International spinal cord injury male sexual function and female sexual and reproductive function basic data sets-version 2.0.

PubMed

Alexander, Marcalee S; New, Peter W; Biering-Sørensen, Fin; Courtois, Frederique; Popolo, Giulio Del; Elliott, Stacy; Kiekens, Carlotte; Vogel, Lawrence; Previnaire, Jean G

2017-01-01

Data set review and modification. To describe modifications in the International Spinal Cord Injury (SCI) Male Sexual Function Basic Data Set Version 2.0 and the International SCI Female Sexual and Reproductive Function Basic Data Set Version 2.0. International expert work group using on line communication. An international team of experts was compiled to review and revise the International SCI Male Sexual Function and Female Sexual and Reproductive Function Basic Data Sets Version 1.0. The group adapted Version 1.0 based upon review of published research, suggestions from concerned individuals and on line work group consensus. The revised data sets were then posted on the International Spinal Cord Society (ISCoS) and American Spinal Injury Association (ASIA) websites for 2 months for review. Subsequently, the data sets were approved by the ISCoS Scientific and Executive Committees and ASIA board of directors. The data sets were modified to a self-report format. They were reviewed for appropriateness for the pediatric age group and adapted to include a new variable to address the issue of sexual orientation. A clarification of the difference between the data sets and the autonomic standards was also developed. Sexuality is a continuously evolving topic. Modifications were needed to address this topic in a comprehensive fashion. It is recommended that Version 2.0 of these data sets are used for ongoing documentation of sexual status in the medical record and for documentation of sexual concerns during on-going research.

International urodynamic basic spinal cord injury data set.

PubMed

Biering-Sørensen, F; Craggs, M; Kennelly, M; Schick, E; Wyndaele, J-J

2008-07-01

To create the International Urodynamic Basic Spinal Cord Injury (SCI) Data Set within the framework of the International SCI Data Sets. International working group. The draft of the data set was developed by a working group consisting of members appointed by the Neurourology Committee of the International Continence Society, the European Association of Urology, the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the Executive Committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review and comments by members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA Board, relevant and interested (international) organizations and societies (around 40) and persons and the ISCoS Council. Endorsement of the data set by relevant organizations and societies will be obtained. To make the data set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. Variables included in the International Urodynamic Basic SCI Data Set are date of data collection, bladder sensation during filling cystometry, detrusor function, compliance during filing cystometry, function during voiding, detrusor leak point pressure, maximum detrusor pressure, cystometric bladder capacity and post-void residual volume.

Impact of H3.3 K27M Mutation on Prognosis and Survival of Grade IV Spinal Cord Glioma on the Basis of New 2016 World Health Organization Classification of the Central Nervous System.

PubMed

Yi, Seong; Choi, Sunkyu; Shin, Dong Ah; Kim, Du Su; Choi, Junjeong; Ha, Yoon; Kim, Keung Nyun; Suh, Chang-Ok; Chang, Jong Hee; Kim, Se Hoon; Yoon, Do Heum

2018-05-01

Spinal cord glioma grade IV is a rare, diffuse midline glioma. H3 K27M-mutant was classified in a different entity in the 2016 World Health Organization (WHO) classification recently. No reports about prognosis of spinal cord glioma grade IV are available yet. To analyze the prognostic factors for spinal cord glioma grade IV. Twenty-five patients with spinal cord glioma of grade IV who underwent surgery in a single institute were selected. All grade IV spinal cord glioma histologically confirmed as glioblastoma or "diffuse midline glioma with H3 K27M-mutant" by the 2016 WHO classification of the central nervous system were included. Basic demographics, treatment modalities, and pathological tumor molecular profiles were investigated for prognosis. Mean age was 39.1 yr; male to female ratio was 18 : 7. Tumor was located in thoracic cord (53.3%), cervical cord (40%), and lumbar area (6.7%). Median overall survival was 37.1 mo; median disease-free survival was 18.5 mo. Treatment modality showed no statistical difference. Only K27M profile showed significant prognostic value, 20 patients (80%) showed K27M mutation positive, K27M mutation patients showed longer overall survival (40.07 mo) than K27M negative patients (11.63 mo, P < .0001), and disease-free survival (20.85 vs 8.72 mo, P = .0241). This study is the first and largest report of the prognosis of primary spinal cord grade IV glioma using the new WHO classification. This study reported survival analysis and prognostic factors, and revealed that H3.3 K27M mutation is not a major poor prognostic factor. Further studies to explore K27M mutations needed for risk stratification and therapy optimization.

Mechanosensory neurons control the timing of spinal microcircuit selection during locomotion

PubMed Central

Knafo, Steven; Fidelin, Kevin; Prendergast, Andrew; Tseng, Po-En Brian; Parrin, Alexandre; Dickey, Charles; Böhm, Urs Lucas; Figueiredo, Sophie Nunes; Thouvenin, Olivier; Pascal-Moussellard, Hugues; Wyart, Claire

2017-01-01

Despite numerous physiological studies about reflexes in the spinal cord, the contribution of mechanosensory feedback to active locomotion and the nature of underlying spinal circuits remains elusive. Here we investigate how mechanosensory feedback shapes active locomotion in a genetic model organism exhibiting simple locomotion—the zebrafish larva. We show that mechanosensory feedback enhances the recruitment of motor pools during active locomotion. Furthermore, we demonstrate that inputs from mechanosensory neurons increase locomotor speed by prolonging fast swimming at the expense of slow swimming during stereotyped acoustic escape responses. This effect could be mediated by distinct mechanosensory neurons. In the spinal cord, we show that connections compatible with monosynaptic inputs from mechanosensory Rohon-Beard neurons onto ipsilateral V2a interneurons selectively recruited at high speed can contribute to the observed enhancement of speed. Altogether, our study reveals the basic principles and a circuit diagram enabling speed modulation by mechanosensory feedback in the vertebrate spinal cord. DOI: http://dx.doi.org/10.7554/eLife.25260.001 PMID:28623664

International spinal cord injury bowel function basic data set (Version 2.0).

PubMed

Krogh, K; Emmanuel, A; Perrouin-Verbe, B; Korsten, M A; Mulcahey, M J; Biering-Sørensen, F

2017-07-01

International expert working group. To revise the International Spinal Cord Injury (SCI) Bowel Function Basic Data Set as a standardized format for the collecting and reporting of a minimal amount of information on bowel function in clinical practice and research. Working group appointed by the American Spinal injury association (ASIA) and the International Spinal Cord Society (ISCoS). The draft prepared by the working group was reviewed by the International SCI Data Set Committee and later by members of the ISCoS Executive and Scientific Committees and the ASIA board. The revised data set was posted on the ASIA and ISCoS websites for 1 month to allow further comments and suggestions. Changes resulting from a Delphi process among experts in children with SCI were included. Members of ISCoS Executive and Scientific Committees and the ASIA board made a final review and approved the data set. The International SCI Bowel Function Basic Data Set (Version 2.0) consists of the following 16 items: date of data collection, gastrointestinal and anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, defecation method and bowel-care procedures, average time required for defecation, frequency of defecation, uneasiness, headache or perspiration during defecation, digital stimulation or evacuation of the anorectum, frequency of fecal incontinence, flatus incontinence, need to wear pad or plug, oral laxatives and prokinetics, anti-diarrheal agents, perianal problems, abdominal pain and discomfort and the neurogenic bowel dysfunction score. The International SCI Bowel Function Basic Data Set (Version 2.0) has been developed.

Multilevel Analysis of Locomotion in Immature Preparations Suggests Innovative Strategies to Reactivate Stepping after Spinal Cord Injury.

PubMed

Brumley, Michele R; Guertin, Pierre A; Taccola, Giuliano

2017-01-01

Locomotion is one of the most complex motor behaviors. Locomotor patterns change during early life, reflecting development of numerous peripheral and hierarchically organized central structures. Among them, the spinal cord is of particular interest since it houses the central pattern generator (CPG) for locomotion. This main command center is capable of eliciting and coordinating complex series of rhythmic neural signals sent to motoneurons and to corresponding target-muscles for basic locomotor activity. For a long-time, the CPG has been considered a black box. In recent years, complementary insights from in vitro and in vivo animal models have contributed significantly to a better understanding of its constituents, properties and ways to recover locomotion after a spinal cord injury (SCI). This review discusses key findings made by comparing the results of in vitro isolated spinal cord preparations and spinal-transected in vivo models from neonatal animals. Pharmacological, electrical, and sensory stimulation approaches largely used to further understand CPG function may also soon become therapeutic tools for potent CPG reactivation and locomotor movement induction in persons with SCI or developmental neuromuscular disorder. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Human Central Pattern Generator for Locomotion.

PubMed

Minassian, Karen; Hofstoetter, Ursula S; Dzeladini, Florin; Guertin, Pierre A; Ijspeert, Auke

2017-03-01

The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

The Spinal Cord Injury- Functional Index: Item Banks to Measure Physical Functioning of Individuals with Spinal Cord Injury

PubMed Central

Tulsky, David S.; Jette, Alan; Kisala, Pamela A.; Kalpakjian, Claire; Dijkers, Marcel P.; Whiteneck, Gale; Ni, Pengsheng; Kirshblum, Steven; Charlifue, Susan; Heinemann, Allen W.; Forchheimer, Martin; Slavin, Mary; Houlihan, Bethlyn; Tate, Denise; Dyson-Hudson, Trevor; Fyffe, Denise; Williams, Steve; Zanca, Jeanne

2012-01-01

Objective To develop a comprehensive set of patient reported items to assess multiple aspects of physical functioning relevant to the lives of people with spinal cord injury (SCI) and to evaluate the underlying structure of physical functioning. Design Cross-sectional Setting Inpatient and community Participants Item pools of physical functioning were developed, refined and field tested in a large sample of 855 individuals with traumatic spinal cord injury stratified by diagnosis, severity, and time since injury Interventions None Main Outcome Measure SCI-FI measurement system Results Confirmatory factor analysis (CFA) indicated that a 5-factor model, including basic mobility, ambulation, wheelchair mobility, self care, and fine motor, had the best model fit and was most closely aligned conceptually with feedback received from individuals with SCI and SCI clinicians. When just the items making up basic mobility were tested in CFA, the fit statistics indicate strong support for a unidimensional model. Similar results were demonstrated for each of the other four factors indicating unidimensional models. Conclusions Though unidimensional or 2-factor (mobility and upper extremity) models of physical functioning make up outcomes measures in the general population, the underlying structure of physical function in SCI is more complex. A 5-factor solution allows for comprehensive assessment of key domain areas of physical functioning. These results informed the structure and development of the SCI-FI measurement system of physical functioning. PMID:22609299

PERSPECTIVE: Consideration of user priorities when developing neural prosthetics

NASA Astrophysics Data System (ADS)

Anderson, Kim D.

2009-10-01

For too long there has been separation of basic science, biomedical engineering, clinical science and the people these disciplines are serving. A key ingredient to understanding the real-life consequences of many neurologic disorders that produce physical disabilities, such as spinal cord injury, is to obtain valuable information from the individuals that are actually living with the disorders everyday. This information can be obtained in an objective and usable format, which can then be used to direct biomedical research in a manner that is meaningful to the intended beneficiaries. In particular, the field of neural prosthetics for spinal cord injury can make great strides if user input is obtained throughout the stages of development. Presented here is the perspective of a scientist who also has 20 years of experience living with a cervical spinal cord injury.

[Integral treatment for bedridden patients].

PubMed

García-Verdugo, M Fernanda Arroyo; Garrido Hernández, M Teresa; Rosell Palomo, Ricardo

2007-05-01

Spinal cord injuries are one of the traumatic injuries which produce the greatest number of patients who are bedridden or incapacitated. Physical effects acquire such importance that one can not forget to attend to aspects as basic as hygiene, correct posture during their bedridden stay or the daily task to transfer patients to the various support elements they need to utilize. Nursing care for patients suffering spinal cord injuries comprise the fundamental axis on which a correct recuperation rotates. At the same time, proper treatment care will lead to a future improvement in a patient's quality of life.

The management of spinal cord injury patients in Greece.

PubMed

Petropoulou, C B; Rapidi, C A; Beltsios, M; Karantonis, G; Lampiris, P E

1992-02-01

In Greece, spinal cord injury patients have serious problems concerning their treatment, social management and vocational integration. Unfortunately the treatment of such patients is usually limited to that offered in institutions for the chronically sick, after they have received their acute initial care in general hospitals. The large number of institutional beds (1287 in 1986) in relation to the small number of active rehabilitation beds (116 beds in 1989) is noteworthy. Generally speaking, the specialisation of health personnel is limited. In practice there is no programme of social rehabilitation, except for special concessions. Disabled individuals can refer to the Professional Integration Service for their vocational reintegration. We must note that vocational counsellors do not take part in the rehabilitation team. The idea of intervention for the adaptation of architectural barriers is now beginning to be considered in theory. Physicians are making efforts to establish 'basic' spinal cord units.

[Functional rehabilitation of spinal cord injured persons using neuroprostheses].

PubMed

Rupp, R; Abel, R

2005-02-01

Recent technological advancements in microelectronics have led to the establishment of systems for restoration of basic functions in spinal cord injured (SCI) persons using functional electrical stimulation (FES). FES systems for the restoration of bladder and diaphragm function are well established in clinical practice. While FES systems in the lower extremities for standing/walking have not yet achieved widespread clinical acceptance, devices which enhance or restore the grasp function in tetraplegic patients with missing control of hand and fingers are demonstrably successful. Especially with the use of implantable systems a reliable, easy to handle application is possible. The most recent developments in micromechanical engineering are aimed at providing minimally invasive, subminiature systems for functional support in incomplete SCI persons. The possibility of direct brain control of FES systems will expand the application of neuroprostheses for patients with injury of the high cervical spinal cord.

Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair

PubMed Central

Grulova, I.; Slovinska, L.; Blaško, J.; Devaux, S.; Wisztorski, M.; Salzet, M.; Fournier, I.; Kryukov, O.; Cohen, S.; Cizkova, D.

2015-01-01

Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate -based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG +GFs), compared to SCI animals without biomaterial treatment. PMID:26348665

Tethered Spinal Cord Syndrome

MedlinePlus

... the spinal cord. These attachments cause an abnormal stretching of the spinal cord. The course of the ... the spinal cord. These attachments cause an abnormal stretching of the spinal cord. The course of the ...

International urinary tract imaging basic spinal cord injury data set.

PubMed

Biering-Sørensen, F; Craggs, M; Kennelly, M; Schick, E; Wyndaele, J-J

2009-05-01

To create an International Urinary Tract Imaging Basic Spinal Cord Injury (SCI) Data Set within the framework of the International SCI Data Sets. An international working group. The draft of the Data Set was developed by a working group comprising members appointed by the Neurourology Committee of the International Continence Society, the European Association of Urology, the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the Executive Committee of the International SCI Standards and Data Sets. The final version of the Data Set was developed after review and comments by members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA Board, relevant and interested international organizations and societies (around 40), individual persons with specific expertise and the ISCoS Council. Endorsement of the Data Sets by relevant organizations and societies will be obtained. To make the Data Set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. The variables included in the International Urinary Tract Imaging Basic SCI Data Set are the results obtained using the following investigations: intravenous pyelography or computer tomography urogram or ultrasound, X-ray, renography, clearance, cystogram, voiding cystogram or micturition cystourogram or videourodynamics. The complete instructions for data collection and the data sheet itself are freely available on the websites of both ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: Elicitation of posterior root-muscle reflexes

PubMed Central

Freundl, Brigitta; Binder, Heinrich; Minassian, Karen

2018-01-01

Epidural electrical stimulation of the lumbar spinal cord is currently regaining momentum as a neuromodulation intervention in spinal cord injury (SCI) to modify dysregulated sensorimotor functions and augment residual motor capacity. There is ample evidence that it engages spinal circuits through the electrical stimulation of large-to-medium diameter afferent fibers within lumbar and upper sacral posterior roots. Recent pilot studies suggested that the surface electrode-based method of transcutaneous spinal cord stimulation (SCS) may produce similar neuromodulatory effects as caused by epidural SCS. Neurophysiological and computer modeling studies proposed that this noninvasive technique stimulates posterior-root fibers as well, likely activating similar input structures to the spinal cord as epidural stimulation. Here, we add a yet missing piece of evidence substantiating this assumption. We conducted in-depth analyses and direct comparisons of the electromyographic (EMG) characteristics of short-latency responses in multiple leg muscles to both stimulation techniques derived from ten individuals with SCI each. Post-activation depression of responses evoked by paired pulses applied either epidurally or transcutaneously confirmed the reflex nature of the responses. The muscle responses to both techniques had the same latencies, EMG peak-to-peak amplitudes, and waveforms, except for smaller responses with shorter onset latencies in the triceps surae muscle group and shorter offsets of the responses in the biceps femoris muscle during epidural stimulation. Responses obtained in three subjects tested with both methods at different time points had near-identical waveforms per muscle group as well as same onset latencies. The present results strongly corroborate the activation of common neural input structures to the lumbar spinal cord—predominantly primary afferent fibers within multiple posterior roots—by both techniques and add to unraveling the basic mechanisms underlying electrical SCS. PMID:29381748

T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock proteins.

PubMed Central

Mor, F; Cohen, I R

1992-01-01

To characterize the cellular immune response in an autoimmune lesion, we investigated the accumulation of specific T cells in the central nervous system in actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats, using a limiting dilution analysis (LDA) assay for T cells that proliferate in response to antigens. Lymphocytes isolated from the spinal cord infiltrate were compared with cells from the popliteal lymph nodes with respect to frequency of cells responding to basic protein (BP), mycobacterium tuberculosis (MT), the 65-kD heat shock protein (hsp65), allogeneic brown norway spleen cells, and concanavalin A. Additionally, we compared the BP frequency in acute EAE of cells from the spinal cord, peripheral blood, spleen and lymph nodes, and the spinal cord and lymph node after recovery from EAE. We found that acute EAE was associated with marked enrichment of BP-reactive T cells in the spinal cord relative to their frequency in the lymphoid organs and peripheral blood. The infiltrate was also enriched for T cells responding to hsp65; alloreactive T cells, in contrast, were not enriched. The frequency of BP reactive T cells in the spinal cord was highest at the peak of paralysis; however, BP-reactive T cells could still be detected at moderate frequencies after clinical recovery. We established BP- and Mycobacteria-reactive T cell lines from the spinal infiltrates that were CD4+ and TcR alpha beta +. Most of the BP lines were found to react to the major encephalitogenic epitope of guinea pig BP for rats (amino acids 71-90); these lines were found to mediate EAE in naive recipients. T cell lines recognizing other epitopes of BP were not encephalitogenic. All of the lines responsive to Mycobacteria recognized hsp65 or hsp70. These results indicating that the immune infiltrate in active EAE is enriched with cells responding to the autoantigen and to hsp65 were confirmed in EAE adoptively transferred by anti-BP T cell clone. Images PMID:1281835

Nerve growth factor pretreatment inhibits lidocaine-induced myelin damage via increasing BDNF expression and inhibiting p38 mitogen activation in the rat spinal cord

PubMed Central

Zhao, Guangyi; Li, Dan; Ding, Xudong; Li, Lu

2017-01-01

The present study aimed to investigate the effect of exogenous nerve growth factor (NGF) pretreatment on demyelination in the spinal cord of lidocaine-treated rats, and explored the potential neuroprotective mechanisms of NGF. A total of 36 rats were randomly assigned to three groups (n=12 per group): Sham group; Lido group, received intrathecal injection of lidocaine; NGF group, received intrathecal injection of NGF followed by intrathecal injection of lidocaine. Tail-flick tests were used to evaluate neurobehavioral function. Ultrastructural alternations were analyzed by transmission electron microscopy. Immunofluorescence was used to examine the expression of myelin basic protein (MBP) and brain-derived neurotrophic factor (BDNF). ELISA was used to determine serum levels of MBP and proteolipid protein (PLP). Western blotting was used to detect the expression of phosphorylated mitogen activated protein kinase (MAPK). NGF pretreatment reduced lidocaine-induced neurobehavioral damage, nerve fiber demyelination, accompanied by a decrease in MBP expression in the spinal cord and an increase in MBP and PLP in serum. In addition, NGF pretreatment increased BDNF expression in the spinal cord of lidocaine-treated rats. Furthermore, NGF pretreatment reduced p38 MAPK phosphorylation in the spinal cord of lidocaine-treated rats. NGF treatment reduces lidocaine-induced neurotoxicity via the upregulation of BDNF and inhibition of p38 MAPK. NGF therapy may improve the clinical use of lidocaine in intravertebral anesthesia. PMID:28849178

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

PubMed Central

2014-01-01

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 spinal cord-injured (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 SCI patients. PMID:24910602

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection.

