose a barrier to semen retrieval in these men. Semen analysis parameters of men with spinal cord injury are unique for this population regardless of the method of retrieval, generally presenting as normal sperm concentration but abnormally low sperm motility and viability. When sperm retrieval is desired in this population, emphasis should be placed on initially trying the simple methods of penile vibratory stimulation or electroejaculation before resorting to more advanced and invasive surgical procedures.

Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury.

Science.gov (United States)

Cheng, Xiaoxin; Zheng, Yiyan; Bu, Ping; Qi, Xiangbei; Fan, Chunling; Li, Fengqiao; Kim, Dong H; Cao, Qilin

2018-01-01

Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role in lipid and cholesterol metabolism, has also been implicated in many neurological diseases. In this study, we examined the effect of apoE on the pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant (apoE -/- ) and wild-type mice received a T9 moderate contusion SCI and were evaluated using histological and behavioral analyses after injury. At 3days after injury, the permeability of spinal cord-blood-barrier, measured by extravasation of Evans blue dye, was significantly increased in apoE -/- mice compared to wild type. The inflammation and spared white matter was also significantly increased and decreased, respectively, in apoE -/- mice compared to the wild type ones. The apoptosis of both neurons and oligodendrocytes was also significantly increased in apoE -/- mice. At 42days after injury, the inflammation was still robust in the injured spinal cord in apoE -/- but not wild type mice. CD45+ leukocytes from peripheral blood persisted in the injured spinal cord of apoE -/- mice. The spared white matter was significantly decreased in apoE -/- mice compared to wild type ones. Locomotor function was significantly decreased in apoE -/- mice compared to wild type ones from week 1 to week 8 after contusion. Treatment of exogenous apoE mimetic peptides partially restored the permeability of spinal cord-blood-barrier in apoE -/- mice after SCI. Importantly, the exogenous apoE peptides decreased inflammation, increased spared white matter and promoted locomotor recovery in apoE -/- mice after SCI. Our results indicate that endogenous apoE plays important roles in maintaining the spinal cord-blood-barrier and decreasing inflammation and spinal cord tissue loss after SCI, suggesting its important neuroprotective function after SCI. Our results further suggest that exogenous apoE mimetic peptides could be a novel and promising neuroprotective reagent for SCI. Copyright �

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury.

Science.gov (United States)

Huang, Lin; Chen, Keng; Chen, Fu-Chao; Shen, Hui-Yong; Ye, Ji-Chao; Cai, Zhao-Peng; Lin, Xi

2017-06-20

This study tried to quantify spinal cord perfusion by using contrast-enhanced ultrasound (CEUS) in rhesus monkey models with acute spinal cord injury. Acute spinal cord perfusion after injury was detected by CEUS, coupling with conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves and perfusion parameters were obtained by autotracking contrast quantification (ACQ) software in the epicenter and adjacent regions of injury, respectively. Neurological and histological examinations were performed to confirm the severity of injury. US revealed spinal cords were hypoechoic and homogeneous, whereas dura maters, pia maters, and cerebral aqueducts were hyperechoic. After spinal cord contusion, the injured spinal cord was hyperechoic on US, and intramedullary vessels of adjacent region of injury were increased and dilated on CDFI. On CEUS hypoperfusion were found in the epicenter of injury, while hyperperfusion in its adjacent region. Quantitative analysis showed that peak intensity (PI) decreased in epicenters of injury but significantly increased in adjacent regions at all time points (p spinal cord injury in overall views and real-time.

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

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

2001-05-15

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

Two-step production of monoamines in monoenzymatic cells in the spinal cord: a different control strategy of neurotransmitter supply?

DEFF Research Database (Denmark)

Zhang, Mengliang

2016-01-01

Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates...... that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord. Published data from different sources and unpublished data from my own ongoing projects...... that dopamine and serotonin could be synthesized sequentially in two monoenzymatic cells in the spinal cord via a TH-AADC and a TPH-AADC cascade respectively. The monoamines synthesized through this pathway may compensate for lost neurotransmitters following spinal cord injury and also may play specific roles...

In-vivo spinal nerve sensing in MISS using Raman spectroscopy

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Chen, Hao; Xu, Weiliang; Broderick, Neil

2016-04-01

In modern Minimally Invasive Spine Surgery (MISS), lack of visualization and haptic feedback information are the main obstacles. The spinal cord is a part of the central nervous system (CNS). It is a continuation of the brain stem, carries motor and sensory messages between CNS and the rest of body, and mediates numerous spinal reflexes. Spinal cord and spinal nerves are of great importance but vulnerable, once injured it may result in severe consequences to patients, e.g. paralysis. Raman Spectroscopy has been proved to be an effective and powerful tool in biological and biomedical applications as it works in a rapid, non-invasive and label-free way. It can provide molecular vibrational features of tissue samples and reflect content and proportion of protein, nucleic acids lipids etc. Due to the distinct chemical compositions spinal nerves have, we proposed that spinal nerves can be identified from other types of tissues by using Raman spectroscopy. Ex vivo experiments were first done on samples taken from swine backbones. Comparative spectral data of swine spinal cord, spinal nerves and adjacent tissues (i.e. membrane layer of the spinal cord, muscle, bone and fatty tissue) are obtained by a Raman micro-spectroscopic system and the peak assignment is done. Then the average spectra of all categories of samples are averaged and normalized to the same scale to see the difference against each other. The results verified the feasibility of spinal cord and spinal nerves identification by using Raman spectroscopy. Besides, a fiber-optic Raman sensing system including a miniature Raman sensor for future study is also introduced. This Raman sensor can be embedded into surgical tools for MISS.

Relationship between Humor and Subjective Well-Being with regard to Mediating Role of Resilience in Caregivers of Patients with Spinal Injury

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M. Abbasi

2017-04-01

Full Text Available Aims: Family members are the main components of the care system for injured spinal cord patients. Taking care of such patients is a tense responsibility. The purpose of this study was to investigate the relationship between humor and subjective well-being with regard to the mediating role of resilience in caregivers of patients with spinal cord injury. Instruments & Methods: In this descriptive-correlational study, 219 caregivers of spinal cord injured patients referred to Borna Scientific-Sport Institute in Isfahan in 2016 were selected using available sampling. Data were collected using Subjective Well-Being Scale (SWBS, Resilience Scale and Sense of Humor Questionnaire (SHQ. Data analysis was performed by Amos 18 software, using Structural Equation Modeling (SEM and Bootstrap test. Finding: Correlation between humor and resilience with subjective well-being was significant (p<0.001. The proposed model was good-fitting model (p<0.05. There was also a significant indirect relationship between humor and subjective well-being through resilience (β=0.22; p<0.006. Conclusion: Psychological resilience in relationship between humor and subjective well-being as mediator plays an important role in improving the psychological state of caregivers of patients with spinal cord injury.

The spatiotemporal relationships between chondroitin sulfate proteoglycans and terminations of calcitonin gene related peptide and parvalbumin immunoreactive afferents in the spinal cord of mouse embryos.

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Wang, Liqing; Yu, Chao; Wang, Jun; Zhao, Hui; Chan, Sun-On

2017-08-10

Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in the extracellular matrix and cell surface that regulate axon growth and guidance during development of the central nervous system. In this study, the expression of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal stages using CS-56 antibody. CS immunoreactivity was observed abundantly in ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS expression spread dorsally, but never reached the superficial layers of the dorsal horn. This pattern was maintained until postnatal day 4, the latest stage examined. Antibodies against calcitonin gene related peptide (CGRP) and parvalbumin (PV) were employed to label primary afferents from nociceptors and proprioceptors, respectively. CGRP-immunoreactive fibers terminated in the superficial regions of the dorsal horn where CSPGs were weakly expressed, whereas PV-immunoreactive fibers were found in CSPG-rich regions in the ventral horn. Therefore, we conclude that CS expression is spatiotemporally regulated in the spinal cord, which correlates to the termination of sensory afferents. This pattern suggests a role of CSPGs on patterning afferents in the spinal cord, probably through a differential response of axons to these growth inhibitory molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

The pathologic mechanisms underlying lumbar distraction spinal cord injury in rabbits.

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Wu, Di; Zheng, Chao; Wu, Ji; Xue, Jing; Huang, Rongrong; Wu, Di; Song, Yueming

2017-11-01

A reliable experimental rabbit model of distraction spinal cord injury (SCI) was established to successfully simulate gradable and replicable distraction SCI. However, further research is needed to elucidate the pathologic mechanisms underlying distraction SCI. The aim of this study was to investigate the pathologic mechanisms underlying lumbar distraction SCI in rabbits. This is an animal laboratory study. Using a self-designed spine distractor, the experimental animals were divided into a control group and 10%, 20%, and 30% distraction groups. Pathologic changes to the spinal cord microvessels in the early stage of distraction SCI were identified by perfusion of the spinal cord vasculature with ink, production of transparent specimens, observation by light microscopy, and observation of corrosion casts of the spinal cord microvascular architecture by scanning electron microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations in the injured spinal cord tissue were measured after 8 hours. With an increasing degree and duration of distraction, the spinal cord microvessels were only partially filled and had the appearance of spasm until rupture and hemorrhage were observed. The MDA concentration increased and the SOD concentration decreased in the spinal cord tissue. Changes to the internal and external spinal cord vessels led to spinal cord ischemia, which is a primary pathologic mechanism of distraction SCI. Lipid peroxidation mediated by free radicals took part in secondary pathologic damage of distraction SCI. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo, noncontact, real-time, optical and spectroscopic assessment of the immediate local physiological response to spinal cord injury in a rat model

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Fillioe, Seth; Bishop, Kyle Kelly; Jannini, Alexander Vincent Struck; Kim, Jon; McDonough, Ricky; Ortiz, Steve; Goodisman, Jerry; Hasenwinkel, Julie; Chaiken, J.

2018-02-01

We report a small study to test a methodology for real-time probing of chemical and physical changes in spinal cords in the immediate aftermath of a localized contusive injury. Raman spectroscopy, optical profilimetry and scanning NIR autofluorescence images were obtained simultaneously in vivo, within a 3 x 7 mm field, on spinal cords that had been surgically exposed between T9 and T10. The collected data was used alone and/or combined in a unique algorithm. A total of six rats were studied in two N=3 groups i.e. Injured and Control. A single 830 nm laser (100 μm round spot) was either 1) spatially scanned across the cord or 2) held at a specified location relative to the injury for a longer period of time to improve signal to noise in the Raman spectra. Line scans reveal photobleaching effects and surface profiles possibly allowing identification of the anterior median longitudinal artery. Analysis of the Raman spectra suggest that the tissues were equally hypoxic for both the control and injured animals i.e. a possible artifact of anesthesia and surgery. On the other hand, only injured cords display Raman features possibly indicating that extensive, localized protein phosphorylation occurs in minutes following spinal cord trauma.

Motor unit firing rates during spasms in thenar muscles of spinal cord injured subjects

NARCIS (Netherlands)

Zijdewind, Inge; Bakels, Robert; Thomas, Christine K.

2014-01-01

Involuntary contractions of paralyzed muscles (spasms) commonly disrupt daily activities and rehabilitation after human spinal cord injury (SCI). Our aim was to examine the recruitment, firing rate modulation, and derecruitment of motor units that underlie spasms of thenar muscles after cervical

Electroacupuncture at Dazhui (GV14 and Mingmen (GV4 protects against spinal cord injury: the role of the Wnt/β-catenin signaling pathway

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Xin Wang

2016-01-01

Full Text Available Electroacupuncture at Dazhui (GV14 and Mingmen (GV4 on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen's weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups: sham (only laminectomy, SCI (induction of spinal cord injury at T10, and EA (induction of spinal cord injury at T10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day. Rats in the SCI and EA groups were further randomly divided into the following subgroups: 1-day (n = 11, 7-day (n = 11, and 14-day (n = 11. At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury.

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

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

2009-01-01

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

Unique in vivo properties of olfactory ensheathing cells that may contribute to neural repair and protection following spinal cord injury

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Kocsis, Jeffery D.; Lankford, Karen L.; Sasaki, Masanori; Radtke, Christine

2009-01-01

Olfactory ensheathing cells (OECs) are specialized glial cells that guide olfactory receptor axons from the nasal mucosa into the brain where they make synaptic contacts in the olfactory bulb. While a number of studies have demonstrated that in vivo transplantation of OECs into injured spinal cord results in improved functional outcome, precise cellular mechanisms underlying this improvement are not fully understood. Current thinking is that OECs can encourage axonal regeneration, provide trophic support for injured neurons and for angiogenesis, and remyelinate axons. However, Schwann cell (SC) transplantation also results in significant functional improvement in animal models of spinal cord injury. In culture SCs and OECs share a number of phenotypic properties such as expression of the low affinity NGF receptor (p75). An important area of research has been to distinguish potential differences in the in vivo behavior of OECs and SCs to determine if one cell type may offer greater advantage as a cellular therapeutic candidate. In this review we focus on several unique features of OECs when they are transplanted into the spinal cord. PMID:19429149

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

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Fakhoury, Marc

2015-01-01

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

Anaerobic power output and propulsion technique in spinal cord injured subjects during wheelchair ergometry

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Dallmeijer, A J; Kappe, Y J; Veeger, DirkJan (H. E. J.); Janssen, T W; van der Woude, L H

1994-01-01

In order to investigate the influence of the level of the spinal cord injury (SCI) on anaerobic or short-term power production and propulsion technique, 23 male SCI subjects performed a 30-second sprint test on a stationary wheelchair ergometer. Kinematic parameters were studied both inter- and

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

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

2018-04-01

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

Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration of function after spinal cord injury.

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Shahdoost, Shahab; Frost, Shawn; Van Acker, Gustaf; DeJong, Stacey; Dunham, Caleb; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2014-01-01

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.

The role of timing in the treatment of spinal cord injury.

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Saghazadeh, Amene; Rezaei, Nima

2017-08-01

Regeneration failure after primary spinal cord injury (SCI) leads to diverse clinical complications in a severity- and level of SCI-dependent manner. The cost of treating both of them (initial regeneration failure and following complications) would be prohibitive, particularly in less developed nations. The well-recognized circumstances arose from primary SCI include excitotoxicity and inflammation. SCI increases concentrations of extracellular amino acids (EAAs) in the severity-dependent manner and the maximum level of EAAs at the injury site will be reduced by distance from the injury site. Increased concentrations of EAAs and their signaling result in energy and metabolic changes and eventually neurotoxicity. Therefore EAAs play a crucial role in moving towards secondary stage of SCI. There is a close correspondence between severity of SCI and intensity of acute inflammatory response, which includes proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and immune cells (neutrophils, microglia, and mast cells). The communication between microglia and astrocytes mediate formation of astroglial scar. The scar is thought to diminish the spread of inflammation and lesion volume, and on the other side poses an obstacle to achieving axon regeneration. Moreover, mast cells exert an anti-inflammatory role in the ground of injured spinal cord by degradation of proinflammatory mediators, while mast cells-derived histamine may cause excitotoxicity. Therefore research suggests a very double-sword remark about the work of inflammatory mediators in the injured spinal cord. Myelin associated inhibitors (MAIs) are among the growing list of extrinsic inhibitors of neuroregeneration in the injured-CNS. They function via NgR-dependent mechanisms. The time for intervention by NgR antagonists must be fixed according to the expression pattern of this receptor and its dependent MAIs after SCI. Altogether, experimental studies suggest potential benefits of combating EAAs, inflammatory

Multishot diffusion-weighted MR imaging features in acute trauma of spinal cord

International Nuclear Information System (INIS)

Zhang, Jin Song; Huan, Yi

2014-01-01

To analyse diffusion-weighted MRI of acute spinal cord trauma and evaluate its diagnostic value. Conventional MRI and multishot, navigator-corrected DWI were performed in 20 patients with acute spinal cord trauma using 1.5-T MR within 72 h after the onset of trauma. Twenty cases were classified into four categories according to the characteristics of DWI: (1) Oedema type: ten cases presented with variable hyperintense areas within the spinal cord. There were significant differences in the apparent diffusion coefficients (ADCs) between lesions and unaffected regions (t = -7.621, P < 0.01). ADC values of lesions were markedly lower than those of normal areas. (2) Mixed type: six cases showed heterogeneously hyperintense areas due to a mixture of haemorrhage and oedema. (3) Haemorrhage type: two cases showed lesions as marked hypointensity due to intramedullary haemorrhage. (4) Compressed type (by epidural haemorrhage): one of the two cases showed an area of mild hyperintensity in the markedly compressed cord due to epidural haematoma. Muti-shot DWI of the spinal cord can help visualise and evaluate the injured spinal cord in the early stage, especially in distinguishing the cytotoxic oedema from vasogenic oedema. It can assist in detecting intramedullary haemorrhage and may have a potential role in the evaluation of compressed spinal cord. (orig.)

Medication before and after a spinal cord lesion.

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Jensen, E K; Biering-Sørensen, F

2014-05-01

To map the impact of spinal cord lesion (SCL) on medication. Registration of medication for 72 patients before SCL and at discharge from the Department for Spinal Cord Injuries. Department for Spinal Cord Injuries, East Denmark. The changes in medication for each Anatomical Therapeutic Chemical (ATC) Classification System group were registered for all patients, who were discharged from Department for Spinal Cord Injuries during 2010. The changes in medication per se were calculated for different parts of the population: non-traumatic, traumatic patients, men, women, paraplegia, tetraplegia, American Spinal Injury Association Impairment Scale (AIS) A, B or C, AIS D, age 0-45, 46-60 and 60+. In addition, comparisons of changes in medication were made between complementary parts of the population. The overall increase in medication after SCL was 3.29 times (Ppopulation, the increase was most constantly seen for the medicine in the groups 'Alimentary tract and metabolism' and 'Nervous system'. The highest overall increases were seen in patients with AIS A, B and C compared with AIS D (P<0.05). There was no difference between traumatic and non-traumatic SCL, men and women, and younger compared with older patients. SCL elicits a general massive need for medicine. The relative increase is most pronounced for the more severely injured (AIS A, B and C). The increase in medication may have implications for side effects and for the economy of all involved.

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

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

2018-01-01

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

Spinal neuropeptide expression and neuropathic behavior in the acute and chronic phases after spinal cord injury: Effects of progesterone administration.

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Coronel, María F; Villar, Marcelo J; Brumovsky, Pablo R; González, Susana L

2017-02-01

Patients with spinal cord injury (SCI) develop chronic pain that severely compromises their quality of life. We have previously reported that progesterone (PG), a neuroprotective steroid, could offer a promising therapeutic strategy for neuropathic pain. In the present study, we explored temporal changes in the expression of the neuropeptides galanin and tyrosine (NPY) and their receptors (GalR1 and GalR2; Y1R and Y2R, respectively) in the injured spinal cord and evaluated the impact of PG administration on both neuropeptide systems and neuropathic behavior. Male rats were subjected to spinal cord hemisection at T13 level, received daily subcutaneous injections of PG or vehicle, and were evaluated for signs of mechanical and thermal allodynia. Real time PCR was used to determine relative mRNA levels of neuropeptides and receptors, both in the acute (1day) and chronic (28days) phases after injury. A significant increase in Y1R and Y2R expression, as well as a significant downregulation in GalR2 mRNA levels, was observed 1day after SCI. Interestingly, PG early treatment prevented Y1R upregulation and resulted in lower NPY, Y2R and GalR1 mRNA levels. In the chronic phase, injured rats showed well-established mechanical and cold allodynia and significant increases in galanin, NPY, GalR1 and Y1R mRNAs, while maintaining reduced GalR2 expression. Animals receiving PG treatment showed basal expression levels of galanin, NPY, GalR1 and Y1R, and reduced Y2R mRNA levels. Also, and in line with previously published observations, PG-treated animals did not develop mechanical allodynia and showed reduced sensitivity to cold stimulation. Altogether, we show that SCI leads to considerable changes in the spinal expression of galanin, NPY and their associated receptors, and that early and sustained PG administration prevents them. Moreover, our data suggest the participation of galaninergic and NPYergic systems in the plastic changes associated with SCI-induced neuropathic pain

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

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Andrea Luchetti

2015-08-01

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

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

Science.gov (United States)

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

2015-08-06

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

Neurorehabilitation and neuroprosthetic technologies to regain motor function following spinal cord injury

OpenAIRE

van den Brand, Rubia

2014-01-01

Spinal cord injury (SCI) leads to a range of disabilities, including locomotor impairments that seriously diminish the patients’ quality of life. Strategies to promote functional recovery after severe SCI will undoubtedly include approaches to regenerate injured pathways. The present work pursues a less ambitious, but potentially more rapidly applicable approach to improve function after SCI by applying neurorehabilitation augmented with neuroprosthetic technologies. In an intact situation, t...

A Direct Comparison between Norepinephrine and Phenylephrine for Augmenting Spinal Cord Perfusion in a Porcine Model of Spinal Cord Injury.

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Streijger, Femke; So, Kitty; Manouchehri, Neda; Gheorghe, Ana; Okon, Elena B; Chan, Ryan M; Ng, Benjamin; Shortt, Katelyn; Sekhon, Mypinder S; Griesdale, Donald E; Kwon, Brian K

2018-03-28

Current clinical guidelines recommend elevating the mean arterial blood pressure (MAP) to increase spinal cord perfusion in patients with acute spinal cord injury (SCI). This is typically achieved with vasopressors such as norepinephrine (NE) and phenylephrine (PE). These drugs differ in their pharmacological properties and potentially have different effects on spinal cord blood flow (SCBF), oxygenation (PO 2 ), and downstream metabolism after injury. Using a porcine model of thoracic SCI, we evaluated how these vasopressors influenced intraparenchymal SCBF, PO 2 , hydrostatic pressure, and metabolism within the spinal cord adjacent to the injury site. Yorkshire pigs underwent a contusion/compression SCI at T10 and were randomized to receive either NE or PE for MAP elevation of 20 mm Hg, or no MAP augmentation. Prior to injury, a combined SCBF/PO 2 sensor, a pressure sensor, and a microdialysis probe were inserted into the spinal cord adjacent to T10 at two locations: a "proximal" site and a "distal" site, 2 mm and 22 mm from the SCI, respectively. At the proximal site, NE and PE resulted in little improvement in SCBF during cord compression. Following decompression, NE resulted in increased SCBF and PO 2 , whereas decreased levels were observed for PE. However, both NE and PE were associated with a gradual decrease in the lactate to pyruvate (L/P) ratio after decompression. PE was associated with greater hemorrhage through the injury site than that in control animals. Combined, our results suggest that NE promotes better restoration of blood flow and oxygenation than PE in the traumatically injured spinal cord, thus providing a physiological rationale for selecting NE over PE in the hemodynamic management of acute SCI.

Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 may help downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the neurogenic bladder of spinal cord injured patient with urinary tract infections: a two-case study.

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Anukam, Kingsley C; Hayes, Keith; Summers, Kelly; Reid, Gregor

2009-01-01

The management of urinary tract infection (UTI) in individuals with spinal cord injury (SCI) continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P = .015) in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.

Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 May Help Downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70 in the Neurogenic Bladder of Spinal Cord Injured Patient with Urinary Tract Infections: A Two-Case Study

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Kingsley C. Anukam

2009-01-01

Full Text Available The management of urinary tract infection (UTI in individuals with spinal cord injury (SCI continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P=.015 in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.

A prospective evaluation of a pressure ulcer prevention and management E-Learning Program for adults with spinal cord injury.

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Brace, Jacalyn A; Schubart, Jane R

2010-08-01

Pressure ulcers are a common complication of spinal cord injury (SCI). Pressure ulcer education programs for spinal cord injured individuals have been found to have a positive effect on care protocol adherence. A prospective study was conducted among hospitalized spinal cord-injured men and women to determine if viewing the Pressure Ulcer Prevention and Management Education for Adults with Spinal Cord Injury: E-Learning Program affects their knowledge scores. A 20-question multiple-choice pre-/post learning test was developed and validated by 12 rehabilitation nurses. Twenty (20) patients (13 men, seven women; mean age 49 years, [SD: 18.26] with injuries to the cervical [seven], thoracic [six], and lumbar [six] regions) volunteered. Most (42%) had completed high school and time since SCI ranged from 2 weeks to 27 years. Eighteen (18) participants completed both the pre- and post test. Of those, 16 showed improvement in pressure ulcer knowledge scores. The median scores improved from 65 (range 25 to 100) pre-program to 92.5 (range 75 to 100) post-program. Descriptive statistics, Student's t-test, and analysis of variance (ANOVA) were used to analyze the data. The results suggest that a single viewing of this e-learning program could improve pressure ulcer knowledge of hospitalized adults with SCI. Research to ascertain the effects of this and other educational programs on pressure ulcer rates is needed.

An investigation into the functional outcomes of individuals with paraplegia, resulting from spinal cord injury, following discharge from a rehabilitation setting

LENUS (Irish Health Repository)

McNamara, Angela Dr.

2005-01-01

The purpose of this study was to investigate if changes occurred in the functional independence of spinal cord injured (SCI) patients, following discharge from a rehabilitation setting. The research was carried out on patients with a paraplegic injury, who underwent rehabilitation in the spinal injury unit of a Dublin based rehabilitation hospital. Eight male subjects residing in the Republic of Ireland were recruited to the study between October 2004 and May 2005.\\r\

Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

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Yahata, Kenichiro; Kanno, Haruo; Ozawa, Hiroshi; Yamaya, Seiji; Tateda, Satoshi; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

2016-12-01

OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in Neu

MOTOR UNIT FIRING RATES DURING SPASMS IN THENAR MUSCLES OF SPINAL CORD INJURED SUBJECTS

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Inge eZijdewind

2014-11-01

Full Text Available Abstract Involuntary contractions of paralyzed muscles (spasms commonly disrupt daily activities and rehabilitation after human spinal cord injury. Our aim was to examine the recruitment, firing rate modulation, and derecruitment of motor units that underlie spasms of thenar muscles after cervical spinal cord injury. Intramuscular electromyographic activity (EMG, surface EMG, and force were recorded during thenar muscle spasms that occurred spontaneously or that were triggered by movement of a shoulder or leg. Most spasms were submaximal (mean: 39%, SD: 33 of the force evoked by median nerve stimulation at 50 Hz with strong relationships between EMG and force (R2>0.69. Unit recruitment occurred over a wide force range (0.2-103% of 50 Hz force. Significant unit rate modulation occurred during spasms (frequency at 25% maximal force: 8.8 Hz, 3.3 SD; at maximal force: 16.1 Hz, 4.1 SD. Mean recruitment frequency (7.1 Hz, 3.2 SD was significantly higher than derecruitment frequency (5.4 Hz, 2.4 SD. Coactive unit pairs that fired for more than 4 s showed high (R2>0.7, n=4 or low (R2:0.3-0.7, n=12 rate-rate correlations, and derecruitment reversals (21 pairs, 29%. Later recruited units had higher or lower maximal firing rates than lower threshold units. These discrepant data show that coactive motoneurons are driven by both common inputs and by synaptic inputs from different sources during muscle spasms. Further, thenar motoneurons can still fire at high rates in response to various peripheral inputs after spinal cord injury, supporting the idea that low maximal voluntary firing rates and forces in thenar muscles result from reduced descending drive.