PubMed

Zhang, Qiang; Shao, Yang; Zhao, Changsong; Cai, Juan; Sun, Sheng

2014-12-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection.

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection

PubMed Central

ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

2014-01-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

Complete segmental resection of the spine, including the spinal cord, for telangiectatic osteosarcoma: a report of 2 cases.

PubMed

Murakami, Hideki; Tomita, Katsuro; Kawahara, Norio; Oda, Makoto; Yahata, Tetsutaro; Yamaguchi, Takehiko

2006-02-15

Two case reports of telangiectatic osteosarcoma treated with complete segmental resection of the spine, including the spinal cord. To report the en bloc tumor excision, including the spinal cord, for telangiectatic osteosarcoma, and discuss the indication of cord transection and influence after cutting the spinal cord. To our knowledge, there are no previous reports describing telangiectatic osteosarcoma of the spine and the subsequent en bloc excision of the spine, including the spinal cord. The clinical and radiographic presentations of 2 cases with telangiectatic osteosarcoma are presented. Because these 2 cases already had complete paralysis for at least 1 month, it was suspected that there was no possibility of recovering spinal cord function. Complete segmental spinal resection (total en bloc spondylectomy) was performed. At that level, the spinal cord was also cut and resected. En bloc excision of the tumor with a wide margin was achieved in both cases. In the resected specimen, the nerve cells in the spinal cord had lapsed into degenerative necrosis. The pathologic findings showed that there was no hope for recovery of spinal cord function. En bloc spinal resection, including the spinal cord, is an operation allowed when there is no hope for recovery of spinal cord function. This surgery should be accepted as an option in spine tumor surgeries.

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to relieve... on the patient's spinal cord and an external transmitter for transmitting the stimulating pulses...

From basics to clinical: a comprehensive review on spinal cord injury.

PubMed

Silva, Nuno A; Sousa, Nuno; Reis, Rui L; Salgado, António J

2014-03-01

Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of individuals each year. Over the past decades an enormous progress has been made in our understanding of the molecular and cellular events generated by SCI, providing insights into crucial mechanisms that contribute to tissue damage and regenerative failure of injured neurons. Current treatment options for SCI include the use of high dose methylprednisolone, surgical interventions to stabilize and decompress the spinal cord, and rehabilitative care. Nonetheless, SCI is still a harmful condition for which there is yet no cure. Cellular, molecular, rehabilitative training and combinatorial therapies have shown promising results in animal models. Nevertheless, work remains to be done to ascertain whether any of these therapies can safely improve patient's condition after human SCI. This review provides an extensive overview of SCI research, as well as its clinical component. It starts covering areas from physiology and anatomy of the spinal cord, neuropathology of the SCI, current clinical options, neuronal plasticity after SCI, animal models and techniques to assess recovery, focusing the subsequent discussion on a variety of promising neuroprotective, cell-based and combinatorial therapeutic approaches that have recently moved, or are close, to clinical testing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-12-1-0587 TITLE: Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord...3. DATES COVERED (From - To) 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on...ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite this fact

International spinal cord injury skin and thermoregulation function basic data set.

PubMed

Karlsson, A K; Krassioukov, A; Alexander, M S; Donovan, W; Biering-Sørensen, F

2012-07-01

To create an international spinal cord injury (SCI) skin and thermoregulation basic data set within the framework of the International SCI Data Sets. An international working group. The draft of the data set was developed by a working group comprising members appointed by the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the Executive Committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review and comments by members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA Board, relevant and interested international organizations and societies, individual persons with specific interest and the ISCoS Council. To make the data set uniform, each variable and each response category within each variable have been specifically defined to promote the collection and reporting of comparable minimal data. Variables included in the present data set are: date of data collection, thermoregulation history after SCI, including hyperthermia or hypothermia (noninfectious or infectious), as well as the history of hyperhidrosis or hypohidrosis above or below level of lesion. Body temperature and the time of measurement are included. Details regarding the presence of any pressure ulcer and stage, location and size of the ulcer(s), date of appearance of the ulcer(s) and whether surgical treatment has been performed are included. The history of any pressure ulcer during the last 12 months is also noted.

Testosterone Plus Finasteride Treatment After Spinal Cord Injury

ClinicalTrials.gov

2018-05-16

Spinal Cord Injury; Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male

Taking Care of Your Bowels--The Basics

MedlinePlus

Home » Information & Education » Pamphlets About Us Patient Care Resources Information & Education SCI Empowerment Project Projects & Research FAQ © 2018 University of Washington SCI Pamphlets: Staying Healthy after a Spinal Cord Injury The pamphlet ...

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

PubMed Central

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

2011-01-01

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

Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

PubMed Central

Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

2015-01-01

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations. PMID:26125597

Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

PubMed

Vahdat, Shahabeddin; Lungu, Ovidiu; Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

2015-06-01

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.

Axonal loss in the multiple sclerosis spinal cord revisited.

PubMed

Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

2018-05-01

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area, reduced by about 20%, appears to be a poor predictor of axonal density. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Optical monitoring of spinal cord hemodynamics, a feasibility study

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Kwon, Brian K.; Streijger, Femke; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Cripton, Peter A.; Macnab, Andrew

2017-02-01

Background: After an acute traumatic spinal cord injury (SCI), the spinal cord is subjected to ischemia, hypoxia, and increased hydrostatic pressure which exacerbate further secondary damage and neuronal deficit. The purpose of this pilot study was to explore the use of near infrared spectroscopy (NIRS) for non-invasive and real-time monitoring of these changes within the injured spinal cord in an animal model. NIRS is a non-invasive optical technique that utilizes light in the near infrared spectrum to monitor changes in the concentration of tissue chromophores from which alterations in tissues oxygenation and perfusion can be inferred in real time. Methods: A custom-made miniaturized NIRS sensor was developed to monitor spinal cord hemodynamics and oxygenation noninvasively and in real time simultaneously with invasive, intraparenchymal monitoring in a pig model of SCI. The spinal cord around the T10 injury site was instrumented with intraparenchymal probes inserted directly into the spinal cord to measure oxygen pressure, blood flow, and hydrostatic pressure, and the same region of the spinal cord was monitored with the custom-designed extradural NIRS probe. We investigated how well the extradural NIRS probe detected intraparenchymal changes adjacent to the injury site after alterations in systemic blood pressure, global hypoxia, and traumatic injury generated by a weight-drop contusion. Results: The NIRS sensor successfully identified periods of systemic hypoxia, re-ventilation and changes in spinal cord perfusion and oxygenation during alterations of mean arterial pressure and following spinal cord injury. Conclusion: This pilot study indicates that extradural NIRS monitoring of the spinal cord is feasible as a non-invasive optical method to identify changes in spinal cord hemodynamics and oxygenation in real time. Further development of this technique would allow clinicians to monitor real-time physiologic changes within the injured spinal cord during the acute post-injury period.

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed Central

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

2015-01-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID:26807119

Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

PubMed

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

2015-11-01

The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

Spinal Cord Infarction in Clinical Neurology: A Review of Characteristics and Long-Term Prognosis in Comparison to Cerebral Infarction.

PubMed

Romi, Fredrik; Naess, Halvor

2016-01-01

Spinal cord stroke is rare accounting for 0.3-1% of all strokes and is classified into upper (cervical) and lower (thoracolumbar) strokes. Patients present with severe deficits but later often show good functional improvement. On admission, younger age, male gender, hypertension, diabetes mellitus and elevated blood glucose indicate more severe spinal cord strokes. Treatment of these risk factors is essential in the acute phase. Biphasic spinal cord strokes are seen in one-fifth of the patients. These present with acute or transient sensory spinal cord deficits often preceded by radiating pain between the shoulders, and should be considered and treated as imminent spinal cord strokes. Spinal cord infarction patients are younger and more often women compared to cerebral infarction patients. Traditional cerebrovascular risk factors are less relevant in spinal cord infarction. Spinal cord infarction patients are more likely to be discharged home and show better improvement after initial treatment compared to cerebral infarction patients. On long-term follow-up, spinal cord infarction patients have lower mortality and higher emotional well-being scores than cerebral infarction patients. Despite more chronic pain, the frequency of re-employment is higher among spinal cord infarction patients compared to cerebral infarction patients who are more often afflicted with cognitive function deficits. © 2016 S. Karger AG, Basel.

Recovery of locomotion in the cat following spinal cord lesions.

PubMed

Rossignol, S; Bouyer, L; Barthélemy, D; Langlet, C; Leblond, H

2002-10-01

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation.

PubMed

Bartlett, Richard D; Choi, David; Phillips, James B

2016-10-01

Spinal cord injury is a severely debilitating condition which can leave individuals paralyzed and suffering from autonomic dysfunction. Regenerative medicine may offer a promising solution to this problem. Previous research has focused primarily on exploring the cellular and biological aspects of the spinal cord, yet relatively little remains known about the biomechanical properties of spinal cord tissue. Given that a number of regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding the biomechanical properties of host spinal cord tissue is important. We review the relevant biomechanical properties of spinal cord tissue and provide the baseline knowledge required to apply these important physical concepts to spinal cord tissue engineering.

Spinal cord injury: promising interventions and realistic goals.

PubMed

McDonald, John W; Becker, Daniel

2003-10-01

Long regarded as impossible, spinal cord repair is approaching the realm of reality as efforts to bridge the gap between bench and bedside point to novel approaches to treatment. It is important to recognize that the research playing field is rapidly changing and that new mechanisms of resource development are required to effectively make the transition from basic science discoveries to effective clinical treatments. This article reviews recent laboratory studies and phase 1 clinical trials in neural and nonneural cell transplantation, stressing that the transition from basic science to clinical applications requires a parallel rather than serial approach, with continuous, two-way feedback to most efficiently translate basic science findings, through evaluation and optimization, to clinical treatments. An example of mobilizing endogenous stem cells for repair is reviewed, with emphasis on the rapid application of basic science to clinical therapy. Successful and efficient transition from basic science to clinical applications requires (1) a parallel rather than a serial approach; (2) development of centers that integrate three spheres of science, translational, transitional, and clinical trials; and (3) development of novel resources to fund the most critically limited step of transitional to clinical trials.

Central nervous system (image)

MedlinePlus

... receive nerve impulses from the spinal cord and cranial nerves. The spinal cord contains the nerves that carry messages between the brain and the body. Spinal cord injury can occur when there is damage to the cells within the spinal cord or ...

[The metabolic profilings study of serum and spinal cord from acute spinal cord injury rats ¹H NMR spectroscopy].

PubMed

Hu, Hua-Hui; Huang, Xiao-Long; Quan, Ren-Fu; Yang, Zong-Bao; Xu, Jing-Jing

2017-02-25

To establish the rat model of acute spinal cord injury, followed by aprimary study on this model with ¹H NMR based on metabonomics and to explore the metabonomics and biomarkers of spinal cord injury rat. Twenty eight-week-old adult male SD rats of clean grade, with body weight of (200±10) g, were divided into sham operation group and model group in accordance with the law of random numbers, and every group had 10 rats. The rats of sham operation group were operated without damaging the spinal cord, and rats of model group were made an animal model of spinal cord incomplete injury according to the modified Allen's method. According to BBB score to observate the motor function of rats on the 1th, 5th, and 7th days after surgery. Postoperative spinal cord tissue was collected in order to pathologic observation at the 7th day, and the metabolic profilings of serum and spinal cord from spinal cord injury rats were studied by ¹H NMR spectroscopy. The hindlimb motion of rats did not obviously change in sham operation group, there was no significant difference at each time point;and rats of model group occurred flaccid paralysis of both lower extremities, there was a significant difference at each time; there was significant differences between two groups at each time. Pathological results showed the spinal cord structure was normal with uniform innervation in shame group, while in model group, the spinal cord structure was mussy, and the neurons were decreased, with inflammatory cells and necrotic tissue. Analysis of metabonomics showed that concentration of very low density fat protein (VLDL), low density fat protein (LDL), glutamine, citric acid, dimethylglycine (DMG) in the serum and glutathione, 3-OH-butyrate, N-Acetyl-L-aspartic acid (NAA), glycerophosphocholine (GPC), glutamic acid, and ascorbate in spinal cord had significant changes( P <0.05). There are significant differences in metabolic profile from serum and spinal cord sample between model group and sham operation group, it conduces to explain the changes of small molecular substances in serum and spinal cord tissue after spinal cord injury, this provides the research basis for targeted research on the role of metabolic markers in patients with acute spinal cord injury.

Image analysis of open-door laminoplasty for cervical spondylotic myelopathy: comparing the influence of cord morphology and spine alignment.

PubMed

Lin, Bon-Jour; Lin, Meng-Chi; Lin, Chin; Lee, Meei-Shyuan; Feng, Shao-Wei; Ju, Da-Tong; Ma, Hsin-I; Liu, Ming-Ying; Hueng, Dueng-Yuan

2015-10-01

Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome - patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology - the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty. Copyright © 2015 Elsevier B.V. All rights reserved.

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

Management of chronic spinal cord dysfunction.

PubMed

Abrams, Gary M; Ganguly, Karunesh

2015-02-01

Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life.

[Research progress in the role of aquaproin-4 and inward rectifying potassium channel 4.1 in spinal cord edema].

PubMed

Chen, Tiege; Dang, Yuexiu; Wang, Ming; Zhang, Dongliang; Guo, Yongqiang; Zhang, Haihong

2018-05-28

Spinal edema is a very important pathophysiological basis for secondary spinal cord injury, which affects the repair and prognosis of spinal cord injury. Aquaporin-4 is widely distributed in various organs of the body, and is highly expressed in the brain and spinal cord. Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system. It interacts with aquaporins in function. Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema, inhibition of glial scar formation and promotion of excitotoxic agents exclusion. The distribution and function of aquaporin-4 and inward rectifying potassium channel 4.1 in the central nervous system and their expression after spinal cord injury have multiple effects on spinal edema. Studies of aquaporin-4 and inward rectifying potassium channel 4.1 in the spinal cord may provide new ideas for the elimination and treatment of spinal edema.

Measurement properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms.

PubMed

Heinemann, Allen W; Dijkers, Marcel P; Ni, Pengsheng; Tulsky, David S; Jette, Alan

2014-07-01

To evaluate the psychometric properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms (basic mobility, self-care, fine motor, ambulation, manual wheelchair, and power wheelchair) based on internal consistency; correlations between short forms banks, full item bank forms, and a 10-item computer adaptive test version; magnitude of ceiling and floor effects; and test information functions. Cross-sectional cohort study. Six rehabilitation hospitals in the United States. Individuals with traumatic spinal cord injury (N=855) recruited from 6 national Spinal Cord Injury Model Systems facilities. Not applicable. SCI-FI full item bank, 10-item computer adaptive test, and parallel short form scores. The SCI-FI short forms (with separate versions for individuals with paraplegia and tetraplegia) demonstrate very good internal consistency, group-level reliability, excellent correlations between short forms and scores based on the total item bank, and minimal ceiling and floor effects (except ceiling effects for persons with paraplegia on self-care, fine motor, and power wheelchair ability and floor effects for persons with tetraplegia on self-care, fine motor, and manual wheelchair ability). The test information functions are acceptable across the range of scores where most persons in the sample performed. Clinicians and researchers should consider the SCI-FI short forms when computer adaptive testing is not feasible. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2016-01-01

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

Brain protection by methylprednisolone in rats with spinal cord injury.

PubMed

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

2009-07-01

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

Clinical and imaging features of spinal cord type of neuro Behçet disease: A case report and systematic review.

PubMed

Liu, Hui-Miao; Dong, Ci; Zhang, Yong-Zhi; Tian, Ya-Yun; Chen, Hong-Xu; Zhang, Sai; Li, Na; Gu, Ping

2017-10-01

To investigate the clinical and MRI characteristics of spinal cord nerve Behçet's disease. One patient with spinal cord nerve Behçet's disease was admitted to our hospital at October 20, 2015. Spinal cord nerve Behçet's disease. Retrospective analysis was performed on such case as well as 16 cases of spinal cord nerve Behçet's disease reported in China or abroad. Seventeen cases of spinal cord type of neuro Behçet's disease include 13 men and 4 women, with an average age of onset of 34.8 years old. The mean time from Behçet's disease symptoms to spinal cord involvement were 10.8 years. The initial symptom in one case was spinal cord injury, and another 4 cases had a recurrence course. The most common performance of spinal cord injury was sensory disturbance (82.4%), following by weakness (76.5%), sphincter or sexual dysfunction (58.8%), and pain in back, backside of neck or lower chest (29.4%). The number of cells was slightly increased or the protein level was increased in cerebrospinal fluid test. And the water channel protein antibody and oligoclonal band of serum levels were all negative. The spinal cord injury involved more than 3 vertebral bodies in 10 cases, and involved more than half of spinal cord in sagittal plane in 8 cases. In acute stage, shock therapy with large dose of glucocorticoid was generally applied both in China and abroad. The clinical features of spinal cord nerve Behçet's disease were various, making it easily misdiagnosed. Longitudinal extensive transverse myelitis performs as a characteristic manifestation.

[APPLICATION OF THREE DIMENSIONAL PRINTING ON MANUFACTURING BIONIC SCAFFOLDS OF SPINAL CORD IN RATS].

PubMed

Chen, Yisheng; Wang, Jingjing; Chen, Xuyi; Chen, Chong; Tu, Yue; Zhang, Sai; Li, Xiaohong

2015-03-01

To fabricate the bionic scaffolds of rat spinal cord by combining three dimensional (3D) printer and 3D software, so as to lay the foundation of theory and technology for the manufacture of scaffolds by using biomaterials. Three female Sprague Dawley rats were scanned by 7.0T MRI to obtain the shape and position data of the cross section and gray matter of T8 to T10 spinal cord. Combined with data of position and shape of nerve conduction beam, the relevant data were obtained via Getdata software. Then the 3D graphics were made and converted to stereolithography (STL) format by using SolidWorks software. Photosensitive resin was used as the materials of spinal cord scaffolds. The bionic scaffolds were fabricated by 3D printer. MRI showed that the section shape of T8 to T10 segments of the spinal cord were approximately oval with a relatively long sagittal diameter of (2.20 ± 0.52) mm and short transverse diameter of (2.05 ± 0.24) mm, and the data of nerve conduction bundle were featured in the STL format. The spinal cord bionic scaffolds of the target segments made by 3D printer were similar to the spinal cord of rat in the morphology and size, and the position of pores simulated normal nerve conduction of rat spinal cord. Spinal cord scaffolds produced by 3D printer which have similar shape and size of normal rat spinal cord are more bionic, and the procedure is simple. This technology combined with biomaterials is also promising in spinal cord repairing after spinal cord injury.

Gene therapy approaches for spinal cord injury

NASA Astrophysics Data System (ADS)

Bright, Corinne

As the biomedical engineering field expands, combination technologies are demonstrating enormous potential for treating human disease. In particular, intersections between the rapidly developing fields of gene therapy and tissue engineering hold promise to achieve tissue regeneration. Nonviral gene therapy uses plasmid DNA to deliver therapeutic proteins in vivo for extended periods of time. Tissue engineering employs biomedical materials, such as polymers, to support the regrowth of injured tissue. In this thesis, a combination strategy to deliver genes and drugs in a polymeric scaffold was applied to a spinal cord injury model. In order to develop a platform technology to treat spinal cord injury, several nonviral gene delivery systems and polymeric scaffolds were evaluated in vitro and in vivo. Nonviral vector trafficking was evaluated in primary neuronal culture to develop an understanding of the barriers to gene transfer in neurons and their supporting glia. Although the most efficient gene carrier in vitro differed from the optimal gene carrier in vivo, confocal and electron microscopy of these nonviral vectors provided insights into the interaction of these vectors with the nucleus. A novel pathway for delivering nanoparticles into the nuclei of neurons and Schwann cells via vesicle trafficking was observed in this study. Reporter gene expression levels were evaluated after direct and remote delivery to the spinal cord, and the optimal nonviral vector, dose, and delivery strategy were applied to deliver the gene encoding the basic fibroblast growth factor (bFGF) to the spinal cord. An injectable and biocompatible gel, composed of the amphiphillic polymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) was evaluated as a drug and gene delivery system in vitro, and combined with the optimized nonviral gene delivery system to treat spinal cord injury. Plasmid DNA encoding the bFGF gene and the therapeutic NEP1--40 peptide were incorporated in the PEG-PCL-PEG gel and injected into a lesion transecting the main dorsomedial and minor ventral medial corticospinal tract (CST). The degree of collateralization of the transected CST was quantified as an indicator of the regenerative potential of these treatments. At one month post-injury, we observed the robust rostral collateralization of the CST tract in response to the bFGF plasmid-loaded gel. In conclusion, we hope that this platform technology can be applied to the sustained local delivery of other proteins for the treatment of spinal cord injury.