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

NARCIS (Netherlands)

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

2003-01-01

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

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

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Andrew P. Lieberman

2014-05-01

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

Nogo-A expression dynamically varies after spinal cord injury

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Jian-wei Wang

2015-01-01

Full Text Available The mechanism involved in neural regeneration after spinal cord injury is unclear. The myelin-derived protein Nogo-A, which is specific to the central nervous system, has been identified to negatively affect the cytoskeleton and growth program of axotomized neurons. Studies have shown that Nogo-A exerts immediate and chronic inhibitory effects on neurite outgrowth. In vivo, inhibitors of Nogo-A have been shown to lead to a marked enhancement of regenerative axon extension. We established a spinal cord injury model in rats using a free-falling weight drop device to subsequently investigate Nogo-A expression. Nogo-A mRNA and protein expression and immunoreactivity were detected in spinal cord tissue using real-time quantitative PCR, immunohistochemistry and western blot analysis. At 24 hours after spinal cord injury, Nogo-A protein and mRNA expression was low in the injured group compared with control and sham-operated groups. The levels then continued to drop further and were at their lowest at 3 days, rapidly rose to a peak after 7 days, and then gradually declined again after 14 days. These changes were observed at both the mRNA and protein level. The transient decrease observed early after injury followed by high levels for a few days indicates Nogo-A expression is time dependent. This may contribute to the lack of regeneration in the central nervous system after spinal cord injury. The dynamic variation of Nogo-A should be taken into account in the treatment of spinal cord injury.

Calcium imaging of living astrocytes in the mouse spinal cord following sensory stimulation.

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Cirillo, Giovanni; De Luca, Daniele; Papa, Michele

2012-01-01

Astrocytic Ca(2+) dynamics have been extensively studied in ex vivo models; however, the recent development of two-photon microscopy and astrocyte-specific labeling has allowed the study of Ca(2+) signaling in living central nervous system. Ca(2+) waves in astrocytes have been described in cultured cells and slice preparations, but evidence for astrocytic activation during sensory activity is lacking. There are currently few methods to image living spinal cord: breathing and heart-beating artifacts have impeded the widespread application of this technique. We here imaged the living spinal cord by two-photon microscopy in C57BL6/J mice. Through pressurized injection, we specifically loaded spinal astrocytes using the red fluorescent dye sulforhodamine 101 (SR101) and imaged astrocytic Ca(2+) levels with Oregon-Green BAPTA-1 (OGB). Then, we studied astrocytic Ca(2+) levels at rest and after right electrical hind paw stimulation. Sensory stimulation significantly increased astrocytic Ca(2+) levels within the superficial dorsal horn of the spinal cord compared to rest. In conclusion, in vivo morphofunctional imaging of living astrocytes in spinal cord revealed that astrocytes actively participate to sensory stimulation.

Descriptions of Community by People with Spinal Cord Injuries: Concepts to Inform Community Integration and Community Rehabilitation

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Kuipers, Pim; Kendall, Melissa B.; Amsters, Delena; Pershouse, Kiley; Schuurs, Sarita

2011-01-01

Effective measurement and optimization of re-entry into the community after injury depends on a degree of understanding of how those injured persons actually perceive their community. In light of the limited research about foundational concepts regarding community integration after spinal cord injury, this study investigated how a large number of…

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.

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

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

2017-11-01

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

Novel aspects of spinal cord evoked potentials (SCEPs) in the evaluation of dorso-ventral and lateral mechanical impacts on the spinal cord

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Rad, Iman; Kouhzaei, Sogolie; Mobasheri, Hamid; Saberi, Hooshang

2015-02-01

Objectives. The aim of the current study was to mimic mechanical impacts on the spinal cord by manifesting the effects of dorsoventral (DVMP) and lateral (LMP) mechanical pressure on neural activity to address points to be considered during surgery for different purposes, including spinal cord decompression. Approaches. Spinal cords of anesthetized rats were compressed at T13. Different characteristics of axons, including vulnerability, excitability, and conduction velocity (CV), in response to promptness, severity, and duration of pressure were assessed by spinal cord evoked potentials (SCEPs). Real-time SCEPs recorded at L4-5 revealed N1, N2, and N3 peaks that were used to represent the activity of injured sensory afferents, interneurons, and MN fibers. The averaged SCEP recordings were fitted by trust-region algorithm to find the equivalent Gaussian and polynomial equations. Main results. The pyramidal and extrapyramidal pathways possessed CVs of 3-11 and 16-80 m s-1, respectively. DVMP decreased the excitability of myelinated neural fibers in antidromic and orthodromic pathways. The excitability of fibers in extrapyramidal and pyramidal pathways of lateral corticospinal (LCS) and anterior corticospinal (ACS) tracts decreased following LMP. A significant drop in the amplitude of N3 and its conduction velocity (CV) revealed higher susceptibility of less-myelinated fibers to both DVMP and LMP. The best parametric fitting model for triplet healthy spinal cord CAP was a six-term Gaussian equation (G6) that fell into a five-term equation (G5) at the complete compression stage. Significance. The spinal cord is more susceptible to dorsoventral than lateral mechanical pressures, and this should be considered in spinal cord operations. SCEPs have shown promising capabilities for evaluating the severity of SCI and thus can be applied for diagnostic or prognostic intraoperative monitoring (IOM).

Reaction to topical capsaicin in spinal cord injury patients with and without central pain

DEFF Research Database (Denmark)

Finnerup, Nanna Brix; Pedersen, Louise H.; Terkelsen, Astrid J.

2007-01-01

of a spinal cord injury which already is hyperexcitable, would cause enhanced responses in patients with central pain at the level of injury compared to patients without neuropathic pain and healthy controls. Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above, at, and below injury......Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence...... for this hypothesis is difficult to obtain. Capsaicin, activating TRPV1 receptors on small sensory afferents, induces enhanced cellular activity in dorsal horn neurons and produces a central mediated area of secondary hyperalgesia. We hypothesized that sensory stimuli and capsaicin applied at and just above the level...

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

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You-jiang Min

2017-01-01

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

Imaging of injured and atherosclerotic arteries in mice using fluorescence-labeled glycoprotein VI-Fc

Energy Technology Data Exchange (ETDEWEB)

Bigalke, Boris, E-mail: boris.bigalke@med.uni-tuebingen.de [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany); Division of Imaging Sciences, St Thomas' Hospital, King' s College London (United Kingdom); Pohlmeyer, Ilka; Schoenberger, Tanja [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany); Griessinger, Christoph M. [Labor fuer Praeklinische Bildgebung und Bildgebungstechnologie der Werner-Siemens-Stiftung, Radiologische Klinik, Eberhard-Karls-Universitaet Tuebingen (Germany); Ungerer, Martin [Corimmun GmbH, Martinsried (Germany); Botnar, Rene M. [Division of Imaging Sciences, St Thomas' Hospital, King' s College London (United Kingdom); Pichler, Bernd J. [Labor fuer Praeklinische Bildgebung und Bildgebungstechnologie der Werner-Siemens-Stiftung, Radiologische Klinik, Eberhard-Karls-Universitaet Tuebingen (Germany); Gawaz, Meinrad [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany)

2011-08-15

Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model. Materials and methods: Three 4-week-old male ApoE-deficient (ApoE{sup -/-})-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n = 10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150 {mu}g/mouse) was administered and assessed by optical imaging 24 h after injury and compared to another group (n = 3) which was injected two days after injury and sacrificed another day later. Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4 {+-} 18.9 vs. 10.4 {+-} 1.0; P = 0.028). Injection of unlabeled GPVI-Fc 20 h and 3 h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6 {+-} 4.6, while intact carotids showed a signal of 9.2 {+-} 1.1; P = 0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53 {+-} 6.18 vs. 16.48 {+-} 5.15; P = 0.039). Three days after injury and 24 h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51 {+-} 2.76 vs. 14.76 {+-} 1.59; P = 0.519). Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary.

Pre-Hospital Care Management of a Potential Spinal Cord Injured Patient: A Systematic Review of the Literature and Evidence-Based Guidelines

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Ahn, Henry; Singh, Jeffrey; Nathens, Avery; MacDonald, Russell D.; Travers, Andrew; Tallon, John; Fehlings, Michael G.

2011-01-01

Abstract An interdisciplinary expert panel of medical and surgical specialists involved in the management of patients with potential spinal cord injuries (SCI) was assembled. Four key questions were created that were of significant interest. These were: (1) what is the optimal type and duration of pre-hospital spinal immobilization in patients with acute SCI?; (2) during airway manipulation in the pre-hospital setting, what is the ideal method of spinal immobilization?; (3) what is the impact of pre-hospital transport time to definitive care on the outcomes of patients with acute spinal cord injury?; and (4) what is the role of pre-hospital care providers in cervical spine clearance and immobilization? A systematic review utilizing multiple databases was performed to determine the current evidence about the specific questions, and each article was independently reviewed and assessed by two reviewers based on inclusion and exclusion criteria. Guidelines were then created related to the questions by a national Canadian expert panel using the Delphi method for reviewing the evidence-based guidelines about each question. Recommendations about the key questions included: the pre-hospital immobilization of patients using a cervical collar, head immobilization, and a spinal board; utilization of padded boards or inflatable bean bag boards to reduce pressure; transfer of patients off of spine boards as soon as feasible, including transfer of patients off spinal boards while awaiting transfer from one hospital institution to another hospital center for definitive care; inclusion of manual in-line cervical spine traction for airway management in patients requiring intubation in the pre-hospital setting; transport of patients with acute traumatic SCI to the definitive hospital center for care within 24 h of injury; and training of emergency medical personnel in the pre-hospital setting to apply criteria to clear patients of cervical spinal injuries, and immobilize patients

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

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

2015-06-25

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

Design and testing of a controlled electromagnetic spinal cord impactor for use in large animal models of acute traumatic spinal cord injury.

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Petteys, Rory J; Spitz, Steven M; Syed, Hasan; Rice, R Andrew; Sarabia-Estrada, Rachel; Goodwin, C Rory; Sciubba, Daniel M; Freedman, Brett A

2017-09-01

Spinal cord injury (SCI) causes debilitating neurological dysfunction and has been observed in warfighters injured in IED blasts. Clinical benefit of SCI treatment remains elusive and better large animal models are needed to assess treatment options. Here, we describe a controlled electromagnetic spinal cord impactor for use in large animal models of SCI. A custom spinal cord impactor and platform were fabricated for large animals (e.g., pig, sheep, dog, etc.). Impacts were generated by a voice coil actuator; force and displacement were measured with a load cell and potentiometer respectively. Labview (National Instruments, Austin, TX) software was used to control the impact cycle and import force and displacement data. Software finite impulse response (FIR) filtering was employed for all input data. Silicon tubing was used a surrogate for spinal cord in order to test the device; repeated impacts were performed at 15, 25, and 40 Newtons. Repeated impacts demonstrated predictable results at each target force. The average duration of impact was 71.2 ±6.1ms. At a target force of 40N, the output force was 41.5 ±0.7N. With a target of 25N, the output force was 23.5 ±0.6N; a target of 15Newtons revealed an output force of 15.2 ±1.4N. The calculated acceleration range was 12.5-21.2m/s 2 . This custom spinal cord impactor reliably delivers precise impacts to the spinal cord and will be utilized in future research to study acute traumatic SCI in a large animal. Published by Elsevier Ltd.

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

Science.gov (United States)

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

1997-01-01

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

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

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

2010-08-01

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

Employment of persons with spinal cord lesions injured more than 20 years ago

DEFF Research Database (Denmark)

Lidal, Ingeborg Beate; Hjeltnes, Nils; Røislien, Jo

2009-01-01

PURPOSE: The primary objective was to study factors influencing post-injury employment and withdrawal from work in persons who sustained traumatic spinal cord injury (SCI) more than 20 years ago. A secondary objective was to study life satisfaction in the same patients. METHOD: A cross...... before, and a history of pre-injury medical condition(s). Life satisfaction was better for currently employed participants. CONCLUSION: The study indicates a low employment-rate in persons with SCI, even several years after injury. From the results, we suggest more support, especially to persons of older...

Co-ultramicronized palmitoylethanolamide/luteolin promotes neuronal regeneration after spinal cord injury

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Rosalia eCrupi

2016-03-01

Full Text Available Spinal cord injury (SCI stimulates activation of astrocytes and infiltration of immune cells at the lesion site; however, the mechanism that promotes the birth of new neurons is still under debate. Neuronal regeneration is restricted after spinal cord injury, but can be stimulated by experimental intervention. Previously we demonstrated that treatment co-ultramicronized palmitoylethanolamide and luteolin, namely co-ultraPEALut, reduced inflammation. The present study was designed to explore the neuroregenerative properties of co-ultra PEALut in an estabished murine model of SCI. A vascular clip was applied to the spinal cord dura at T5 to T8 to provoke injury. Mice were treated with co-ultraPEALut (1 mg/kg, intraperitoneally daily for 72 h after SCI. Co-ultraPEALut increased the numbers of both bromodeoxyuridine-positive nuclei and doublecortin-immunoreactive cells in the spinal cord of injured mice. To correlate neuronal development with synaptic plasticity a Golgi method was employed to analyze dendritic spine density. Co-ultraPEALut administration stimulated expression of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, nerve growth factor and neurotrophin-3. These findings show a prominent effect of co-ultraPEALut administration in the management of survival and differentiation of new neurons and spine maturation, and may represent a therapeutic treatment for spinal cord and other traumatic diseases.

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.

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

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Yana O. Mukhamedshina

2017-10-01

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

Presentation and outcome of traumatic spinal fractures

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Ahmed El-Faramawy

2012-01-01

Full Text Available Background: Motor vehicle crashes and falls account for most of the spine fractures with subsequent serious disability. Aim: To define the incidence, causes, and outcome of spinal fractures. Materials and Methods: Data were collected retrospectively from trauma registry database of all traumatic spinal injuries admitted to the section of trauma surgery in Qatar from November 2007 to December 2009. Results: Among 3712 patients who were admitted to the section of trauma surgery, 442 (12% injured patients had spinal fractures with a mean age of 33.2 ± 12 years. The male to female ratio was 11.6:1. Motor vehicle crashes (36.5% and falls from height (19.3% were the leading causes of cervical injury (P = 0.001. The injury severity score ranged between 4 and 75. Nineteen percent of cases with cervical injury had thoracic injury as well (P = 0.04. Lumber injury was associated with thoracic injury in 27% of cases (P < 0.001. Combined thoracic and lumber injuries were associated with cervical injury in 33% of cases (P < 0.001. The total percent of injuries associated with neurological deficit was 5.4%. Fifty-three cases were managed surgically for spine fractures; 14 of them had associated neurological deficits. Overall mortalityrate was 5%. Conclusions: Spine fractures are not uncommon in Qatar. Cervical and thoracic spine injuries carry the highest incidence of associated neurological deficit and injuries at other spinal levels. Young males are the most exposed population that deserves more emphasis on injury prevention programs in the working sites and in enforcement of traffic laws.

Incidence, aetiology and injury characteristics of traumatic spinal cord injury in Stockholm, Sweden: A prospective, population-based update.

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Joseph, Conran; Andersson, Nina; Bjelak, Sapko; Giesecke, Kajsa; Hultling, Claes; Nilsson Wikmar, Lena; Phillips, Julie; Seiger, Åke; Stenimahitis, Vasilios; Trok, Katarzyna; Åkesson, Elisabet; Wahman, Kerstin

2017-05-16

To update the incidence rate, aetiology and injury characteristics of acutely-injured adults with traumatic spinal cord injury in Stockholm, Sweden, using international standards of reporting. Prospective, (regional) population-based observation. Forty-nine consecutively enrolled individuals. A surveillance system of newly-injured adults with traumatic spinal cord injury was implemented for an 18-month period. The International Spinal Cord Injury Core Data Set was used to collect data on those who survived the first 7 days post-injury. After an 18-month period, 49 incident cases were registered, of whom 45 were included in this study. The crude incidence rate was 19.0 per million, consisting mainly of men (60%), and the mean age of the cohort was 55 years (median 58). Causes of injury were almost exclusively limited to falls and transport-related events, accounting for 58% and 40% of cases, respectively. The incidence has remained stable when compared with the previous study; however, significant differences exist for injury aetiology (p = 0.004) and impairment level (p = 0.01) in that more fall- and transport-related spinal cord injury occurred, and a larger proportion of persons was left with resultant tetraplegia, in the current study, compared with more sport-related injuries and those left with paraplegia in the previous study. The incidence rate appeared to remain stable in Stockholm, Sweden. However, significant changes in injury aetiology and impairment-level post injury were found, compared with the previous study. There remains a need for developing fall-related prevention strategies in rehabilitation settings as well as in population-based programmes.

Imaging of injured and atherosclerotic arteries in mice using fluorescence-labeled glycoprotein VI-Fc

International Nuclear Information System (INIS)

Bigalke, Boris; Pohlmeyer, Ilka; Schoenberger, Tanja; Griessinger, Christoph M.; Ungerer, Martin; Botnar, Rene M.; Pichler, Bernd J.; Gawaz, Meinrad

2011-01-01

Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model. Materials and methods: Three 4-week-old male ApoE-deficient (ApoE -/- )-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n = 10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150 μg/mouse) was administered and assessed by optical imaging 24 h after injury and compared to another group (n = 3) which was injected two days after injury and sacrificed another day later. Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4 ± 18.9 vs. 10.4 ± 1.0; P = 0.028). Injection of unlabeled GPVI-Fc 20 h and 3 h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6 ± 4.6, while intact carotids showed a signal of 9.2 ± 1.1; P = 0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53 ± 6.18 vs. 16.48 ± 5.15; P = 0.039). Three days after injury and 24 h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51 ± 2.76 vs. 14.76 ± 1.59; P = 0.519). Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary.

Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

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Alexis M. Ziemba

2017-05-01

Full Text Available Affecting approximately 17,000 new people each year, spinal cord injury (SCI is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present studies using a variety of biomaterials, including hydrogels, particles, and fibers/conduits for drug delivery. Subsequently, we discuss how each may be manipulated to optimize drug release during a specific time frame following SCI. Developing polymer biomaterials that can effectively release drug to target specific aspects of SCI pathophysiology will result in more efficacious approaches leading to better regeneration and recovery following SCI.

Immunohistochemical visualization of mouse interneuron subtypes

DEFF Research Database (Denmark)

Jensen, Simon Mølgaard; Ulrichsen, Maj; Boggild, Simon

2014-01-01

, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies...... of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location...

Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients.

Science.gov (United States)

Moviglia, G A; Varela, G; Brizuela, J A; Moviglia Brandolino, M T; Farina, P; Etchegaray, G; Piccone, S; Hirsch, J; Martinez, G; Marino, S; Deffain, S; Coria, N; Gonzáles, A; Sztanko, M; Salas-Zamora, P; Previgliano, I; Aingel, V; Farias, J; Gaeta, C A; Saslavsky, J; Blasseti, N

2009-06-01

With the intention to ameliorate the clinical condition of patients with chronic spinal cord injury (SCI), a program that combines three cell therapies and an appropriate neurorehabilitation program were used to recreate and enhance the natural conditions of SCI repair. Vascularization recovery is approached by selective artery infusion of BMMNCs (bone marrow mononuclear cells) to the disrupted area. Eighteen days later, with the aim to restore the specific inflammatory activity, an i.v. infusion of spinal cord specific ETCs (effector T cells) is carried out. With the intention of supplying cellular components for the process of repair, an infusion of autologous neural stem cells (NSCs) through selective feeding artery infusion is carried out, followed by an appropriate neurorehabilitation program. A total of eight ASIA (American Spinal Injury Association) A patients (five with jeopardized brachial plexus and three without) received the treatment. No severe adverse events was observed in any of the receptor patients: five patients evolved from ASIA A to ASIA D and regained the ability to stand up and, with varying effectiveness, to walk; two patients remained in the same condition, but exhibited motor and sensitive improvements; and one patient could not be evaluated. These reports suggest that the biological characteristics of acute SCI may be recreated in a comprehensive, safe and effective manner.

Functional characterization of dI6 interneurons in the neonatal mouse spinal cord.

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Dyck, Jason; Lanuza, Guillermo M; Gosgnach, Simon

2012-06-01

Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of the postnatal spinal cord that have not been investigated. In the present study, we utilized a novel transgenic mouse line to electrophysiologically characterize dI6 interneurons located close to the central canal and study their function during fictive locomotion. The majority of dI6 cells investigated were found to be rhythmically active during fictive locomotion and could be divided into two electrophysiologically distinct populations of interneurons. The first population fired rhythmic trains of action potentials that were loosely coupled to ventral root output and contained several intrinsic membrane properties of rhythm-generating neurons, raising the possibility that these cells may be involved in the generation of rhythmic activity in the locomotor CPG. The second population fired rhythmic trains of action potentials that were tightly coupled to ventral root output and lacked intrinsic oscillatory mechanisms, indicating that these neurons may be driven by a rhythm-generating network. Together these results indicate that dI6 neurons comprise an important component of the locomotor CPG that participate in multiple facets of motor behavior.

Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

International Nuclear Information System (INIS)

Kilcoyne, Michelle; Sharma, Shashank; McDevitt, Niamh; O’Leary, Claire; Joshi, Lokesh; McMahon, Siobhán S.

2012-01-01

Highlights: ► Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. ► Neuronal glycosylation in injury and after ChABC treatment is unknown. ► In silico mining verified that glyco-related genes were differentially regulated after SCI. ► In vitro model system revealed abnormal sialylation in an injured environment. ► The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually α-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment with ChABC was successful in returning neuronal glycosylation to normal conditions at all timepoints for MAA, PNA and SNA-I staining

Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

Energy Technology Data Exchange (ETDEWEB)

Kilcoyne, Michelle; Sharma, Shashank [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McDevitt, Niamh; O' Leary, Claire [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland); Joshi, Lokesh [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McMahon, Siobhan S., E-mail: siobhan.mcmahon@nuigalway.ie [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland)

2012-04-13

Highlights: Black-Right-Pointing-Pointer Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. Black-Right-Pointing-Pointer Neuronal glycosylation in injury and after ChABC treatment is unknown. Black-Right-Pointing-Pointer In silico mining verified that glyco-related genes were differentially regulated after SCI. Black-Right-Pointing-Pointer In vitro model system revealed abnormal sialylation in an injured environment. Black-Right-Pointing-Pointer The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually {alpha}-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment

What is the potential of oligodendrocyte progenitor cells to successfully treat human spinal cord injury?

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Yeung Trevor M

2011-09-01

Full Text Available Abstract Background Spinal cord injury is a serious and debilitating condition, affecting millions of people worldwide. Long seen as a permanent injury, recent advances in stem cell research have brought closer the possibility of repairing the spinal cord. One such approach involves injecting oligodendrocyte progenitor cells, derived from human embryonic stem cells, into the injured spinal cord in the hope that they will initiate repair. A phase I clinical trial of this therapy was started in mid 2010 and is currently underway. Discussion The theory underlying this approach is that these myelinating progenitors will phenotypically replace myelin lost during injury whilst helping to promote a repair environment in the lesion. However, the importance of demyelination in the pathogenesis of human spinal cord injury is a contentious issue and a body of literature suggests that it is only a minor factor in the overall injury process. Summary This review examines the validity of the theory underpinning the on-going clinical trial as well as analysing published data from animal models and finally discussing issues surrounding safety and purity in order to assess the potential of this approach to successfully treat acute human spinal cord injury.

Overexpression of GDNF in the uninjured DRG exerts analgesic effects on neuropathic pain following segmental spinal nerve ligation in mice.

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Takasu, Kumiko; Sakai, Atsushi; Hanawa, Hideki; Shimada, Takashi; Suzuki, Hidenori

2011-11-01

Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Matrix Metalloproteinases as a Therapeutic Target to Improve Neurologic Recovery After Spinal Cord Injury

Science.gov (United States)

2014-10-01

mice that served as baseline controls. Conducted 3D reconstruction of representative spinal cords from the moderately injured -vehicle and GM6001...Appendices 13 CONCLUSIONS In a preliminary study, GM6001 (dissolved in 4% carboxy methyl cellulose and delivered via intraperitoneal route) when given...exceeded that necessary to block MMP-9 in vitro. As some MMPs modulate the formation of a glial scar and axonal plasticity [4], their subacute/chronic

Microarray analysis of gene expression by skeletal muscle of three mouse models of Kennedy disease/spinal bulbar muscular atrophy.

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Kaiguo Mo

2010-09-01

Full Text Available Emerging evidence implicates altered gene expression within skeletal muscle in the pathogenesis of Kennedy disease/spinal bulbar muscular atrophy (KD/SBMA. We therefore broadly characterized gene expression in skeletal muscle of three independently generated mouse models of this disease. The mouse models included a polyglutamine expanded (polyQ AR knock-in model (AR113Q, a polyQ AR transgenic model (AR97Q, and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR. HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.We performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. Several patterns of gene expression relevant to the disease process were observed. Notably, patterns of gene expression typical of loss of AR function were observed in all three models, as were alterations in genes involved in cell adhesion, energy balance, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.By comparing patterns of gene expression in three independent models of KD/SBMA, we have been able to identify candidate genes that might mediate the core myogenic features of KD/SBMA.