Spinal cord injury arising in anaesthesia practice.

PubMed

Hewson, D W; Bedforth, N M; Hardman, J G

2018-01-01

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury - vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis - will be discussed in turn. For each condition, we draw attention to practical, evidence-based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

In-vivo spinal cord deformation in flexion

NASA Astrophysics Data System (ADS)

Yuan, Qing; Dougherty, Lawrence; Margulies, Susan S.

1997-05-01

Traumatic mechanical loading of the head-neck complex results cervical spinal cord injury when the distortion of the cord is sufficient to produce functional or structural failure of the cord's neural and/or vascular components. Characterizing cervical spinal cord deformation during physiological loading conditions is an important step to defining a comprehensive injury threshold associated with acute spinal cord injury. In this study, in vivo quasi- static deformation of the cervical spinal cord during flexion of the neck in human volunteers was measured using magnetic resonance (MR) imaging of motion with spatial modulation of magnetization (SPAMM). A custom-designed device was built to guide the motion of the neck and enhance more reproducibility. the SPAMM pulse sequence labeled the tissue with a series of parallel tagging lines. A single- shot gradient-recalled-echo sequence was used to acquire the mid-sagittal image of the cervical spine. A comparison of the tagged line pattern in each MR reference and deformed image pair revealed the distortion of the spinal cord. The results showed the cervical spinal cord elongates during head flexion. The elongation experienced by the spinal cord varies linearly with head flexion, with the posterior surface of the cord stretching more than the anterior surface. The maximal elongation of the cord is about 12 percent of its original length.

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

PubMed

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

2017-01-01

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

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report.

PubMed

Hylands-White, Nicholas; Duarte, Rui V; Beeson, Paul; Mayhew, Stephen D; Raphael, Jon H

2016-12-01

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2-P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.

Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation after Acute Spinal Cord Injury

DTIC Science & Technology

2017-09-01

oxygen delivery and oxygen consumption . The oxygen portion of the Oxylite probe emits short pulses of blue LED light resulting in a fluorescent...Award Number: W81XWH-16-1-0602 TITLE: Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation after Acute Spinal Cord Injury...COVERED 1 Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation

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

PubMed

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.

Meningocele repair - series (image)

MedlinePlus

... containing a portion of the spinal cord membrane (meninges), spinal fluid, and a portion of spinal cord ... The spinal cord is covered with the membranes (meninges) and the skin is closed over the protruding ...

Part 1: recognizing neonatal spinal cord injury.

PubMed

Brand, M Colleen

2006-02-01

Neonatal spinal cord injury can occur in utero, as well as after either a difficult delivery or a nontraumatic delivery. Spinal cord injury can also be related to invasive nursery procedures or underlying neonatal pathology. Early clinical signs of spinal cord injury that has occurred in utero or at delivery includes severe respiratory compromise and profound hypotonia. Knowledge of risk factors and awareness of symptoms is required for early recognition and appropriate treatment. This article reviews the embryological development of the spinal column highlighting mechanisms of injury and identifying underlying factors that increase the risk of spinal cord injury in newborns. Signs and symptoms of injury, cervical spine immobilization, and the differential diagnosis are discussed. Nursing implications, general prognosis, and research in spinal cord injury are provided.

Retraining the injured spinal cord

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Leon, R. D.; Harkema, S. J.; Hodgson, J. A.; London, N.; Reinkensmeyer, D. J.; Roy, R. R.; Talmadge, R. J.; Tillakaratne, N. J.; Timoszyk, W.;

A spinal thecal sac constriction model supports the theory that induced pressure gradients in the cord cause edema and cyst formation.

PubMed

Josephson, A; Greitz, D; Klason, T; Olson, L; Spenger, C

2001-03-01

Spinal cord cysts are a devastating condition that occur secondary to obstructions of the spinal canal, which may be caused by congenital malformations, trauma, spinal canal stenosis, tumors, meningitis, or arachnoiditis. A hypothesis that could explain how spinal cord cysts form in these situations has been presented recently. Therefore, a novel spinal thecal sac constriction model was implemented to test various aspects of this hypothesis. Thecal sac constriction was achieved by subjecting rats to an extradural silk ligature at the T8 spinal cord level. Rats with complete spinal cord transection served as a second model for comparison. The animals underwent high-resolution magnetic resonance imaging and histological analysis. Thecal sac constriction caused edema cranial and caudal to the ligation within 3 weeks, and cysts developed after 8 to 13 weeks. In contrast, cysts in rats with spinal cord transection were located predominantly in the cranial spinal cord. Histological sections of spinal cords confirmed the magnetic resonance imaging results. Magnetic resonance imaging provided the specific advantage of enabling characterization of events as they occurred repeatedly over time in the spinal cords of individual living animals. The spinal thecal sac constriction model proved useful for investigation of features of the cerebrospinal fluid pulse pressure theory. Edema and cyst distributions were in accordance with this theory. We conclude that induced intramedullary pressure gradients originating from the cerebrospinal fluid pulse pressure may underlie cyst formation in the vicinity of spinal canal obstructions and that cysts are preceded by edema.

Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science.

PubMed

Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan

2012-08-15

To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science. Data retrieval was performed using key words "spinal cord injury", "spinal injury", "neurogenic bladder", "neuropathic bladder", "neurogenic lower urinary tract dysfunction", "neurogenic voiding dysfunction", "neurogenic urination disorder" and "neurogenic vesicourethral dysfunction". (a) published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: no limitation. (a) articles that required manual searching or telephone access; (b) Corrected papers and book chapters. (1) Annual publication output; (2) distribution according to journals; (3) distribution according to subject areas; (4) distribution according to country; (5) distribution according to institution; and (6) top cited publications. There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science. Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946. The United States, Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s. However, in the 1990s, the United States, the United Kingdom, the Netherlands, Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland, and Ireland fell off the top ten countries list. In this century, the United States ranks first in spinal cord injury-induced neurogenic bladder studies, followed by France, the United Kingdom, Germany, Switzerland and Japan. Subject categories including urology, nephrology and clinical neurology, as well as rehabilitation, are represented in spinal cord injury-induced neurogenic bladder studies. From our analysis of the literature and research trends, we conclude that spinal cord injury-induced neurogenic bladder is a hot topic that will continue to generate considerable research interest in the future.

Combined Effects of Acrobatic Exercise and Magnetic Stimulation on the Functional Recovery after Spinal Cord Lesions

PubMed Central

Wieraszko, Andrzej

2008-01-01

Abstract The objective of the study was to determine whether physical exercise combined with epidural spinal cord magnetic stimulation could improve recovery after injury of the spinal cord. Spinal cord lesioning in mice resulted in reduced locomotor function and negatively affected the muscle strength tested in vitro. Acrobatic exercise attenuated the behavioral effects of spinal cord injury. The exposure to magnetic fields facilitated further this improvement. The progress in behavioral recovery was correlated with reduced muscle degeneration and enhanced muscle contraction. The acrobatic exercise combined with stimulation with magnetic fields significantly facilitates behavioral recovery and muscle physiology in mice following spinal cord injury. PMID:18986227

Exploration of Spinal Cord Aging-Related Proteins Using a Proteomics Approach.

PubMed

Kamiya, Koshiro; Furuya, Takeo; Hashimoto, Masayuki; Mannoji, Chikato; Inada, Taigo; Ota, Mitsutoshi; Maki, Satoshi; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Orita, Sumihisa; Inage, Kazuhide; Yamazaki, Masashi; Koda, Masao

2017-01-01

How aging affects the spinal cord at a molecular level is unclear. The aim of this study was to explore spinal cord aging-related proteins that may be involved in pathological mechanisms of age-related changes in the spinal cord. Spinal cords of 2-year-old and 8-week-old female Sprague-Dawley rats were dissected from the animals. Protein samples were subjected to 2-dimentional polyacrylamide gel electrophoresis followed by mass spectrometry. Screened proteins were further investigated with immunohistochemistry and Western blotting. Among the screened proteins, we selected α-crystallin B-subunit (αB-crystallin) and peripherin for further investigation because these proteins were previously reported to be related to central nervous system pathologies. Immunohistochemistry and Western blotting revealed significant upregulation of αB-crystallin and peripherin expression in aged rat spinal cord. Further exploration is needed to elucidate the precise mechanism and potential role of these upregulated proteins in spinal cord aging processes.

Spinal Cord Lesions in Congenital Toxoplasmosis Demonstrated with Neuroimaging, Including Their Successful Treatment in an Adult.

PubMed

Burrowes, Delilah; Boyer, Kenneth; Swisher, Charles N; Noble, A Gwendolyn; Sautter, Mari; Heydemann, Peter; Rabiah, Peter; Lee, Daniel; McLeod, Rima

2012-03-01

Neuroimaging studies for persons in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) with symptoms and signs referable to the spinal cord were reviewed. Three infants had symptomatic spinal cord lesions, another infant a Chiari malformation, and another infant a symptomatic peri-spinal cord lipoma. One patient had an unusual history of prolonged spinal cord symptoms presenting in middle age. Neuroimaging was used to establish her diagnosis and response to treatment. This 43 year-old woman with congenital toxoplasmosis developed progressive leg spasticity, weakness, numbness, difficulty walking, and decreased visual acuity and color vision without documented re-activation of her chorioretinal disease. At 52 years of age, spinal cord lesions in locations correlating with her symptoms and optic atrophy were diagnosed with 3 Tesla MRI scan. Treatment with pyrimethamine and sulfadiazine decreased her neurologic symptoms, improved her neurologic examination, and resolved her enhancing spinal cord lesions seen on MRI.

Are there endogenous stem cells in the spinal cord?

PubMed

Ferrucci, Michela; Ryskalin, Larisa; Busceti, Carla L; Gaglione, Anderson; Biagioni, Francesca; Fornai, Francesco

2017-12-01

Neural progenitor cells (NPC) represent the stem-like niche of the central nervous system that maintains a regenerative potential also in the adult life. Despite NPC in the brain are well documented, the presence of NPC in the spinal cord has been controversial for a long time. This is due to a scarce activity of NPC within spinal cord, which also makes difficult their identification. The present review recapitulates the main experimental studies, which provided evidence for the occurrence of NPC within spinal cord, with a special emphasis on spinal cord injury and amyotrophic lateral sclerosis. By using experimental models, here we analyse the site-specificity, the phenotype and the main triggers of spinal cord NPC. Moreover, data are reported on the effect of specific neurogenic stimuli on these spinal cord NPC in an effort to comprehend the endogenous neurogenic potential of this stem cell niche.

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for pain relief. 882.5880 Section 882.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator...

76 FR 71623 - Agency Information Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review AGENCY: Veterans Benefits Administration... INFORMATION: Title: Spinal Cord Injury Patient Care Survey, VA Form 10-0515. OMB Control Number: OMB Control... 10-0515 will be used to determine spinal cord patients' satisfaction with VA rehabilitation and...

DTI and pathological changes in a rabbit model of radiation injury to the spinal cord after 125I radioactive seed implantation

PubMed Central

Cao, Xia; Fang, Le; Cui, Chuan-yu; Gao, Shi; Wang, Tian-wei

2018-01-01

Excessive radiation exposure may lead to edema of the spinal cord and deterioration of the nervous system. Magnetic resonance imaging can be used to judge and assess the extent of edema and to evaluate pathological changes and thus may be used for the evaluation of spinal cord injuries caused by radiation therapy. Radioactive 125I seeds to irradiate 90% of the spinal cord tissue at doses of 40–100 Gy (D90) were implanted in rabbits at T10 to induce radiation injury, and we evaluated their safety for use in the spinal cord. Diffusion tensor imaging showed that with increased D90, the apparent diffusion coefficient and fractional anisotropy values were increased. Moreover, pathological damage of neurons and microvessels in the gray matter and white matter was aggravated. At 2 months after implantation, obvious pathological injury was visible in the spinal cords of each group. Magnetic resonance diffusion tensor imaging revealed the radiation injury to the spinal cord, and we quantified the degree of spinal cord injury through apparent diffusion coefficient and fractional anisotropy. PMID:29623940

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

PubMed

Norrsell, H; Eliasson, T; Mannheimer, C; Augustinsson, L E; Bergh, C H; Andersson, B; Waagstein, F; Friberg, P

1997-12-01

Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

Fatty Acid Binding Protein 5 Modulates Docosahexaenoic Acid-Induced Recovery in Rats Undergoing Spinal Cord Injury

PubMed Central

Figueroa, Johnny D.; Serrano-Illan, Miguel; Licero, Jenniffer; Cordero, Kathia; Miranda, Jorge D.

2016-01-01

Abstract Omega-3 polyunsaturated fatty acids (n-3 PUFAs) promote functional recovery in rats undergoing spinal cord injury (SCI). However, the precise molecular mechanism coupling n-3 PUFAs to neurorestorative responses is not well understood. The aim of the present study was to determine the spatiotemporal expression of fatty acid binding protein 5 (FABP5) after contusive SCI and to investigate whether this protein plays a role in n-3 PUFA–mediated functional recovery post-SCI. We found that SCI resulted in a robust spinal cord up-regulation in FABP5 mRNA levels (556 ± 187%) and protein expression (518 ± 195%), when compared to sham-operated rats, at 7 days post-injury (dpi). This upregulation coincided with significant alterations in the metabolism of fatty acids in the injured spinal cord, as revealed by metabolomics-based lipid analyses. In particular, we found increased levels of the n-3 series PUFAs, particularly docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA; 20:5 n-3) at 7 dpi. Animals consuming a diet rich in DHA and EPA exhibited a significant upregulation in FABP5 mRNA levels at 7 dpi. Immunofluorescence showed low basal FABP5 immunoreactivity in spinal cord ventral gray matter NeuN+ neurons of sham-operated rats. SCI resulted in a robust induction of FABP5 in glial (GFAP+, APC+, and NG2+) and precursor cells (DCX+, nestin+). We found that continuous intrathecal administration of FABP5 silencing with small interfering RNA (2 μg) impaired spontaneous open-field locomotion post-SCI. Further, FABP5 siRNA administration hindered the beneficial effects of DHA to ameliorate functional recovery at 7 dpi. Altogether, our findings suggest that FABP5 may be an important player in the promotion of cellular uptake, transport, and/or metabolism of DHA post-SCI. Given the beneficial roles of n-3 PUFAs in ameliorating functional recovery, we propose that FABP5 is an important contributor to basic repair mechanisms in the injured spinal cord. PMID:26715431

The change tendency of PI3K/Akt pathway after spinal cord injury

PubMed Central

Zhang, Peixun; Zhang, Luping; Zhu, Lei; Chen, Fangmin; Zhou, Shuai; Tian, Ting; Zhang, Yuqiang; Jiang, Xiaorui; Li, Xuekun; Zhang, Chuansen; Xu, Lin; Huang, Fei

2015-01-01

Spinal cord injury (SCI) refers to the damage of spinal cord’s structure and function due to a variety of causes. At present, many scholars have confirmed that apoptosis is the main method of secondary injury in spinal cord injury. In view of understanding the function of PI3K/Akt pathway on spinal cord injury, this study observed the temporal variation of key molecules (PI3K, Akt, p-Akt) in the PI3K/Akt pathway after spinal cord injury by immunohistochemistry and Western-blot. The results showed that the expression of PI3K, Akt and p-Akt display a sharp increase one day after the spinal cord injury, and then it decreased gradually with the time passing by, but the absolute expression was certainly higher than the normal group. These results indicate that the PI3K/Akt signaling pathway is involved in the spinal cord injury and the mechanism may be related to apoptosis. PMID:26807170

Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

PubMed Central

2012-01-01

Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

Twiddler's syndrome in spinal cord stimulation.

PubMed

Al-Mahfoudh, Rafid; Chan, Yuen; Chong, Hsu Pheen; Farah, Jibril Osman

2016-01-01

The aims are to present a case series of Twiddler's syndrome in spinal cord stimulators with analysis of the possible mechanism of this syndrome and discuss how this phenomenon can be prevented. Data were collected retrospectively between 2007 and 2013 for all patients presenting with failure of spinal cord stimulators. The diagnostic criterion for Twiddler's syndrome is radiological evidence of twisting of wires in the presence of failure of spinal cord stimulation. Our unit implants on average 110 spinal cord stimulators a year. Over the 5-year study period, all consecutive cases of spinal cord stimulation failure were studied. Three patients with Twiddler's syndrome were identified. Presentation ranged from 4 to 228 weeks after implantation. Imaging revealed repeated rotations and twisting of the wires of the spinal cord stimulators leading to hardware failure. To the best of our knowledge this is the first reported series of Twiddler's syndrome with implantable pulse generators (IPGs) for spinal cord stimulation. Hardware failure is not uncommon in spinal cord stimulation. Awareness and identification of Twiddler's syndrome may help prevent its occurrence and further revisions. This may be achieved by implanting the IPG in the lumbar region subcutaneously above the belt line. Psychological intervention may have a preventative role for those who are deemed at high risk of Twiddler's syndrome from initial psychological screening.

Characteristics of spinal cord stroke in clinical neurology.

PubMed

Romi, Fredrik; Naess, Halvor

2011-01-01

Spinal cord stroke accounts for about 0.3% of all strokes in our department. Thirty-two patients (15 males, 17 females; mean age 63.3 years) treated in the period 1995-2010 were included. Patients underwent thorough investigation including the use of different stroke scales (National Institute of Health Stroke Scale, Barthel Index and modified Rankin Scale). Twenty-eight patients had infarctions, 3 had hemorrhages, and 1 had arterio-venous fistula. Twenty-eight spinal cord strokes were spontaneous, 2 were secondary to aorta aneurysms, and 2 post surgery. Biphasic ictus was seen in 17% of all spontaneous infarctions. Younger age, male gender, hypertension, diabetes mellitus, and higher blood glucose on admission regardless of diabetes mellitus, were risk factors associated with more severe spinal cord stroke. Treatment and prevention of these risk factors should be essential in spinal cord stroke. We recommend a clinical classification into upper (cervical) and lower (thoracic or medullary conus) spinal cord strokes. Patients with upper strokes in this study had more severe strokes initially, but they had a better prognosis. Therefore it is important to identify this patient group.Acute sensory spinal cord deficit symptoms, common initial symptoms in biphasic spinal cord strokes, should be considered as possible spinal cord stroke, especially when preceded by radiating pain between the shoulders. Copyright © 2011 S. Karger AG, Basel.

Electrical field distribution within the injured cat spinal cord: injury potentials and field distribution.

PubMed

Khan, T; Myklebust, J; Swiontek, T; Sayers, S; Dauzvardis, M

1994-12-01

This study investigated the spontaneous injury potentials measured after contusion or transection injury to the cat spinal cord. In addition, the distribution of electrical field potentials on the surface and within the spinal cord were measured following applied electrical fields after transection and contusion injuries. After transection of the spinal cord, the injury potentials were -19.8 +/- 2.6 mV; after contusion of the spinal cord, the injury potentials were -9.5 +/- 2.2 mV. These potentials returned to control values within 2.5-4h after injury. The electrical field distribution measured on the dorsal surface, as well as within the spinal cord, after the application of a 10 microA current, showed little difference between contusion and transection injuries. Scalar potential fields were measured using two configurations of stimulating electrodes: dorsal to dorsal (D-D), in which both electrodes were placed epidurally on the dorsal surface of the spinal cord, and ventral to dorsal (V-D), in which one electrode was placed dorsally and one ventrally. As reported in normal uninjured cats, the total current in the midsagittal plane for the D-D configuration was largely confined to the dorsal portion of the spinal cord; with the V-D configuration, the current distribution was uniform throughout the spinal cord. In the injured spinal cord, the equipotential lines midway between the stimulating electrodes have a wider separation than in the uninjured spinal cord. Because the magnitude of the electrical field E is equal to the current density J multiplied by the resistivity r, this suggests that either the current density is reduced or that the resistivity is reduced.

Gastrointestinal symptoms in spinal cord injury: relationships with level of injury and psychologic factors.

PubMed

Ng, Clinton; Prott, Gillian; Rutkowski, Susan; Li, Yueming; Hansen, Ross; Kellow, John; Malcolm, Allison

2005-08-01

Previous surveys of gastrointestinal symptoms after spinal cord injury have not used validated questionnaires and have not focused on the full spectrum of such symptoms and their relationship to factors, such as level of spinal cord injury and psychologic dysfunction. This study was designed to detail the spectrum and prevalence of gastrointestinal symptoms in spinal cord injury and to determine clinical and psychologic factors associated with such symptoms. Established spinal cord injury patients (>12 months) randomly selected from a spinal cord injury database completed the following three questionnaires: 1) Rome II Integrative Questionnaire, 2) Hospital Anxiety and Depression Scale, and 3) Burwood Bowel Dysfunction after spinal cord injury. A total of 110 patients participated. The prevalence of abdominal bloating and constipation were 22 and 46 percent, respectively. Bloating was associated with cervical (odds ratio = 9.5) and lumbar (odds ratio = 12.1) level but not with thoracic level of injury. Constipation was associated with a higher level of injury (cervical odds ratio = 5.6 vs. lumbar) but not with psychologic factors. In contrast, abdominal pain (33 percent) and fecal incontinence (41 percent) were associated with higher levels of anxiety (odds ratio = 6.8, and odds ratio = 2.4) but not with the level of injury. There is a high prevalence and wide spectrum of gastrointestinal symptoms in spinal cord injury. Abdominal bloating and constipation are primarily related to specific spinal cord levels of injury, whereas abdominal pain and fecal incontinence are primarily associated with higher levels of anxiety. Based on our findings, further physiologic and psychologic research studies in spinal cord injury patients should lead to more rational management strategies for the common gastrointestinal symptoms in spinal cord injury.

Topologically preserving straightening of spinal cord MRI.

PubMed

De Leener, Benjamin; Mangeat, Gabriel; Dupont, Sara; Martin, Allan R; Callot, Virginie; Stikov, Nikola; Fehlings, Michael G; Cohen-Adad, Julien

2017-10-01

To propose a robust and accurate method for straightening magnetic resonance (MR) images of the spinal cord, based on spinal cord segmentation, that preserves spinal cord topology and that works for any MRI contrast, in a context of spinal cord template-based analysis. The spinal cord curvature was computed using an iterative Non-Uniform Rational B-Spline (NURBS) approximation. Forward and inverse deformation fields for straightening were computed by solving analytically the straightening equations for each image voxel. Computational speed-up was accomplished by solving all voxel equation systems as one single system. Straightening accuracy (mean and maximum distance from straight line), computational time, and robustness to spinal cord length was evaluated using the proposed and the standard straightening method (label-based spline deformation) on 3T T 2 - and T 1 -weighted images from 57 healthy subjects and 33 patients with spinal cord compression due to degenerative cervical myelopathy (DCM). The proposed algorithm was more accurate, more robust, and faster than the standard method (mean distance = 0.80 vs. 0.83 mm, maximum distance = 1.49 vs. 1.78 mm, time = 71 vs. 174 sec for the healthy population and mean distance = 0.65 vs. 0.68 mm, maximum distance = 1.28 vs. 1.55 mm, time = 32 vs. 60 sec for the DCM population). A novel image straightening method that enables template-based analysis of quantitative spinal cord MRI data is introduced. This algorithm works for any MRI contrast and was validated on healthy and patient populations. The presented method is implemented in the Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1209-1219. © 2017 International Society for Magnetic Resonance in Medicine.

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

PubMed

Hague, D W; Joslyn, S; Bush, W W; Glass, E N; Durham, A C

2015-01-01

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. Multi-institutional retrospective study. Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases. Copyright © 2015 by the American College of Veterinary Internal Medicine.

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

PubMed

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.

Management of subaxial cervical facet dislocation through anterior approach monitored by spinal cord evoked potential.

PubMed

Du, Wei; Wang, Cheng; Tan, Jiangwei; Shen, Binghua; Ni, Shuqin; Zheng, Yanping

2014-01-01

Retrospective case series. To discuss the clinical efficacy of anterior cervical surgery of decompression, reduction, stabilization, and fusion in treating subaxial cervical facet dislocation without spinal cord injury or with mild spinal cord injury monitored by spinal cord evoked potential. The optimal treatment of lower cervical facet dislocation has been controversial. Because of the risk of iatrogenic damage of neurological function, it is challenging for surgeons to manage the lower cervical facet dislocation without or with mild spinal cord injury. To avoid the risks, more secure strategy need to be designed. A retrospective study was performed on 17 cases of subaxial cervical facet dislocation without spinal cord injury or with mild spinal cord injury treated by anterior cervical surgery under spinal cord evoked potential monitor from January 2008 to June 2012. There were 12 males, 5 females, with a mean age of 40.1 years (from 21 to 73 yr). Dislocation sites: 1 in C3-C4, 2 in C4-C5, 6 in C5-C6, 8 in C6-C7; 10 cases with unilateral cervical facet dislocation, 7 cases with bilateral dislocation. Thirteen patients were preoperatively classified as grade D and 4 as E according to Frankel standard. All patients were followed up for average of 16 months. All operations were completed successfully. Postoperative radiographs showed that the sequence and curvature of the cervical spine were well recovered. And, evidence of intervertebral fusion was observed at 3 months in all cases. No redislocation or symptoms of spinal cord injury occurred. Thirteen cases with mild spinal cord injury recovered at 1 month after operation. Anterior cervical surgery of decompression, reduction, stabilization, and fusion monitored by spinal cord evoked potential is an effective and safe method for treatment of subaxial cervical facet dislocation without or with mild spinal cord injury. 4.

General Information about Childhood Brain and Spinal Cord Tumors

MedlinePlus

... Cord Tumors Treatment Overview (PDQ®)–Patient Version General Information About Childhood Brain and Spinal Cord Tumors Go ... types of brain and spinal cord tumors. The information from tests and procedures done to detect (find) ...

The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

PubMed

Ilha, Jocemar; Centenaro, Lígia A; Broetto Cunha, Núbia; de Souza, Daniela F; Jaeger, Mariane; do Nascimento, Patrícia S; Kolling, Janaína; Ben, Juliana; Marcuzzo, Simone; Wyse, Angela T S; Gottfried, Carmem; Achaval, Matilde

2011-06-01

Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.

Cellular Scaling Rules for Primate Spinal Cords

PubMed Central

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

2010-01-01

The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an exponent close to 1/3. This relationship suggests that the extension, mass and number of neurons that compose the spinal cord are related to body length, rather than to body mass or surface. Moreover, we show that although brain mass increases linearly with cord mass, the number of neurons in the brain increases with the number of neurons in the spinal cord raised to the power of 1.7. This faster addition of neurons to the brain than to the spinal cord is consistent with current views on how larger brains add complexity to the processing of environmental and somatic information. PMID:20926855

Functional MR imaging of the spinal cord in cervical spinal cord injury patients by acupuncture at LI 4 (Hegu) and LI 11(Quchi).

PubMed

Chen, Y X; Kong, K M; Wang, W D; Xie, C H; Wu, R H

2007-01-01

To investigate the cervical spinal cord mapping on acupuncture at LI 4 (Hegu) and LI 11 (Quchi) by using 'Signal Enhancement by Extravascular water Protons' (SEEP)-fMRI, and to establish the response of using acupuncture in the cervical spinal cord. This research may provide some laboratory evidences from the acupuncture treatment on the cervical spinal cord of injuried patients. Seven healthy volunteers (healthy group) and three cervical spinal cord injury patients (injury group) were underwent low-frequency electrical stimulation at LI 4 and LI 11. Meanwhile, a single-shot fast spin-echo (SSFSE) sequence was used to perform functional MR imaging on a 1.5 T GE Signa MR system. The signals from the cervical spinal cord activated was measured both in sagittal and transverse imaging planes and then analyzed by AFNI (Analysis of Functional Neuroimages) system. It was found that in the sagittal view, two groups had an fMRI response in the cervical spinal cord after given acupuncture treatments at LI 4 and LI 11. The localizations of the segmental fMRI activation were focused at C6 and C2 cervical spinal cord level. In the transverse imaging plane, significant fMRI responses could be measured from the four of seven healthy volunteers and from two of three cervical spinal cord injury patients. They were located at C6/7 segments. The cross-sectional localization of the activity measured in the spinal cord was most in terms of the ipsilateral posterior direction. The signal amplitude varied mainly between 6.8%17.8%. However, the difference found between the two groups had no statistical meaning. The fMRI technique had detected an activation focused at C6 and C2 cervical spinal cord levels by use of acupuncture at LI 4 and LI 11 on a 1.5T GE clinical system. This proved that the meridians and points are found to be in existence. The fMRI can be used as a harmless research method to discuss the mechanisms of acupuncture as well as study the mechanisms of spinal cord diseases. It can be used to direct or monitor the related therapy on the spinal cord injury patients.

What Are the Key Statistics about Brain and Spinal Cord Cancers?

MedlinePlus

... Brain and Spinal Cord Tumors in Adults Key Statistics for Brain and Spinal Cord Tumors The American ... Cord Tumors . Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Written by References ...

Involvement of the Spinal Cord in Mitochondrial Disorders.

PubMed

Finsterer, Josef; Zarrouk-Mahjoub, Sinda

2018-01-01

This review aims at summarising and discussing the current status concerning the clinical presentation, pathogenesis, diagnosis, and treatment of spinal cord affection in mitochondrial disorders (MIDs). A literature search using the database Pubmed was carried out by application of appropriate search terms and their combinations. Involvement of the spinal cord in MIDs is more frequent than anticipated. It occurs in specific and non-specific MIDs. Among the specific MIDs it has been most frequently described in LBSL, LS, MERRF, KSS, IOSCA, MIRAS, and PCH and only rarely in MELAS, CPEO, and LHON. Clinically, spinal cord involvement manifests as monoparesis, paraparesis, quadruparesis, sensory disturbances, hypotonia, spasticity, urinary or defecation dysfunction, spinal column deformities, or as transverse syndrome. Diagnosing spinal cord involvement in MIDs requires a thoroughly taken history, clinical exam, and imaging studies. Additionally, transcranial magnetic stimulation, somato-sensory-evoked potentials, and cerebro-spinal fluid can be supportive. Treatment is generally not at variance compared to the underlying MID but occasionally surgical stabilisation of the spinal column may be necessary. It is concluded that spinal cord involvement in MIDs is more frequent than anticipated but may be missed if cerebral manifestations prevail. Spinal cord involvement in MIDs may strongly determine the mobility of these patients.

Update on traumatic acute spinal cord injury. Part 2.

PubMed

Mourelo Fariña, M; Salvador de la Barrera, S; Montoto Marqués, A; Ferreiro Velasco, M E; Galeiras Vázquez, R

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers). Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

A five-layer users' need hierarchy of computer input device selection: a contextual observation survey of computer users with cervical spinal injuries (CSI).

PubMed

Tsai, Tsai-Hsuan; Nash, Robert J; Tseng, Kevin C

2009-05-01

This article presents how the researcher goes about answering the research question, 'how assistive technology impacts computer use among individuals with cervical spinal cord injury?' through an in-depth investigation into the real-life situations among computer operators with cervical spinal cord injuries (CSI). An in-depth survey was carried out to provide an insight into the function abilities and limitation, habitual practice and preference, choices and utilisation of input devices, personal and/or technical assistance, environmental set-up and arrangements and special requirements among 20 experienced computer users with cervical spinal cord injuries. Following the survey findings, a five-layer CSI users' needs hierarchy of input device selection and use was proposed. These needs were ranked in order: beginning with the most basic criterion at the bottom of the pyramid; lower-level criteria must be met before one moves onto the higher level. The users' needs hierarchy for CSI computer users, which had not been applied by previous research work and which has established a rationale for the development of alternative input devices. If an input device achieves the criteria set up in the needs hierarchy, then a good match of person and technology will be achieved.

Imaging spinal cord atrophy in progressive myelopathies: HTLV-I-associated neurological disease (HAM/TSP) and multiple sclerosis (MS).

PubMed

Azodi, Shila; Nair, Govind; Enose-Akahata, Yoshimi; Charlip, Emily; Vellucci, Ashley; Cortese, Irene; Dwyer, Jenifer; Billioux, B Jeanne; Thomas, Chevaz; Ohayon, Joan; Reich, Daniel S; Jacobson, Steven

2017-11-01

Previous work measures spinal cord thinning in chronic progressive myelopathies, including human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Quantitative measurements of spinal cord atrophy are important in fully characterizing these and other spinal cord diseases. We aimed to investigate patterns of spinal cord atrophy and correlations with clinical markers. Spinal cord cross-sectional area was measured in individuals (24 healthy controls [HCs], 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 relapsing-remitting MS [RRMS], 17 secondary progressive MS [SPMS], and 40 primary progressive MS [PPMS]) from C1 to T10. Clinical disability scores, viral markers, and immunological parameters were obtained for patients and correlated with representative spinal cord cross-sectional area regions at the C2 to C3, C4 to C5, and T4 to T9 levels. In 2 HAM/TSP patients, spinal cord cross-sectional area was measured over 3 years. All spinal cord regions are thinner in HAM/TSP (56 mm 2 [standard deviation, 10], 59 [10], 23 [5]) than in HC (76 [7], 83 [8], 38 [4]) and AC (71 [7], 78 [9], 36 [7]). SPMS (62 [9], 66 [9], 32 [6]) and PPMS (65 [11], 68 [10], 35 [7]) have thinner cervical cords than HC and RRMS (73 [9], 77 [10], 37 [6]). Clinical disability scores (Expanded Disability Status Scale [p = 0.009] and Instituto de Pesquisas de Cananeia [p = 0.03]) and CD8 + T-cell frequency (p = 0.04) correlate with T4 to T9 spinal cord cross-sectional area in HAM/TSP. Higher cerebrospinal fluid HTLV-1 proviral load (p = 0.01) was associated with thinner spinal cord cross-sectional area. Both HAM/TSP patients followed longitudinally showed thoracic thinning followed by cervical thinning. Group average spinal cord cross-sectional area in HAM/TSP and progressive MS show spinal cord atrophy. We further hypothesize in HAM/TSP that is possible that neuroglial loss from a thoracic inflammatory process results in anterograde and retrograde degeneration of axons, leading to the temporal progression of thoracic to cervical atrophy described here. Ann Neurol 2017;82:719-728. © 2017 American Neurological Association.

Migration of luque rods through a laminectomy defect causing spinal cord compression.

PubMed

Quint, D J; Salton, G

1993-01-01

Internal fixation of traumatic spinal injuries has been associated with spinal canal stenosis, spinal cord compression, and nerve root impingement. We present a case of spinal cord/cauda equina compression due to migration of intact, anchored thoracolumbar Luque rods into the spinal canal through a laminectomy defect, leading to neurologic complications 10 years after the original operation.

Discrete mitochondrial aberrations in the spinal cord of sporadic ALS patients.

PubMed

Delic, Vedad; Kurien, Crupa; Cruz, Josean; Zivkovic, Sandra; Barretta, Jennifer; Thomson, Avery; Hennessey, Daniel; Joseph, Jaheem; Ehrhart, Jared; Willing, Alison E; Bradshaw, Patrick; Garbuzova-Davis, Svitlana

2018-08-01

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord leading to muscle atrophy, paralysis, and death. Mitochondrial dysfunction is a major contributor to motor neuron degeneration associated with ALS progression. Mitochondrial abnormalities have been determined in spinal cords of animal disease models and ALS patients. However, molecular mechanisms leading to mitochondrial dysfunction in sporadic ALS (sALS) patients remain unclear. Also, segmental or regional variation in mitochondrial activity in the spinal cord has not been extensively examined in ALS. In our study, the activity of mitochondrial electron transport chain complex IV was examined in post-mortem gray and white matter of the cervical and lumbar spinal cords from male and female sALS patients and controls. Mitochondrial distribution and density in spinal cord motor neurons, lateral funiculus, and capillaries in gray and white matter were analyzed by immunohistochemistry. Results showed that complex IV activity was significantly decreased only in gray matter in both cervical and lumbar spinal cords from ALS patients. In ALS cervical and lumbar spinal cords, significantly increased mitochondrial density and altered distribution were observed in motor neurons, lateral funiculus, and cervical white matter capillaries. Discrete decreased complex IV activity in addition to changes in mitochondria distribution and density determined in the spinal cord in sALS patients are novel findings. These explicit mitochondrial defects in the spinal cord may contribute to ALS pathogenesis and should be considered in development of therapeutic approaches for this disease. © 2018 Wiley Periodicals, Inc.

Functional MR imaging of the cervical spinal cord by use of electrical stimulation at LI4 (Hegu).

PubMed

Wang, W D; Kong, K M; Xiao, Y Y; Wang, X J; Liang, B; Qi, W L; Wu, R H

2006-01-01

The purpose is to investigate the cervical spinal cord mapping on electrical stimulation at LI4 (Hegu) by using 'signal enhancement by extravascular water protons' (SEEP)-fMRI, and to establish the response of acupoint-stimulation in spinal cord. Three healthy volunteers were underwent low-frequency electrical stimulation at LI4. Meanwhile, a single-shot fast spin-echo (SSFSE) sequence was used to perform functional MR imaging on a 1.5 T GE Signa MR system. Cord activation was measured both in the sagittal and transverse imaging planes and then analyzed by AFNI (analysis of functional neuroimages) system. In the sagittal view, two subjects had an fMRI response in the cervical spinal cord upon electrical stimulation at LI4. The localizations of the segmental fMRI activation are both at C6 through T1 and C2/3 cervical spinal cord level. In the transverse imaging plane, significant fMRI responses could be measured in the last subjects locating at C6/7 segment, the cross-sectional localization of the activity measured in the spinal cord was most in terms of the ipsilateral posterior direction. It is concluded that the fMRI technique can be used for detecting with activity in the human cervical spinal cord by a single-shot fast spin-echo sequence on a 1.5 T GE clinical system. Investigating the acupoint-stimulation response in the spinal cord using the spinal fMRI will be helpful for the further discussion on the mechanisms of acupuncture to spinal cord diseases.

Long-Term Extensive Ectopic Hair Growth on the Spinal Cord of Mice from Transplanted Whisker Follicles.

PubMed

Cao, Wenluo; Li, Lingna; Mii, Sumiyuki; Amoh, Yasuyuki; Liu, Fang; Hoffman, Robert M

2015-01-01

We have previously demonstrated that hair follicles contain nestin-expressing pluripotent stem cells that can effect nerve and spinal cord repair upon transplantation. In the present study, isolated whisker follicles from nestin-driven green fluorescent protein (ND-GFP) mice were histocultured on Gelfoam for 3 weeks for the purpose of transplantation to the spinal cord to heal an induced injury. The hair shaft was cut off from Gelfoam-histocultured whisker follicles, and the remaining part of the whisker follicles containing GFP-nestin expressing pluripotent stem cells were transplanted into the injured spinal cord of nude mice, along with the Gelfoam. After 90 days, the mice were sacrificed and the spinal cord lesion was observed to have healed. ND-GFP expression was intense at the healed area of the spinal cord, as observed by fluorescence microscopy, demonstrating that the hair follicle stem cells were involved in healing the spinal cord. Unexpectedly, the transplanted whisker follicles sprouted out remarkably long hair shafts in the spinal cord during the 90 days after transplantation of Gelfoam whisker histocultures to the injured spine. The pigmented hair fibers, grown from the transplanted whisker histocultures, curved and enclosed the spinal cord. The unanticipated results demonstrate the great potential of hair growth after transplantation of Gelfoam hair follicle histocultures, even at an ectopic site.

Development of a comprehensive survey of sexuality issues including a self-report version of the International Spinal Cord Injury sexual function basic data sets.

PubMed

New, P W; Currie, K E

2016-08-01

Questionnaire development, validation and completion. Develop comprehensive survey of sexuality issues including validated self-report versions of the International Spinal Cord Injury male sexual function and female sexual and reproductive function basic data sets (SR-iSCI-sexual function). People with spinal cord damage (SCD) living in the community, Australia from August 2013 to June 2014. An iterative process involving rehabilitation medicine clinicians, a nurse specialising in sexuality issues in SCD and people with SCD who developed a comprehensive survey that included the SR-iSCI-sexual function. Participants recruitment through spinal rehabilitation review clinic and community organisations that support people with SCD. Surveys completed by 154 people. Most were male (n=101, 65.6%). Respondents' median age was 50 years (interquartile range (IQR) 38-58), and they were a median of 10 years (IQR 4-20) after the onset of SCD. Sexual problems unrelated to SCD were reported by 12 (8%) respondents, and 114 (n=75.5%) reported sexual problems because of SCD. Orgasms were much less likely (χ(2)=13.1, P=0.006) to be normal in males (n=5, 5%) compared with females (n=11, 22%). Males had significantly worse (χ(2)=26.0, P=0.001) psychogenic genital functioning (normal n=9, 9%) than females (normal n=13, 26%) and worse (χ(2)=10.8, P=0.013) reflex genital functioning. Normal ejaculation was reported in only three (3%) men. Most (n=26, 52%) women reported reduced or absent menstruation pattern since SCD. The SR-iSCI-sexual function provides a useful tool for researchers and clinicians to collect information regarding patient-reported sexual functioning after SCD and to facilitate comparative studies.