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

Science.gov (United States)

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

2018-01-01

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

Modified Ashworth scale and spasm frequency score in spinal cord injury

DEFF Research Database (Denmark)

Baunsgaard, C. B.; Nissen, U. V.; Christensen, K. B.

2016-01-01

.94 and inter-rater κweighted=0.93. Correlation between MAS and SFS showed non-significant correlation coefficients from-0.11 to 0.90. CONCLUSION: Reliability of MAS is highly affected by the weighting scheme. With a weighted-κ it was overall reliable and simple-κ overall unreliability. Repeated tests should......STUDY DESIGN: Intra- and inter-rater reliability study. OBJECTIVES: To assess intra- and inter-rater reliability of the Modified Ashworth Scale (MAS) and Spasm Frequency Score (SFS) in lower extremities in a population of spinal cord-injured persons, as well as correlations between the two scales....... SETTING: Clinic for Spinal Cord Injuries, Rigshospitalet, Hornbaek, Denmark. METHODS: Thirty-one persons participated in the study and were tested four times in total with MAS and SFS by three experienced raters. Cohen's kappa (κ), simple and quadratic weighted (nominal and ordinal scale level...

Quantitative assessment of spinal cord injury using circularly polarized coherent anti-Stokes Raman scattering microscopy

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Bae, Kideog; Zheng, Wei; Huang, Zhiwei

2017-08-01

We report the quantitative assessment of spinal cord injury using the circularly polarized coherent anti-Stokes Raman scattering (CP-CARS) technique together with Stokes parameters in the Poincaré sphere. The pump and Stokes excitation beams are circularly polarized to suppress both the linear polarization-dependent artifacts and the nonresonant background of tissue CARS imaging, enabling quantitative CP-CARS image analysis. This study shows that CP-CARS imaging uncovers significantly increased phase retardance of injured spinal cord tissue as compared to normal tissue, suggesting that CP-CARS is an appealing label-free imaging tool for determining the degree of tissue phase retardance, which could serve as a unique diagnostic parameter associated with nervous tissue injury.

Dental Apical Papilla as Therapy for Spinal Cord Injury.

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De Berdt, P; Vanacker, J; Ucakar, B; Elens, L; Diogenes, A; Leprince, J G; Deumens, R; des Rieux, A

2015-11-01

Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the neural crest, express numerous neurogenic markers, and mediate neurite outgrowth and axonal targeting. The goal of the present work was to investigate for the first time their potential to promote motor recovery after SCI in a rat hemisection model when delivered in their original stem cell niche-that is, by transplantation of the human apical papilla tissue itself into the lesion. Control groups consisted of animals subjected to laminectomy only (shams) and to lesion either untreated or injected with a fibrin hydrogel with or without human SCAP. Basso-Beattie-Bresnahan locomotor scores at 1 and 3 d postsurgery confirmed early functional decline in all SCI groups. This significant impairment was reversed, as seen in CatWalk analyses, after transplantation of apical papilla into the injured spinal cord wound, whereas the other groups demonstrated persistent functional impairment. Moreover, tactile allodynia did not develop as an unwanted side effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the microglial marker Iba-1, which has been frequently associated with allodynia. Notably, the apical papilla transplant group presented with reduced Iba-1 expression level. Masson trichrome and human mitochondria staining showed the preservation of the apical papilla integrity and the presence of numerous human cells, while human cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point. Altogether, our data suggest that the transplantation of a human apical papilla at the lesion site improves gait in spinally injured rats and reduces glial reactivity. It also underlines the potential interest for the application of delivering SCAP in their original niche, as compared with use of a fibrin hydrogel. © International & American

Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down

Science.gov (United States)

Willenberg, Rafer; Zukor, Katherine; Liu, Kai; He, Zhigang; Steward, Oswald

2016-01-01

Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting PTEN in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the “wrong” side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical AAV-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral BDA injections in PTEN-deleted mice with spinal cord injury and in non-injured PTEN-floxed mice that had not received AAV-Cre. In non-injured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in grey matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side, in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using shRNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the non-injured CST, highlighting one aspect for how resultant circuitry from regenerating axons may differ from that of the uninjured CST. PMID:26878190

The effect of impedance-controlled robotic gait training on walking ability and quality in individuals with chronic incomplete spinal cord injury : An explorative study

NARCIS (Netherlands)

Fleerkotte, B.M.; Koopman, B.; Buurke, J.H.; Van Asseldonk, E.H.F.; Van der Kooij, H.; Rietman, J.S.

2014-01-01

Background There is increasing interest in the use of robotic gait-training devices in walking rehabilitation of incomplete spinal cord injured (iSCI) individuals. These devices provide promising opportunities to increase the intensity of training and reduce physical demands on therapists. Despite

The effect of impedance-controlled robotic gait training on walking ability and quality in individuals with chronic incomplete spinal cord injury: An explorative study

NARCIS (Netherlands)

Fleerkotte, B.M.; Koopman, Bram; Buurke, Jaap; van Asseldonk, Edwin H.F.; van der Kooij, Herman; Rietman, Johan Swanik

2014-01-01

Background There is increasing interest in the use of robotic gait-training devices in walking rehabilitation of incomplete spinal cord injured (iSCI) individuals. These devices provide promising opportunities to increase the intensity of training and reduce physical demands on therapists. Despite

A transgenic mouse line for molecular genetic analysis of excitatory glutamatergic neurons

DEFF Research Database (Denmark)

Borgius, Lotta; Restrepo, C. Ernesto; Leao, Richardson N.

2010-01-01

Excitatory glutamatergic neurons are part of most of the neuronal circuits in the mammalian nervous system. We have used BAC-technology to generate a BAC-Vglut2::Cre mouse line where Cre expression is driven by the vesicular glutamate transporter 2 (Vglut2) promotor. This BAC-Vglut2::Cre mouse line...... showed specific expression of Cre in Vglut2 positive cells in the spinal cord with no ectopic expression in GABAergic or glycinergic neurons. This mouse line also showed specific Cre expression in Vglut2 positive structures in the brain such as thalamus, hypothalamus, superior colliculi, inferior...... colliculi and deep cerebellar nuclei together with nuclei in the midbrain and hindbrain. Cre-mediated recombination was restricted to Cre expressing cells in the spinal cord and brain and occurred as early as E 12.5. Known Vglut2 positive neurons showed normal electrophysiological properties in the BAC...

Prevention of deep venous thrombosis in patients with acute spinal cord injuries: use of rotating treatment tables

International Nuclear Information System (INIS)

Becker, D.M.; Gonzalez, M.; Gentili, A.; Eismont, F.; Green, B.A.

1987-01-01

A randomized clinical trial of 15 patients with acute spinal cord injuries was performed to test the hypothesis that rotating treatment tables prevent deep venous thrombosis in this population. Four of 5 control (nonrotated) patients developed distal and proximal thrombi, assessed by 125 I fibrinogen leg scans and impedance plethysmography. In comparison, only 1 of 10 treated (rotated) patients developed both distal and proximal thrombosis. These results suggest but do not prove that rotating treatment tables prevent the development of proximal deep venous thrombosis in spinal cord-injured patients. Larger clinical trials are needed to confirm this heretofore undocumented benefit of rotating treatment tables

Therapeutic effects of neurotrophic factors in experimental spinal cord injury models

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Enomoto M

2016-03-01

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

Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice.

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Takahashi, Hiroshi; Koda, Masao; Hashimoto, Masayuki; Furuya, Takeo; Sakuma, Tsuyoshi; Kato, Kei; Okawa, Akihiko; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Takahashi, Kazuhisa; Yamazaki, Masashi; Mannoji, Chikato

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration

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

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

2014-10-01

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

HYSTOMORPHOLOGIC CHANGES IN INJURED MENISCI IN CHILDREN

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V. B. Bogatov

2010-01-01

Full Text Available The purpose of the work was studying histological changes in the injured menisci in children. The histological evaluation of injured menisci received during arthroscopy was performed. The prescription of injury varied from several days till 3 years. It was shown that injured fragment of the meniscus is viable up to 3 months since trauma. It was also obvious that active migration of the meniscus cells occur in the injured fragment and microvessels are seen in 50% of the meniscus tissues.

Injured athletes' perceptions about social support.

Science.gov (United States)

Clement, Damien; Shannon, Vanessa R

2011-11-01

According to the buffering hypothesis, social support moderates the harmful effects of stress and, in turn, indirectly affects injured athletes' health and well-being. Previous research suggests that perceptions of social support influence athletes' psychological reactions, as well as their rehabilitation adherence, but additional research in this area is warranted. To examine injured athletes' perceptions regarding satisfaction, availability, and contribution for each of the 8 types of social support. Descriptive. Mid-Atlantic Division II and III institutions. 49 injured athletes. Social support was assessed using a modified version of the Social Support Survey. Injured athletes were significantly more satisfied with social support provided by athletic trainers (ATCs) than that provided by coaches and teammates. In addition, injured athletes reported that social support provided by ATCs contributed significantly more to their overall well-being. Athletes reported several significant differences regarding satisfaction and contribution to well-being among the 8 different types of social support. Injury, an unavoidable part of sport, is often accompanied by negative psychological reactions. This reaction may have a negative influence on an athlete's experience of injury and rehabilitation. Findings suggest that perceptions of social support provided by ATCs have the greatest influence on injured athletes' rehabilitation and well-being.

Role of biomaterials in neurorestoration after spinal cord injuries

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Ioana Stanescu

2016-05-01

Full Text Available Despite advances in knowledge and technology SCI remains one of the most severe and disabling disorders affecting young people. Spinal cord lesions result in permanent loss of motor, sensory and autonomic functions, causing an enormous impact on patient’s personal, social, familial and professional life. There is currently no effective treatment available to improve severe neurologic deficits and to decrease disability. Tissue-engineering techniques have developed a variety of scaffolds, made by biomaterials, used alone, incapsulated with cells or embedded with molecules, which are delivered to lesion site to achieve neural regeneration. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Biomaterials acts like cell-carriers for the injury site, but also as reservoirs for growth factors or biomolecules. Hydrogels are a promising therapeutical strategy in spinal cord repair. Nano-fibers provide a three-dimensional network, which mimic closely the native extracellular matrix, thus offering a better support for cell attachment and proliferation than traditional micro-structure. New strategies like pharmacologic treatments, cell therapies, gene therapies and biomaterial tissue engineering should combine to increase their synergistic effect and to obtain the expected functional recovery in spinal cord injured patients

[Description of the severely injured in the DRG system: is treatment of the severely injured still affordable?].

Science.gov (United States)

Mahlke, L; Lefering, R; Siebert, H; Windolf, J; Roeder, N; Franz, D

2013-11-01

Due to the heterogeneity of severely injured patients (multiple trauma) it is difficult to assign them to homogeneic diagnosis-related groups (DRG). In recent years this has led to a systematic underfunding in the German reimbursement system (G-DRG) for cases of multiply injured patients. This project aimed to improve the reimbursement by modifying the case allocation algorithms of multiply injured patients within the G-DRG system. A retrospective analysis of standardized G-DRG data according to §21 of the Hospital Reimbursement Act (§ 21 KHEntgG) including case-related cost data from 3,362 critically injured patients from 2007 and 2008 from 10 university hospitals and 7 large municipal hospitals was carried out. For 1,241 cases complementary detailed information was available from the trauma registry of the German Trauma Society to monitor the case allocation of multiply injured patients within the G-DRG system. Analysis of coding and grouping, performance of case allocation and the homogeneity of costs in the G-DRG versions 2008-2012 was carried out. The results showed systematic underfunding of trauma patients in the G-DRG version 2008 but adequate cost covering in the majority of cases with the G-DRG versions 2011 and 2012. Cost coverage was foundfor multiply injured patients from the clinical viewpoint who were identified as multiple trauma by the G-DRG system. Some of the overfunded trauma patients had high intensive care costs. Also there was underfunding for multiple injured patients not identified as such in the G-DRG system. Specific modifications of the G-DRG allocation structures could increase the appropriateness of reimbursement of multiply injured patients. Data-based analysis is an essential prerequisite for a constructive development of the G-DRG system and a necessary tool for the active participation of medical specialist societies.

Transplantation of specific human astrocytes promotes functional recovery after spinal cord injury.

Directory of Open Access Journals (Sweden)

Stephen J A Davies

2011-03-01

Full Text Available Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human

[Current status of thoracoscopic surgery for thoracic and lumbar spine. Part 2: treatment of the thoracic disc hernia, spinal deformities, spinal tumors, infections and miscellaneous].

Science.gov (United States)

Verdú-López, Francisco; Beisse, Rudolf

2014-01-01

Thoracoscopic surgery or video-assisted thoracic surgery (VATS) of the thoracic and lumbar spine has evolved greatly since it appeared less than 20 years ago. It is currently used in a large number of processes and injuries. The aim of this article, in its two parts, is to review the current status of VATS of the thoracic and lumbar spine in its entire spectrum. After reviewing the current literature, we developed each of the large groups of indications where VATS takes place, one by one. This second part reviews and discusses the management, treatment and specific thoracoscopic technique in thoracic disc herniation, spinal deformities, tumour pathology, infections of the spine and other possible indications for VATS. Thoracoscopic surgery is in many cases an alternative to conventional open surgery. The transdiaphragmatic approach has made endoscopic treatment of many thoracolumbar junction processes possible, thus widening the spectrum of therapeutic indications. These include the treatment of spinal deformities, spinal tumours, infections and other pathological processes, as well as the reconstruction of injured spinal segments and decompression of the spinal canal if lesion placement is favourable to antero-lateral approach. Good clinical results of thoracoscopic surgery are supported by growing experience reflected in a large number of articles. The degree of complications in thoracoscopic surgery is comparable to open surgery, with benefits in regard to morbidity of the approach and subsequent patient recovery. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Expert medical testimony for your injured patients.

Science.gov (United States)

Lang, Gerald J

2013-10-01

Many injured patients sustain some type of loss. If someone else is responsible for the injury, the injured patient can pursue compensation for this loss. In the course of treating an injured patient, you may be asked to participate in the legal process to resolve such claims. The basic components of a personal injury claim are reviewed. An overview of the legal process will help clarify your role in the legal process. Enhanced understanding will allow you to provide important medical testimony for your injured patient.

Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

Science.gov (United States)

Murashov, A. K.; Ul Haq, I.; Hill, C.; Park, E.; Smith, M.; Wang, X.; Wang, X.; Goldberg, D. J.; Wolgemuth, D. J.

2001-01-01

The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

Implantable porous gelatin microspheres sustained release of bFGF and improved its neuroprotective effect on rats after spinal cord injury.

Directory of Open Access Journals (Sweden)

Li Lan

Full Text Available In this study, porous gelatin microspheres (GMSs were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35μm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200μg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05. At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01, indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury.

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

OpenAIRE

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

2011-01-01

A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any ...

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

Science.gov (United States)

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

2017-08-15

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

Intraspinal Pressure Monitoring in a Patient with Spinal Cord Injury Reveals Different Intradural Compartments: Injured Spinal Cord Pressure Evaluation (ISCoPE) Study.

OpenAIRE

Phang, I; Papadopoulos, MC

2015-01-01

BACKGROUND: We recently described a technique for monitoring intraspinal pressure (ISP) after traumatic spinal cord injury (TSCI). This is analogous to intracranial pressure monitoring after brain injury. We showed that, after severe TSCI, ISP at the injury site is elevated as the swollen cord is compressed against the dura. METHODS: In a patient with complete thoracic TSCI, we sequentially monitored subdural ISP above the injury, at the injury site, and below the injury intraoperatively. Pos...

Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain.

Science.gov (United States)

Eisenberg, Elon; Burstein, Yulia; Suzan, Erica; Treister, Roi; Aviram, Joshua

2015-03-01

Evidence has shown that electrical stimulation at the dorsal columns attenuated the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study was aimed to test the effect of spinal cord stimulation (SCS) on temporal summation (TS), the clinical correlate of the wind-up phenomenon in patients with radicular leg pain. Eighteen patients with SCS implants were tested both 30 minutes after SCS activation ("ON") and 2 hours after turning it off ("OFF"), in a random order. Temporal summation was evaluated in the most painful site in the affected leg and in the corresponding area in the contralateral leg by applying a tonic painful heat stimulus (46.5°C; 120 seconds) and simultaneous recording of the perceived heat pain intensity. Patients were also requested to report their clinical pain intensity (0-100 numerical pain scale) during SCS "ON" and "OFF". The Wilcoxon signed rank test was used in the comparisons between SCS "ON" and "OFF". Spinal cord stimulation activation significantly attenuated clinical pain intensity (from 66 ± 18 to 27 ± 31, P spinal cord neurons, is a possible mechanism underlying SCS analgesia in patients with neuropathic pain.

miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair.

Science.gov (United States)

Gaudet, Andrew D; Mandrekar-Colucci, Shweta; Hall, Jodie C E; Sweet, David R; Schmitt, Philipp J; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia; Popovich, Phillip G

2016-08-10

Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155-5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. Axon regeneration after spinal cord injury (SCI) fails due to neuron

miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

Science.gov (United States)

Mandrekar-Colucci, Shweta; Hall, Jodie C.E.; Sweet, David R.; Schmitt, Philipp J.; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia

2016-01-01

Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155–5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. SIGNIFICANCE STATEMENT Axon regeneration after spinal cord injury (SCI) fails

Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

Directory of Open Access Journals (Sweden)

Feng Xue

2015-01-01

Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

Science.gov (United States)

Xue, Feng; Wu, Er-jun; Zhang, Pei-xun; Li-ya, A; Kou, Yu-hui; Yin, Xiao-feng; Han, Na

2015-01-01

We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury. PMID:25788929

Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

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Kamimura, Rantaro; Hossain, Mohammad Z; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Takahashi, Kojiro; Otake, Masanori; Saito, Isao; Kitagawa, Junichi

2018-03-24

Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

Pre-differentiated GABAergic neural precursor transplants for alleviation of dysesthetic central pain following excitotoxic spinal cord injury

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Jeung Woon eLee

2012-05-01

Full Text Available Intraspinal quisqualic acid (QUIS injury induce (i mechanical and thermal hyperalgesia, (ii progressive self-injurious overgrooming of the affected dermatome. The latter is thought to resemble painful dysesthesia observed in spinal cord injury (SCI patients. We have reported previously loss of endogenous GABA immunoreactive (IR cells in the superficial dorsal horn of QUIS rats 2 weeks post-injury. Further histological evaluation showed that GABA-, glycine-, and synaptic vesicular transporter VIAAT-IR persisted but were substantially decreased in the injured spinal cord. In this study, partially-differentiated GABA-IR embryonic neural precursor cells (NPCs were transplanted into the spinal cord of QUIS rats to reverse overgrooming by replenishing lost inhibitory circuitry. Rat E14 NPCs were predifferentiated in 0.1 ng/ml FGF-2 for 4 hrs prior to transplantation. In vitro immunocytochemistry of transplant cohort showed large population of GABA-IR NPCs that double labeled with nestin but few co-localized with NeuN, indicating partial maturation. Two weeks following QUIS lesion at T12-L1, and following the onset of overgrooming, NPCs were transplanted into the QUIS lesion sites; bovine adrenal fibroblast cells were used as control. Overgrooming was reduced in >55.5% of NPC grafted animals, with inverse relationship between the number of surviving GABA-IR cells and the size of overgrooming. Fibroblast-control animals showed a progressive worsening of overgrooming. At 3 weeks post-transplantation, numerous GABA-, nestin-, and GFAP-IR cells were present in the lesion site. Surviving grafted GABA-IR NPCs were NeuN+ and GFAP-. These results indicate that partially-differentiated NPCs survive and differentiate in vivo into neuronal cells following transplantation into an injured spinal cord. GABA-IR NPC transplants can restore lost dorsal horn inhibitory signaling and are useful in alleviating central pain following SCI.

Infections in the spinal cord-injured population: a systematic review.

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Garcia-Arguello, L Y; O'Horo, J C; Farrell, A; Blakney, R; Sohail, M R; Evans, C T; Safdar, N

2017-06-01

Spinal cord injury (SCI) patients are an increasing population due to recent military conflicts. SCI patients are at an increased risk of infection, but the epidemiology management and prevention strategies for these infections are unclear. To review the incidence, microbiology and management of pneumonia, skin and soft tissue infections (SSTI), urinary tract infections (UTI) and bloodstream infections in the SCI population via literature review. With the assistance of an experienced medical librarian, we developed a search strategy for the Ovid MEDLINE database and then adapted it for the Ovid Embase, Scopus and Web of Science databases. The databases were searched from their inception to April 2014 with no restrictions on language or time period. Data were extracted using a standardized form. All studies were reviewed by two independent investigators. Forty-one studies reporting on the described infections were identified. UTIs were the most commonly identified infections, but studies failed to identify consistently effective preventive strategies. SSTIs were also common, and the best preventive strategies focused on decubitus ulcer prevention and skin decolonization protocols. Pneumonia management and course were not significantly different from the general population. Bloodstream infections were associated with delays in recognition, and were most often secondary to UTI, pneumonia or SSTI. There is a paucity of literature on consistently effective infection prevention strategies in SCI patients. Identification and implementation of evidence-based interventions that optimize prevention and management of infections in this patient population are needed.

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

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

2014-01-01

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

LncRNA expression in the spinal cord modulated by minocycline in a mouse model of spared nerve injury

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Liu ZH

2017-10-01

Full Text Available Zihao Liu, Ying Liang, Honghua Wang, Zhenhe Lu, Jinsheng Chen, Qiaodong Huang, Lei Sheng, Yinghong Ma, Huiying Du, Qingjuan GongDepartment of Pain Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Abstract: Neuropathic pain is a common and refractory chronic pain that affects millions of people worldwide. Its underlying mechanisms are still unclear, but they may involve long noncoding RNAs (lncRNAs, which play crucial roles in a variety of biological functions, including nociception. We used microarrays to investigate the possible interactions between lncRNAs and neuropathic pain and identified 22,213 lncRNAs and 19,528 mRNAs in the spinal cord in a mouse model of spared nerve injury (SNI-induced neuropathic pain. The abundance levels of 183 lncRNAs and 102 mRNAs were significantly modulated by both SNI and administration of minocycline. A quantitative real-time polymerase chain reaction analysis validated expression changes in three lncRNAs (NR_015491, ENSMUST00000174263, and ENSMUST00000146263. Class distribution analysis of differentially expressed lncRNAs revealed intergenic lncRNAs as the largest category. Functional analysis indicated that SNI-induced gene regulations might be involved in the activities of cytokines (IL17A and IL17F and chemokines (CCL2, CCL5, and CCL7, whereas minocycline might exert a pain-alleviating effect on mice through actin binding, thereby regulating nociception by controlling the cytoskeleton. Thus, lncRNAs might be responsible for SNI-induced neuropathic pain and the attenuation caused by minocycline. Our study could implicate lncRNAs as potential targets for future treatment of neuropathic pain. Keywords: LncRNA, neuropathic pain, spinal cord, minocycline

Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

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Wilson Pak-Kin Lou

2018-01-01

Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

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Rui-ping Zhang

2015-01-01

Full Text Available An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T 7-8 . Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.

Alpha-2 agonist attenuates ischemic injury in spinal cord neurons.

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Freeman, Kirsten A; Puskas, Ferenc; Bell, Marshall T; Mares, Joshua M; Foley, Lisa S; Weyant, Michael J; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong; Herson, Paco S; Reece, T Brett

2015-05-01

Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion. Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 μM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis. Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P control cells by 50% (P neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Can PRP effectively treat injured tendons?

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Wang, James H-C

2014-01-01

PRP is widely used to treat tendon and other tissue injuries in orthopaedics and sports medicine; however, the efficacy of PRP treatment on injured tendons is highly controversial. In this commentary, I reason that there are many PRP- and patient-related factors that influence the outcomes of PRP treatment on injured tendons. Therefore, more basic science studies are needed to understand the mechanism of PRP on injured tendons. Finally, I suggest that better understanding of the PRP action mechanism will lead to better use of PRP for the effective treatment of tendon injuries in clinics.

Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

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Caldeira, Vanessa; Dougherty, Kimberly J.; Borgius, Lotta

2017-01-01

Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we...... than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion....... use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype...

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.

Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

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Danner, Simon M.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

2015-01-01

In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22–60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5–26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits. PMID:25904708

Comparison of Diffusion MRI Acquisition Protocols for the In Vivo Characterization of the Mouse Spinal Cord: Variability Analysis and Application to an Amyotrophic Lateral Sclerosis Model.

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Figini, Matteo; Scotti, Alessandro; Marcuzzo, Stefania; Bonanno, Silvia; Padelli, Francesco; Moreno-Manzano, Victoria; García-Verdugo, José Manuel; Bernasconi, Pia; Mantegazza, Renato; Bruzzone, Maria Grazia; Zucca, Ileana

2016-01-01

Diffusion-weighted Magnetic Resonance Imaging (dMRI) has relevant applications in the microstructural characterization of the spinal cord, especially in neurodegenerative diseases. Animal models have a pivotal role in the study of such diseases; however, in vivo spinal dMRI of small animals entails additional challenges that require a systematical investigation of acquisition parameters. The purpose of this study is to compare three acquisition protocols and identify the scanning parameters allowing a robust estimation of the main diffusion quantities and a good sensitivity to neurodegeneration in the mouse spinal cord. For all the protocols, the signal-to-noise and contrast-to noise ratios and the mean value and variability of Diffusion Tensor metrics were evaluated in healthy controls. For the estimation of fractional anisotropy less variability was provided by protocols with more diffusion directions, for the estimation of mean, axial and radial diffusivity by protocols with fewer diffusion directions and higher diffusion weighting. Intermediate features (12 directions, b = 1200 s/mm2) provided the overall minimum inter- and intra-subject variability in most cases. In order to test the diagnostic sensitivity of the protocols, 7 G93A-SOD1 mice (model of amyotrophic lateral sclerosis) at 10 and 17 weeks of age were scanned and the derived diffusion parameters compared with those estimated in age-matched healthy animals. The protocols with an intermediate or high number of diffusion directions provided the best differentiation between the two groups at week 17, whereas only few local significant differences were highlighted at week 10. According to our results, a dMRI protocol with an intermediate number of diffusion gradient directions and a relatively high diffusion weighting is optimal for spinal cord imaging. Further work is needed to confirm these results and for a finer tuning of acquisition parameters. Nevertheless, our findings could be important for the

Spontaneous development of full weight-supported stepping after complete spinal cord transection in the neonatal opossum, Monodelphis domestica.

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Benjamin J Wheaton

Full Text Available Spinal cord trauma in the adult nervous system usually results in permanent loss of function below the injury level. The immature spinal cord has greater capacity for repair and can develop considerable functionality by adulthood. This study used the marsupial laboratory opossum Monodelphis domestica, which is born at a very early stage of neural development. Complete spinal cord transection was made in the lower-thoracic region of pups at postnatal-day 7 (P7 or P28, and the animals grew to adulthood. Injury at P7 resulted in a dense neuronal tissue bridge that connected the two ends of the cord; retrograde neuronal labelling indicated that supraspinal and propriospinal innervation spanned the injury site. This repair was associated with pronounced behavioural recovery, coordinated gait and an ability to use hindlimbs when swimming. Injury at P28 resulted in a cyst-like cavity encased in scar tissue forming at the injury site. Using retrograde labelling, no labelled brainstem or propriospinal neurons were found above the lesion, indicating that detectable neuronal connectivity had not spanned the injury site. However, these animals could use their hindlimbs to take weight-supporting steps but could not use their hindlimbs when swimming. White matter, demonstrated by Luxol Fast Blue staining, was present in the injury site of P7- but not P28-injured animals. Overall, these studies demonstrated that provided spinal injury occurs early in development, regrowth of supraspinal innervation is possible. This repair appears to lead to improved functional outcomes. At older ages, even without detectable axonal growth spanning the injury site, substantial development of locomotion was still possible. This outcome is discussed in conjunction with preliminary findings of differences in the local propriospinal circuits following spinal cord injury (demonstrated with fluororuby labelling, which may underlie the weight bearing locomotion observed in the

Crosstalk Between Activated Myofibroblasts and β Cells in Injured Mouse Pancreas.

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Bayan, Jennifer-Ann; Peng, Zhechu; Zeng, Ni; He, Lina; Chen, Jingyu; Stiles, Bangyan L

2015-10-01

In injury conditions, myofibroblasts are induced to lay down matrix proteins and support the repair process. In this study, we investigated the role of myofibroblasts, particularly stellate cells, in the growth and regeneration of pancreatic β cells. We used both in vitro and in vivo approaches to address whether stellate cells may promote the growth of β cells. Our experiments demonstrated that activated stellate cells support the proliferation of β cells in vitro. In vivo, mesenchymals surrounding the pancreatic islets are activated (induced to proliferate) in the islet regeneration model of Pten null mice. These mesenchymals display markers of pancreatic stellate cells, such as desmin and to a lesser extent, smooth muscle actin α. We have shown previously that targeted β-cell deletion of Pten lead to a significant increase in total islet mass. This phenotype was accompanied by an increase in peri-islet mitotic activity, particularly in islets injured by streptozotocin, a β cell-specific toxin. Together with the in vitro observations, our data, here, suggest that that these mesenchymal cells may support the regeneration of the islets. Identifying how the communication occurs may provide clinically relevant mechanism for inducing β-cell regeneration.

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

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Keefe, Kathleen M.; Sheikh, Imran S.; Smith, George M.

2017-01-01

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord. PMID:28273811

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury.

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Keefe, Kathleen M; Sheikh, Imran S; Smith, George M

2017-03-03

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

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

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Adam R Ferguson

2012-10-01

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

Functional Brain Connectivity during Multiple Motor Imagery Tasks in Spinal Cord Injury

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Alkinoos Athanasiou

2018-01-01

Full Text Available Reciprocal communication of the central and peripheral nervous systems is compromised during spinal cord injury due to neurotrauma of ascending and descending pathways. Changes in brain organization after spinal cord injury have been associated with differences in prognosis. Changes in functional connectivity may also serve as injury biomarkers. Most studies on functional connectivity have focused on chronic complete injury or resting-state condition. In our study, ten right-handed patients with incomplete spinal cord injury and ten age- and gender-matched healthy controls performed multiple visual motor imagery tasks of upper extremities and walking under high-resolution electroencephalography recording. Directed transfer function was used to study connectivity at the cortical source space between sensorimotor nodes. Chronic disruption of reciprocal communication in incomplete injury could result in permanent significant decrease of connectivity in a subset of the sensorimotor network, regardless of positive or negative neurological outcome. Cingulate motor areas consistently contributed the larger outflow (right and received the higher inflow (left among all nodes, across all motor imagery categories, in both groups. Injured subjects had higher outflow from left cingulate than healthy subjects and higher inflow in right cingulate than healthy subjects. Alpha networks were less dense, showing less integration and more segregation than beta networks. Spinal cord injury patients showed signs of increased local processing as adaptive mechanism. This trial is registered with NCT02443558.

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

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Chen, Qin; Shine, H David

2013-10-01

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

Biomechanical Evaluation of the MACSTL Internal Fixator for Thoracic Spinal Stabilisation

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R. Veselý

2008-01-01

Full Text Available Unstable fractures of the thoracic spine in humans represent a serious social and economic issue. They may lead to persistent consequences and chronic disease. The anatomical and biomechanical characteristics of the thoracic spine are different from all the other spinal parts due to its higher mobility. The vertebrae of the chest area are less mobile, conferring a higher degree of rigidity to the spine. To destabilize this relatively rigid system, a considerable force is necessary. The treatment of unstable spinal fractures is solely surgical. The decompression of the spinal canal with reposition and stabilisation of the fracture is indicated urgently. This intervention is performed mostly from the posterior approach in the first phase. However, the anterior spinal column is the structure responsible for the stability of the spine. Therefore, the recent advances in spine surgery focus on this area of expertise. For this reason, we carried out a bio-mechanical study aimed at assessing the effectiveness of two surgical tactics used. The study consisted of comparative experiments performed by computer-aided device on segments of pig cadavers (n = 5. The experiment involved a comparison of segments of the thoracic spine under the following conditions: an anatomically intact segment, a spine segment with an artificially created anterior instability, and a segment with an applied internal fixator. The experiment compared the mechanical characteristics of these segments. The experiment has demonstrated that after application of the internal fixator used for stabilisation of the injured anterior spinal column at defined pre-loading of 200 N, the stability of damaged spinal segment in torsion increased twofold. It was also verified that sufficient stability can be ensured using the Modular Anterior Construct System (MACSTL implant for ventral stabilisation of thoracic spine unstable injuries. Endoscopic application of this implant represents an

Cervical spinal cord injuries in patients with cervical spondylosis.

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Regenbogen, V S; Rogers, L F; Atlas, S W; Kim, K S

1986-02-01

Eighty-eight patients over age 40 with traumatic cervical spinal cord injuries were clinically and radiographically evaluated, and comparison was made with 35 spinal cord injury patients under age 36. While most older patients sustained obvious bony and/or ligamentous damage commensurate with their neurologic findings, 25 (28%) of the 88 patients had no demonstrable bony abnormalities and 17 (20%) of the 88 patients had only minimal evidence of bony injury. Of particular interest are the patients with severe cord injuries, yet no bony abnormalities, who seem to form a distinct subgroup of the cervical spinal cord injury patient on the basis of radiographic and clinical features. Of these 25 patients, 24 (96%) had severe cervical spondylosis. Fourteen (56%) of the 25 patients were injured in falls, five (36%) of these 14 being of a seemingly trivial nature. Of the 42 patients with minimal or no demonstrable bony abnormalities, 33 (79%) were evaluated with plain tomography and no occult fractures or other significant pathology was demonstrated. Pantopaque myelography in 27 (64%) of the 42 cases revealed no extruded disk or other surgical lesion in any patient. In large measure, these injuries can be attributed to cervical spondylosis, which narrows the canal and makes the cord more susceptible to compression by the bulging ligamenta flava during hyperextension.

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

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

2013-04-12

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

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

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

2013-01-01

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

The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice.

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Uchida, Kenzo; Nakajima, Hideaki; Hirai, Takayuki; Yayama, Takafumi; Chen, Kebing; Guerrero, Alexander Rodriguez; Johnson, William Eustace; Baba, Hisatoshi

2012-12-15

The twy/twy mouse undergoes spontaneous chronic mechanical compression of the spinal cord; this in vivo model system was used to examine the effects of retrograde adenovirus (adenoviral vector [AdV])-mediated brain-derived neurotrophic factor (BDNF) gene delivery to spinal neural cells. To investigate the targeting and potential neuroprotective effect of retrograde AdV-mediated BDNF gene transfection in the chronically compressed spinal cord in terms of prevention of apoptosis of neurons and oligodendrocytes. Several studies have investigated the neuroprotective effects of neurotrophins, including BDNF, in spinal cord injury. However, no report has described the effects of retrograde neurotrophic factor gene delivery in compressed spinal cords, including gene targeting and the potential to prevent neural cell apoptosis. AdV-BDNF or AdV-LacZ (as a control gene) was injected into the bilateral sternomastoid muscles of 18-week old twy/twy mice for retrograde gene delivery via the spinal accessory motor neurons. Heterozygous Institute of Cancer Research mice (+/twy), which do not undergo spontaneous spinal compression, were used as a control for the effects of such compression on gene delivery. The localization and cell specificity of β-galactosidase expression (produced by LacZ gene transfection) and BDNF expression in the spinal cord were examined by coimmunofluorescence staining for neural cell markers (NeuN, neurons; reactive immunology protein, oligodendrocytes; glial fibrillary acidic protein, astrocytes; OX-42, microglia) 4 weeks after gene injection. The possible neuroprotection afforded by retrograde AdV-BDNF gene delivery versus AdV-LacZ-transfected control mice was assessed by scoring the prevalence of apoptotic cells (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells) and immunoreactivity to active caspases -3, -8, and -9, p75, neurofilament 200 kD (NF), and for the oligodendroglial progenitor marker, NG2. RESULTS

Development of a 3D matrix for modeling mammalian spinal cord injury in vitro

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Juan Felipe Diaz Quiroz

2016-01-01

Full Text Available Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difficulty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells after exposure to drugs.

Residual cognitive disability after completion of inpatient rehabilitation among injured children.

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Zonfrillo, Mark R; Durbin, Dennis R; Winston, Flaura K; Zhang, Xuemei; Stineman, Margaret G

2014-01-01

To determine the prevalence and nature of residual cognitive disability after inpatient rehabilitation for children aged 7-18 years with traumatic injuries. This retrospective cohort study included children aged 7-18 years in the Uniform Data System for Medical Rehabilitation who underwent inpatient rehabilitation for traumatic injuries in 523 facilities from 2002-2011. Traumatic injuries were identified by standardized Medicare Inpatient Rehabilitation Facility-Patient Assessment Instrument codes. Cognitive outcomes were measured by the Functional Independence Measure instrument. A validated, categorical staging system derived from responses to the items in the cognitive domain of the functional independence measure was used and consisted of clinically relevant levels of cognitive achievement from stage 1 (total cognitive disability) to stage 7 (completely independent cognitive function). There were 13,798 injured children who completed inpatient rehabilitation during the 10-year period. On admission to inpatient rehabilitation, patients with traumatic brain injury (TBI) had more cognitive disability (median stage 2) than those with spinal cord injury or other injuries (median stage 5). Cognitive functioning improved for all patients, but children with TBI still tended to have significant residual cognitive disability (median stage on discharge, 4). Injured children gained cognitive functionality throughout inpatient rehabilitation. Those with TBI had more severe cognitive disability on admission and more residual disability on discharge. This is important not only for patient and family expectation setting but also for resource and service planning, as discharge from inpatient rehabilitation is a critical milestone for reintegration into society for children with serious injury. Copyright © 2014 Mosby, Inc. All rights reserved.

Cortical control of intraspinal microstimulation: Toward a new approach for restoration of function after spinal cord injury.

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Shahdoost, Shahab; Frost, Shawn; Dunham, Caleb; DeJong, Stacey; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2015-08-01

Approximately 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress toward developing a miniaturized brain-machine-spinal cord interface (BMSI) that converts in real time the neural command signals recorded from the cortical motor regions to electrical stimuli delivered to the spinal cord below the injury level. Using a combination of custom integrated circuit (IC) technology for corticospinal interfacing and field-programmable gate array (FPGA)-based technology for embedded signal processing, we demonstrate proof-of-concept of distinct muscle pattern activation via intraspinal microstimulation (ISMS) controlled in real time by intracortical neural spikes in an anesthetized laboratory rat.

Characterization of A11 neurons projecting to the spinal cord of mice.

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Kathrin Koblinger

Full Text Available The hypothalamic A11 region has been identified in several species including rats, mice, cats, monkeys, zebrafish, and humans as the primary source of descending dopamine (DA to the spinal cord. It has been implicated in the control of pain, modulation of the spinal locomotor network, restless leg syndrome, and cataplexy, yet the A11 cell group remains an understudied dopaminergic (DAergic nucleus within the brain. It is unclear whether A11 neurons in the mouse contain the full complement of enzymes consistent with traditional DA neuronal phenotypes. Given the abundance of mouse genetic models and tools available to interrogate specific neural circuits and behavior, it is critical first to fully understand the phenotype of A11 cells. We provide evidence that, in addition to tyrosine hydroxylase (TH that synthesizes L-DOPA, neurons within the A11 region of the mouse contain aromatic L-amino acid decarboxylase (AADC, the enzyme that converts L-DOPA to dopamine. Furthermore, we show that the A11 neurons contain vesicular monoamine transporter 2 (VMAT2, which is necessary for packaging DA into vesicles. On the contrary, A11 neurons in the mouse lack the dopamine transporter (DAT. In conclusion, our data suggest that A11 neurons are DAergic. The lack of DAT, and therefore the lack of a DA reuptake mechanism, points to a longer time of action compared to typical DA neurons.

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

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

2017-01-01

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

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

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

2012-01-01

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

Calcium dynamics and buffering in motoneurones of the mouse spinal cord

Czech Academy of Sciences Publication Activity Database

Paleček, Jiří; Lips, M. B.; Keller, B. U.

1999-01-01

Roč. 520, č. 2 (1999), s. 485-502 ISSN 0928-4257 R&D Projects: GA ČR(CZ) GA305/96/0680 Institutional research plan: CEZ:AV0Z5011922 Keywords : spinal cord * motor neuron toxicity * amyotrophic lateral sclerosis Subject RIV: FH - Neurology Impact factor: 1.130, year: 1999

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

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Shing-Hwa Lu

2007-10-01

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

Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord

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Jeffrey B. Russ

2013-09-01

Full Text Available During perinatal development, corticospinal tract (CST projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65. In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of descending spinal pathways, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

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Kathleen M. Keefe

2017-03-01

Full Text Available Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI. We focus on nerve growth factor (NGF, brain derived neurotrophic factor (BDNF, and neurotrophin-3 (NT-3, and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

A study of burden of care and its correlates among family members supporting relatives and loved ones with traumatic spinal cord injuries.

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Castellano-Tejedor, Carmina; Lusilla-Palacios, Pilar

2017-07-01

To understand and describe in a sample of caregivers of persons with spinal cord injury, their burden of care, resilience and life satisfaction and to explore the relationship between these variables. Cross-sectional design. One Spinal Cord Injury Acute Inpatient Unit from a general hospital. Seventy-five relatives of persons with spinal cord injuries (84% women) with a mean age of 48.55 ( SD = 12.55) years. None. Demographics (neurological loss and severity according to the American Spinal Injury Association criteria), the Zarit Burden Interview, the Resilience Scale and the Life Satisfaction Checklist. All caregivers experienced feelings of different intensities of burden (52% mild-to-moderate, 43% moderate-to-severe and 5% severe), and none of them expressed little or no burden at the assessment moment. Caregivers' main worries were "dependence" and "the future of the injured." Resilience was medium-to-high (mean = 141.93, SD = 23.44) for the whole sample with just a minority of them revealing low (15%) or very low resilience (7%). The highest scores were obtained in relation to "caregivers' independence" and "meaning of their lives." Life satisfaction scores were medium-to-high (mean = 36.6, SD = 6). These scores were not related to demographics or the severity of the injury. Zarit Burden Interview scores were negatively correlated to Resilience Scale ( r = -.370, P = .001) and Life Satisfaction Checklist scores ( r = -.412, P resilient and satisfied caregivers experienced lower burden. Burden is moderate-to-high and mainly related to uncertainty about the future, caregivers' insecurity with caregiving and dependence of the injured.

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

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A. Schiaveto-de-Souza

2013-12-01

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

Transmitters and pathways mediating inhibition of spinal itch-signaling neurons by scratching and other counterstimuli.

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Tasuku Akiyama

Full Text Available Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous firing that was significantly attenuated by cutaneous scratching, pinch and noxious heat. Scratch-evoked inhibition was nearly abolished by spinal delivery of the glycine antagonist, strychnine, and was markedly attenuated by respective GABA(A and GABA(B antagonists bicuculline and saclofen. Scratch-evoked inhibition was also significantly attenuated (but not abolished by interruption of the upper cervical spinal cord, indicating the involvement of both segmental and suprasegmental circuits that engage glycine- and GABA-mediated inhibition of spinal itch-signaling neurons by noxious counterstimuli.

Transcriptional regulation of Nfix by NFIB drives astrocytic maturation within the developing spinal cord.

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Matuzelski, Elise; Bunt, Jens; Harkins, Danyon; Lim, Jonathan W C; Gronostajski, Richard M; Richards, Linda J; Harris, Lachlan; Piper, Michael

2017-12-15

During mouse spinal cord development, ventricular zone progenitor cells transition from producing neurons to producing glia at approximately embryonic day 11.5, a process known as the gliogenic switch. The transcription factors Nuclear Factor I (NFI) A and B initiate this developmental transition, but the contribution of a third NFI member, NFIX, remains unknown. Here, we reveal that ventricular zone progenitor cells within the spinal cord express NFIX after the onset of NFIA and NFIB expression, and after the gliogenic switch has occurred. Mice lacking NFIX exhibit normal neurogenesis within the spinal cord, and, while early astrocytic differentiation proceeds normally, aspects of terminal astrocytic differentiation are impaired. Finally, we report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord. This hierarchical organisation of NFI protein expression and function during spinal cord gliogenesis reveals a previously unrecognised auto-regulatory mechanism within this gene family. Copyright © 2017 Elsevier Inc. All rights reserved.

The nature and impact of stigma towards injured workers.

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Kirsh, Bonnie; Slack, Tesha; King, Carole Anne

2012-06-01

Many injured workers experience high levels of stigma and discrimination, which compound their physical injuries and cause social and psychological harm. Despite a growing awareness of the prevalence of such stigma, there is little research that focuses on the sources, nature and consequences of stigma with respect to the lives of injured workers. The purpose of this paper is to advance knowledge related to stigma towards injured workers, specifically to explain the nature and processes of stigma and their influence on injured workers' lives. Using a constructivist grounded theory approach, data from focus groups (n = 28 participants) and individual interviews (n = 18) were analyzed to discern how stigma is exhibited and perpetuated, and its impact on the lives of injured workers. The study culminated in a preliminary theoretical framework that delineates the key components of the manifestations and impacts of stigma that includes stereotypes, unethical practices and maltreatment negatively affecting work, relationships and the mental health of injured workers. The development of sound conceptualizations in this area can advance our understanding of stigma processes and provide a framework for anti-stigma efforts. The findings have implications for public education, workplace interventions and services for injured workers.

Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury

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Nan Gu

2016-07-01

Full Text Available Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

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

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

2015-01-01

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

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

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

2007-09-01

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

Natural IgM antibodies that bind neoepitopes exposed as a result of spinal cord injury , drive secondary injury by activating complement.

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Narang, Aarti; Qiao, Fei; Atkinson, Carl; Zhu, Hong; Yang, Xiaofeng; Kulik, Liudmila; Holers, V Michael; Tomlinson, Stephen

2017-06-19

Natural IgM antibodies (Abs) function as innate immune sensors of injury via recognition of neoepitopes expressed on damaged cells, although how this recognition systems function following spinal cord injury (SCI) exposes various neoepitopes and their precise nature remains largely unknown. Here, we investigated the role of two natural IgM monoclonal Abs (mAbs), B4 and C2, that recognize post-ischemic neoepitopes following ischemia and reperfusion in other tissues. Identification of post-SCI expressed neoepitopes was examined using previously characterized monoclonal Abs (B4 and C2 mAbs). The role of post-SCI neoepitopes and their recognition by natural IgM Abs in propagating secondary injury was examined in Ab-deficient Rag1-/- or wild type C57BL/6 mice using Ab reconstitution experiments and neoepitope-targeted therapeutic studies, respectively. Administration of B4 or C2 mAb following murine SCI increased lesion size and worsened functional outcome in otherwise protected Ab-deficient Rag1-/- mice. Injury correlated with colocalized deposition of IgM and C3d in injured spinal cords from both mAb reconstituted Rag1-/- mice and untreated wild-type mice. Depletion of peritoneal B1 B cells, a source of natural Abs, reduced circulating levels of IgM with B4 (annexin-IV) and C2 (subset of phospholipids) reactivity, reduced IgM and complement deposition in the spinal cord, and protected against SCI. We therefore investigated whether the B4 neoepitope represents a therapeutic target for complement inhibition. B4-Crry, a fusion protein consisting of a single-chain Ab derived from B4 mAb, linked to the complement inhibitor Crry, significantly protected against SCI. B4-Crry exhibited a dual function in that it inhibited both the binding of pathogenic IgM and blocked complement activation in the spinal cord. This study identifies important neoepitopes expressed within the spinal cord after injury. These neoepitopes are recognized by clonally specific natural IgM Abs that

Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

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Euler Moraes Penha

2014-01-01

Full Text Available The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.

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Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

2016-12-01

We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain. A thoracic spinal cord hemisection significantly increased both astrocyte activation and Cx43 expression in lumbar dorsal horn. Sig-1Rs were also increased in lumbar dorsal horn astrocytes, but not neurons or microglia. Intrathecal injection of an astrocyte metabolic inhibitor (fluorocitrate); a gap junction/hemichannel blocker (carbenoxolone); or a Cx43 mimetic peptide ( 43 Gap26) significantly reduced SCI-induced bilateral below-level mechanical allodynia. Blockade of Sig-1Rs with BD1047 during the induction phase of pain significantly suppressed the SCI-induced development of mechanical allodynia, astrocyte activation, increased expression of Cx43 in both total and membrane levels, and increased association of Cx43 with Sig-1R. However, SCI did not change the expression of oligodendrocyte (Cx32) or neuronal (Cx36) gap junction proteins. These findings demonstrate that SCI activates astrocyte Sig-1Rs leading to increases in the expression of the gap junction protein, Cx43 and astrocyte activation in the lumbar dorsal horn, and ultimately contribute to the induction of bilateral below-level mechanical allodynia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioinformatic Analysis of Potential Biomarkers for Spinal Cord Injured Patients With Intractable Neuropathic Pain.

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Wang, Yimin; Ye, Fang; Huang, Chanyan; Xue, Faling; Li, Yingyuan; Gao, Shaowei; Qiu, Zeting; Li, Si; Chen, Qinchang; Zhou, Huaqiang; Song, Yiyan; Huang, Wenqi; Tan, Wulin; Wang, Zhongxing

2018-03-15

Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting patients' life quality. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and MicroRNAs(miRNAs) related to neuropathic pain by bioinformatics method. Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from patients with or without neuropathic pain after spinal cord injury (SCI) were collected. 12 samples with neuropathic pain and 13 samples without pain as control were included in the downloaded microarray. Differentially expressed genes (DEGs) between neuropathic pain group and control group were detected using GEO2R online tool. Functional enrichment analysis of DEGs was performed using DAVID database. Protein-protein interaction (PPI) network was constructed from STRING database. MiRNAs targeting these DEGs were obtained from miRNet database. A merged miRNA-DEG network was constructed and analyzed with Cytoscape software. Total 1134 DEGs were identified between patients with or without neuropathic pain(case and control) and 454 biological processes were enriched. We identified 4 targeted miRNAs, including mir-204-5p, mir-519d-3p, mir-20b-5p, mir-6838-5p, which may be the potential biomarker for SCI patients. Protein modification and regulation biological process of central nervous system may be a risk factor of in SCI patients. Certain genes and miRNAs may be potential biomarkers for the prediction of and potential targets for prevention and treatment of neuropathic pain after SCI.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http

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

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

2014-01-30

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement. Copyright © 2014 Elsevier Inc. All rights reserved.

Retrospective analysis of spinal trauma in patients with ankylosing spondylitis: a descriptive study in Indian population.

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Mahajan, R; Chhabra, H S; Srivastava, A; Venkatesh, R; Kanagaraju, V; Kaul, R; Tandon, V; Nanda, A; Sangondimath, G; Patel, N

2015-05-01

This study aims to understand the demographics, mode of trauma, hospital stay, complications, neurological improvement, mortality and expenditure incurred by Indian patients with spinal trauma and ankylosing spondylitis (AS). Retrospective analysis of the patient data admitted to a tertiary referral hospital from 2008 to 2013 with the diagnosis of AS and spinal trauma was carried out. The variables studied were demographics, mode of trauma, neurological status, neurological improvement, involved vertebral level, duration of hospital stay, comorbid factors, expenditure and complications during the stay. Forty-six patients with diagnosis of AS with spine trauma were admitted over the last 5 years with a total of 52 fractures. All were male patients; 58.6% had injury because of trivial trauma and 78.2% patients presented with neurological injury. C5 C6, C6 C7, C7 D1 and D12 were the most common injured level. Fractures through intervertebral disc were most common in cervical spine. Of the patients, 52.7% had shown neurological improvement of at least grade 1(AIS). Mean expenditure of patient admitted with spinal cord injury (SCI) with AS is 7957 USD (United States dollar), which is around five times the per capita income in India (as per year 2013). Males with AS are much more prone to spinal fractures than females and its incidence may be higher than previously reported. Domestic falls are the most common mechanism of spinal trauma in this population. High velocity injuries are associated with complete SCI. The study reinforces the need for development of subsidized spinal care services for SCI management.