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

Spinal cord stimulation for refractory angina in a patient implanted with a cardioverter defibrillator.

PubMed

Ferrero, Paolo; Grimaldi, Roberto; Massa, Riccardo; Chiribiri, Amedeo; De Luca, Anna; Castellano, Maddalena; Cardano, Paola; Trevi, Gian Paolo

2007-01-01

Spinal cord stimulation is currently used to treat refractory angina. Some concerns may arise about the possible interaction concerning the spinal cord stimulator in patients already implanted with a pacemaker or a cardioverter defibrillator. We are going to describe the successful implantation of a spinal cord stimulator in a patient previously implanted with a cardioverter defibrillator.

Spinal cord stress injury assessment (SCOSIA): clinical applications of mechanical modeling of the spinal cord and brainstem

NASA Astrophysics Data System (ADS)

Wong, Kenneth H.; Choi, Jae; Wilson, William; Berry, Joel; Henderson, Fraser C., Sr.

2009-02-01

Abnormal stretch and strain is a major cause of injury to the spinal cord and brainstem. Such forces can develop from age-related degeneration, congenital malformations, occupational exposure, or trauma such as sporting accidents, whiplash and blast injury. While current imaging technologies provide excellent morphology and anatomy of the spinal cord, there is no validated diagnostic tool to assess mechanical stresses exerted upon the spinal cord and brainstem. Furthermore, there is no current means to correlate these stress patterns with known spinal cord injuries and other clinical metrics such as neurological impairment. We have therefore developed the spinal cord stress injury assessment (SCOSIA) system, which uses imaging and finite element analysis to predict stretch injury. This system was tested on a small cohort of neurosurgery patients. Initial results show that the calculated stress values decreased following surgery, and that this decrease was accompanied by a significant decrease in neurological symptoms. Regression analysis identified modest correlations between stress values and clinical metrics. The strongest correlations were seen with the Brainstem Disability Index (BDI) and the Karnofsky Performance Score (KPS), whereas the weakest correlations were seen with the American Spinal Injury Association (ASIA) scale. SCOSIA therefore shows encouraging initial results and may have wide applicability to trauma and degenerative disease involving the spinal cord and brainstem.

Effects of vertebral column distraction on transcranial electrical stimulation-motor evoked potential and histology of the spinal cord in a porcine model.

PubMed

Yang, Jae Hyuk; Suh, Seung Woo; Modi, Hitesh N; Ramani, Easwar T; Hong, Jae Young; Hwang, Jin Ho; Jung, Woon Yong

2013-05-01

Spinal cord injury can occur following surgical procedures for correction of scoliosis and kyphosis, as these procedures produce lengthening of the vertebral column. The objective of this study was to cause spinal cord injury by vertebral column distraction and evaluate the histological changes in the spinal cord in relationship to the pattern of recovery from the spinal cord injury. Global osteotomy of all three spinal columns was performed on the ninth thoracic vertebra of sixteen pigs. The osteotomized vertebra was distracted until transcranial electrical stimulation-motor evoked potential (TES-MEP) signals disappeared or decreased by >80% compared with the baseline amplitude; this was defined as spinal cord injury. The distraction distance at which spinal cord injury occurred was measured, the distraction was released, and the TES-MEP recovery pattern was observed. A wake-up test was performed, two days of observations were made, and histological changes were evaluated in relationship to the recovery pattern. Spinal cord injury developed at a distraction distance of 20.2 ± 4.7 mm, equivalent to 3.6% of the thoracolumbar spinal length, and the distraction distance was correlated with the thoracolumbar spinal length (r = 0.632, p = 0.009). No animals exhibited complete recovery according to TES-MEP testing, eleven exhibited incomplete recovery, and five exhibited no recovery. During the two days of observation, all eleven animals with incomplete recovery showed positive responses to sensory and motor tests, whereas none of the five animals with no recovery had positive responses. On histological evaluation, three animals that exhibited no recovery all showed complete severance of nerve fibers (axotomy), whereas six animals that exhibited incomplete recovery all showed partial white-matter injury. Parallel distraction of approximately 3.6% of the thoracolumbar length after global osteotomy resulted in spinal cord injury and histological evidence of spinal cord damage. The pattern of recovery from the spinal cord injury after release of the distraction was consistent with the degree of axonal damage. Axotomy was observed in animals that exhibited no recovery on TES-MEP, and only hemorrhagic changes in the white matter were observed in animals that exhibited incomplete recovery.

Exploration of Spinal Cord Aging–Related Proteins Using a Proteomics Approach

PubMed Central

Kamiya, Koshiro; Furuya, Takeo; Hashimoto, Masayuki; Mannoji, Chikato; Inada, Taigo; Ota, Mitsutoshi; Maki, Satoshi; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Orita, Sumihisa; Inage, Kazuhide; Yamazaki, Masashi; Koda, Masao

2017-01-01

How aging affects the spinal cord at a molecular level is unclear. The aim of this study was to explore spinal cord aging–related proteins that may be involved in pathological mechanisms of age-related changes in the spinal cord. Spinal cords of 2-year-old and 8-week-old female Sprague-Dawley rats were dissected from the animals. Protein samples were subjected to 2-dimentional polyacrylamide gel electrophoresis followed by mass spectrometry. Screened proteins were further investigated with immunohistochemistry and Western blotting. Among the screened proteins, we selected α-crystallin B-subunit (αB-crystallin) and peripherin for further investigation because these proteins were previously reported to be related to central nervous system pathologies. Immunohistochemistry and Western blotting revealed significant upregulation of αB-crystallin and peripherin expression in aged rat spinal cord. Further exploration is needed to elucidate the precise mechanism and potential role of these upregulated proteins in spinal cord aging processes. PMID:28634429

Is neuroinflammation in the injured spinal cord different than in the brain? Examining intrinsic differences between the brain and spinal cord.

PubMed

Zhang, B; Gensel, J C

2014-08-01

The field of neuroimmunology is rapidly advancing. There is a growing appreciation for heterogeneity, both in inflammatory composition and region-specific inflammatory responses. This understanding underscores the importance of developing targeted immunomodulatory therapies for treating neurological disorders. Concerning neurotrauma, there is a dearth of publications directly comparing inflammatory responses in the brain and spinal cord after injury. The question therefore remains as to whether inflammatory cells responding to spinal cord vs. brain injury adopt similar functions and are therefore amenable to common therapies. In this review, we address this question while revisiting and modernizing the conclusions from publications that have directly compared inflammation across brain and spinal cord injuries. By examining molecular differences, anatomical variations, and inflammatory cell phenotypes between the injured brain and spinal cord, we provide insight into how neuroinflammation relates to neurotrauma and into fundamental differences between the brain and spinal cord. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional characterization of mouse spinal cord infiltrating CD8+ lymphocytes

PubMed Central

Deb, Chandra; Howe, Charles L

2011-01-01

Understanding the immunopathogenesis of neuroimmunological diseases of the CNS requires a robust method for isolating and characterizing the immune effector cells that infiltrate the spinal cord in animal models. We have developed a simple and rapid isolation method that produces high yields of spinal cord infiltrating leukocytes from a single demyelinated spinal cord and which maintains high surface expression of key immunophenotyping antigens. Using this method and the Theiler’s virus model of chronic demyelination, we report the presence of spinal cord infiltrating acute effector CD8+ lymphocytes that are CD45hiCD44loCD62L− and a population of spinal cord infiltrating target effector memory CD8+ lymphocytes that are CD45hiCD44hiCD62L−. These cells respond robustly to ex vivo stimulation by producing interferon γ but do not exhibit specificity for Theiler’s virus in a cytotoxicity assay. We conclude that target-derived lymphocytes in a mouse model of chronic spinal cord demyelination may have unique functional specificities. PMID:19596449

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury

PubMed Central

Ji, Yiming; Meng, Bin; Yuan, Chenxi; Yang, Huilin; Zou, Jun

2013-01-01

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30–180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in-creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potential latency can reflect the degree of spinal cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury. PMID:25206629

Plasticity and regeneration in the injured spinal cord after cell transplantation therapy.

PubMed

Nori, Satoshi; Nakamura, Masaya; Okano, Hideyuki

2017-01-01

Spinal cord injury (SCI) typically damages the long axonal tracts of the spinal cord which results in permanent disability. However, regeneration of the injured spinal cord is approaching reality according to the advances in stem cell biology. Cell transplantation therapy holds potential to lead to recovery following SCI through some positive mechanisms. Grafted cells induce plasticity and regeneration in the injured spinal cord by promoting remyelination of damaged axons, reconstruction of neural circuits by synapse formation between host neurons and graft-derived neurons, and secreting neurotrophic factors to promote axonal elongation as well as reduce retrograde axonal degeneration. In this review, we will delineate (1) the microenvironment of the injured spinal cord that influence the plasticity and regeneration capacity after SCI, (2) a number of different kinds of cell transplantation therapies for SCI that has been extensively studied by researchers, and (3) potential mechanisms of grafted cell-induced regeneration and plasticity in the injured spinal cord. © 2017 Elsevier B.V. All rights reserved.

Naturally Occurring Disk Herniation in Dogs: An Opportunity for Pre-Clinical Spinal Cord Injury Research

PubMed Central

Levine, Gwendolyn J.; Porter, Brian F.; Topp, Kimberly; Noble-Haeusslein, Linda J.

2011-01-01

Abstract Traumatic spinal cord injuries represent a significant source of morbidity in humans. Despite decades of research using experimental models of spinal cord injury to identify candidate therapeutics, there has been only limited progress toward translating beneficial findings to human spinal cord injury. Thoracolumbar intervertebral disk herniation is a naturally occurring disease that affects dogs and results in compressive/contusive spinal cord injury. Here we discuss aspects of this disease that are analogous to human spinal cord injury, including injury mechanisms, pathology, and metrics for determining outcomes. We address both the strengths and weaknesses of conducting pre-clinical research in these dogs, and include a review of studies that have utilized these animals to assess efficacy of candidate therapeutics. Finally, we consider a two-species approach to pre-clinical data acquisition, beginning with a reproducible model of spinal cord injury in the rodent as a tool for discovery with validation in pet dogs with intervertebral disk herniation. PMID:21438715

Interrater reliability of the Korean version of the International Spinal Cord Injury Basic Pain Data Set.

PubMed

Kim, H R; Kim, H B; Lee, B S; Ko, H Y; Shin, H I

2014-11-01

To provide a Korean translation of the International Spinal Cord Injury Basic Pain Data Set (ISCIBPDS) and evaluate the interrater reliability of the translated version. Survey of community-dwelling people with spinal cord injury (SCI) in South Korea. The initial translation was performed by two translators with an in-depth knowledge of SCI, and was then checked by another person with a similar background. A total of 115 SCI participants (87 men, 28 women; 48.4±14.1 years) were evaluated using the Korean version of the ISCIBPDS by two different raters. Intraclass correlation coefficient (ICC) or Cohen's kappa (κ) was used for analysis. All 115 participants had at least one pain problem on both surveys. Seventeen (14.8%) participants described their pain as a single pain problem to one rater while reporting the same pain as two or more different pain problems to the other rater. Twenty-two (19.1%) other participants reported their pain problems in a different order of severity on the surveys. The Korean version of the ISCIBPDS had acceptable interrater reliability, except in the 'limit activities (how much do you limit your activities in order to keep your pain from getting worse?)' item (ICC=0.318). Provision of criteria for pain separation may facilitate the consistent application of ISCIBPDS. In addition, the ISCIBPDS, which evaluated pain problems separately, reflected the multiple and complex characteristics of SCI-related pain; this was a strength of this data set.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

PubMed

Rossini, P M; Burke, D; Chen, R; Cohen, L G; Daskalakis, Z; Di Iorio, R; Di Lazzaro, V; Ferreri, F; Fitzgerald, P B; George, M S; Hallett, M; Lefaucheur, J P; Langguth, B; Matsumoto, H; Miniussi, C; Nitsche, M A; Pascual-Leone, A; Paulus, W; Rossi, S; Rothwell, J C; Siebner, H R; Ugawa, Y; Walsh, V; Ziemann, U

2015-06-01

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Quantitative measurement of intervertebral disc signal using MRI.

PubMed

Niemeläinen, R; Videman, T; Dhillon, S S; Battié, M C

2008-03-01

To investigate the spinal cord as an alternative intra-body reference to cerebrospinal fluid (CSF) in evaluating thoracic disc signal intensity. T2-weighted magnetic resonance imaging (MRI) images of T6-T12 were obtained using 1.5 T machines for a population-based sample of 523 men aged 35-70 years. Quantitative data on the signal intensities were acquired using an image analysis program (SpEx). A random sample of 30 subjects and intraclass correlation coefficients (ICC) were used to examine the repeatability of the spinal cord measurements. The validity of using the spinal cord as a reference was examined by correlating cord and CSF samples. Finally, thoracic disc signal was validated by correlating it with age without adjustment and adjusting for either cord or CSF. Pearson's r was used for correlational analyses. The repeatability of the spinal cord signal measurements was extremely high (>or=0.99). The correlations between the signals of spinal cord and CSF by level were all above 0.9. The spinal cord-adjusted disc signal and age correlated similarly with CSF-adjusted disc signal and age (r=-0.30 to -0.40 versus r=-0.26 to -0.36). Adjacent spinal cord is a good alternative reference to the current reference standard, CSF, for quantitative measurements of disc signal intensity. Clearly fewer levels were excluded when using spinal cord as compared to CSF due to missing reference samples.

Magnetic resonance imaging tractography as a diagnostic tool in patients with spinal cord injury treated with human embryonic stem cells.

PubMed

Shroff, Geeta

2017-02-01

Introduction Spinal cord injury is a cause of severe disability and mortality. The pharmacological and non-pharmacological methods used, are unable to improve the quality of life in spinal cord injury. Spinal disorders have been treated with human embryonic stem cells. Magnetic resonance imaging and tractography were used as imaging modality to document the changes in the damaged cord, but the magnetic resonance imaging tractography was seen to be more sensitive in detecting the changes in the spinal cord. The present study was conducted to evaluate the diagnostic modality of magnetic resonance imaging tractography to determine the efficacy of human embryonic stem cells in chronic spinal cord injury. Materials and methods The study included the patients with spinal cord injury for whom magnetic resonance imaging tractography was performed before and after the therapy. Omniscan (gadodiamide) magnetic resonance imaging tractography was analyzed to assess the spinal defects and the improvement by human embryonic stem cell treatment. The patients were also scored by American Spinal Injury Association scale. Results Overall, 15 patients aged 15-44 years with clinical manifestations of spinal cord injury had magnetic resonance imaging tractography performed. The average treatment period was nine months. The majority of subjects ( n = 13) had American Spinal Injury Association score A, and two patients were at score C at the beginning of therapy. At the end of therapy, 10 patients were at score A, two patients were at score B and three patients were at score C. Improvements in patients were clearly understood through magnetic resonance imaging tractography as well as in clinical signs and symptoms. Conclusion Magnetic resonance imaging tractography can be a crucial diagnostic modality to assess the improvement in spinal cord injury patients.

Cervical spinal stenosis and sports-related cervical cord neurapraxia in children.

PubMed

Boockvar, J A; Durham, S R; Sun, P P

2001-12-15

Congenital spinal stenosis has been demonstrated to contribute to cervical cord neurapraxia after cervical spinal cord injury in adult athletes. A sagittal canal diameter <14 mm and/or a Torg ratio (sagittal diameter of the spinal canal: midcervical sagittal vertebral body diameter) of <0.8 are indicative of significant cervical spinal stenosis. Although sports-related cervical spine injuries are common in children, the role of congenital cervical stenosis in the etiology of these injuries remains unclear. The authors measured the sagittal canal diameter and the Torg ratio in children presenting with cervical cord neurapraxia resulting from sports-related cervical spinal cord injuries to determine the presence of congenital spinal stenosis. A total of 13 children (9 male, 4 female) presented with cervical cord neurapraxia after a sports-related cervical spinal cord injury. Age ranged from 7 to 15 years (mean +/- SD, 11.5 +/- 2.7 years). The sports involved were football (n = 4), wrestling (n = 2), hockey (n = 2), and soccer, gymnastics, baseball, kickball, and pogosticking (n = 1 each). Lateral cervical spine radiographs were used to determine the sagittal canal diameter and the Torg ratio at C4. The sagittal canal diameter (mean +/- SD, 17.58 +/- 1.63 mm) and the Torg ratio (mean +/- SD, 1.20 +/- 0.24) were normal in all of these children. Using the sagittal canal diameter and the Torg ratio as a measurement of congenital spinal stenosis, the authors did not find evidence of congenital cervical spinal stenosis in a group of children with sports-related cervical spinal cord neurapraxia. The occurrence of cervical cord neurapraxia in pediatric patients can be attributed to the mobility of the pediatric spine rather than to congenital cervical spinal stenosis.

White matter organization in cervical spinal cord relates differently to age and control of grip force in healthy subjects.

PubMed

Lindberg, Påvel G; Feydy, Antoine; Maier, Marc A

2010-03-17

Diffusion tensor imaging (DTI) can be used to elucidate relations between CNS structure and function. We hypothesized that the degree of spinal white matter organization relates to the accuracy of control of grip force. Healthy subjects of different age were studied using DTI and visuomotor tracking of precision grip force. The latter is a prime component of manual dexterity. A regional analysis of spinal white matter [fractional anisotropy (FA)] across multiple cervical levels (C2-C3, C4-C5, and C6-C7) and in different regions of interest (left and right lateral or medial spinal cord) was performed. FA was highest at the C2-C3 level, higher on the right than the left side, and higher in the lateral than in the medial spinal cord (p < 0.001). FA of whole cervical spinal cord (C2-C7) was lower in subjects with high tracking error (r = -0.56, p = 0.004) and decreased with age (r = -0.63, p = 0.001). A multiple regression analysis revealed an independent contribution of each predictor (semipartial correlations: age, r = -0.55, p < 0.001; tracking error, r = -0.49, p = 0.003). The closest relation between FA and tracking error was found at the C6-C7 level in the lateral spinal cord, in which the corticospinal tract innervates spinal circuitry controlling hand and digit muscles. FA of the medial spinal cord correlated consistently with age across all cervical levels, whereas FA of the lateral spinal cord did not. The results suggest (1) a functionally relevant specialization of lateral spinal cord white matter and (2) an increased sensitivity to age-related decline in medial spinal cord white matter in healthy subjects.

Recurrent ‘universal tumour’ of the spinal cord

PubMed Central

O'Grady, John; Kaliaperumal, Chandrasekaran; O'Sullivan, Michael

2012-01-01

Lipoma is popularly known as the ‘universal tumour’ because of its ubiquitous presence anywhere in the body. This is the first documented case of recurrent thoracic spinal cord intramedullary lipoma in a 44-year-old man, with a background of spinal dysraphism, which recurred 15 years after initial surgery. He was followed up every 2 years and currently presented with an 8-month history of progressive weakness in his lower limbs. An MRI of the spine confirmed recurrence of lipoma. He underwent redo laminectomy and partial resection and spinal cord decompression with duroplasty. Lipoma, although a low-grade tumour, can cause significant neurological deficits because of its location. Surgical exploration and removal of lipoma is recommended. However, to preserve the functionality of the spinal cord, one may resort to partial resection and aim for spinal cord decompression. The literature on spinal cord lipoma is reviewed and the aetiopathogenesis of this rare occurrence is described. PMID:22675149

Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

PubMed

Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

2014-07-03

Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

Neuropeptide Y in human spinal cord.

PubMed

Allen, J M; Gibson, S J; Adrian, T E; Polak, J M; Bloom, S R

1984-08-06

The distribution of a newly described peptide, neuropeptide Y (NPY) within the human spinal cord has been determined using radioimmunoassay and immunocytochemistry. Higher concentrations were found in the lumbar (49.9 +/- 6.8 pmol/g) and sacral (47.0 +/- 10.6 pmol/g) regions than in the cervical (27.6 +/- 2.7 pmol/g) and thoracic spinal cord (33.8 +/- 5.3 pmol/g). Immunocytochemistry revealed numerous nerve fibers containing NPY in the spinal cord; these were particularly concentrated in the substantia gelatinosa of the dorsal horn. In the ventral spinal cord NPY-containing nerves were sparse becoming more abundant in lumbosacral segments.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

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

PubMed

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.

Living with Spinal Cord Injury

MedlinePlus

... With Spinal Cord Injury A spinal cord injury (SCI) can result from trauma, such as a motor ... these injuries occur in men. A person with SCI typically has some paralysis and decreased or loss ...

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

PubMed

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

2007-01-01

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

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

PubMed

Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

2017-05-01

Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

Spinal cord injury - Symptoms and causes

MedlinePlus

... are the leading cause of spinal cord injuries, accounting for almost half of new spinal cord injuries ... address these problems if they affect you. Respiratory system. Your injury may make it more difficult to ...

Spinal cord injury following operative shoulder intervention: A case report.

PubMed

Cleveland, Christine; Walker, Heather

2015-07-01

Cervical myelopathy is a spinal cord dysfunction that results from extrinsic compression of the spinal cord, its blood supply, or both. It is the most common cause of spinal cord dysfunction in patients greater than 55 years of age. A 57-year-old male with right shoulder septic arthritis underwent surgical debridement of his right shoulder and sustained a spinal cord injury intraoperatively. The most likely etiology is damage to the cervical spinal cord during difficult intubation requiring multiple attempts in this patient with underlying asymptomatic severe cervical stenosis. Although it is not feasible to perform imaging studies on all patients undergoing intubation for surgery, this patient's outcome would suggest consideration of inclusion of additional pre-surgical screening examination techniques, such as testing for a positive Hoffman's reflex, is appropriate to detect asymptomatic patients who may have underlying cervical stenosis.

Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.

PubMed

Zhou, Yue-fei; Li, Liang; Feng, Feng; Yuan, Hua; Gao, Da-kuan; Fu, Luo-an; Fei, Zhou

2013-12-01

Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats. Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function. We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors. All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome.

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

The triple monoamine re-uptake inhibitor DOV 216,303 promotes functional recovery after spinal cord contusion injury in mice.

PubMed

Chu, Tak-Ho; Cummins, Karen; Stys, Peter K

2018-05-14

Serotonin, noradrenaline and dopamine are important neuromodulators for locomotion in the spinal cord. Disruption of descending axons after spinal cord injury resulted in reduction of excitatory and neuromodulatory inputs to spinal neurons for locomotion. Receptor agonists or reuptake inhibitors for these neuromodulators have been shown to be beneficial in incomplete spinal cord injury. In this study, we tested a triple re-uptake inhibitor, DOV 216,303, for its ability to affect motor function recovery after spinal cord injury in mice. We impacted C57 mouse spinal cord at the T11 vertebral level and administered vehicle or DOV 216,303 at 10 mg/kg, b.i.d via intraperitoneal injections for 7 days. We monitored motor function with the Basso Mouse Scale for locomotion for 4 weeks. Spinal cords were harvested and histological examinations were performed to assess tissue sparing and lesion severity. Results showed that DOV 216,303-treated mice recovered significantly better than vehicle treated mice starting at 14 days post injury until the end of the survival period. Lesion size of the DOV 216,303 treated mice was also smaller compared to that of vehicle treated mice. This study suggests DOV 216,303 as a potential therapeutic after spinal cord injury warrants further investigation. Copyright © 2018 Elsevier B.V. All rights reserved.

Exercise Preconditioning Protects against Spinal Cord Injury in Rats by Upregulating Neuronal and Astroglial Heat Shock Protein 72

PubMed Central

Chang, Cheng-Kuei; Chou, Willy; Lin, Hung-Jung; Huang, Yi-Ching; Tang, Ling-Yu; Lin, Mao-Tsun; Chang, Ching-Ping

2014-01-01

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI. PMID:25334068

(18)F-FDG uptake of the spinal cord was decreased after conventional dose radiotherapy in esophageal cancer patients.

PubMed

Harata, Naoki; Yoshida, Katsuya; Oota, Sayako; Fujii, Hayahiko; Isogai, Jun; Yoshimura, Ryoichi

2016-01-01

We retrospectively investigated changes of (18)F-fluorodeocyglucose ((18)F-FDG) uptake in the spinal cord, inside and outside the radiation fields, in patients with esophageal cancer before and after conventional dose radiotherapy. A total of 17 consecutive patients with esophageal cancer (16 males, one female; age 50-83 years, mean 67.0 years), who underwent conventional dose radiotherapy and (18)F-FDG PET/CT before and 5.1 months (range 1.6-8.6 months) after the radiotherapy, were retrospectively evaluated. Sixteen patients had esophageal cancer and one patient had esophageal metastasis from thyroid cancer. Mean standardized uptake values (SUVmean) of the cervical, thoracic (inside and outside the radiation fields) and lumbar spinal cord were measured. SUVmean of the thoracic spinal cord inside the radiation field was decreased significantly after radiotherapy compared to those before radiotherapy (p < 0.001). SUVmean of the cervical spinal cord showed the same trend but it was not statistically significant (p = 0.051). SUVmean of the thoracic spinal cord outside the radiation field and the lumbar spinal cord did not differ significantly before and after the radiotherapy (p = 0.146 and p = 0.701, respectively). The results suggest that glucose metabolism of the spinal cord is decreased in esophageal cancer patients after conventional dose radiotherapy.

The adaptation to pregnancy of spinal cord injured women.

PubMed

Craig, D I

1990-01-01

This study explored the experiences encountered by spinal cord injured women during pregnancy. The spinal cord injured women experienced complications associated with pregnancy: recurring urinary tract infections, an increase in incontinence, and autonomic dysreflexia. (The first two of these are not unique to spinal cord injury, but are common in all pregnancies.) They neither developed pressure areas nor experienced premature deliveries, major complications predicted by the literature. All felt they were victims of inadequate environmental design that hindered their mobility and inhibited their independence. Many of the psychosocial aspects studied proved to be common to pregnant women in general and not specific to the spinal cord injured population.

Modeling spinal cord biomechanics

NASA Astrophysics Data System (ADS)

Luna, Carlos; Shah, Sameer; Cohen, Avis; Aranda-Espinoza, Helim

2012-02-01

Regeneration after spinal cord injury is a serious health issue and there is no treatment for ailing patients. To understand regeneration of the spinal cord we used a system where regeneration occurs naturally, such as the lamprey. In this work, we analyzed the stress response of the spinal cord to tensile loading and obtained the mechanical properties of the cord both in vitro and in vivo. Physiological measurements showed that the spinal cord is pre-stressed to a strain of 10%, and during sinusoidal swimming, there is a local strain of 5% concentrated evenly at the mid-body and caudal sections. We found that the mechanical properties are homogeneous along the body and independent of the meninges. The mechanical behavior of the spinal cord can be characterized by a non-linear viscoelastic model, described by a modulus of 20 KPa for strains up to 15% and a modulus of 0.5 MPa for strains above 15%, in agreement with experimental data. However, this model does not offer a full understanding of the behavior of the spinal cord fibers. Using polymer physics we developed a model that relates the stress response as a function of the number of fibers.

NORADRENERGIC INNERVATION OF THE RAT SPINAL CORD CAUDAL TO A COMPLETE SPINAL CORD TRANSECTION: EFFECTS OF OLFACTORY ENSHEATHING GLIA

PubMed Central

Takeoka, Aya; Kubasak, Marc D.; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R.; Phelps, Patricia E.

2010-01-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. PMID:20025875

Evaluation of Staff’s Job Satisfaction in the Spinal Cord Unit in Italy

PubMed Central

Laura, Cominetti; Lorenza, Garrino; Rita, Decorte; Nadia, Felisi; Ebe, Matta; Vittoria, Actis Maria; Roberto, Carone; Silvano, Gregorino; Valerio, Dimonte

2013-01-01

In July 2007 a Spinal Cord Unit was set up in Turin (Italy) within the newly integrated structure of the Orthopaedic Traumatologic Centre, warranting a multidisciplinary and professional approach according to International Guidelines. This approach will be possible through experimentation of a personalized care model. To analyze job satisfaction of health care professionals operating within the Spinal Cord Unit, preliminary to organizational change. Data collection was carried out by using questionnaires, interviews, shadowing. Results from quantitative analysis on the self-filled questionnaires were integrated with results from qualitative analysis. All the health care professionals operating in the field were involved. Positive aspects were the perception of carrying out a useful job, the feeling of personal fulfilment and the wish to engage new energies and resources. Problematic aspects included role conflict among staff categories and communication with managers. The positive aspects can be exploited to create professional practices facilitating role and expertise integration, information spreading and staff identification within the organization rather than team work. Data of job satisfaction and self efficacy of health care workers can be considered basic requirement before implementing an organizational change. The main challenges is multiprofessional collaboration. PMID:23750186

Temporal components of the motor patterns expressed by the human spinal cord reflect foot kinematics.

PubMed

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

2003-11-01

What are the building blocks with which the human spinal cord constructs the motor patterns of locomotion? In principle, they could correspond to each individual activity pattern in dozens of different muscles. Alternatively, there could exist a small set of constituent temporal components that are common to all activation patterns and reflect global kinematic goals. To address this issue, we studied patients with spinal injury trained to step on a treadmill with body weight support. Patients learned to produce foot kinematics similar to that of healthy subjects but with activity patterns of individual muscles generally different from the control group. Hidden in the muscle patterns, we found a basic set of five temporal components, whose flexible combination accounted for the wide range of muscle patterns recorded in both controls and patients. Furthermore, two of the components were systematically related to foot kinematics across different stepping speeds and loading conditions. We suggest that the components are related to control signals output by spinal pattern generators, normally under the influence of descending and afferent inputs.

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

PubMed Central

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

Spinal cord repair in MS

PubMed Central

Ciccarelli, O.; Altmann, D. R.; McLean, M. A.; Wheeler-Kingshott, C. A.; Wimpey, K.; Miller, D. H.; Thompson, A. J.

2010-01-01

Objective: To investigate the mechanisms of spinal cord repair and their relative contribution to clinical recovery in patients with multiple sclerosis (MS) after a cervical cord relapse, using spinal cord 1H-magnetic resonance spectroscopy (MRS) and volumetric imaging. Methods: Fourteen patients with MS and 13 controls underwent spinal cord imaging at baseline and at 1, 3, and 6 months. N-acetyl-aspartate (NAA) concentration, which reflects axonal count and metabolism in mitochondria, and the cord cross-sectional area, which indicates axonal count, were measured in the affected cervical region. Mixed effect linear regression models investigated the temporal evolution of these measures and their association with clinical changes. Ordinal logistic regressions identified predictors of recovery. Results: Patients who recovered showed a sustained increase in NAA after 1 month. In the whole patient group, a greater increase of NAA after 1 month was associated with greater recovery. Patients showed a significant decline in cord area during follow-up, which did not correlate with clinical changes. A worse recovery was predicted by a longer disease duration at study entry. Conclusions: The partial recovery of N-acetyl-aspartate levels after the acute event, which is concurrent with a decline in cord cross-sectional area, may be driven by increased axonal mitochondrial metabolism. This possible repair mechanism is associated with clinical recovery, and is less efficient in patients with longer disease duration. These insights into the mechanisms of spinal cord repair highlight the need to extend spinal cord magnetic resonance spectroscopy to other spinal cord disorders, and explore therapies that enhance recovery by modulating mitochondrial activity. GLOSSARY CI = confidence interval; EDSS = Expanded Disability Status Scale; FOV = field of view; MR = magnetic resonance; MRS = magnetic resonance spectroscopy; MS = multiple sclerosis; NAA = N-acetyl-aspartate; SC = spinal cord; TE = echo time; TI = inversion time; TR = repetition time. PMID:20107138

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

PubMed Central

Mishra, Asht M.; Pal, Ajay; Gupta, Disha

2017-01-01

Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

PubMed

Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Comparison of Motor-Evoked Potentials Versus Somatosensory-Evoked Potentials as Early Indicators of Neural Compromise in Rat Model of Spinal Cord Compression.

PubMed

Morris, Susan H; Howard, Jason J; El-Hawary, Ron

2017-03-15

Randomized controlled study comparing the efficacy of intraoperative somatosensory-evoked potentials (SSEPs) versus transcranial motor-evoked potentials (TcMEPs) as early indicators of neural compromise and predictors of postoperative function in a rat model of spinal cord compression. To compare the relative efficacy of SSEPs and TcMEPs to detect spinal cord compromise and predict postoperative functional deficit after spinal cord compression. There is controversy regarding the efficacy of SSEPs versus TcMEPs to detect intraoperative spinal cord compromise and predict functional outcomes. Previous trials provide some guidance as to the role of each modality in spinal cord monitoring but randomized controlled trials, which are not feasible in humans, are lacking. Twenty-four adult male Wistar rats were evenly divided into three experimental groups and one control group. The experimental groups were determined according to the length of time that 100% TcMEP signal loss was maintained: 0, 5, or 15 minutes. All animals had standardized preoperative functional testing. Spinal cord compromise was initiated utilizing a validated protocol, which involved compression via a balloon catheter introduced into the thoracic sublaminar space. Both SSEPs and TcMEPs were recorded during cord compression for each experimental group. Functional behavioral testing using two validated methods (tilt and modified Tarlov) was repeated 24 hours after termination of spinal cord compression. Post hoc, animals were redistributed into two functional subgroups, noncompromised and compromised, for statistical analysis. TcMEPs consistently detected spinal cord compromise either in advance of or at the same time as SSEPs; however, the delay in SSEP response was not significant for cases when compromised postoperative function resulted. Both SSEP and TcMEP amplitude recovery correlated well with postoperative functional scores. TcMEPs are more sensitive to spinal cord compromise than SSEPs, but the recovery profiles of both SSEP and TcMEP amplitudes are good predictors of postoperative function. 2.

Brain stem origins of spinal projections in the lizard Tupinambis nigropunctatus.

PubMed

Cruce, W L; Newman, D B

1981-05-10

In order to study brainstem origins of spinal projections, ten Tegu lizards (Tupinambis nigropunctatus) received complete or partial hemisections of the spinal cord at the first or second cervical segment. Their brains were processed for conventional Nissl staining. The sections were surveyed for the presence or absence of retrograde chromatolysis. Based on analysis and comparison of results from lesions in the various spinal cord funiculi, the following conclusions were reached: The interstitial nucleus projects ipsilaterally to the spinal cord via the medial longitudinal fasciculus, as does the middle reticular field of the metencephalon. The red nucleus and dorsal vagal motor nucleus both project contralaterally to the spinal cord via the dorsal part of the lateral funiculus. The superior reticular field in the rostral metencephalon and the ventrolateral vestibular nucleus project ipsilaterally to the spinal cord via the ventral funiculus. The dorsolateral metencephalic nucleus and the ventral part of the inferior reticular nucleus of the myelencephalon both project ipsilaterally to the spinal cord via the dorsal part of the lateral funiculus. Several brainstem nuclei in Tupinambis project bilaterally to the spinal cord. The ventrolateral metencephalic nucleus, for example, projects ipsilaterally to the cord via the medial longitudinal fasciculus and contralaterally via the dorsal part of the lateral funiculus. The dorsal part of the inferior reticular nucleus projects bilaterally to the spinal cord via the dorsal part of the lateral funiculus. The nucleus solitarius complex projects contralaterally via the dorsal part of the lateral funiculus but ipsilaterally via the middle of the lateral funiculus. The inferior raphe nucleus projects bilaterally to the spinal cord via the middle part of the lateral funiculus. These data suggest that supraspinal projections in reptiles, especially reticulospinal systems, are more highly differentiated than previously thought. On the other hand, recent findings in cat, opossum, and monkey reveal that the organization of supraspinal pathways in the Tegu lizard bears a striking resemblance to that observed in mammals.

Spinal cord aspergillus invasion--complication of an aspergilloma.

PubMed

Sheth, N K; Varkey, B; Wagner, D K

1985-12-01

Acute paraplegia developed in a 53-year-old man with pulmonary aspergilloma because of contiguous extension of Aspergillus infection to the epidural and subdural spaces and spinal cord. Histopathologic findings of the spinal cord showed Aspergillus hyphae penetrating the myelin sheath and myelomalacia, predominantly in the anterior and lateral columns. To the authors' knowledge, there have been no previous descriptions or illustrations of spinal cord involvement and the pathologic changes caused by Aspergillus infection.

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2014-10-01

atrophy. Interestingly, there is a clinical phenomenon that stretching can lead to muscle fiber hypertrophy , but that doesn’t appear to be...specific muscle groups) on functional recovery after spinal cord injury in a rat model. We have undertaken these studies because of an observation we...spinal cord injury, locomotor recovery, physical therapy, muscle stretch, joint range- of-motion, rat. Overall Project Summary: In this, the

Discrimination of heterogenous mRNAs encoding strychnine-sensitive glycine receptors in Xenopus oocytes by antisense oligonucleotides.

PubMed Central

Akagi, H; Patton, D E; Miledi, R

1989-01-01

Three synthetic oligodeoxynucleotides complementary to different parts of an RNA encoding a glycine receptor subunit were used to discriminate heterogenous mRNAs coding for glycine receptors in adult and neonatal rat spinal cord. Injection of the three antisense oligonucleotides into Xenopus oocytes specifically inhibited the expression of glycine receptors by adult spinal cord mRNA. In contrast, the antisense oligonucleotides were much less potent in inhibiting the expression of glycine receptors encoded by neonatal spinal cord mRNA. Northern blot analysis revealed that the oligonucleotides hybridized mostly to an adult cord transcript of approximately 10 kilobases in size. This band was also present in neonatal spinal cord mRNA but its density was about one-fourth of the adult cord message. There was no intense band in the low molecular weight position (approximately 2 kilobases), the existence of which was expected from electrophysiological studies with size-fractionated mRNA of neonatal spinal cord. Our results suggest that in the rat spinal cord there are at least three different types of mRNAs encoding functional strychnine-sensitive glycine receptors. Images PMID:2479016

Systemic hypothermia for the treatment of acute cervical spinal cord injury in sports.

PubMed

Dietrich, William Dalton; Cappuccino, Andrew; Cappuccino, Helen

2011-01-01

Spinal cord injury is a devastating condition that affects approximately 12,000 patients each year in the United States. Major causes for spinal cord injury include motor vehicle accidents, sports-related injuries, and direct trauma. Moderate hypothermia has gained attention as a potential therapy due to recent experimental and clinical studies and the use of modest systemic hypothermia (MSH) in high profile case of spinal cord injury in a National Football League (NFL) player. In experimental models of spinal cord injury, moderate hypothermia has been shown to improve functional recovery and reduce overall structural damage. In a recent Phase I clinical trial, systemic hypothermia has been shown to be safe and provide some encouraging results in terms of functional recovery. This review will summarize recent preclinical data, as well as clinical findings that support the continued investigations for the use of hypothermia in severe cervical spinal cord injury.

Spinal Cord Ischemia Secondary to Hypovolemic Shock

PubMed Central

Kapoor, Siddhant; Koh, Roy KM; Yang, Eugene WR; Hee, Hwan-Tak

2014-01-01

A 44-year-old male presented with symptoms of spinal cord compression secondary to metastatic prostate cancer. An urgent decompression at the cervical-thoracic region was performed, and there were no complications intraoperatively. Three hours postoperatively, the patient developed acute bilateral lower-limb paralysis (motor grade 0). Clinically, he was in class 3 hypovolemic shock. An urgent magnetic resonance imaging (MRI) was performed, showing no epidural hematoma. He was managed aggressively with medical therapy to improve his spinal cord perfusion. The patient improved significantly, and after one week, he was able to regain most of his motor functions. Although not commonly reported, spinal cord ischemia post-surgery should be recognized early, especially in the presence of hypovolemic shock. MRI should be performed to exclude other potential causes of compression. Spinal cord ischemia needs to be managed aggressively with medical treatment to improve spinal cord perfusion. The prognosis depends on the severity of deficits, and is usually favorable. PMID:25558328

Revisiting the segmental organization of the human spinal cord.