Gene Expression Profiling in the Injured Spinal Cord of Trachemys scripta elegans: An Amniote with Self-Repair Capabilities

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Valentin-Kahan, Adrián; García-Tejedor, Gabriela B.; Robello, Carlos; Trujillo-Cenóz, Omar; Russo, Raúl E.; Alvarez-Valin, Fernando

2017-01-01

Slider turtles are the only known amniotes with self-repair mechanisms of the spinal cord that lead to substantial functional recovery. Their strategic phylogenetic position makes them a relevant model to investigate the peculiar genetic programs that allow anatomical reconnection in some vertebrate groups but are absent in others. Here, we analyze the gene expression profile of the response to spinal cord injury (SCI) in the turtle Trachemys scripta elegans. We found that this response comprises more than 1000 genes affecting diverse functions: reaction to ischemic insult, extracellular matrix re-organization, cell proliferation and death, immune response, and inflammation. Genes related to synapses and cholesterol biosynthesis are down-regulated. The analysis of the evolutionary distribution of these genes shows that almost all are present in most vertebrates. Additionally, we failed to find genes that were exclusive of regenerating taxa. The comparison of expression patterns among species shows that the response to SCI in the turtle is more similar to that of mice and non-regenerative Xenopus than to Xenopus during its regenerative stage. This observation, along with the lack of conserved “regeneration genes” and the current accepted phylogenetic placement of turtles (sister group of crocodilians and birds), indicates that the ability of spinal cord self-repair of turtles does not represent the retention of an ancestral vertebrate character. Instead, our results suggest that turtles developed this capability from a non-regenerative ancestor (i.e., a lineage specific innovation) that was achieved by re-organizing gene expression patterns on an essentially non-regenerative genetic background. Among the genes activated by SCI exclusively in turtles, those related to anoxia tolerance, extracellular matrix remodeling, and axonal regrowth are good candidates to underlie functional recovery. PMID:28223917

Gene Expression Profiling in the Injured Spinal Cord of Trachemys scripta elegans: An Amniote with Self-Repair Capabilities.

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Valentin-Kahan, Adrián; García-Tejedor, Gabriela B; Robello, Carlos; Trujillo-Cenóz, Omar; Russo, Raúl E; Alvarez-Valin, Fernando

2017-01-01

Slider turtles are the only known amniotes with self-repair mechanisms of the spinal cord that lead to substantial functional recovery. Their strategic phylogenetic position makes them a relevant model to investigate the peculiar genetic programs that allow anatomical reconnection in some vertebrate groups but are absent in others. Here, we analyze the gene expression profile of the response to spinal cord injury (SCI) in the turtle Trachemys scripta elegans . We found that this response comprises more than 1000 genes affecting diverse functions: reaction to ischemic insult, extracellular matrix re-organization, cell proliferation and death, immune response, and inflammation. Genes related to synapses and cholesterol biosynthesis are down-regulated. The analysis of the evolutionary distribution of these genes shows that almost all are present in most vertebrates. Additionally, we failed to find genes that were exclusive of regenerating taxa. The comparison of expression patterns among species shows that the response to SCI in the turtle is more similar to that of mice and non-regenerative Xenopus than to Xenopus during its regenerative stage. This observation, along with the lack of conserved "regeneration genes" and the current accepted phylogenetic placement of turtles (sister group of crocodilians and birds), indicates that the ability of spinal cord self-repair of turtles does not represent the retention of an ancestral vertebrate character. Instead, our results suggest that turtles developed this capability from a non-regenerative ancestor (i.e., a lineage specific innovation) that was achieved by re-organizing gene expression patterns on an essentially non-regenerative genetic background. Among the genes activated by SCI exclusively in turtles, those related to anoxia tolerance, extracellular matrix remodeling, and axonal regrowth are good candidates to underlie functional recovery.

Fictive locomotion in the adult decerebrate and spinal mouse in vivo

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

2012-01-01

Recently, transgenic mice have been created with mutations affecting the components of the mammalian spinal central pattern generator (CPG) for locomotion, however, it has currently only been possible to evoke fictive locomotion in mice, using neonatal in vitro preparations. Here, we demonstrate...... organisation and allowing for future results in transgenic mice to be extrapolated to existing knowledge of CPG components and circuitry obtained in larger species....

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

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Battaglia G

2014-04-01

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

Spinal cord hemisection facilitates aromatic L-amino acid decarboxylase cells to produce serotonin in the subchronic but not the chronic phase

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Azam, Bushra; Wienecke, Jacob; Jensen, Dennis Bo

2015-01-01

12) were used with a postoperation interval at 5 days or 60 days. Using immunohistochemistry, first, we observed a significant reduction in the density of 5-HT-immunoreactive fibers in the spinal cord below the lesion on the injured side for both groups. Second, we found that the AADC cells were...... similarly expressed on both injured and uninjured sides in both groups. Third, increased production of 5-HT in AADC cells following 5-HTP was seen in 5-day but not in 60-day postinjury group. These results suggest that plastic changes of the 5-HT system might happen primarily in the subchronic phase...... and for longer period its function could be compensated by plastic changes of other intrinsic and/or supraspinal modulation systems....

Stem cell-derived neurotrophic support for the neuromuscular junction in spinal muscular atrophy.

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Wyatt, Tanya J; Keirstead, Hans S

2010-11-01

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by specific degeneration of α-motor neurons in the spinal cord. The use of cell transplantation to restore lost function through cell replacement or prevent further degeneration of motor neurons and synapses through neurotrophic support heralds tremendous hope in the SMA field. Much research has been carried out in the last decade on the use of embryonic stem cells in cell replacement strategies for various neurodegenerative diseases. Cell replacement is contingent on the ability of transplanted cells to integrate and form new functional connections with host cells. In the case of SMA, cell replacement is a tall order in that axons of transplanted cells would be required to grow over long distances from the spinal cord through growth-averse terrain to synapse with muscles in the periphery. The efficacy of neurotrophic support is contingent on the ability of transplanted cells to secrete neurotrophins appropriate for degenerating motor neurons in the spinal cord or development/stability of the neuromuscular junction (NMJ) in the periphery. The reader will gain an understanding of the potential of neurotrophins to promote development of the NMJ in a diseased or injured environment. Neurotrophins play a major role in NMJ development and thus may be a key factor in the pathogenesis of NMJs in SMA. Further research into the signaling mechanisms involved in NMJ maturation may identify additional mechanisms by which transplanted cells may be of therapeutic benefit.

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

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Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

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Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

2011-01-01

SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

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

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

2017-06-01

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

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

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Matthew D. Budde

2017-12-01

. Overall, the results and optimizations describe a protocol that mitigates several difficulties with DTI of the spinal cord. Detection of acute axonal damage in the injured or diseased spinal cord will benefit the optimized filter-probe diffusion MRI protocol outlined here.

Selective adenosine A2A receptor agonists and antagonists protect against spinal cord injury through peripheral and central effects

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Esposito Emanuela

2011-04-01

Full Text Available Abstract Background Permanent functional deficits following spinal cord injury (SCI arise both from mechanical injury and from secondary tissue reactions involving inflammation. Enhanced release of adenosine and glutamate soon after SCI represents a component in the sequelae that may be responsible for resulting functional deficits. The role of adenosine A2A receptor in central ischemia/trauma is still to be elucidated. In our previous studies we have demonstrated that the adenosine A2A receptor-selective agonist CGS21680, systemically administered after SCI, protects from tissue damage, locomotor dysfunction and different inflammatory readouts. In this work we studied the effect of the adenosine A2A receptor antagonist SCH58261, systemically administered after SCI, on the same parameters. We investigated the hypothesis that the main action mechanism of agonists and antagonists is at peripheral or central sites. Methods Spinal trauma was induced by extradural compression of SC exposed via a four-level T5-T8 laminectomy in mouse. Three drug-dosing protocols were utilized: a short-term systemic administration by intraperitoneal injection, a chronic administration via osmotic minipump, and direct injection into the spinal cord. Results SCH58261, systemically administered (0.01 mg/kg intraperitoneal. 1, 6 and 10 hours after SCI, reduced demyelination and levels of TNF-α, Fas-L, PAR, Bax expression and activation of JNK mitogen-activated protein kinase (MAPK 24 hours after SCI. Chronic SCH58261 administration, by mini-osmotic pump delivery for 10 days, improved the neurological deficit up to 10 days after SCI. Adenosine A2A receptors are physiologically expressed in the spinal cord by astrocytes, microglia and oligodendrocytes. Soon after SCI (24 hours, these receptors showed enhanced expression in neurons. Both the A2A agonist and antagonist, administered intraperitoneally, reduced expression of the A2A receptor, ruling out the possibility that the

Magnetic resonance imaging of spinal cord injury

International Nuclear Information System (INIS)

Shakudo, Miyuki; Inoue, Yuichi; Fukuda, Teruo

1988-01-01

Forty-three MR examinations of 30 patients with spinal cord injuries were retrospectively reviewed to evaluate MR findings of the injured cord and to correlate them with the time interval from the day of spinal cord injury. There were 18 cysts, 8 ''myelomalacias'', 2 cord atrophies, one intramedullary hematoma and two transections. In one patient, ''myelomalacia'' became a cyst on the follow-up study. Large cysts of more than 6 vertebral segments were found in 7 patients, all of whom had had trauma more than 5 years prior to examination. Small cysts of less than half a vertebral height were seen in 5 patients, all of whom were studied 3 to 6 months after the injury. Intermediate cysts were seen in 7 patients who had sustained trauma more than a year before. In a majority (13/14 scans) of ''myelomalacia'', the time interval from injury until examination was only 2 weeks to 6 months. Of the 14 patients who showed post-traumatic progressive myelopathy, seven had large cysts. It is known that intramedullary hematoma becomes a cyst, and that post-traumatic myelomalacia probably results in a cyst in animal studies. Our clinical study seems to support a strong causal relation between myelomalacia and post-traumatic cysts. Since post-traumatic progressive myelopathy with a cyst is surgically treatable, follow-up MR imaging is preferable in cases with myelomalacia. (author)

Sialic acid accelerates the electrophoretic velocity of injured dorsal root ganglion neurons

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Chen-xu Li

2015-01-01

Full Text Available Peripheral nerve injury has been shown to result in ectopic spontaneous discharges on soma and injured sites of sensory neurons, thereby inducing neuropathic pain. With the increase of membrane proteins on soma and injured site neurons, the negatively charged sialic acids bind to the external domains of membrane proteins, resulting in an increase of this charge. We therefore speculate that the electrophoretic velocity of injured neurons may be faster than non-injured neurons. The present study established rat models of neuropathic pain via chronic constriction injury. Results of the cell electrophoresis test revealed that the electrophoretic velocity of injured neuronal cells was faster than that of non-injured (control cells. We then treated cells with divalent cations of Ca 2+ and organic compounds with positive charges, polylysine to counteract the negatively charged sialic acids, or neuraminidase to specifically remove sialic acids from the membrane surface of injured neurons. All three treatments significantly reduced the electrophoretic velocity of injured neuronal cells. These findings suggest that enhanced sialic acids on injured neurons may accelerate the electrophoretic velocity of injured neurons.

Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.

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Bowers, Christian A; Kundu, Bornali; Hawryluk, Gregory W J

2016-06-01

Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.

Survival and cause of death after traumatic spinal cord injury. A long-term epidemiological survey from Denmark

DEFF Research Database (Denmark)

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

1997-01-01

Life expectancy among individuals with spinal cord injuries (SCI) has remained lower than in the normal population, even with optimal medical management. But significant improvement has been achieved, as will be illustrated in this retrospective study of an unselected group of traumatic survivors...... treatment and were rehabilitated at the centre for Spinal Cord Injured in Hornbaek, Denmark. At the end of the follow-up, 31st December 1992, 236 (197 men and 39 women) had died. The commonest causes of death were lung diseases, particularly pneumonia; suicide; and ischaemic heart disease. Among...... and pneumonia. A significant decrease in the overall mortality was observed from the first (1953-1973) to the second half of the observation period (1972-1992). Similarly the survival curves for both men and women demonstrate that the gap in survival probability between the normal population and the SCI has...

Trb2, a mouse homolog of tribbles, is dispensable for kidney and mouse development

International Nuclear Information System (INIS)

Takasato, Minoru; Kobayashi, Chiyoko; Okabayashi, Koji; Kiyonari, Hiroshi; Oshima, Naoko; Asashima, Makoto; Nishinakamura, Ryuichi

2008-01-01

Glomeruli comprise an important filtering apparatus in the kidney and are derived from the metanephric mesenchyme. A nuclear protein, Sall1, is expressed in this mesenchyme, and we previously reported that Trb2, a mouse homolog of Drosophila tribbles, is expressed in the mesenchyme-derived tissues of the kidney by microarray analyses using Sall1-GFP knock-in mice. In the present report, we detected Trb2 expression in a variety of organs during gestation, including the kidneys, mesonephros, testes, heart, eyes, thymus, blood vessels, muscle, bones, tongue, spinal cord, and ganglions. In the developing kidney, Trb2 signals were detected in podocytes and the prospective mesangium of the glomeruli, as well as in ureteric bud tips. However, Trb2 mutant mice did not display any apparent phenotypes and no proteinuria was observed, indicating normal glomerular functions. These results suggest that Trb2 plays minimal roles during kidney and mouse development

MicroRNA expression in the adult mouse central nervous system

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Bak, Mads; Silahtaroglu, Asli; Møller, Morten

2008-01-01

distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

Spinal curvature and characteristics of postural change in pregnant women.

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Okanishi, Natsuko; Kito, Nobuhiro; Akiyama, Mitoshi; Yamamoto, Masako

2012-07-01

Pregnant women often report complaints due to physiological and postural changes. Postural changes during pregnancy may cause low back pain and pelvic girdle pain. This study aimed to compare the characteristics of postural changes in pregnant compared with non-pregnant women. Prospective case-control study. Pregnancy care center. Fifteen women at 17-34 weeks pregnancy comprised the study group, while 10 non-pregnant female volunteers comprised the control group. Standing posture was evaluated in the sagittal plane with static digital pictures. Two angles were measured by image analysis software: (1) between the trunk and pelvis; and (2) between the trunk and lower extremity. Spinal curvature was measured with Spinal Mouse® to calculate the means of sacral inclination, thoracic and lumbar curvature and inclination. The principal components were calculated until eigenvalues surpassed 1. Three distinct factors with eigenvalues of 1.00-2.49 were identified, consistent with lumbosacral spinal curvature and inclination, thoracic spine curvature, and inclination of the body. These factors accounted for 77.2% of the total variance in posture variables. Eleven pregnant women showed postural characteristics of lumbar kyphosis and sacral posterior inclination. Body inclination showed a variety of patterns compared with those in healthy women. Spinal curvature demonstrated a tendency for lumbar kyphosis in pregnant women. Pregnancy may cause changes in spinal curvature and posture, which may in turn lead to relevant symptoms. Our data provide a basis for investigating the effects of spinal curvature and postural changes on symptoms during pregnancy. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice.

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Deguise, Marc-Olivier; De Repentigny, Yves; McFall, Emily; Auclair, Nicole; Sad, Subash; Kothary, Rashmi

2017-02-15

Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis. © The Author 2017. Published by Oxford University Press.

Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats

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Chen, Bo; He, Jianyu; Yang, Hao; Zhang, Qian; Zhang, Lingling; Zhang, Xian; Xie, En; Liu, Cuicui; Zhang, Rui; Wang, Yi; Huang, Linhong; Hao, Dingjun

2015-03-01

There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.

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

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Peng Xie

2016-01-01

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

Increased Cx32 expression in spinal cord TrkB oligodendrocytes following peripheral axon injury.

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Coulibaly, Aminata P; Isaacson, Lori G

2016-08-03

Following injury to motor axons in the periphery, retrograde influences from the injury site lead to glial cell plasticity in the vicinity of the injured neurons. Following the transection of peripherally located preganglionic axons of the cervical sympathetic trunk (CST), a population of oligodendrocyte (OL) lineage cells expressing full length TrkB, the cognate receptor for brain derived neurotrophic factor (BDNF), is significantly increased in number in the spinal cord. Such robust plasticity in OL lineage cells in the spinal cord following peripheral axon transection led to the hypothesis that the gap junction communication protein connexin 32 (Cx32), which is specific to OL lineage cells, was influenced by the injury. Following CST transection, Cx32 expression in the spinal cord intermediolateral cell column (IML), the location of the parent cell bodies, was significantly increased. The increased Cx32 expression was localized specifically to TrkB OLs in the IML, rather than other cell types in the OL cell lineage, with the population of Cx32/TrkB cells increased by 59%. Cx32 expression in association with OPCs was significantly decreased at one week following the injury. The results of this study provide evidence that peripheral axon injury can differentially affect the gap junction protein expression in OL lineage cells in the adult rat spinal cord. We conclude that the retrograde influences originating from the peripheral injury site elicit dramatic changes in the CNS expression of Cx32, which in turn may mediate the plasticity of OL lineage cells observed in the spinal cord following peripheral axon injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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Jenell R Smith

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

Nursing care of the thermally injured patient.

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Elfving, U

1980-01-01

Team work is required in the treatment of the thermally injured patient--nursing staff being part of the team. The nurses are with the patient for 24 hours a day and they have to understand the objectives of all other members of the team involved in the treatment as well as thoroughly mastering their own work. For the nursing staff the care of the thermally injured patient is a challenge. The work demands strong motivation and interest--it includes at times painful treatment, isolation and also constant alertness. It is important that the nursing staff is given continuous training so that they are able to give the required care efficiently and to keep up active interest. Practical work is the best way of getting aquainted with the complex forms of treatment of the thermally injured patient. It also lessens the fear of a badly burned patient. Nursing care of the thermally injured patient consists of good basic care, local attention and active observation. The basic care consists of basic hygiene, diet, observation of the patient's psychological condition, giving emotional support, encouraging initiative physiotherapy and postural treatment.

Evaluation of the thin agar layer method for the recovery of pressure-injured and heat-injured Listeria monocytogenes.

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Lavieri, Nicolas A; Sebranek, Joseph G; Cordray, Joseph C; Dickson, James S; Jung, Stephanie; Manu, David K; Mendonça, Aubrey F; Brehm-Stecher, Byron F; Stock, Joseph; Stalder, Kenneth J

2014-05-01

A sublethally injured bacterial cell has been defined as a cell that survives a stress such as heating, freezing, acid treatment, or other antimicrobial intervention but can repair the cellular damage exerted by the stressor and later regain its original ability to grow. Consequently, sublethally injured cells are not likely to be included in conventional enumeration procedures, which could result in unrealistically low counts unless efforts are made to encourage recovery of the injured cells before enumeration. The objective of this study was to evaluate the use of the thin agar layer (TAL) method for the recovery of pressure-injured and heat-injured Listeria monocytogenes in a tryptic soy broth with 0.6% yeast extract system. Pressure injury consisted of treatment of a culture of mixed L. monocytogenes strains with high hydrostatic pressure at 400 or 600 MPa for 1 s, 2 min, 4 min, or 6 min at a process temperature of 12±2 °C. Heat injury consisted of treatment of a culture of mixed L. monocytogenes strains at 60±1 °C for 3, 6, or 9 min. Growth media were tryptic soy agar (TSA) with 0.6% yeast extract, modified Oxford medium (MOX), and TAL, which consisted of a 7-ml layer of TSA overlaid onto solidified MOX. Counts of viable L. monocytogenes on TAL were higher than those on MOX in the heat-injury experiment but not in the pressure-injury experiment. Therefore, the effectiveness of the TAL method may be specific to the type of injury applied to the microorganism and should be investigated in a variety of cellular injury scenarios.

Spinal sagittal contour affecting falls: cut-off value of the lumbar spine for falls.

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Ishikawa, Yoshinori; Miyakoshi, Naohisa; Kasukawa, Yuji; Hongo, Michio; Shimada, Yoichi

2013-06-01

Spinal deformities reportedly affect postural instability or falls. To prevent falls in clinical settings, the determination of a cut-off angle of spinal sagittal contour associated with increase risk for falls would be useful for screening for high-risk fallers. The purpose of this study was to calculate the spinal sagittal contour angle associated with increased risk for falls during medical checkups in community dwelling elders. The subjects comprised 213 patients (57 men, 156 women) with a mean age of 70.1 years (range, 55-85 years). The upright and flexion/extension thoracic kyphosis and lumbar lordosis angles, and the spinal inclination were evaluated with SpinalMouse(®). Postural instability was evaluated by stabilometry, using the total track length (LNG), enveloped areas (ENV), and track lengths in the lateral and anteroposterior directions (X LNG and Y LNG, respectively). The back extensor strength (BES) was measured using a strain-gauge dynamometer. The relationships among the parameters were analyzed statistically. Age, lumbar lordosis, spinal inclination, LNG, X LNG, Y LNG, and BES were significantly associated with falls (Pfalls about lumbar lordosis angles revealed that angles of 3° and less were significant for falls. The present findings suggest that increased age, spinal inclination, LNG, X LNG, Y LNG, and decreased BES and lumbar lordosis, are associated with falls. An angle of lumbar lordosis of 3° or less was associated with falls in these community-dwelling elders. Copyright © 2012 Elsevier B.V. All rights reserved.

Spinal sagittal balance substantially influences locomotive syndrome and physical performance in community-living middle-aged and elderly women.

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Muramoto, Akio; Imagama, Shiro; Ito, Zenya; Hirano, Kenichi; Ishiguro, Naoki; Hasegawa, Yukiharu

2016-03-01

Spinal sagittal imbalance has been well known risk factor of decreased quality of life in the field of adult spinal deformity. However, the impact of spinal sagittal balance on locomotive syndrome and physical performance in community-living elderly has not yet been clarified. The present study investigated the influence of spinal sagittal alignment on locomotive syndrome (LS) and physical performance in community-living middle-aged and elderly women. A total of 125 women between the age of 40-88 years (mean 66.2 ± 9.7 years) who completed the questionnaires, spinal mouse test, physical examination and physical performance tests in Yakumo study were enrolled in this study. Participants answered the 25-Question Geriatric Locomotive Function Scale (GLFS-25), the visual analog scale (VAS) for low back pain (LBP), knee pain. LS was defined as having a score of >16 points on the GLFS-25. Using spinal mouse, spinal inclination angle (SIA), thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sacral slope angle (SSA), thoracic spinal range of motion (TSROM), lumbar spinal range of motion (LSROM) were measured. Timed-up-and-go test (TUG), one-leg standing time with eyes open (OLS), and maximum stride, back muscle strength were also measured. The relationship between spinal sagittal parameters and GLFS-25, VAS and physical performance tests were analyzed. 26 people were diagnosed as LS and 99 were diagnosed as non-LS. LBP and knee pain were greater, physical performance tests were poorer, SIA were greater, LLA were smaller in LS group compared to non-LS group even after adjustment by age. SIA significantly correlated with GLFS-25, TUG, OLS and maximum stride even after adjustment by age. The cutoff value of SIA for locomotive syndrome was 6°. People with a SIA of 6° or greater were grouped as "Inclined" and people with a SIA of less than 6° were grouped as "Non-inclined". 21 people were "Inclined" and 104 were "Non-inclined". Odds ratio to fall in LS of

Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury

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Gaudin, Alice; Yemisci, Müge; Eroglu, Hakan; Lepetre-Mouelhi, Sinda; Turkoglu, Omer Faruk; Dönmez-Demir, Buket; Caban, Seçil; Sargon, Mustafa Fevzi; Garcia-Argote, Sébastien; Pieters, Grégory; Loreau, Olivier; Rousseau, Bernard; Tagit, Oya; Hildebrandt, Niko; Le Dantec, Yannick; Mougin, Julie; Valetti, Sabrina; Chacun, Hélène; Nicolas, Valérie; Desmaële, Didier; Andrieux, Karine; Capan, Yilmaz; Dalkara, Turgay; Couvreur, Patrick

2014-12-01

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.

Distinguishing active from passive components of ankle plantar flexor stiffness in stroke, spinal cord injury and multiple sclerosis

DEFF Research Database (Denmark)

Lorentzen, Jakob; Grey, Michael James; Crone, Clarissa

2010-01-01

to distinguish the contribution of active reflex mechanisms from passive muscle properties to ankle joint stiffness in 31 healthy, 10 stroke, 30 multiple sclerosis and 16 spinal cord injured participants. The results were compared to routine clinical evaluation of spasticity. METHODS: A computer...... (Ashworth score1) showed normal reflex torque without normalization. With normalization this was only the case in 11 participants. Increased reflex mediated stiffness was detected in only 64% participants during clinical examination. CONCLUSION: The findings confirm that the clinical diagnosis of spasticity...

Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

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David L García-Ramírez

Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

Regulation of choline acetyltransferase expression by 17 β-oestradiol in NSC-34 cells and in the spinal cord.

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Johann, S; Dahm, M; Kipp, M; Zahn, U; Beyer, C

2011-09-01

Motoneurones located in the ventral horn of the spinal cord conciliate cholinergic innervation of skeletal muscles. These neurones appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis. The dysfunction of motoneurones is typically accompanied by alterations of cholinergic metabolism and signalling, as demonstrated by a decrease in choline acetyltransferase (ChAT) expression. 17 β-Oestradiol (E(2)) is generally accepted as neuroprotective factor in the brain under acute toxic and neurodegenerative conditions and also appears to exert a protective role for motoneurones. In the present study, we attempted to analyse the role of E(2) signalling on ChAT expression in the motoneurone-like cell line NSC-34 and in vivo. In a first step, we demonstrated the presence of oestrogen receptor α and β in NSC-34 cells, as well as in the cervical and lumbar parts, of the male mouse spinal cord. Subsequently, we investigated the effect of E(2) treatment on ChAT expression. The application of E(2) significantly increased the transcription of ChAT in NSC-34 cells and in the cervical but not lumbar part of the spinal cord. Our results indicate that E(2) can influence the cholinergic system by increasing ChAT expression in the mouse spinal cord. This mechanism might support motoneurones, in addition to survival-promoting mechanisms, in the temporal balance toxic or neurodegenerative challenges. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.

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Yao, L; Daly, W; Newland, B; Yao, S; Wang, W; Chen, B K K; Madigan, N; Windebank, A; Pandit, A

2013-12-01

Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.

[Maximal exercise in spinal cord injured subjects: effects of an antigravity suit].

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Bazzi-Grossin, C; Bonnin, P; Bailliart, O; Bazzi, H; Kedra, A W; Martineaud, J P

1996-01-01

Paraplegics have low aerobic capacity because of the spinal cord injury. Their functional muscle mass is reduced and usually untrained. They have to use upperbody muscles for displacements and daily activities. Sympathic nervous system injury is responsible of vasomotricity disturbances in leg vessels and possible abdominal vessels, proportionally to level injury. If cord injury level is higher than T5, then sympathic cardiac efferences may be damaged. Underbody muscles atrophy and vasomotricity disturbances contribute to phlebostasis. This stasis may decrease venous return, preload and stroke volume (Starling). To maintain appropriate cardiac output, tachycardia is necessary, especially during exercise. Low stroke volume, all the more since it is associated with cardio-acceleration disturbances, may reduce cardiac output reserve, and so constitutes a limiting factor for adaptation to exercise. The aim of this study was to verify if use of an underlesional pressure suit may increase cardiac output reserve because of lower venous stasis, and increase performance. We studied 10 able-bodied and 14 traumatic paraplegic subjects. Able-bodied subjects were 37 +/- 6 years old, wellbeing, not especially trained with upperbody muscles: there were 2 women and 8 men. Paraplegics were 27 +/- 7 years old, wellbeing except paraplegia, five of them practiced sport regularly (athletism or basket for disabled), and the others just daily propelled their wheelchair; there were 5 women and 9 men. For 8 of them, cord injury levels were located below T7, between T1 and T6 for the others. The age disability varied from 6 months to 2 years for 9 of them, it was approximately five years for 4 of them, and 20 years for one. We used a maximal triangular arm crank exercise with an electro-magnetic ergocycle Gauthier frame. After five minutes warm up, it was proceeded in one minute successive stages until maximal oxygen consumption is raised. VO2, VCO2, RER were measured by direct method with

Survival and differentiation of human embryonic stem cell-derived neural precursors grafted spinally in spinal ischemia-injured rats or in naive immunosuppressed minipigs: a qualitative and quantitative study

Czech Academy of Sciences Publication Activity Database

Kakinohana, O.; Juhásová, Jana; Juhás, Štefan; Motlík, Jan; Platoshyn, O.; Galik, J.; Hefferan, M. P.; Yuan, S. H.; Vidal, J. G.; Carson, C. T.; Van Gorp, S.; Goldberg, D.; Leerink, M.; Lazar, P.; Maršala, S.; Miyanohara, A.; Keshavarzi, S.; Ciacci, J. D.; Maršala, M.

2012-01-01

Roč. 21, č. 12 (2012), s. 2603-2619 ISSN 0963-6897 R&D Projects: GA MŠk 1M0538; GA TA ČR TA01011466 Institutional research plan: CEZ:AV0Z50450515 Keywords : spinal cord ischemia * human embryonic stem (ES) cells * neuronal precursors (NPCs) Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.422, year: 2012

Differentiation of different mixed Listeria strains and also acid-injured, heat-injured, and repaired cells of Listeria monocytogenes using fourier transform infrared spectroscopy.

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Nyarko, Esmond; Donnelly, Catherine

2015-03-01

Fourier transform infrared (FT-IR) spectroscopy was used to differentiate mixed strains of Listeria monocytogenes and mixed strains of L. monocytogenes and Listeria innocua. FT-IR spectroscopy was also applied to investigate the hypothesis that heat-injured and acid-injured cells would return to their original physiological integrity following repair. Thin smears of cells on infrared slides were prepared from cultures for mixed strains of L. monocytogenes, mixed strains of L. monocytogenes and L. innocua, and each individual strain. Heat-injured and acid-injured cells were prepared by exposing harvested cells of L. monocytogenes strain R2-764 to a temperature of 56 ± 0.2°C for 10 min or lactic acid at pH 3 for 60 min, respectively. Cellular repair involved incubating aliquots of acid-injured and heat-injured cells separately in Trypticase soy broth supplemented with 0.6% yeast extract for 22 to 24 h; bacterial thin smears on infrared slides were prepared for each treatment. Spectral collection was done using 250 scans at a resolution of 4 cm(-1) in the mid-infrared wavelength region. Application of multivariate discriminant analysis to the wavelength region from 1,800 to 900 cm(-1) separated the individual L. monocytogenes strains. Mixed strains of L. monocytogenes and L. monocytogenes cocultured with L. innocua were successfully differentiated from the individual strains when the discriminant analysis was applied. Different mixed strains of L. monocytogenes were also successfully separated when the discriminant analysis was applied. A data set for injury and repair analysis resulted in the separation of acid-injured, heat-injured, and intact cells; repaired cells clustered closer to intact cells when the discriminant analysis (1,800 to 600 cm(-1)) was applied. FT-IR spectroscopy can be used for the rapid source tracking of L. monocytogenes strains because it can differentiate between different mixed strains and individual strains of the pathogen.

Myeloid-derived suppressor cells mediate immune suppression in spinal cord injury.

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Wang, Lei; Yu, Wei-bo; Tao, Lian-yuan; Xu, Qing

2016-01-15

Spinal cord injury (SCI) is characterized by the loss of motor and sensory functions in areas below the level of the lesion and numerous accompanying deficits. Previous studies have suggested that myeloid-derived suppressor cell (MDSC)-induced immune depression may play a pivotal role in the course of SCI. However, the concrete mechanism of these changes regarding immune suppression remains unknown. Here, we created an SCI mouse model to gain further evidence regarding the relationship between MDSCs following SCI and T lymphocyte suppression. We showed that in the SCI mouse model, the expanding MDSCs have the capacity to suppress T cell proliferation, and this suppression could be reversed by blocking the arginase. Copyright © 2015 Elsevier B.V. All rights reserved.

Pressure ulcers from spinal immobilization in trauma patients: a systematic review.

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Ham, Wietske; Schoonhoven, Lisette; Schuurmans, Marieke J; Leenen, Luke P H

2014-04-01

To protect the (possibly) injured spine, trauma patients are immobilized on backboard or vacuum mattress, with a cervical collar, lateral headblocks, and straps. Several studies identified pressure ulcer (PU) development from these devices. The aim of this literature study was to gain insight into the occurrence and development of PUs, the risk factors, and the possible interventions to prevent PUs related to spinal immobilization with devices in adult trauma patients. We systematically searched PubMed (MEDLINE), EMBASE, Cochrane, and CINAHL for the period 1970 to September 2011. Studies were included if participants were healthy volunteers under spinal immobilization or trauma patients under spinal immobilization until spine injuries were diagnosed or excluded. Outcomes of primary interest included occurrence, severity, and risk for PU development as well as prevention of PU development related to spinal immobilization devices. The results of included studies show an incidence of collar-related PUs ranging from 6.8% to 38%. Described locations are the occiput, chin, shoulders, and back. The severity of these PUs varies between Stages 1 and 3, and one study describes PUs requiring surgical debridement, indicating a Stage 4 PU. Described risk factors for PU development are high pressure and pain from immobilizing devices, the length of time in/on a device, intensive care unit admission, high Injury Severity Scores (ISSs), mechanical ventilation, and intracranial pressure monitoring. Preventive interventions for collar-related PUs include early replacement of the extrication collar and regular skin assessment, collar refit, and position change. The results from this systematic review show that immobilization with devices increases the risk for PU development. This risk is demonstrated in nine experimental studies with healthy volunteers and in four clinical studies. Systematic review, level III.

Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury

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Youngjeon Lee

2014-01-01

Full Text Available Endogenous neural stem/progenitor cells (eNSPCs proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI. We have previously shown that melatonin (MT plus exercise (Ex had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups.These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.

Does vitamin C have the ability to augment the therapeutic effect of bone marrow-derived mesenchymal stem cells on spinal cord injury?

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Nesrine Salem

2017-01-01

Full Text Available Methylprednisolone (MP is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury (SCI. Vitamin C (VC is a natural water-soluble antioxidant that exerts neuroprotective effects through eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem cells (BMMSCs, as multipotent stem cells, are promising candidates in SCI repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic SCI, 80 adult male rats were randomly divided into seven groups: control, SCI (SCI induction by weight-drop method, MP (SCI induction, followed by administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for five times, VC (SCI induction, followed by intraperitoneal administration of 100 mg/kg VC once a day, for 28 days, MP + VC (SCI induction, followed by administration of MP and VC as the former, BMMSCs (SCI induction, followed by injection of 3 × 106 BMMSCs at the injury site, and BMMSCs + VC (SCI induction, followed by BMMSCs injection and VC administration as the former. Locomotor recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was evaluated using hematoxylin-eosin staining and immunohistochemical staining. Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes was determined using real-time quantitative PCR. BMMSCs intervention better promoted recovery of nerve function of rats with SCI, mitigated nerve cell damage, and decreased expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes than MP and/or VC. More importantly, BMMSCs in combination with VC induced more obvious improvements. These results suggest that VC can enhance the neuroprotective effects of BMMSCs against SCI.

Cerebrospinal fluid volume depletion in chronic whiplash-associated disorders from motor vehicle-related spinal injuries

International Nuclear Information System (INIS)

Takeshita, Iwao; Ohta, Masaru; Samoto, Ken; Hamamura, Takeshi; Watanabe, Hideyuki

2007-01-01

To evaluate cerebrospinal fluid (CSF) volume depletion in chronic cases of whiplash-associated disorders, 111 In radioisotope (RI) cisternography, brain magnetic resonance imaging (MRI) and lumbar MR myelography were consecutively conducted on 460 individuals with chronic whiplash-associated disorders resulting from motor vehicle collision (Group A, n=225) and other traumatic injuries (Group B, n=57), spontaneous intracranial hypotension syndromes and other miscellaneous disorders (Group C, n=155), iatrogenic intracranial hypotension syndrome (Group D, n=11), and communicating hydrocephalus (Group E, n=12). Movement of intrathecally administered RI via a lumbar puncture was sequentially scanned at 1, 2 or 3, 5 and 24 hours. A whole body neuroaxis scanned figure showing high spinal parathecal activity at any time was considered to be a CSF leak, if small enough meningeal diverticula evidenced by MR myelography were present. Retention rate (%) of intrathecal RI for each scan was calculated using the formula: (whole body count-urinary bladder count)/whole body count (cpm) at 1 h x 100. All CSF leaks, although having single to multiple poles, were located in the spinal canal. CSF leakage was observed in 99/225 (44%), 24/57 (42%), 61/155 (39%), 9/11 (82%), and 4/12 (33%), in Groups A, B, C, D and E respectively. All CSF leakages was involved with the lumbar spine in Group A, although 20 cases extended to mid-thoracic levels. In Group A, spinal vertebrae were concomitantly injured in 7 cases (1 cervical spine dislocation, 1 cervical spine fracture, 2 thoracic and 1 lumbar compression fracture (s), and 2 lumbar disc hernia). CSF leakage for 2 cervical spine injuries was not at the injured site but at the lumbar spinal canal. CSF leakage limited to the lumbar spine involved 22 and 43 cases in groups B and C, respectively. Of all CSF leaks, 24 h retention rates less than 30% accounted for 90% of cases. In Group A, early CSF excretion and less than a 30% retention rate at 24

Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis.

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Liu, Kevin X; Edwards, Benjamin; Lee, Sheena; Finelli, Mattéa J; Davies, Ben; Davies, Kay E; Oliver, Peter L

2015-05-01

Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder characterized by the progressive loss of spinal motor neurons. While the aetiological mechanisms underlying the disease remain poorly understood, oxidative stress is a central component of amyotrophic lateral sclerosis and contributes to motor neuron injury. Recently, oxidation resistance 1 (OXR1) has emerged as a critical regulator of neuronal survival in response to oxidative stress, and is upregulated in the spinal cord of patients with amyotrophic lateral sclerosis. Here, we tested the hypothesis that OXR1 is a key neuroprotective factor during amyotrophic lateral sclerosis pathogenesis by crossing a new transgenic mouse line that overexpresses OXR1 in neurons with the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Interestingly, we report that overexpression of OXR1 significantly extends survival, improves motor deficits, and delays pathology in the spinal cord and in muscles of SOD1(G93A) mice. Furthermore, we find that overexpression of OXR1 in neurons significantly delays non-cell-autonomous neuroinflammatory response, classic complement system activation, and STAT3 activation through transcriptomic analysis of spinal cords of SOD1(G93A) mice. Taken together, these data identify OXR1 as the first neuron-specific antioxidant modulator of pathogenesis and disease progression in SOD1-mediated amyotrophic lateral sclerosis, and suggest that OXR1 may serve as a novel target for future therapeutic strategies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.

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Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole

2017-01-27

Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2 Δ/Δ mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

Evo-engineering and the cellular and molecular origins of the vertebrate spinal cord.

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Steventon, Ben; Martinez Arias, Alfonso

2017-12-01

The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken, Xenopus and zebrafish and relate them to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development. Copyright © 2017. Published by Elsevier Inc.

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

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

2016-03-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

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

2017-02-16

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

Spinal cord contusion.

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Ju, Gong; Wang, Jian; Wang, Yazhou; Zhao, Xianghui

2014-04-15

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

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

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

2006-07-01

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

Short-scan-time multi-slice diffusion MRI of the mouse cervical spinal cord using echo planar imaging.

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Callot, Virginie; Duhamel, Guillaume; Cozzone, Patrick J; Kober, Frank

2008-10-01

Mouse spinal cord (SC) diffusion-weighted imaging (DWI) provides important information on tissue morphology and structural changes that may occur during pathologies such as multiple sclerosis or SC injury. The acquisition scheme of the commonly used DWI techniques is based on conventional spin-echo encoding, which is time-consuming. The purpose of this work was to investigate whether the use of echo planar imaging (EPI) would provide good-quality diffusion MR images of mouse SC, as well as accurate measurements of diffusion-derived metrics, and thus enable diffusion tensor imaging (DTI) and highly resolved DWI within reasonable scan times. A four-shot diffusion-weighted spin-echo EPI (SE-EPI) sequence was evaluated at 11.75 T on a group of healthy mice (n = 10). SE-EPI-derived apparent diffusion coefficients of gray and white matter were compared with those obtained using a conventional spin-echo sequence (c-SE) to validate the accuracy of the method. To take advantage of the reduction in acquisition time offered by the EPI sequence, multi-slice DTI acquisitions were performed covering the cervical segments (six slices, six diffusion-encoding directions, three b values) within 30 min (vs 2 h for c-SE). From these measurements, fractional anisotropy and mean diffusivities were calculated, and fiber tracking along the C1 to C6 cervical segments was performed. In addition, high-resolution images (74 x 94 microm(2)) were acquired within 5 min per direction. Clear delineation of gray and white matter and identical apparent diffusion coefficient values were obtained, with a threefold reduction in acquisition time compared with c-SE. While overcoming the difficulties associated with high spatially and temporally resolved DTI measurements, the present SE-EPI approach permitted identification of reliable quantitative parameters with a reproducibility compatible with the detection of pathologies. The SE-EPI method may be particularly valuable when multiple sets of images

Subject-specific regional measures of water diffusion are associated with impairment in chronic spinal cord injury.

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Choe, Ann S; Sadowsky, Cristina L; Smith, Seth A; van Zijl, Peter C M; Pekar, James J; Belegu, Visar

2017-08-01

We aimed to identify non-invasive imaging parameters that can serve as biomarkers for the integrity of the spinal cord, which is paramount to neurological function. Diffusion tensor imaging (DTI) indices are sensitive to axonal and myelin damage, and have strong potential to serve as such biomarkers. However, averaging DTI indices over large regions of interest (ROIs), a common approach to analyzing the images of injured spinal cord, leads to loss of subject-specific information. We investigated if DTI-tractography-driven, subject-specific demarcation approach can yield measures that are more specific to impairment. In 18 individuals with chronic spinal cord injury (SCI), subject-specific demarcation of the injury region was performed using DTI tractography, which yielded three regions relative to injury (RRI; regions superior to, at, and below injury epicenter). DTI indices averaged over each RRI were correlated with measures of residual motor and sensory function, obtained using the International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI). Total ISNCSCI score (ISNCSCI-tot; sum of ISNCSCI motor and sensory scores) was significantly (p injury epicenter (IRRI), the degree of which exceeded that of those measured from the entire cervical cord-suggesting contribution from Wallerian degeneration. DTI tractography-driven, subject-specific injury demarcation approach provided measures that were more specific to impairment. Notably, DTI indices obtained from the IRRI region showed the highest specificity to impairment, demonstrating their strong potential as biomarkers for the SCI severity.

Nuclear magnetic imaging for MTRA. Spinal canal and spinal cord

International Nuclear Information System (INIS)

Fritzsch, Dominik; Hoffmann, Karl-Titus

2011-01-01

The booklet covers the following topics: (1) Clinical indications for NMR imaging of spinal cord and spinal canal; (2) Methodic requirements: magnets and coils, image processing, contrast media: (3) Examination technology: examination conditions, sequences, examination protocols; (4) Disease pattern and indications: diseases of the myelin, the spinal nerves and the spinal canal (infections, tumors, injuries, ischemia and bleedings, malformations); diseases of the spinal cord and the intervertebral disks (degenerative changes, infections, injuries, tumors, malformations).

Spinal Cord Injury 101

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

Spinal Cord Injury 101

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

Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse

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Shang Yuze

2008-04-01

Full Text Available Abstract Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS. In the present study, we used heterozygous Cx3cr1GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC, prefrontal cortex (PFC, primary and secondary somatosensory cortex (S1 and S2, insular cortex (IC, amygdala, hippocampus, periaqueductal gray (PAG and rostral ventromedial medulla (RVM. Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons.

Intrinsic and Extrinsic Contributions to Seated Balance in the Sagittal and Coronal Planes: Implications for Trunk Control After Spinal Cord Injury.

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Audu, Musa L; Triolo, Ronald J

2015-08-01

The contributions of intrinsic (passive) and extrinsic (active) properties of the human trunk, in terms of the simultaneous actions about the hip and spinal joints, to the control of sagittal and coronal seated balance were examined. Able-bodied (ABD) and spinal-cord-injured (SCI) volunteers sat on a moving platform which underwent small amplitude perturbations in the anterior-posterior (AP) and medial-lateral (ML) directions while changes to trunk orientation were measured. A linear parametric model that related platform movement to trunk angle was fit to the experimental data by identifying model parameters in the time domain. The results showed that spinal cord injury leads to a systematic reduction in the extrinsic characteristics, while most of the intrinsic characteristics were rarely affected. In both SCI and ABD individuals, passive characteristics alone were not enough to maintain seated balance. Passive stiffness in the ML direction was almost 3 times that in the AP direction, making more extrinsic mechanisms necessary for balance in the latter direction. Proportional and derivative terms of the extrinsic model made the largest contribution to the overall output from the active system, implying that a simple proportional plus derivative (PD) controller structure will suffice for restoring seated balance after spinal cord injury.

Firing patterns of spontaneously active motor units in spinal cord-injured subjects.

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Zijdewind, Inge; Thomas, Christine K

2012-04-01

Involuntary motor unit activity at low rates is common in hand muscles paralysed by spinal cord injury. Our aim was to describe these patterns of motor unit behaviour in relation to motoneurone and motor unit properties. Intramuscular electromyographic activity (EMG), surface EMG and force were recorded for 30 min from thenar muscles of nine men with chronic cervical SCI. Motor units fired for sustained periods (>10 min) at regular (coefficient of variation ≤ 0.15, CV, n =19 units) or irregular intervals (CV>0.15, n =14). Regularly firing units started and stopped firing independently suggesting that intrinsic motoneurone properties were important for recruitment and derecruitment. Recruitment (3.6 Hz, SD 1.2), maximal (10.2 Hz, SD 2.3, range: 7.5-15.4 Hz) and derecruitment frequencies were low (3.3 Hz, SD 1.6), as were firing rate increases after recruitment (~20 intervals in 3 s). Once active, firing often covaried, promoting the idea that units received common inputs.Half of the regularly firing units showed a very slow decline (>40 s) in discharge before derecruitment and had interspike intervals longer than their estimated after hyperpolarisation potential (AHP) duration (estimated by death rate and breakpoint analyses). The other units were derecruited more abruptly and had shorter estimated AHP durations. Overall, regularly firing units had longer estimated AHP durations and were weaker than irregularly firing units, suggesting they were lower threshold units. Sustained firing of units at regular rates may reflect activation of persistent inward currents, visible here in the absence of voluntary drive, whereas irregularly firing units may only respond to synaptic noise.

What Is Being Trained? How Divergent Forms of Plasticity Compete To Shape Locomotor Recovery after Spinal Cord Injury.

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Huie, J Russell; Morioka, Kazuhito; Haefeli, Jenny; Ferguson, Adam R

2017-05-15

Spinal cord injury (SCI) is a devastating syndrome that produces dysfunction in motor and sensory systems, manifesting as chronic paralysis, sensory changes, and pain disorders. The multi-faceted and heterogeneous nature of SCI has made effective rehabilitative strategies challenging. Work over the last 40 years has aimed to overcome these obstacles by harnessing the intrinsic plasticity of the spinal cord to improve functional locomotor recovery. Intensive training after SCI facilitates lower extremity function and has shown promise as a tool for retraining the spinal cord by engaging innate locomotor circuitry in the lumbar cord. As new training paradigms evolve, the importance of appropriate afferent input has emerged as a requirement for adaptive plasticity. The integration of kinematic, sensory, and loading force information must be closely monitored and carefully manipulated to optimize training outcomes. Inappropriate peripheral input may produce lasting maladaptive sensory and motor effects, such as central pain and spasticity. Thus, it is important to closely consider the type of afferent input the injured spinal cord receives. Here we review preclinical and clinical input parameters fostering adaptive plasticity, as well as those producing maladaptive plasticity that may undermine neurorehabilitative efforts. We differentiate between passive (hindlimb unloading [HU], limb immobilization) and active (peripheral nociception) forms of aberrant input. Furthermore, we discuss the timing of initiating exposure to afferent input after SCI for promoting functional locomotor recovery. We conclude by presenting a candidate rapid synaptic mechanism for maladaptive plasticity after SCI, offering a pharmacological target for restoring the capacity for adaptive spinal plasticity in real time.

Detection of phosphorylated mitogen-activated protein kinase in the developing spinal cord of the mouse embryo

International Nuclear Information System (INIS)

Teraishi, Toshiya; Miura, Kenji

2011-01-01

Highlights: → We detected physiologically phosphorylated MAPKs in developing spinal cord. → We detected physiologically phosphorylated MAPKs by an improved method. → p-ERK1/2 and p-JNK1/2 were detected in the marginal layer and the dorsal horn. → p-ERK1/2 and p-JNK1/2 might play critical roles in the developing spinal cord. → Constructing phosphoprotein atlases will be possible if expanding this work. -- Abstract: Global understanding of the proteome is a major research topic. The comprehensive visualization of the distribution of proteins in vivo or the construction of in situ protein atlases may be a valuable strategy for proteomic researchers. Information about the distribution of various proteins under physiological and pathological conditions should be extremely valuable for the basic and clinical sciences. The mitogen-activated protein kinase (MAPK) cascade plays an essential role in intracellular signaling in organisms. This cascade also regulates biological processes involving development, differentiation, and proliferation. Phosphorylation and dephosphorylation are integral reactions in regulating the activity of MAPKs. Changes in the phosphorylation state of MAPKs are rapid and reversible; therefore, the localizations of physiologically phosphorylated MAPKs in vivo are difficult to accurately detect. Furthermore, phosphorylated MAPKs are likely to change phosphorylated states through commonly used experimental manipulations. In the present study, as a step toward the construction of in situ phosphoprotein atlases, we attempted to detect physiologically phosphorylated MAPKs in vivo in developing spinal cords of mice. We previously reported an improved immunohistochemical method for detecting unstable phosphorylated MAPKs. The distribution patterns of phosphorylated MAPKs in the spinal cords of embryonic mice from embryonic day 13 (E13) to E17 were observed with an improved immunohistochemical method. Phosphorylated extracellular signal

Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics

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Yingyu Zhou

2018-01-01

Full Text Available The active compounds in Acanthopanax senticosus (AS have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters—AUC, MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract’s protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC of mouse brain included tubulin protein family (α-, β-tubulin subunits, dihydropyrimidinase-related protein 2 (CRMP2, γ-actin, 14-3-3 protein family (14-3-3ζ, ε, heat shock protein 90β (HSP90β, and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells’ structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B, Neurotrophin, Rap1 (Ras-related protein RAP-1A, gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1 signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could

Wearable Multi-Channel Microelectrode Membranes for Elucidating Electrophysiological Phenotypes of Injured Myocardium

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Cao, Hung; Yu, Fei; Zhao, Yu; Zhang, Xiaoxiao; Tai, Joyce; Lee, Juhyun; Darehzereshki, Ali; Bersohn, Malcolm; Lien, Ching-Ling; Chi, Neil C.; Tai, Yu-Chong; Hsiai, Tzung K.

2014-01-01

Understanding the regenerative capacity of small vertebrate models has provided new insights into the plasticity of injured myocardium. Here, we demonstrated the application of flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes of zebrafish and neonatal mouse models of heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals in the aquatic environment. They were micro-fabricated to adhere to the non-planar body surface of zebrafish and neonatal mice. The acquired signals were processed to display electrocardiogram (ECG) with high signal-to-noise-ratios, and were validated via the use of conventional micro-needle electrodes. The 4-channel MEA provided signal stability and spatial resolution, revealing the site-specific electrical injury currents such as ST-depression in response to ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes provided electrophysiological insights in long-term conduction phenotypes for small vertebral models of heart injury and regeneration with a translational implication for monitoring cardiac patients. PMID:24945366

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

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Keynes Roger J

2009-05-01

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

Overreaching in coordination dynamics therapy in an athlete with a spinal cord injury.

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Schalow, G; Vaher, I; Jaigma, P

2008-03-01

A motocross athlete suffered a clinically complete spinal cord injury (SCI) during competition. Although MRIs (magnetic resonance imaging) showed a complete spinal cord injury at the Thoracic 11/12 levels, surface EMG recordings indicated the survival of few tract fibres across the injury site. Six weeks after the accident the subject began intensive Coordination Dynamics Therapy (CDT) at an up-to-date therapy centre. The subject trained at his physical limits to induce structural and functional repair. Exercising at variable loads between 20 and 200N (on a special CDT and recording device) generated periods of overreaching and super-compensation. By plotting coordination dynamics values (kinesiology), including high-load exertion (200N) and hysteresis curves, periods of overreaching and super-compensation were made graphically visible. It was found that symmetrical improvements of central nervous system (CNS) functioning occurred during overreaching. Improvements in spinal cord functioning were achieved throughout one year of CDT in this chronically injured subject with an almost anatomically complete SCI. It is discussed that the measuring of CNS functions by means of recording coordination dynamics is a powerful and non-invasive tool ideal for exact quantitative and qualitative measurements of improvement (or change) in CNS functioning. Such diagnostics may be of particular importance in sport during training and before competition. Also, coordination dynamics might be used to measure the effects of prolonged exposure to reduced gravitational conditions on CNS functions, such as faced by astronauts.

Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury

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Mehar Naseem

2014-01-01

Full Text Available Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS. Traumatic brain injury (TBI is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-κβ, disruption of blood-brain barrier (BBB, and oxidative stress. Spinal cord injury (SCI includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it.

The Brain and Spinal Injury Center score: a novel, simple, and reproducible method for assessing the severity of acute cervical spinal cord injury with axial T2-weighted MRI findings.

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Talbott, Jason F; Whetstone, William D; Readdy, William J; Ferguson, Adam R; Bresnahan, Jacqueline C; Saigal, Rajiv; Hawryluk, Gregory W J; Beattie, Michael S; Mabray, Marc C; Pan, Jonathan Z; Manley, Geoffrey T; Dhall, Sanjay S

2015-10-01

Previous studies that have evaluated the prognostic value of abnormal changes in signals on T2-weighted MRI scans of an injured spinal cord have focused on the longitudinal extent of this signal abnormality in the sagittal plane. Although the transverse extent of injury and the degree of spared spinal cord white matter have been shown to be important for predicting outcomes in preclinical animal models of spinal cord injury (SCI), surprisingly little is known about the prognostic value of altered T2 relaxivity in humans in the axial plane. The authors undertook a retrospective chart review of 60 patients who met the inclusion criteria of this study and presented to the authors' Level I trauma center with an acute blunt traumatic cervical SCI. Within 48 hours of admission, all patients underwent MRI examination, which included axial and sagittal T2 images. Neurological symptoms, evaluated with the grades according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS), at the time of admission and at hospital discharge were correlated with MRI findings. Five distinct patterns of intramedullary spinal cord T2 signal abnormality were defined in the axial plane at the injury epicenter. These patterns were assigned ordinal values ranging from 0 to 4, referred to as the Brain and Spinal Injury Center (BASIC) scores, which encompassed the spectrum of SCI severity. The BASIC score strongly correlated with neurological symptoms at the time of both hospital admission and discharge. It also distinguished patients initially presenting with complete injury who improved by at least one AIS grade by the time of discharge from those whose injury did not improve. The authors' proposed score was rapid to apply and showed excellent interrater reliability. The authors describe a novel 5-point ordinal MRI score for classifying acute SCIs on the basis of axial T2-weighted imaging. The proposed BASIC score stratifies the SCIs according to the extent of transverse T2

S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.

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Antinone, Sarah E; Ghadge, Ghanashyam D; Ostrow, Lyle W; Roos, Raymond P; Green, William N

2017-01-25

Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord.

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

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

2015-01-01

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

The modulatory role of alpha-melanocyte stimulating hormone administered spinally in the regulation of blood glucose level in d-glucose-fed and restraint stress mouse models.

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Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-08-01

Alpha-melanocyte stimulating hormone (α-MSH) is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of α-MSH located in the spinal cord in the regulation of the blood glucose level were investigated in d-glucose-fed and immobilization stress (IMO) mouse models. We found in the present study that intrathecal (i.t.) injection with α-MSH alone did not affect the blood glucose level. However, i.t. administration with α-MSH reduced the blood glucose level in d-glucose-fed model. The plasma insulin level was increased in d-glucose-fed model and was further increased by α-MSH, whereas α-MSH did not affect plasma corticosterone level in d-glucose-fed model. In addition, i.t. administration with glucagon alone enhanced blood glucose level and, i.t. injection with glucagon also increased the blood glucose level in d-glucose-fed model. In contrasted to results observed in d-glucose-fed model, i.t. treatment with α-MSH caused enhancement of the blood glucose level in IMO model. The plasma insulin level was increased in IMO model. The increased plasma insulin level by IMO was reduced by i.t. treatment with α-MSH, whereas i.t. pretreatment with α-MSH did not affect plasma corticosterone level in IMO model. Taken together, although spinally located α-MSH itself does not alter the blood glucose level, our results suggest that the activation of α-MSH system located in the spinal cord play important modulatory roles for the reduction of the blood glucose level in d-glucose fed model whereas α-MSH is responsible for the up-regulation of the blood glucose level in IMO model. The enhancement of insulin release may be responsible for modulatory action of α-MSH in down-regulation of the blood glucose in d-glucose fed model whereas reduction of insulin release may be responsible for modulatory action of α-MSH in up-regulation of the blood glucose in IMO model. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan

Science.gov (United States)

Watanabe, Hideto; Nakata, Ken; Kimata, Koji; Nakanishi, Isao; Yamada, Yoshihiko

1997-01-01

Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (−/−) are characterized by cleft palate and short limbs, tail, and snout. They die just after birth because of respiratory failure, and the heterozygotes (+/−) appear normal at birth. Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age. Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration. PMID:9192671

A Cystine-Rich Whey Supplement (Immunocal® Delays Disease Onset and Prevents Spinal Cord Glutathione Depletion in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

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Erika K. Ross

2014-12-01

Full Text Available Depletion of the endogenous antioxidant, glutathione (GSH, underlies progression of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS. Thus, strategies aimed at elevating GSH may yield new therapeutics for ALS. Here, we investigated the effects of a unique non-denatured whey protein supplement, Immunocal®, in the transgenic Gly position 93 to Ala (G93A mutant hSOD1 (hSOD1G93A mouse model of ALS. Immunocal® is rich in the GSH precursor, cystine, and is therefore capable of bolstering GSH content. Transgenic hSOD1G93A mice receiving Immunocal® displayed a significant delay in disease onset compared to untreated hSOD1G93A controls. Additionally, Immunocal® treatment significantly decreased the rate of decline in grip strength and prevented disease-associated reductions in whole blood and spinal cord tissue GSH levels in end-stage hSOD1G93A mice. However, Immunocal® did not extend survival, likely due to its inability to preserve the mitochondrial GSH pool in spinal cord. Combination treatment with Immunocal® and the anti-glutamatergic compound, riluzole, delayed disease onset and extended survival in hSOD1G93A mice. These findings demonstrate that sustaining tissue GSH with Immunocal® only modestly delays disease onset and slows the loss of skeletal muscle strength in hSOD1G93A mice. Moreover, the inability of Immunocal® to rescue mitochondrial GSH in spinal cord provides a possible mechanism for its lack of effect on survival and is a limiting factor in the potential utility of this supplement as a therapeutic for ALS.

Spinal Cord Injury 101

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

SnoN facilitates axonal regeneration after spinal cord injury.

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Jiun L Do

Full Text Available Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

Matrix metalloproteinases and left ventricular function and structure in spinal cord injured subjects.

Science.gov (United States)

Schreiber, Roberto; Paim, Layde R; de Rossi, Guilherme; Matos-Souza, José R; Costa E Silva, Anselmo de A; Souza, Cristiane M; Borges, Mariane; Azevedo, Eliza R; Alonso, Karina C; Gorla, José I; Cliquet, Alberto; Nadruz, Wilson

2014-11-01

Subjects with spinal cord injury (SCI) exhibit impaired left ventricular (LV) diastolic function, which has been reported to be attenuated by regular physical activity. This study investigated the relationship between circulating matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) and echocardiographic parameters in SCI subjects and the role of physical activity in this regard. Forty-two men with SCI [19 sedentary (S-SCI) and 23 physically-active (PA-SCI)] were evaluated by clinical, anthropometric, laboratory, and echocardiographic analysis. Plasmatic pro-MMP-2, MMP-2, MMP-8, pro-MMP-9, MMP-9, TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay and zymography. PA-SCI subjects presented lower pro-MMP-2 and pro-MMP-2/TIMP-2 levels and improved markers of LV diastolic function (lower E/Em and higher Em and E/A values) than S-SCI ones. Bivariate analysis showed that pro-MMP-2 correlated inversely with Em and directly with E/Em, while MMP-9 correlated directly with LV mass index and LV end-diastolic diameter in the whole sample. Following multiple regression analysis, pro-MMP-2, but not physical activity, remained associated with Em, while MMP-9 was associated with LV mass index in the whole sample. These findings suggest differing roles for MMPs in LV structure and function regulation and an interaction among pro-MMP-2, diastolic function and physical activity in SCI subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2015-11-01

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

Spray method for recovery of heat-injured Salmonella Typhimurium and Listeria monocytogenes.

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Back, Kyeong-Hwan; Kim, Sang-Oh; Park, Ki-Hwan; Chung, Myung-Sub; Kang, Dong-Hyun

2012-10-01

Selective agar is inadequate for supporting recovery of injured cells. During risk assessment of certain foods, both injured and noninjured cells must be enumerated. In this study, a new method (agar spray method) for recovering sublethally heat-injured microorganisms was developed and used for recovery of heat-injured Salmonella Typhimurium and Listeria monocytogenes. Molten selective agar was applied as an overlay to presolidified nonselective tryptic soy agar (TSA) by spray application. Heat-injured cells (55°C for 10 min in 0.1% peptone water or 55°C for 15 min in sterilized skim milk) were inoculated directly onto solidified TSA. After a 2-h incubation period for cell repair, selective agar was applied to the TSA surface with a sprayer, and the plates were incubated. The recovery rate for heat-injured Salmonella Typhimurium and L. monocytogenes with the spray method was compared with the corresponding rates associated with TSA alone, selective media alone, and the conventional overlay method (selective agar poured on top of resuscitated cells grown on TSA and incubated for 2 h). No significant differences (P > 0.05) were found in pathogen recovery obtained with TSA, the overlay method, and the spray method. However, a lower recovery rate (P recovery and detection of injured cells.

Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity

DEFF Research Database (Denmark)

Iba, K; Durkin, M E; Johnsen, L

2001-01-01

and muscle. To test the functional role of tetranectin directly, we have generated mice with a targeted disruption of the gene. We report that the tetranectin-deficient mice exhibit kyphosis, a type of spinal deformity characterized by an increased curvature of the thoracic spine. The kyphotic angles were...... in the morphology of the vertebrae. Histological analysis of the spines of these mice revealed an apparently asymmetric development of the growth plate and of the intervertebral disks of the vertebrae. In the most advanced cases, the growth plates appeared disorganized and irregular, with the disk material...... in tissue growth and remodeling. The tetranectin-deficient mouse is the first mouse model that resembles common human kyphotic disorders, which affect up to 8% of the population....

Comparisons of MR findings of the spinal metastasis and the spinal tuberculosis

International Nuclear Information System (INIS)

Hong, Myung Sun; Lee, Kil Woo; Kang, Ik Won; Yun, Ku Sub; Choi, Chul Sun; Bae, Sang Hoon

1994-01-01

MR findings of the spinal metastasis and the tuberculosis are well known, but sometimes it might be difficult to differentiate these lesions. Therefore we reviewed and analyzed the MR findings which would be useful for the differentiation. T1- and T2- weighted spin echo images and gadolinium-enhanced T1- weighted images were obtained with 1.5 T and 1.0 T superconductive MR imager. We reviewed MR findings in 16 cases of spinal metastases and 24 cases of spinal tuberculosis in terms of signal intensity, contrast enhancement pattern, disc space involvement, spinal canal compressing feature and paraspinal soft tissue mass. The signal intensities of both lesions were hypointense on T1WI and hyperintense on T2WI except those of the metastatic lesions from the prostatic carcinoma. Heterogeneous enhancement was noted in 63% of metastasis, whereas peripheral rim enhancement was noted 83% of spinal tuberculosis(p < .001). Spinal canal compression by collapsed vertebra was only noted in spinal metastasis, and that by paraspinal soft tissue was noted in both spinal metastasis and tuberculosis(p<.001). Disc space invasion was noted in 19% of spinal metastasis and 88% of spinal tuberculosis. Spinal tuberculosis was common at lower thoracic spine(T10) and typically involved two or more adjacent vertebral bodies(96%). The important differential point between spinal metastasis and tuberculosis was the enhancement pattern, involvement of two or more contiguous vertebral bodies and the feature of spinal canal compressing. The secondary importance was the disc space involvement pattern

The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair.

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Ravid Shechter

Full Text Available The inflammatory response in the injured spinal cord, an immune privileged site, has been mainly associated with the poor prognosis. However, recent data demonstrated that, in fact, some leukocytes, namely monocytes, are pivotal for repair due to their alternative anti-inflammatory phenotype. Given the pro-inflammatory milieu within the traumatized spinal cord, known to skew monocytes towards a classical phenotype, a pertinent question is how parenchymal-invading monocytes acquire resolving properties essential for healing, under such unfavorable conditions. In light of the spatial association between resolving (interleukin (IL-10 producing monocytes and the glial scar matrix chondroitin sulfate proteoglycan (CSPG, in this study we examined the mutual relationship between these two components. By inhibiting the de novo production of CSPG following spinal cord injury, we demonstrated that this extracellular matrix, mainly known for its ability to inhibit axonal growth, serves as a critical template skewing the entering monocytes towards the resolving phenotype. In vitro cell culture studies demonstrated that this matrix alone is sufficient to induce such monocyte polarization. Reciprocal conditional ablation of the monocyte-derived macrophages concentrated at the lesion margins, using diphtheria toxin, revealed that these cells have scar matrix-resolving properties. Replenishment of monocytic cell populations to the ablated mice demonstrated that this extracellular remodeling ability of the infiltrating monocytes requires their expression of the matrix-degrading enzyme, matrix metalloproteinase 13 (MMP-13, a property that was found here to be crucial for functional recovery. Altogether, this study demonstrates that the glial scar-matrix, a known obstacle to regeneration, is a critical component skewing the encountering monocytes towards a resolving phenotype. In an apparent feedback loop, monocytes were found to regulate scar resolution. This

Advantages of soft subdural implants for the delivery of electrochemical neuromodulation therapies to the spinal cord

Science.gov (United States)

Capogrosso, Marco; Gandar, Jerome; Greiner, Nathan; Moraud, Eduardo Martin; Wenger, Nikolaus; Shkorbatova, Polina; Musienko, Pavel; Minev, Ivan; Lacour, Stephanie; Courtine, Grégoire

2018-04-01

Objective. We recently developed soft neural interfaces enabling the delivery of electrical and chemical stimulation to the spinal cord. These stimulations restored locomotion in animal models of paralysis. Soft interfaces can be placed either below or above the dura mater. Theoretically, the subdural location combines many advantages, including increased selectivity of electrical stimulation, lower stimulation thresholds, and targeted chemical stimulation through local drug delivery. However, these advantages have not been documented, nor have their functional impact been studied in silico or in a relevant animal model of neurological disorders using a multimodal neural interface. Approach. We characterized the recruitment properties of subdural interfaces using a realistic computational model of the rat spinal cord that included explicit representation of the spinal roots. We then validated and complemented computer simulations with electrophysiological experiments in rats. We additionally performed behavioral experiments in rats that received a lateral spinal cord hemisection and were implanted with a soft interface. Main results. In silico and in vivo experiments showed that the subdural location decreased stimulation thresholds compared to the epidural location while retaining high specificity. This feature reduces power consumption and risks of long-term damage in the tissues, thus increasing the clinical safety profile of this approach. The hemisection induced a transient paralysis of the leg ipsilateral to the injury. During this period, the delivery of electrical stimulation restricted to the injured side combined with local chemical modulation enabled coordinated locomotor movements of the paralyzed leg without affecting the non-impaired leg in all tested rats. Electrode properties remained stable over time, while anatomical examinations revealed excellent bio-integration properties. Significance. Soft neural interfaces inserted subdurally provide the

Comparison of postural stability between injured and uninjured ballet dancers.

Science.gov (United States)

Lin, Cheng-Feng; Lee, I-Jung; Liao, Jung-Hsien; Wu, Hong-Wen; Su, Fong-Chin

2011-06-01

Ballet movements require a limited base of support; thus, ballet dancers require a high level of postural control. However, postural stability in ballet dancers is still unclear and needs to be understood. To evaluate ballet dancers' postural stability in performing single-leg standing, the en pointe task, and the first and fifth positions and to determine differences in task performance among healthy nondancers, healthy dancers, and dancers with ankle sprains. Controlled laboratory study. Injured dancers, uninjured dancers, and nondancers were recruited for this study (N = 33 age-matched participants; n= 11 per group). The tasks tested were single-leg standing with eyes open and closed, first position, fifth position, and en pointe. Center of pressure parameters were calculated from the ground-reaction force collected with 1 force plate. Analysis of variance was used to assess the differences of center of pressure parameters among 3 groups in single-leg standing; independent t test was used to examine the differences of center of pressure parameters between injured and uninjured dancers. During single-leg standing, injured dancers had significantly greater maximum displacement in the medial-lateral direction and total trajectory of center of pressure, compared with the uninjured dancers and nondancers. During the first and fifth positions, the injured dancers demonstrated significantly greater standard deviation of center of pressure position in the medial-lateral and anterior-posterior directions, compared with the uninjured dancers. During en pointe, the injured dancers had significantly greater maximum displacement in the medial-lateral direction and the anterior-posterior direction, compared with the uninjured dancers. The injured and uninjured dancers demonstrated differences in postural stability in the medial-lateral direction during single-leg standing and the ballet postures. Although the injured dancers received ballet training, their postural stability

Mechanisms of adhesion and subsequent actions of a haematopoietic stem cell line, HPC-7, in the injured murine intestinal microcirculation in vivo.

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Dean P J Kavanagh

Full Text Available Although haematopoietic stem cells (HSCs migrate to injured gut, therapeutic success clinically remains poor. This has been partially attributed to limited local HSC recruitment following systemic injection. Identifying site specific adhesive mechanisms underpinning HSC-endothelial interactions may provide important information on how to enhance their recruitment and thus potentially improve therapeutic efficacy. This study determined (i the integrins and inflammatory cyto/chemokines governing HSC adhesion to injured gut and muscle (ii whether pre-treating HSCs with these cyto/chemokines enhanced their adhesion and (iii whether the degree of HSC adhesion influenced their ability to modulate leukocyte recruitment.Adhesion of HPC-7, a murine HSC line, to ischaemia-reperfused (IR injured mouse gut or cremaster muscle was monitored intravitally. Critical adhesion molecules were identified by pre-treating HPC-7 with blocking antibodies to CD18 and CD49d. To identify cyto/chemokines capable of recruiting HPC-7, adhesion was monitored following tissue exposure to TNF-α, IL-1β or CXCL12. The effects of pre-treating HPC-7 with these cyto/chemokines on surface integrin expression/clustering, adhesion to ICAM-1/VCAM-1 and recruitment in vivo was also investigated. Endogenous leukocyte adhesion following HPC-7 injection was again determined intravitally.IR injury increased HPC-7 adhesion in vivo, with intestinal adhesion dependent upon CD18 and muscle adhesion predominantly relying on CD49d. Only CXCL12 pre-treatment enhanced HPC-7 adhesion within injured gut, likely by increasing CD18 binding to ICAM-1 and/or CD18 surface clustering on HPC-7. Leukocyte adhesion was reduced at 4 hours post-reperfusion, but only when local HPC-7 adhesion was enhanced using CXCL12.This data provides evidence that site-specific molecular mechanisms govern HPC-7 adhesion to injured tissue. Importantly, we show that HPC-7 adhesion is a modulatable event in IR injury and

Non-contiguous spinal injury in cervical spinal trauma: evaluation with cervical spine MRI

International Nuclear Information System (INIS)

Choi, Soo Jung; Shin, Myung Jin; Kim, Sung Moon; Bae, Sang Jin

2004-01-01

We wished to evaluate the incidence of non-contiguous spinal injury in the cervicothoracic junction (CTJ) or the upper thoracic spines on cervical spinal MR images in the patients with cervical spinal injuries. Seventy-five cervical spine MR imagings for acute cervical spinal injury were retrospectively reviewed (58 men and 17 women, mean age: 35.3, range: 18-81 years). They were divided into three groups based on the mechanism of injury; axial compression, hyperflexion or hyperextension injury, according to the findings on the MR and CT images. On cervical spine MR images, we evaluated the presence of non-contiguous spinal injury in the CTJ or upper thoracic spine with regard to the presence of marrow contusion or fracture, ligament injury, traumatic disc herniation and spinal cord injury. Twenty-one cases (28%) showed CTJ or upper thoracic spinal injuries (C7-T5) on cervical spinal MR images that were separated from the cervical spinal injuries. Seven of 21 cases revealed overt fractures in the CTJs or upper thoracic spines. Ligament injury in these regions was found in three cases. Traumatic disc herniation and spinal cord injury in these regions were shown in one and two cases, respectively. The incidence of the non-contiguous spinal injuries in CTJ or upper thoracic spines was higher in the axial compression injury group (35.5%) than in the hyperflexion injury group (26.9%) or the hyperextension (25%) injury group. However, there was no statistical significance (ρ > 0.05). Cervical spinal MR revealed non-contiguous CTJ or upper thoracic spinal injuries in 28% of the patients with cervical spinal injury. The mechanism of cervical spinal injury did not significantly affect the incidence of the non-contiguous CTJ or upper thoracic spinal injury

Non-contiguous spinal injury in cervical spinal trauma: evaluation with cervical spine MRI

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Choi, Soo Jung; Shin, Myung Jin; Kim, Sung Moon [University of Ulsan College of Medicine, Seoul (Korea, Republic of); Bae, Sang Jin [Sanggyepaik Hospital, Inje University, Seoul (Korea, Republic of)

2004-12-15

We wished to evaluate the incidence of non-contiguous spinal injury in the cervicothoracic junction (CTJ) or the upper thoracic spines on cervical spinal MR images in the patients with cervical spinal injuries. Seventy-five cervical spine MR imagings for acute cervical spinal injury were retrospectively reviewed (58 men and 17 women, mean age: 35.3, range: 18-81 years). They were divided into three groups based on the mechanism of injury; axial compression, hyperflexion or hyperextension injury, according to the findings on the MR and CT images. On cervical spine MR images, we evaluated the presence of non-contiguous spinal injury in the CTJ or upper thoracic spine with regard to the presence of marrow contusion or fracture, ligament injury, traumatic disc herniation and spinal cord injury. Twenty-one cases (28%) showed CTJ or upper thoracic spinal injuries (C7-T5) on cervical spinal MR images that were separated from the cervical spinal injuries. Seven of 21 cases revealed overt fractures in the CTJs or upper thoracic spines. Ligament injury in these regions was found in three cases. Traumatic disc herniation and spinal cord injury in these regions were shown in one and two cases, respectively. The incidence of the non-contiguous spinal injuries in CTJ or upper thoracic spines was higher in the axial compression injury group (35.5%) than in the hyperflexion injury group (26.9%) or the hyperextension (25%) injury group. However, there was no statistical significance ({rho} > 0.05). Cervical spinal MR revealed non-contiguous CTJ or upper thoracic spinal injuries in 28% of the patients with cervical spinal injury. The mechanism of cervical spinal injury did not significantly affect the incidence of the non-contiguous CTJ or upper thoracic spinal injury.

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

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Min-Jae Jo

2018-05-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

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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.

Antecedent control in the treatment of brain-injured clients.

Science.gov (United States)

Zencius, A H; Wesolowski, M D; Burke, W H; McQuade, P

1989-01-01

Three brain-injured clients failed to respond significantly to consequence management programmes designed to increase attendance, use of a cane, and to reduce unauthorized breaks. When antecedent stimulus control procedures were applied, attendance and use of a cane increased and unauthorized breaks decreased. The study shows that antecedent control may be the treatment of choice when treating brain-injured clients with memory loss.

Ectopic cross-talk between thyroid and retinoic acid signaling: A possible etiology for spinal neural tube defects.

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Li, Huili; Bai, Baoling; Zhang, Qin; Bao, Yihua; Guo, Jin; Chen, Shuyuan; Miao, Chunyue; Liu, Xiaozhen; Zhang, Ting

2015-12-01

Previous studies have highlighted the connections between neural tube defects (NTDs) and both thyroid hormones (TH) and vitamin A. However, whether the two hormonal signaling pathways interact in NTDs has remained unclear. We measured the expression levels of TH signaling genes in human fetuses with spinal NTDs associated with maternal hyperthyroidism as well as levels of retinoic acid (RA) signaling genes in mouse fetuses exposed to an overdose of RA using NanoString or real-time PCR on spinal cord tissues. Interactions between the two signaling pathways were detected by ChIP assays. The data revealed attenuated DIO2/DIO3 switching in fetuses with NTDs born to hyperthyroid mothers. The promoters of the RA signaling genes CRABP1 and RARB were ectopically occupied by increased RXRG and RXRB but displayed decreased levels of inhibitory histone modifications, suggesting that elevated TH signaling abnormally stimulates RA signaling genes. Conversely, in the mouse model, the observed decrease in Dio3 expression could be explained by increased levels of inhibitory histone modifications in the Dio3 promoter region, suggesting that overactive RA signaling may ectopically derepress TH signaling. This study thus raises in vivo a possible abnormal cross-promotion between two different hormonal signals through their common RXRs and the subsequent recruitment of histone modifications, prompting further investigation into their involvement in the etiology of spinal NTDs. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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Changxing Wang

2017-03-01

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

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

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Coral-Ann B Lewis

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

Participation restriction and assistance needs in people with spinal cord injuries of more than 40 year duration.

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Savic, Gordana; Frankel, Hans L; Jamous, Mohamed Ali; Soni, Bakulesh M; Charlifue, Susan

2018-01-01

Prospective observational. Examine changes in participation restriction and assistance needs in a sample of people with long-standing spinal cord injuries (SCIs). Two British spinal centres. The sample consisted of British ageing with SCI study participants who were seen at baseline (1990 or 1993) and in the final follow-up (2010). Outcome measures were the Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF) and interview questions about assistance needs. Eighty-five Ageing study participants took part in 2010; their mean age was 67.65 years and the mean time since injury was 46.26 years. The mean CHART-SF physical independence subscore decreased from 97.44 in 1990 to 91.26 in 2010, mobility from 95.58 to 82.10, occupation from 86.82 to 64.49 and social integration from 96.29 to 88.68 (all p  < 0.05). Increasing assistance needs were reported by 10.1% of participants in 1990, by 36.6% in 2010 ( p  < 0.05) and by 62.4% over the entire 20-year study period. Persons requiring more assistance were older and injured longer, had a more severe SCI and lower self-reported quality of life and life satisfaction ( p  < 0.05). In the multivariate logistic regression, the strongest predictor of needing more assistance was injury severity ( p  < 0.05). An increase in participation restriction and in assistance needs was reported over the 20 year follow-up in persons injured more than 40 years ago. SCI severity was the main risk factor for needing more assistance. Clinical awareness of how participation changes with age may help provide timely intervention and offset declines.

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

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

2015-07-01

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

Midodrine improves orgasm in spinal cord-injured men: the effects of autonomic stimulation.

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Soler, Jean Marc; Previnaire, Jean Gabriel; Plante, Pierre; Denys, Pierre; Chartier-Kastler, Emmanuel

2008-12-01

Orgasm is less frequent in men with spinal cord injury (SCI) than in able-bodied subjects, and is poorly understood. To assess the effect of autonomic stimulation on orgasm in SCI men using midodrine, an alpha1-adrenergic agonist agent. Penile vibratory stimulation (PVS) was performed in 158 SCI men on midodrine as part of a treatment for anejaculation, after they failed a baseline PVS. A maximum of four trials were performed, weekly, with increasing doses of midodrine. The presence and type of ejaculation, orgasm experiences, and cardiovascular data were collected. Ejaculation either antegrade or retrograde was obtained in 102 SCI men (65%). Orgasm without ejaculation was reported by 14 patients (9%) on baseline PVS. Ninety-three patients (59%) experienced orgasm during PVS on midodrine. Orgasm was significantly related to the presence of ejaculation in 86 patients (84%), and more strikingly to antegrade ejaculation (pure or mixed with retrograde), i.e., in 98% of 70 patients. Orgasm was significantly more frequent in patients with upper motor neuron and incomplete lesions who present somatic responses during PVS. There was no effect of the presence of psychogenic erection. There was a significant increase in both systolic and diastolic blood pressure. Sixteen patients, mainly tetraplegics, developed intense autonomic dysreflexia (AD) that required an oral nicardipine chlorhydrate. Orgasm is the brain's cognitive interpretation of genital sensations and somatic responses, AD, and ejaculation. Intact sacral and T10-L2 cord segments are mandatory, allowing coordination between internal and external sphincters. Autonomic stimulation with midodrine enhances orgasm rate, mainly by creating antegrade ejaculation.

Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

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Gabriel Olmos

2013-05-01

Full Text Available Spinal muscular atrophy (SMA is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD. In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.

Differential diagnoses of spinal tumors; Differenzialdiagnose spinaler Tumoren

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

2011-12-15

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

One day of motor training with amphetamine impairs motor recovery following spinal cord injury.

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Wong, Jamie K; Steward, Oswald

2012-02-01

It has previously been reported that a single dose of amphetamine paired with training on a beam walking task can enhance locomotor recovery following brain injury (Feeney et al., 1982). Here, we investigated whether this same drug/training regimen could enhance functional recovery following either thoracic (T9) or cervical (C5) spinal cord injury. Different groups of female Sprague-Dawley rats were trained on a beam walking task, and in a straight alley for assessment of hindlimb locomotor recovery using the BBB locomotor scale. For rats that received C5 hemisections, forelimb grip strength was assessed using a grip strength meter. Three separate experiments assessed the consequences of training rats on the beam walking task 24 h following a thoracic lateral hemisection with administration of either amphetamine or saline. Beginning 1 h following drug administration, rats either received additional testing/retraining on the beam hourly for 6 h, or they were returned to their home cages without further testing/retraining. Rats with thoracic spinal cord injuries that received amphetamine in conjunction with testing/retraining on the beam at 1 day post injury (DPI) exhibited significantly impaired recovery on the beam walking task and BBB. Rats with cervical spinal cord injuries that received training with amphetamine also exhibited significant impairments in beam walking and locomotion, as well as impairments in gripping and reaching abilities. Even when administered at 14 DPI, the drug/training regimen significantly impaired reaching ability in cervical spinal cord injured rats. Impairments were not seen in rats that received amphetamine without training. Histological analyses revealed that rats that received training with amphetamine had significantly larger lesions than saline controls. These data indicate that an amphetamine/training regimen that improves recovery after cortical injury has the opposite effect of impairing recovery following spinal cord injury

Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

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Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

2015-01-01

Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

Chronic spinal subdural hematoma; Spinales chronisches subdurales Haematom

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Hagen, T.; Lensch, T. [Radiologengemeinschaft, Augsburg (Germany)

2008-10-15

Compared with spinal epidural hematomas, spinal subdural hematomas are rare; chronic forms are even more uncommon. These hematomas are associated not only with lumbar puncture and spinal trauma, but also with coagulopathies, vascular malformations and tumors. Compression of the spinal cord and the cauda equina means that the patients develop increasing back or radicular pain, followed by paraparesis and bladder and bowel paralysis, so that in most cases surgical decompression is carried out. On magnetic resonance imaging these hematomas present as thoracic or lumbar subdural masses, their signal intensity varying with the age of the hematoma. We report the clinical course and the findings revealed by imaging that led to the diagnosis in three cases of chronic spinal subdural hematoma. (orig.) [German] Spinale subdurale Haematome sind im Vergleich zu epiduralen Haematomen selten, chronische Verlaufsformen noch seltener. Ursaechlich sind neben Lumbalpunktionen und traumatischen Verletzungen auch Blutgerinnungsstoerungen, Gefaessmalformationen und Tumoren. Aufgrund der Kompression von Myelon und Cauda equina kommt es zu zunehmenden Ruecken- oder radikulaeren Schmerzen mit anschliessender Paraparese sowie einer Darm- und Blasenstoerung, weshalb in den meisten Faellen eine operative Entlastung durchgefuehrt wird. Magnetresonanztomographisch stellen sich die Haematome meist als thorakale bzw. lumbale subdurale Raumforderungen dar, die Signalintensitaet variiert mit dem Blutungsalter. Wir berichten ueber den klinischen Verlauf und die bildgebende Diagnostik von 3 Patienten mit spinalen chronischen subduralen Haematomen. (orig.)

Spinal Cord Injury 101

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

Spinal Cord Injury 101

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

Radiation injuries of the spinal marrow of rats after irradiation with fast electrons

International Nuclear Information System (INIS)

Bruce-Micah, B.

1973-01-01

Twenty rats were fractionated irradiated on five days of the week with fast electrons of 42 MeV energy with a single dose of 200 r/day. After 1,000 r, 2,000 r, 3,000 r and 4,000 r HD, the animals were supravitally fixed and the spinal marrow was removed. The histological investigation already showed after 1,000 r HD distinct changes of the nerve cells and nerve fibers whereas the vessels appeared not to be injured. After 2,000 r HD, vessel changes with edemas occured for the first time. After 3,000 r HD, all nerve cells were severely injured, the glia tissue was denser and the vessels were enlarged despite endothelial proliferations. Furthermore, there were big edemas around the vessels and a beginning of demyelinisation in the dorsal column. After 4,000 r HD, a great part of the nerve cells and also a few glia cells were destroyed. The remaining glia cells were pyknotic and had partly several nucleoli. The tractus of the white matter consisted almost only now of a glia felt. With a survival time of six weeks, the glia had greatly regenerated and numerous new capillaries had sprouted in the grey matter. The white matter was strongly demyelinised. In the front lateral column, small round necrosis centres were visible. 18 weeks after irradiation, the glia tissue had greatly rebuilt itself. There were only very few nerve cells present. The strong sprouting of new capillaries in the grey matter was most noticeable. The results show that the application of fast electrons is of no advantage as regards injuring the nerve tissue compared to X-rays. (orig./LH) [de

Investigation of spinal cerebrospinal fluid-contacting neurons expressing PKD2L1: evidence for a conserved system from fish to primates

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Djenoune, Lydia; Khabou, Hanen; Joubert, Fanny; Quan, Feng B.; Nunes Figueiredo, Sophie; Bodineau, Laurence; Del Bene, Filippo; Burcklé, Céline; Tostivint, Hervé; Wyart, Claire

2014-01-01

Over 90 years ago, Kolmer and Agduhr identified spinal cerebrospinal fluid-contacting neurons (CSF-cNs) based on their morphology and location within the spinal cord. In more than 200 vertebrate species, they observed ciliated neurons around the central canal that extended a brush of microvilli into the cerebrospinal fluid (CSF). Although their morphology is suggestive of a primitive sensory cell, their function within the vertebrate spinal cord remains unknown. The identification of specific molecular markers for these neurons in vertebrates would benefit the investigation of their physiological roles. PKD2L1, a transient receptor potential channel that could play a role as a sensory receptor, has been found in cells contacting the central canal in mouse. In this study, we demonstrate that PKD2L1 is a specific marker for CSF-cNs in the spinal cord of mouse (Mus musculus), macaque (Macaca fascicularis) and zebrafish (Danio rerio). In these species, the somata of spinal PKD2L1+ CSF-cNs were located below or within the ependymal layer and extended an apical bulbous extension into the central canal. We found GABAergic PKD2L1-expressing CSF-cNs in all three species. We took advantage of the zebrafish embryo for its transparency and rapid development to identify the progenitor domains from which pkd2l1+ CSF-cNs originate. pkd2l1+ CSF-cNs were all GABAergic and organized in two rows—one ventral and one dorsal to the central canal. Their location and marker expression is consistent with previously described Kolmer–Agduhr cells. Accordingly, pkd2l1+ CSF-cNs were derived from the progenitor domains p3 and pMN defined by the expression of nkx2.2a and olig2 transcription factors, respectively. Altogether our results suggest that a system of CSF-cNs expressing the PKD2L1 channel is conserved in the spinal cord across bony vertebrate species. PMID:24834029

Investigation of spinal cerebrospinal fluid-contacting neurons expressing PKD2L1: evidence for a conserved system from fish to primates

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Lydia eDjenoune

2014-05-01

Full Text Available Over ninety years ago, Kolmer and Agduhr identified spinal cerebrospinal fluid-contacting neurons (CSF-cNs based on their morphology and location within the spinal cord. In more than two hundred vertebrate species, they observed ciliated neurons around the central canal that extended a brush of microvilli into the cerebrospinal fluid (CSF. Although their morphology is suggestive of a primitive sensory cell, their function within the vertebrate spinal cord remains unknown. The identification of specific molecular markers for these neurons in vertebrates would benefit the investigation of their physiological roles. PKD2L1, a transient receptor potential channel that could play a role as a sensory receptor, has been found in cells contacting the central canal in mouse. In this study, we demonstrate that PKD2L1 is a specific marker for CSF-cNs in the spinal cord of mouse (Mus musculus, macaque (Macaca fascicularis and zebrafish (Danio rerio. In these species, the somata of spinal PKD2L1+ CSF-cNs were located below or within the ependymal layer and extended an apical bulbous extension into the central canal. We found GABAergic PKD2L1-expressing CSF-cNs in all three species. We took advantage of the zebrafish embryo for its transparency and rapid development to identify the progenitor domains from which pkd2l1+ CSF-cNs originate. pkd2l1+ CSF-cNs were all GABAergic and organized in two rows—one ventral and one dorsal to the central canal. Their location and marker expression is consistent with previously described Kolmer-Agduhr cells. Accordingly, pkd2l1+ CSF-cNs were derived from the progenitor domains p3 and pMN defined by the expression of nkx2.2a and olig2 transcription factors, respectively. Altogether our results suggest that a system of CSF-cNs expressing the PKD2L1 channel is conserved in the spinal cord across bony vertebrate species.

Spinal segmental dysgenesis

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N Mahomed

2009-06-01

Full Text Available Spinal segmental dysgenesis is a rare congenital spinal abnormality , seen in neonates and infants in which a segment of the spine and spinal cord fails to develop normally . The condition is segmental with normal vertebrae above and below the malformation. This condition is commonly associated with various abnormalities that affect the heart, genitourinary, gastrointestinal tract and skeletal system. We report two cases of spinal segmental dysgenesis and the associated abnormalities.

Health and Occupational Outcomes Among Injured, Nonstandard Shift Workers.

Science.gov (United States)

Wong, Imelda S; Smith, Peter M; Mustard, Cameron A; Gignac, Monique A M

2015-11-01

This study compares health and occupational outcomes following a work-related injury for nonstandard and day-shift workers. National Population Health Survey data were used to explore outcomes 2 years post-work injury. Retrospective-matched cohort analyses examined main effects and interactions of shift schedule and work injury with changes in health, shift schedule, and labor force status. Models were adjusted for respondent characteristics, baseline health status, and occupational strength requirements. Injured nonstandard shift workers reported lower health utility index scores, compared with uninjured and injured daytime workers and uninjured nonstandard-shift workers. No significant interactions between shift and injury were found with schedule change and leaving the labor force. Injured nonstandard-shift workers are as likely to remain employed as other groups, but may be vulnerable in terms of diminished health.

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

Science.gov (United States)

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

2013-04-01

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

Causes of death after traumatic spinal cord injury-a 70-year British study.

Science.gov (United States)

Savic, G; DeVivo, M J; Frankel, H L; Jamous, M A; Soni, B M; Charlifue, S

2017-10-01

Retrospective and prospective observational. Analyse causes of death after traumatic spinal cord injury (tSCI) in persons surviving the first year post injury, and establish any trend over time. Two spinal centres in Great Britain. The sample consisted of 5483 patients with tSCI admitted to Stoke Mandeville and Southport spinal centres who were injured between 1943 and 2010, survived first year post injury, had residual neurological deficit on discharge and were British residents. Mortality information, including causes of death, was collected up to 31 December 2014. Age-standardised cause-specific mortality rates were calculated for selected causes of death, and included trends over time and comparison with the general population. In total, 2322 persons (42.3% of the sample) died, with 2170 (93.5%) having a reliable cause of death established. The most frequent causes of death were respiratory (29.3% of all certified causes), circulatory, including cardiovascular and cerebrovascular diseases (26.7%), neoplasms (13.9%), urogenital (11.5%), digestive (5.3%) and external causes, including suicides (4.5%). Compared to the general population, age-standardised cause-specific mortality rates were higher for all causes, especially skin, urogenital and respiratory; rates showed improvement over time for suicides, circulatory and urogenital causes, no significant change for neoplasms, and increase for skin and respiratory causes. Leading causes of death after tSCI in persons surviving the first year post injury were respiratory, circulatory, neoplasms and urogenital. Cause-specific mortality rates showed improvement over time for most causes, but were still higher than the general population rates, especially for skin, urinary and respiratory causes.

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

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

2009-08-25

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

Hyperacute spinal subdural haematoma as a complication of lumbar spinal anaesthesia: MRI

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Pedraza Gutierrez, S.; Suescun, M.; Rovira Canellas, A.; Coll Masfarre, S.; Castano Duque, C.H.

1999-01-01

We report two cases of hyperacute spinal subdural haematoma secondary to lumbar spinal anaesthesia, identified with MRI. Prompt diagnosis of this infrequent, potentially serious complication of spinal anaesthesia is essential, as early surgical evacuation may be needed. Suggestive MRI findings in this early phase include diffuse occupation filling of the spinal canal with poor delineation of the spinal cord on T1-weighted images, and a poorly-defined high-signal lesion with a low-signal rim on T2-weighted images. (orig.)

MULTIPLE SPINAL CANAL MENINGIOMAS

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Nandigama Pratap Kumar

2016-10-01

Full Text Available BACKGROUND Meningiomas of the spinal canal are common tumours with the incidence of 25 percent of all spinal cord tumours. But multiple spinal canal meningiomas are rare in compare to solitary lesions and account for 2 to 3.5% of all spinal meningiomas. Most of the reported cases are both intra cranial and spinal. Exclusive involvement of the spinal canal by multiple meningiomas are very rare. We could find only sixteen cases in the literature to the best of our knowledge. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for single lesion. We analysed the literature, with illustration of our case. MATERIALS AND METHODS In September 2016, we performed a literature search for multiple spinal canal meningiomas involving exclusively the spinal canal with no limitation for language and publication date. The search was conducted through http://pubmed.com, a wellknown worldwide internet medical address. To the best of our knowledge, we could find only sixteen cases of multiple meningiomas exclusively confined to the spinal canal. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for solitary intradural extra medullary spinal canal meningioma at D4-D6 level, again presented with spastic quadriparesis of two years duration and MRI whole spine demonstrated multiple intradural extra medullary lesions, which were excised completely and the histopathological diagnosis was transitional meningioma. RESULTS Patient recovered from his weakness and sensory symptoms gradually and bladder and bowel symptoms improved gradually over a period of two to three weeks. CONCLUSION Multiple

Identifying the Long-Term Role of Inducible Nitric Oxide Synthase after Contusive Spinal Cord Injury Using a Transgenic Mouse Model

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Dominic M. Maggio

2017-01-01

Full Text Available Inducible nitric oxide synthase (iNOS is a potent mediator of oxidative stress during neuroinflammation triggered by neurotrauma or neurodegeneration. We previously demonstrated that acute iNOS inhibition attenuated iNOS levels and promoted neuroprotection and functional recovery after spinal cord injury (SCI. The present study investigated the effects of chronic iNOS ablation after SCI using inos-null mice. iNOS−/− knockout and wild-type (WT control mice underwent a moderate thoracic (T8 contusive SCI. Locomotor function was assessed weekly, using the Basso Mouse Scale (BMS, and at the endpoint (six weeks, by footprint analysis. At the endpoint, the volume of preserved white and gray matter, as well as the number of dorsal column axons and perilesional blood vessels rostral to the injury, were quantified. At weeks two and three after SCI, iNOS−/− mice exhibited a significant locomotor improvement compared to WT controls, although a sustained improvement was not observed during later weeks. At the endpoint, iNOS−/− mice showed significantly less preserved white and gray matter, as well as fewer dorsal column axons and perilesional blood vessels, compared to WT controls. While short-term antagonism of iNOS provides histological and functional benefits, its long-term ablation after SCI may be deleterious, blocking protective or reparative processes important for angiogenesis and tissue preservation.

Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice.

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Lim, Hee-Young; Albuquerque, Boris; Häussler, Annett; Myrczek, Thekla; Ding, Aihao; Tegeder, Irmgard

2012-04-01

Progranulin haploinsufficiency is associated with frontotemporal dementia in humans. Deficiency of progranulin led to exaggerated inflammation and premature aging in mice. The role of progranulin in adaptations to nerve injury and neuropathic pain are still unknown. Here we found that progranulin is up-regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons. Progranulin knockdown by continuous intrathecal spinal delivery of small interfering RNA after sciatic nerve injury intensified neuropathic pain-like behaviour and delayed the recovery of motor functions. Compared to wild-type mice, progranulin-deficient mice developed more intense nociceptive hypersensitivity after nerve injury. The differences escalated with aging. Knockdown of progranulin reduced the survival of dissociated primary neurons and neurite outgrowth, whereas addition of recombinant progranulin rescued primary dorsal root ganglia neurons from cell death induced by nerve growth factor withdrawal. Thus, up-regulation of progranulin after neuronal injury may reduce neuropathic pain and help motor function recovery, at least in part, by promoting survival of injured neurons and supporting regrowth. A deficiency in this mechanism may increase the risk for injury-associated chronic pain. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Reciprocal functional interactions between the brainstem and the lower spinal cord

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Yazawa, Itaru

2014-01-01

The interplay of the neuronal discharge patterns regarding respiration and locomotion was investigated using electrophysiological techniques in a decerebrate and arterially perfused in situ mouse preparation. The phrenic, tibial, and/or peroneal nerve discharge became clearly organized into discharge episodes of increasing frequency and duration, punctuated by periods of quiescence as the perfusion flow rate increased at room temperature. The modulated sympathetic tone induced by the hyperoxic/normocapnic state was found to activate the locomotor pattern generator (LPG) via descending pathways and generate a left and right alternating discharge during discharge episodes in the motor nerves. The rhythm coupling of respiration and locomotion occurred at a 1:1 frequency ratio. Although the phrenic discharge synchronized with the tibial discharge at all flow rates tested, the time lag between peaks of the two discharges during locomotion was ≈400 ms rather than ≈200 ms, suggesting spinal feedback via ascending pathways. The incidence of the phrenic and tibial discharge episodes decreased by ≈50% after spinalization at the twelfth thoracic cord and the respiratory rhythm was more regular. These results indicate that: (i) locomotion can be generated in a hyperoxic/normocapnic state induced by specific respiratory conditions, (ii) the central mechanism regarding entrainment of respiratory and locomotor rhythms relies on spinal feedback via ascending pathways, initiated by the activated LPG generating locomotion, and (iii) the increase in respiratory rate seen during locomotion is caused not only by afferent mechanical and nociceptive inputs but also by impulses from the activated spinal cord producing a locomotor-like discharge via ascending pathways. PMID:24910591

Reciprocal functional interactions between the brainstem and the lower spinal cord

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Itaru eYazawa

2014-05-01

Full Text Available The interplay of the neuronal discharge patterns regarding respiration and locomotion was investigated using electrophysiological techniques in a decerebrate and arterially perfused in situ mouse preparation. The phrenic, tibial and/or peroneal nerve discharge became clearly organized into discharge episodes of increasing frequency and duration, punctuated by periods of quiescence as the perfusion flow rate increased at room temperature. The modulated sympathetic tone induced by the hyperoxic/normocapnic state was found to activate the locomotor pattern generator (LPG via descending pathways and generate a left and right alternating discharge during discharge episodes in the motor nerves. The rhythm coupling of respiration and locomotion occurred at a 1:1 frequency ratio. Although the phrenic discharge synchronized with the tibial discharge at all flow rates tested, the time lag between peaks of the two discharges during locomotion was ≈400 ms rather than ≈200 ms, suggesting spinal feedback via ascending pathways. The incidence of the phrenic and tibial discharge episodes decreased by ≈50% after spinalization at the twelfth thoracic vertebra and the respiratory rhythm was more regular. These results indicate that: (i locomotion can be generated in a hyperoxic/normocapnic state induced by specific respiratory conditions, (ii the central mechanism regarding entrainment of respiratory and locomotor rhythms relies on spinal feedback via ascending pathways, initiated by the activated LPG generating locomotion, and (iii the increase in respiratory rate seen during locomotion is caused not only by afferent mechanical and nociceptive inputs but also by impulses from the activated spinal cord producing a locomotor-like discharge via ascending pathways.

Trends in new injuries, prevalent cases, and aging with spinal cord injury.

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DeVivo, Michael J; Chen, Yuying

2011-03-01

To determine the characteristics of the newly injured and prevalent population with spinal cord injury (SCI) and assess trends over time. Prospective cohort study. SCI Model Systems and Shriners Hospital SCI units. The study population included people whose injuries occurred from 1935 to 2008 (N=45,442). The prevalent population was estimated based on those who were still alive in 2008. Losses to follow-up (approximately 10%) were excluded from the prevalent population. Not applicable. Demographic and injury characteristics, mortality, self-reported health, rehospitalization, FIM, Craig Handicap Assessment and Reporting Technique, and the Diener Satisfaction with Life Scale. Mean age at injury increased 9 years since the 1970s. Injuries caused by falls and injuries resulting in high-level tetraplegia and ventilator dependency are increasing, while neurologically complete injuries are decreasing. Discharge to a nursing home is increasing. The mean age of the prevalent population is slightly higher than that of newly injured individuals, and the percentage of incident and prevalent cases older than 60 years is the same (13%). Prevalent cases tend to be less severely injured than incident cases, and less than 5% of prevalent cases reside in nursing homes. Within the prevalent population, life satisfaction and community participation are greater among persons who are at least 30 years postinjury. These findings are a result of very high mortality rates observed after 60 years of age. Within the prevalent population, the percentage of elderly persons will not increase meaningfully. Those who reach older ages will typically have incomplete and/or lower-level injuries and will have relatively high degrees of independence and overall good health. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Imaging and differentiation of mouse embryo tissues by ToF-SIMS

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Wu, L; Lu, X; Kulp, K; Knize, M; Berman, E; Nelson, E; Felton, J; Wu, K J

2006-06-16

Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) equipped with a gold ion gun was used to image mouse embryos and differentiate tissue types (brain, spinal cord, skull, rib, heart and liver). Embryos were paraffin-embedded and then de-paraffinized. The robustness and repeatability of the method was determined by analyzing nine tissue slices from three different embryos over a period of several weeks. Using Principal Component Analysis (PCA) to reduce the spectral data generated by ToF-SIMS, histopathologically identified tissue types of the mouse embryos can be differentiated based on the characteristic differences in their mass spectra. These results demonstrate the ability of ToF-SIMS to determine subtle chemical differences even in fixed histological specimens.

Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation is Essential for Functional Regeneration

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