PubMed

Leijnse, J N; D'Herde, K

2016-09-01

In classic anatomic atlases, the spinal cord is standardly represented in its anatomical form with symmetrically emerging anterior and posterior roots, which at the level of the intervertebral foramen combine into the spinal nerves. The parts of the cord delimited by the boundaries of the roots are called segments or myelomeres. Associated with their regular repetitive appearance is the notion that the cord is segmentally organized. This segmental view is reinforced by clinical practice. Spinal cord roots innervate specific body parts. The level of cord trauma is diagnosed by the de-innervation symptoms of these parts. However, systemically, the case for a segmentally organized cord is not so clear. To date, developmental and genetic research points to a regionally rather than a segmentally organized cord. In the present study, to what degree the fila radicularia are segmentally implanted along the cord was investigated. The research hypothesis was that if the fila radicularia were non-segmentally implanted at the cord surface, it would be unlikely that the internal neuron stratum would be segmented. The visual segmented aspect of the myelomeres would then be the consequence of the necessary bundling of axons towards the vertebral foramen as the only exits of the vertebral canal, rather than of an underlying segment organization of the cord itself. To investigate the research hypothesis, the fila radicularia in the cervical-upper thoracic part of five spinal cords were detached from their spinal nerves and dissected in detail. The principal research question was if the fila radicularia are separated from their spinal nerves and dissected from their connective tissues up to the cord, would it be possible to reconstruct the original spinal segments from the morphology and interspaces of the fila? The dissections revealed that the anterior fila radicularia emerge from the cord at regular regionally modulated interspaces without systematic segmental delineations. The posterior fila radicularia are somewhat more segmentally implanted, but the pattern is individually inconsistent. The posterior and anterior roots have notable morphological differences, and hypotheses are presented to help explain these. The macroscopic observations are consistent with a regionally but not a segmentally organized cord. This conclusion was visually summarized in photographs of spinal cords with ipsilateral intact roots and contralateral individually dissected fila radicularia. It was suggested that this dual view of the spinal cord be added to the standard anatomic textbooks to counterbalance the current possibly biased view of a segmented cord. © 2016 Anatomical Society.

MRI Atlas-Based Measurement of Spinal Cord Injury Predicts Outcome in Acute Flaccid Myelitis.

PubMed

McCoy, D B; Talbott, J F; Wilson, Michael; Mamlouk, M D; Cohen-Adad, J; Wilson, Mark; Narvid, J

2017-02-01

Recent advances in spinal cord imaging analysis have led to the development of a robust anatomic template and atlas incorporated into an open-source platform referred to as the Spinal Cord Toolbox. Using the Spinal Cord Toolbox, we sought to correlate measures of GM, WM, and cross-sectional area pathology on T2 MR imaging with motor disability in patients with acute flaccid myelitis. Spinal cord imaging for 9 patients with acute flaccid myelitis was analyzed by using the Spinal Cord Toolbox. A semiautomated pipeline using the Spinal Cord Toolbox measured lesion involvement in GM, WM, and total spinal cord cross-sectional area. Proportions of GM, WM, and cross-sectional area affected by T2 hyperintensity were calculated across 3 ROIs: 1) center axial section of lesion; 2) full lesion segment; and 3) full cord atlas volume. Spearman rank order correlation was calculated to compare MR metrics with clinical measures of disability. Proportion of GM metrics at the center axial section significantly correlated with measures of motor impairment upon admission ( r [9] = -0.78; P = .014) and at 3-month follow-up ( r [9] = -0.66; P = .05). Further, proportion of GM extracted across the full lesion segment significantly correlated with initial motor impairment ( r [9] = -0.74, P = .024). No significant correlation was found for proportion of WM or proportion of cross-sectional area with clinical disability. Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis. This is the first atlas-based study to correlate clinical outcomes with segmented measures of T2 signal abnormality in the spinal cord. © 2017 by American Journal of Neuroradiology.

Dynamic Detection of Spinal Cord Position During Postural Changes Using Near-Infrared Reflectometry.

PubMed

Wolf, Erich W

2015-08-01

Motion of the spinal cord relative to a spinal cord stimulator epidural electrode array can cause suboptimal stimulation: either noxious, inefficient, or insufficient. Adaptive stimulation attempts to mitigate these effects by modulating stimulation parameters in a position-dependent fashion. Near-infrared (NIR) reflectometry is demonstrated to provide real-time direct measurement of spinal cord position at the site of stimulation, which can facilitate closed-loop adaptive stimulation during static and dynamic motion states. A miniature sensor array consisting of an NIR light emitting diode flanked by phototransistors potted in epoxy was placed in the dorsal epidural space of a human cadaver at the T8 level via laminotomy. Turgor of the subarachnoid space was maintained by intrathecal infusion of saline. NIR reflectance was measured as the cadaver was rotated about its longitudinal axis on a gantry. NIR reflectance was correlated with gantry position and velocity. NIR reflectometry suggests gravitational force is the primary determinant of cord position in static, ordinal positions. Under dynamic motion conditions, there was statistically significant cross-correlation between reflectometry data and the tangential velocity squared, suggesting that centripetal force was the primary determinant of cord position as the gantry was rotated. Reflectometry data strongly correlated with a simple geometric model of anticipated spinal cord precession within the spinal canal. Spinal cord position during dynamic motion has been shown to differ from static predictions due to additional influences such as centripetal force. These findings underscore limitations in extrapolating spinal cord position from surrogates such as body position or body acceleration at sites remote from the stimulating electrodes. NIR reflectometry offers a real-time direct measure of spinal cord position in both static and dynamic motion states, which may facilitate closed-loop adaptive stimulation applications. © 2015 International Neuromodulation Society.

Posttraumatic growth in people with traumatic long-term spinal cord injury: predictive role of basic hope and coping.

PubMed

Byra, S

2016-06-01

Participants with spinal cord injury (SCI) sustained at least 15 years before the study completed questionnaires measuring posttraumatic growth (PTG), basic hope and coping strategies. To determine contribution of basic hope and coping strategies to accounting for PTG variability in participants with traumatic long-term SCI. Polish rehabilitation centres, foundations and associations implementing social inclusion and professional activation programmes. Participants were enrolled based on their medical history by trained rehabilitation specialists and psychologists. The set of questionnaires included the following: The Post-traumatic Growth Inventory; The Coping Orientations to Problems Experienced (COPE); and Basic Hope Inventory. A study of 169 individuals with paraplegia in the range of PTG showed the highest degree of positive changes in appreciation of life (AL) and the lowest in self-perception. Regression analysis showed that coping strategies such as religion (REL), focus on the problem, humour, alcohol/drug use ideation and basic hope jointly account for 60% of variance of PTG. The highest contribution to accounting for this variability had REL. Also, it was found that coping strategies and basic hope allow to predict variance of individual growth aspects. Age at trauma exposure positively correlated with changes in AL and spiritual change. No significant relationship between growth and age of participants was confirmed. PTG occurring in people with long-term traumatic SCI is primarily manifested in increased AL. Specific coping strategies and basic hope have a significant role in fostering positive changes.

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

PubMed

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.

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

PubMed

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

2003-01-01

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

[Anesthesia for surgery of degenerative and abnormal cervical spine].

PubMed

Béal, J L; Lopin, M C; Binnert, M

1993-01-01

A feature common to all congenital or inflammatory abnormalities of the cervical spine is an actual or potential reduction in the lumen of the spinal canal. The spinal cord and nerve roots are at risk. During intubation, and positioning the patient on the table, all untoward movements of the cervical spine may lead to spinal cord compression. Abnormalities of the cervical spine carry the risk of a difficult intubation. If there is much debate as to what constitutes optimum management of the airway, there is no evidence that any one method is the best. Recognizing the possible instability and intubating with care, are probably much more important in preserving neurological function than any particular mode of intubation. During maintenance of anaesthesia, the main goal is to preserve adequate spinal cord perfusion in order to prevent further damage. Spinal cord blood flow seems to be regulated by the same factors as cerebral blood flow. Hypercapnia increases cord blood flow while hypocapnia decreases it. Therefore, normocapnia or mild hypocapnia is recommended. Induced hypotension is frequently used to decrease blood loss. However, in patients with a marginally perfused spinal cord, the reduction in blood flow may cause ischaemia of the spinal cord and may therefore be relatively contraindicated. In addition to standard intraoperative monitoring, spinal cord monitoring is almost mandatory. Monitoring somatosensory evoked potentials is used routinely. However, the major limitation is that this technique only monitors dorsal column function; theoretically, motor paralysis can occur despite a lack of change in recorded signals. Neurogenic motor evoked potentials may now be used to monitor anterior spinal cord integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic spinal cord injury in the cervical spine of a young soccer player.

PubMed

Kato, Yoshihiko; Koga, Michiaki; Taguchi, Toshihiko

2010-05-12

A 17-year-old male soccer player presented with numbness in the upper- and lower-left extremities of 6 months' duration. He had no apparent history of trauma but experienced neck pain during heading of the ball 5 years prior. A high-signal intensity area was seen on T2-weighted magnetic resonance imaging (MRI) of the cervical spine. No muscle weakness was observed. Hypoesthesia was observed in bilateral forearms, hands, and extremities below the inguinal region. Plain radiographs in the neutral position showed local kyphosis at C3/4. A small protrusion of the C3/4 disk was observed on T1-weighted MRI. A high-signal area in the spinal cord at the C3/4 level was observed on T2-weighted MRI, but this was not enhanced by gadolinium. Multiple sclerosis, intramedullary spinal cord tumor, sarcoidosis and malignant lymphoma, and spinal cord injury were all considered in the differential diagnosis. However, in view of the clinical, laboratory, and radiological investigations, we concluded that repeated impacts to the neck caused by heading of the ball during soccer induced a chronic, minor spinal cord injury. This contributed to the high-signal intensity change of the spinal cord in T2-weighted MRI. The present case demonstrates that repeated impact may cause chronic spinal cord injury. Soccer, American football, or rugby players presenting with neck or extremity symptoms should not be overlooked for the possibility of latent spinal cord injury, as this could present later development of more severe or unrecoverable spinal cord injuries. Copyright 2010, SLACK Incorporated.

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

PubMed

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

2015-11-01

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

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

PubMed

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

2015-05-01

The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.

PubMed

Wang, Qiang; Ding, Qian; Zhou, Yiming; Gou, Xingchun; Hou, Lichao; Chen, Shaoyang; Zhu, Zhenghua; Xiong, Lize

2009-06-01

Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process. EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay. The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion. These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

PubMed

Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

2013-01-21

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

In memoriam: Dr. Gary A. Dudley (1952-2006) a modern pioneer in the study of muscle and resistance training.

PubMed

2007-02-01

Dr. Gary Alton Dudley was a modern pioneer in the study of muscle. His work encompassed almost 30 years of study with dramatic discoveries in the areas of muscle physiology, resistance training, and spinal cord injury and therapy. The greater understanding of muscle fiber changes with training, as well as novel experiments using magnetic resonance imaging and single fiber analyses, allowed for many discoveries in the areas of resistance training and detraining, the roles of electrical stimulation in training muscle, the compatibility of different exercise modes, and the characteristics of and treatment interventions for spinal cord injury. His work and insights will provide future investigators a knowledge base from which to work for both basic and applied research in muscle and exercise physiology.

Concomitance of cervical intramedullary traumatic neuroma and cervical cord herniation in a tetraplegic woman.

PubMed

Su, Hui-Yi; Wu, Yung-Tsan; Liu, Ming-Ying; Lin, Yu-Chun; Chu, Heng-Yi; Chang, Shin-Tsu

2013-01-01

We present the first case of concomitant intramedullary traumatic neuroma and spinal cord herniation. A 57-year-old woman injured her cervical spine with subluxation and cord compression at the C5-C6 level. After the operation, the patient received intensive rehabilitation for one year with well response. Unfortunately, she experienced weakness and progressive numbness extending to all the limbs later. Cervical magnetic resonance imaging revealed spinal cord herniation at the C5-C6 level and pathology proved intramedullary traumatic neuroma. After the second operation, the paresthesia over the trunk and limbs persisted, and the patient was nearly totally assisted in her activities of daily living. The intramedullary traumatic neuroma and spinal cord herniation are rare causes in patients with spinal cord dysfunction. The case presented here indicates the possibility of the coexisting conditions leading to progressive neurologic deficits in patients with old spinal cord injury.

Spinal cord tumors: new views and future directions.

PubMed

Mechtler, Laszlo L; Nandigam, Kaveer

2013-02-01

Spinal cord tumors are uncommon neoplasms that, without treatment, can cause significant neurologic morbidity and mortality. The historic classification of spine tumors is based on the use of myelography with 3 main groups: (1) extramedullary extradural, (2) intradural extramedullary, and (3) intradural intramedullary. This chapter focuses on intramedullary spinal cord tumors (ISCTs), with an emphasis on new diagnostic imaging modalities and treatment options. The common ISCTs include ependymoma, astrocytoma and hemangioblastoma, which together account for over 90% of primary ISCTs. Rare tumors such as gangliglioma, oligodendroglioma, paraganglioma, melanocytoma, lipoma, and primary spinal cord lymphoma are also included in this review, in addition to spinal cord metastatic disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

PubMed Central

Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

2016-01-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

PubMed

Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

2016-11-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

The negotiated equilibrium model of spinal cord function.

PubMed

Wolpaw, Jonathan R

2018-04-16

The belief that the spinal cord is hardwired is no longer tenable. Like the rest of the CNS, the spinal cord changes during growth and aging, when new motor behaviours are acquired, and in response to trauma and disease. This paper describes a new model of spinal cord function that reconciles its recently appreciated plasticity with its long recognized reliability as the final common pathway for behaviour. According to this model, the substrate of each motor behaviour comprises brain and spinal plasticity: the plasticity in the brain induces and maintains the plasticity in the spinal cord. Each time a behaviour occurs, the spinal cord provides the brain with performance information that guides changes in the substrate of the behaviour. All the behaviours in the repertoire undergo this process concurrently; each repeatedly induces plasticity to preserve its key features despite the plasticity induced by other behaviours. The aggregate process is a negotiation among the behaviours: they negotiate the properties of the spinal neurons and synapses that they all use. The ongoing negotiation maintains the spinal cord in an equilibrium - a negotiated equilibrium - that serves all the behaviours. This new model of spinal cord function is supported by laboratory and clinical data, makes predictions borne out by experiment, and underlies a new approach to restoring function to people with neuromuscular disorders. Further studies are needed to test its generality, to determine whether it may apply to other CNS areas such as the cerebral cortex, and to develop its therapeutic implications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0132 TITLE: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury...Sept 2015 4. TITLE AND SUBTITLE Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury 5a...evaluate the restoration of bladder and bowel function using electrical stimulation and block after spinal cord injury in human subjects. All staff

Coupling between the spinal cord and cervical vertebral column under tensile loading.

PubMed

Kroeker, Shannon G; Ching, Randal P

2013-02-22

Current neck injury criteria are based on structural failure of the spinal (vertebral) column without consideration of injury to the spinal cord. Since one of the primary functions of the vertebral column is to protect the cord, it stands to reason that a more refined measure of neck injury threshold would be the onset of spinal cord injury (SCI). This study investigated the relationship between axial strains in the cervical vertebral column and the spinal cord using an in vitro primate model (n=10) under continuous tensile loading. Mean failure loads occurred at 1951.5±396N with failure strains in the vertebral column of 16±5% at the level of failure. Average tensile strains in the spinal cord at failure were 11±5% resulting in a mean coupling ratio of 0.54±0.17 between C1 and C7. The level of peak strain measured in the spinal cord did not always occur at the location of vertebral column failure. Spinal cord strains were less than spine strains and coupling ratios were not significantly different along the length of the spine. The largest coupling ratio was measured in the atlanto-occipital joint whereas the smallest coupling ratio occurred at the adjacent C1-C2 joint. Copyright © 2012 Elsevier Ltd. All rights reserved.

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: effects of olfactory ensheathing glia.

PubMed

Takeoka, Aya; Kubasak, Marc D; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R; Phelps, Patricia E

2010-03-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. Copyright 2009 Elsevier Inc. All rights reserved.

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis.

PubMed

Marini, Cecilia; Cistaro, Angelina; Campi, Cristina; Calvo, Andrea; Caponnetto, Claudia; Nobili, Flavio Mariano; Fania, Piercarlo; Beltrametti, Mauro C; Moglia, Cristina; Novi, Giovanni; Buschiazzo, Ambra; Perasso, Annalisa; Canosa, Antonio; Scialò, Carlo; Pomposelli, Elena; Massone, Anna Maria; Bagnara, Maria Caludia; Cammarosano, Stefania; Bruzzi, Paolo; Morbelli, Silvia; Sambuceti, Gianmario; Mancardi, Gianluigi; Piana, Michele; Chiò, Adriano

2016-10-01

In amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms. A new computational three-dimensional method to extract the spinal cord from (18)F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls. The algorithm identified the skeleton on the CT images by using an extension of the Hough transform and then extracted the spinal canal and the spinal cord. In these regions, (18)F-FDG standardized uptake values were measured to estimate the metabolic activity of the spinal canal and cord. Measurements were performed in the cervical and dorsal spine and normalized to the corresponding value in the liver. Uptake of (18)F-FDG in the spinal cord was significantly higher in patients than in controls (p < 0.05). By contrast, no significant differences were observed in spinal cord and spinal canal volumes between the two groups. (18)F-FDG uptake was completely independent of age, gender, degree of functional impairment, disease duration and riluzole treatment. Kaplan-Meier analysis showed a higher mortality rate in patients with standardized uptake values above the fifth decile at the 3-year follow-up evaluation (log-rank test, p < 0.01). The independence of this value was confirmed by multivariate Cox analysis. Our computational three-dimensional method enabled the evaluation of spinal cord metabolism and volume and might represent a potential new window onto the pathophysiology of amyotrophic lateral sclerosis.

Spinal cord injury below-level neuropathic pain relief with dorsal root entry zone microcoagulation performed caudal to level of complete spinal cord transection.

PubMed

Falci, Scott; Indeck, Charlotte; Barnkow, Dave

2018-06-01

OBJECTIVE Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically been performed at and cephalad to, but not below, the level of SCI. This study was initiated to investigate the validity of 3 proposed concepts regarding the DREZ in SCI central pain: 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through sympathetic nervous system (SNS) pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain-generators. METHODS Three unique patients with both intractable SCI below-level central pain and complete spinal cord transection at the level of SCI were identified. All 3 patients had previously undergone surgical intervention to their spinal cords-only cephalad to the level of spinal cord transection-with either DREZ microcoagulation or cyst shunting, in failed attempts to relieve their SCI below-level central pain. Subsequent to these surgeries, DREZ lesioning of the spinal cord solely caudal to the level of complete spinal cord transection was performed using electrical intramedullary guidance. The follow-up period ranged from 1 1/2 to 11 years. RESULTS All 3 patients in this study had complete or near-complete relief of all below-level neuropathic pain. The analyzed electrical data confirmed and enhanced a previously proposed somatotopic map of SCI below-level DREZ pain generators. CONCLUSIONS The results of this study support the following hypotheses. 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through SNS pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain generators.

Restoration of motor function after operative reconstruction of the acutely transected spinal cord in the canine model.

PubMed

Liu, Zehan; Ren, Shuai; Fu, Kuang; Wu, Qiong; Wu, Jun; Hou, Liting; Pan, Hong; Sun, Linlin; Zhang, Jian; Wang, Bingjian; Miao, Qing; Sun, Guiyin; Bonicalzi, Vincenzo; Canavero, Sergio; Ren, Xiaoping

2018-05-01

Cephalosomatic anastomosis or what has been called a "head transplantation" requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. We conducted a randomized, controlled study of a complete transection of the spinal cord at the level of T10 in dogs at Harbin Medical University, Harbin, China. These dogs were followed for up to 8 weeks postoperatively by assessments of recovery of motor function, somato-sensory evoked potentials, and diffusion tensor imaging using magnetic resonance imaging. A total of 12 dogs were subjected to operative exposure of the dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy followed by a very sharp, controlled, full-thickness, complete transection of the spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was applied to the site of transection in the remaining 5 control dogs. Dogs were selected randomly to receive polyethylene glycol or saline. All polyethylene glycol-treated dogs reacquired a substantial amount of motor function versus none in controls over these first 2 months as assessed on the 20-point (0-19), canine, Basso-Beattie-Bresnahan rating scale (P<.006). Somatosensory evoked potentials confirmed restoration of electrical conduction cranially across the site of spinal cord transection which improved over time. Diffusion tensor imaging, a magnetic resonance permutation that assesses the integrity of nerve fibers and cells, showed restitution of the transected spinal cord with polyethylene glycol treatment (at-injury level difference: P<.02). A sharply and fully transected spinal cord at the level of T10 can be reconstructed with restoration of many aspects of electrical continuity in large animals following the GEMINI spinal cord fusion protocol, with objective evidence of motor recovery and of electrical continuity across the site of transection, opening the way to the first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.). Copyright © 2017. Published by Elsevier Inc.

Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

PubMed

Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

2006-12-01

Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

Twitching in Sensorimotor Development from Sleeping Rats to Robots

PubMed Central

Marques, Hugo Gravato; Iida, Fumiya

2013-01-01

It is still not known how the “rudimentary” movements of fetuses and infants are transformed into the coordinated, flexible, and adaptive movements of adults. In addressing this important issue, we consider a behavior that has been perennially viewed as a functionless by-product of a dreaming brain: the jerky limb movements called myoclonic twitches. Recent work has identified the neural mechanisms that produce twitching as well as those that convey sensory feedback from twitching limbs to the spinal cord and brain. In turn, these mechanistic insights have helped inspire new ideas about the functional roles that twitching might play in the self-organization of spinal and supraspinal sensorimotor circuits. Striking support for these ideas is coming from the field of developmental robotics: When twitches are mimicked in robot models of the musculoskeletal system, basic neural circuitry self-organizes. Mutually inspired biological and synthetic approaches promise not only to produce better robots, but also to solve fundamental problems concerning the developmental origins of sensorimotor maps in the spinal cord and brain. PMID:23787051

Sexuality and sexual dysfunction in spinal cord-injured men in Turkey.

PubMed

Akman, Ramazan Yavuz; Coşkun Çelik, Evrim; Karataş, Metin

2015-01-01

To provide a comprehensive evaluation of sexual function and dysfunction in spinal cord-injured men based on self-reports of patients. Forty-seven spinal cord-injured men who completed the spinal shock and rehabilitation period were included. Patients were asked to complete a questionnaire developed to assess social status, sexual activities, abilities, and sexuality education after injury. Neurologic levels of patients were classified according to American Spinal Cord Injury Association protocol. Erectile function was evaluated by International Index of Erectile Function-5 (IIEF-5) questionnaire. Patients were aged between 20 and 62 years (mean: 35.2). Twenty-eight patients had T10 and above, 15 between T11 and L2, and 4 cauda conus injury. While 61.7% of the patients declared sexual activity, 93.6% declared some degree of erection. Mean IIEF-5 score was 5.3 and 87.3% of the patients had moderate to severe erectile dysfunction. Continuation of sexual activity after injury is very important and has a great impact on quality of life and interpersonal relationships for spinal cord-injured men. More attention must be given to sexuality after spinal cord injury. A very high rate of sexual dysfunction in spinal cord-injured patients was found and the importance of sexual education was emphasized in this study.

Complete spinal cord injury and brain dissection protocol for subsequent wholemount in situ hybridization in larval sea lamprey.

PubMed

Barreiro-Iglesias, Antón; Zhang, Guixin; Selzer, Michael E; Shifman, Michael I

2014-10-14

After a complete spinal cord injury, sea lampreys at first are paralyzed below the level of transection. However, they recover locomotion after several weeks, and this is accompanied by short distance regeneration (a few mm) of propriospinal axons and spinal-projecting axons from the brainstem. Among the 36 large identifiable spinal-projecting neurons, some are good regenerators and others are bad regenerators. These neurons can most easily be identified in wholemount CNS preparations. In order to understand the neuron-intrinsic mechanisms that favor or inhibit axon regeneration after injury in the vertebrates CNS, we determine differences in gene expression between the good and bad regenerators, and how expression is influenced by spinal cord transection. This paper illustrates the techniques for housing larval and recently transformed adult sea lampreys in fresh water tanks, producing complete spinal cord transections under microscopic vision, and preparing brain and spinal cord wholemounts for in situ hybridization. Briefly, animals are kept at 16°C and anesthetized in 1% Benzocaine in lamprey Ringer. The spinal cord is transected with iridectomy scissors via a dorsal approach and the animal is allowed to recover in fresh water tanks at 23 °C. For in situ hybridization, animals are reanesthetized and the brain and cord removed via a dorsal approach.

Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T.

PubMed

San Emeterio Nateras, Oscar; Yu, Fang; Muir, Eric R; Bazan, Carlos; Franklin, Crystal G; Li, Wei; Li, Jinqi; Lancaster, Jack L; Duong, Timothy Q

2016-04-01

To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P < .0001). The centroid coordinates across the four trials deviated by 2 in-plane voxels ± 2 mm (standard deviation) and up to one adjacent image section ± 3 mm. ICA of group resting-state functional MR imaging data revealed prominent functional connectivity patterns within the spinal cord gray matter. There were statistically significant (z score > 3, P < .001) bilateral, unilateral, and intersegmental correlations in the ventral horns, dorsal horns, and central spinal cord gray matter. Three-dimensional surface rendering provided visualization of these components along the length of the spinal cord. Seed-based analysis showed that many ICA components exhibited strong and significant (P < .05) correlations, corroborating the ICA results. Resting-state functional MR imaging connectivity networks are qualitatively consistent with known neuroanatomic and functional structures in the spinal cord. Resting-state functional MR imaging of the human cervical spinal cord with a 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the spinal cord gray matter, consistent with known functional and anatomic layouts of the spinal cord.

Spinal Cord as an Adjunct to Brain Magnetic Resonance Imaging in Defining “No Evidence of Disease Activity” in Multiple Sclerosis

PubMed Central

Tummala, Subhash; Singhal, Tarun; Oommen, Vinit V.; Kim, Gloria; Khalid, Fariha; Healy, Brian C.

2017-01-01

Background: Monitoring patients with multiple sclerosis (MS) for “no evidence of disease activity” (NEDA) may help guide disease-modifying therapy (DMT) management decisions. Whereas surveillance brain magnetic resonance imaging (MRI) is common, the role of spinal cord monitoring for NEDA is unknown. Objective: To evaluate the role of brain and spinal cord 3T MRI in the 1-year evaluation of NEDA. Methods: Of 61 study patients (3 clinically isolated syndrome, 56 relapsing-remitting, 2 secondary progressive), 56 (91.8%) were receiving DMT. The MRI included brain fluid-attenuated inversion recovery and cervical/thoracic T2-weighted fast spin echo images. On MRI, NEDA was defined as the absence of new or enlarging T2 lesions at 1 year. Results: Thirty-nine patients (63.9%) achieved NEDA by brain MRI, only one of whom had spinal cord activity. This translates to a false-positive rate for NEDA based on the brain of 2.6% (95% CI, 0.1%–13.5%). Thirty-eight patients (62.3%) had NEDA by brain and spinal cord MRI. Fifty-five patients (90.2%) had NEDA by spinal cord MRI, 17 of whom had brain activity. Of the 22 patients (36.1%) with brain changes, 5 had spinal cord changes. No evidence of disease activity was sustained in 48.3% of patients at 1 year and was the same with the addition of spinal cord MRI. Patients with MRI activity in either the brain or the spinal cord only were more likely to have activity in the brain (P = .0001). Conclusions: Spinal cord MRI had a low diagnostic yield as an adjunct to brain MRI at 3T in monitoring patients with MS for NEDA over 1 year. Studies with larger data sets are needed to confirm these findings. PMID:28603465

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

PubMed Central

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

The distribution and origin of a novel brain peptide, neuropeptide Y, in the spinal cord of several mammals.

PubMed

Gibson, S J; Polak, J M; Allen, J M; Adrian, T E; Kelly, J S; Bloom, S R

1984-07-20

The distribution of neuropeptide Y [NPY]-immunoreactive material was examined in the spinal cord and dorsal root ganglia of rat, guinea-pig, cat, marmoset, and horse. Considerable concentrations of NPY and similar distribution patterns of immunoreactive nerve fibres were found in the spinal cord of all species investigated. The dorsal root ganglia of the cat and the horse contained numerous immunoreactive nerve fibres, but in these species, as in the other three studied [rat, guinea-pig, marmoset], no positively stained cell bodies were found. Neuropeptide Y-immunoreactive nerves were observed at all levels of the spinal cord, being most concentrated in the dorsal horn. In the rat, guinea-pig, and marmoset, there was a marked increase of NPY-immunoreactive fibres in the lumbosacral regions of the spinal cord, and this was reflected by a considerable increase of extractable NPY. Estimations of NPY-immunoreactive material in the various regions of the rat spinal cord were as follows: cervical, 13.8 +/- 1.0; thoracic, 21.1 +/- 2.5; lumbar, 16.3 +/- 2.9; sacral, 92.4 +/- 8.5 pmol/gm wet weight of tissue +/- SEM. In the ventral portion of the guinea-pig spinal cord they were as follows: cervical, 7.1 +/- 1.2; thoracic, 8.2 +/- 3.6; lumbar, 22.6 +/- 7.0; sacral, 36.7 +/- 9.5 pmol/gm wet weight of tissue +/- SEM. Analysis of spinal cord extracts by reverse phase high performance liquid chromatography [HPLC] demonstrated that NPY-immunoreactive material elutes in the position of pure NPY standard. No changes in the concentration and distribution of the NPY-like material in the rat spinal cord were observed following a variety of surgical and pharmacological manipulations, including cervical rhizotomy, sciatic nerve section and ligation, and local application of capsaicin [50 mM] to one sciatic nerve. It is therefore suggested that most of the NPY-immunoreactive material in the spinal cord is derived either from intrinsic nerve cell bodies or from supraspinal tracts.

Effects of wheelchair propulsion on neuropathic pain and resting electroencephalography after spinal cord injury.

PubMed

Sato, Gosuke; Osumi, Michihiro; Morioka, Shu

2017-01-31

To investigate the effects of wheelchair propulsion on neuropathic pain and to examine resting electroencephalography pre- and post-wheelchair propulsion after spinal cord injury. Cross-sectional study. Eleven individuals with spinal cord injury and pain and 10 healthy controls. Single-session 15-min wheelchair propulsion and measurement of resting electroence-phalography. Effects of wheelchair propulsion were investigated using numerical rating scale (NRS) for neuropathic pain and short-form Profile of Mood States-Brief for mood. Peak alpha frequency on electroencephalography was calculated in 4 regions of interest; frontal, central, parietal and occipital areas. These outcomes were compared between pre- and post-wheelchair propulsion. Ten participants with spinal cord injury and all healthy controls completed the wheelchair propulsion exercise. NRS scores and negative mood were significantly improved following the wheelchair propulsion exercise. Pre-wheelchair propulsion, parietal and occipital peak alpha frequencies were significantly lower in the spinal cord injury group compared with the healthy controls group. Post-wheelchair propulsion, central peak alpha frequency increased in the spinal cord injury group. Wheelchair propulsion exercise temporarily decreased neuropathic pain intensity, improved negative mood, and modified alpha activity in spinal cord injury.

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

PubMed Central

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

2011-01-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Stem Cells 2011;29:2062–2076. PMID:22038821

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

PubMed

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

2011-12-01

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

Variations in the formation of the human caudal spinal cord.

PubMed

Saraga-Babić, M; Sapunar, D; Wartiovaara, J

1995-01-01

Collection of 15 human embryos between 4-8 developmental weeks was used to histologically investigate variations in the development of the caudal part of the spinal cord and the neighboring axial organs (notochord and vertebral column). In the 4-week embryo, two types of neurulation were parallelly observed along the anteroposterior body axis: primary in the areas cranial to the neuroporus caudalis and secondary in the more caudal tail regions. In the 5-week embryos, both parts of the neural tube fused, forming only one continuous lumen in the developing spinal cord. In the three examined embryos we found anomalous pattern of spinal cord formation. Caudal parts of these spinal cords displayed division of their central canal into two or three separate lumina, each surrounded by neuroepithelial layer. In the caudal area of the spinal cord, derived by secondary neurulation, formation of separate lumina was neither connected to any anomalous notochord or vertebral column formation, nor the appearance of any major axial disturbances. We suggest that development of the caudal part of the spinal cord differs from its cranial region not only in the type of neurulation, but also in the destiny of its derivatives and possible modes of abnormality formation.

Central Pain Syndrome

MedlinePlus

... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ... cord. This syndrome can be caused by stroke, multiple sclerosis, tumors, epilepsy, brain or spinal cord trauma, or ...

Significance of fixation of the vertebral column for spinal cord injury experiments.

PubMed

Liu, Fei; Luo, Zhuo-Jin; You, Si-Wei; Jiao, Xi-Ying; Meng, Xiao-Mei; Shi, Ming; Wang, Chun-Ting; Ju, Gong

2003-08-01

Thoracic spinal cord transections were performed in adult rats. The animals were divided into two groups, with or without internal fixation of the involved vertebral column. Histologic and immunohistochemical studies were performed to compare the effect of internal fixation of the vertebral column. To find out the aspects and extent of beneficial effects of vertebral column fixation for spinal cord repair. Vertebral column fixation is a routine procedure in clinical spinal cord surgery. Paradoxically, most, if not all, animal spinal cord experiments seem to have ignored the importance of vertebral column fixation. During trunk movements, the vertebral column flexes to different directions, accompanied by bending of the spinal cord. Following spinal cord lesions, with frequent bending of the cord there will be repeated bleeding, inflammation, and other pathologic processes at the lesion site. Thus, the healing process will be hampered. The severity of the damages that will be brought about by bending of the cord is, to a certain degree, unpredictable. There will be rather big individual variations in injury and repair among the same type of experiments, rendering quantification and conclusion difficult. Adult Sprague-Dawley rats were used. The thoracic spinal cord was transected. Strong stainless steel wires were used for internal fixation of the vertebral column. The histology of the horizontal sections of the spinal cord segment, which included the lesion site, was examined at the 14th postoperative day. The volumes of the secondary degeneration and meningeal scar, the gap between the borders of the proximal and distal stumps of the transected spinal cord, the thickness of the meningeal scar, the astrocytic reaction, and the abundance of regenerating nerve fibers at the lesion site were compared between the vertebral column fixed and nonfixed groups. Whenever possible, the results were evaluated quantitatively. In all these aspects, the internally fixed group was consistently far better than the unfixed group. The quantitative analyses were as follows (fixed/unfixed): 1)volume of secondary degeneration: 1.07 +/- 0.20/1.81 +/- 0.43 mm3 (P < 0.01); 2) volume of meningeal scar: 2.38 +/- 0.55/4.34 +/- 1.40 mm3 (P < 0.05); 3) distance between cord stumps: 1.38 +/- 0.34/2.35 +/- 0.79 mm (P < 0.05); 4) the mean thinnest dimension of the meningeal scar: 0.90 +/- 0.43/1.98 +/- 0.85 mm (P < 0.05). Vertebral column fixation is a crucial procedure for spinal cord animal experiments.

Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury.

PubMed

Kwiatkoski, Marcelo; Guimarães, Francisco Silveira; Del-Bel, Elaine

2012-04-01

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.

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

PubMed

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

2015-02-01

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. 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. 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. 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).

Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal Cord Ischemia in Rats.

PubMed

Takahashi, Shinya; Nakagawa, Kei; Tomiyasu, Mayumi; Nakashima, Ayumu; Katayama, Keijiro; Imura, Takeshi; Herlambang, Bagus; Okubo, Tomoe; Arihiro, Koji; Kawahara, Yumi; Yuge, Louis; Sueda, Taijiro

2018-05-01

Spinal cord ischemia is a devastating complication after thoracic and thoracoabdominal aortic operations. In this study, we aimed to investigate the effects of mesenchymal stem cells (MSCs), which have regenerative capability and exert paracrine actions on damaged tissues, injected into rat models of spinal cord ischemia-reperfusion injury. Forty-five Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord ischemia was induced in the latter two groups by balloon occlusion of the thoracic aorta. MSCs and PBS were then immediately injected into the left carotid artery of the MSC and PBS groups, respectively. Hindlimb motor function was evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after ischemia-reperfusion injury, and histologic and immunohistochemical analyses and real-time polymerase chain reaction assessments were performed. Rats in the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively. Hindlimb function was significantly better at 6 and 24 hours after ischemia-reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were observed in the spinal cord 24 hours after ischemia-reperfusion injury. The MSC therapy by transarterial injection immediately after spinal cord ischemia-reperfusion injury may improve lower limb function by preventing apoptosis of neuron cells in the spinal cord. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals.

PubMed

Savikj, Mladen; Ruby, Maxwell A; Kostovski, Emil; Iversen, Per O; Zierath, Juleen R; Krook, Anna; Widegren, Ulrika

2018-06-01

Despite the well-known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord-injured and six able-bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR. Abundance of differentiation markers and regulatory proteins was determined by Western blotting. Protein synthesis and fatty acid oxidation were measured by radioactive tracer-based assays. Activated satellite cells (myoblasts) and differentiated myotubes derived from skeletal muscle of able-bodied and spinal cord-injured individuals expressed similar (P > 0.05) mRNA levels of myogenic regulatory factors. Myogenic differentiation factor 1 expression was higher in myoblasts from spinal cord-injured individuals. Desmin and myogenin protein content was increased upon differentiation in both groups, while myotubes from spinal cord-injured individuals contained more type I and II myosin heavy chain. Phosphorylated and total protein levels of Akt-mechanistic target of rapamycin and forkhead box protein O signalling axes and protein synthesis rate in myotubes were similar (P > 0.05) between groups. Additionally, fatty acid oxidation of myotubes from spinal cord-injured individuals was unchanged (P > 0.05) compared to able-bodied controls. Our results indicate that the intrinsic differentiation capacity of satellite cells and metabolic characteristics of myotubes are preserved following spinal cord injury. This may inform potential interventions targeting satellite cell activation to alleviate skeletal muscle atrophy. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

PubMed Central

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

2016-01-01

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 < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that 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. PMID:26754788

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

PubMed Central

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

2015-01-01

Objective The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Methods Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future. PMID:26113960

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

PubMed Central

Mannheimer, C; Eliasson, T; Andersson, B; Bergh, C H; Augustinsson, L E; Emanuelsson, H; Waagstein, F

1993-01-01

OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal. PMID:8400930

Tissue-Engineered Regeneration of Hemisected Spinal Cord Using Human Endometrial Stem Cells, Poly ε-Caprolactone Scaffolds, and Crocin as a Neuroprotective Agent.

PubMed

Terraf, Panieh; Kouhsari, Shideh Montasser; Ai, Jafar; Babaloo, Hamideh

2017-09-01

Loss of motor and sensory function as a result of neuronal cell death and axonal degeneration are the hallmarks of spinal cord injury. To overcome the hurdles and achieve improved functional recovery multiple aspects, it must be taken into account. Tissue engineering approaches by coalescing biomaterials and stem cells offer a promising future for treating spinal cord injury. Here we investigated human endometrial stem cells (hEnSCs) as our cell source. Electrospun poly ε-caprolactone (PCL) scaffolds were used for hEnSC adhesion and growth. Scanning electron microscopy (SEM) confirmed the attachment and survival of stem cells on the PCL scaffolds. The scaffold-stem cell construct was transplanted into the hemisected spinal cords of adult male rats. Crocin, an ethanol-extractable component of Crocus sativus L., was administered to rats for 15 consecutive days post injury. Neurite outgrowth and axonal regeneration were investigated using immunohistochemical staining for neurofilament marker NF-H and luxol-fast blue (LFB) staining, respectively. TNF-α staining was performed to determine the inflammatory response in each group. Functional recovery was assessed via the Basso-Beattie-Bresnahan (BBB) scale. Results showed that PCL scaffolds seeded with hEnSCs restored the continuity of the damaged spinal cord and decreased cavity formation. Additionally, hEnSC-seeded scaffolds contributed to the functional recovery of the spinal cord. Hence, hEnSC-seeded PCL scaffolds may serve as promising transplants for spinal cord tissue engineering purposes. Furthermore, crocin had an augmenting effect on spinal cord regeneration and proved to exert neuroprotective effects on damaged neurons and may be further studied as a promising drug for spinal cord injury.

Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons.

PubMed

Cocks, Graham; Romanyuk, Nataliya; Amemori, Takashi; Jendelova, Pavla; Forostyak, Oksana; Jeffries, Aaron R; Perfect, Leo; Thuret, Sandrine; Dayanithi, Govindan; Sykova, Eva; Price, Jack

2013-06-07

The use of immortalized neural stem cells either as models of neural development in vitro or as cellular therapies in central nervous system (CNS) disorders has been controversial. This controversy has centered on the capacity of immortalized cells to retain characteristic features of the progenitor cells resident in the tissue of origin from which they were derived, and the potential for tumorogenicity as a result of immortalization. Here, we report the generation of conditionally immortalized neural stem cell lines from human fetal spinal cord tissue, which addresses these issues. Clonal neural stem cell lines were derived from 10-week-old human fetal spinal cord and conditionally immortalized with an inducible form of cMyc. The derived lines were karyotyped, transcriptionally profiled by microarray, and assessed against a panel of spinal cord progenitor markers with immunocytochemistry. In addition, the lines were differentiated and assessed for the presence of neuronal fate markers and functional calcium channels. Finally, a clonal line expressing eGFP was grafted into lesioned rat spinal cord and assessed for survival, differentiation characteristics, and tumorogenicity. We demonstrate that these clonal lines (a) retain a clear transcriptional signature of ventral spinal cord progenitors and a normal karyotype after extensive propagation in vitro, (b) differentiate into relevant ventral neuronal subtypes with functional T-, L-, N-, and P/Q-type Ca(2+) channels and spontaneous calcium oscillations, and (c) stably engraft into lesioned rat spinal cord without tumorogenicity. We propose that these cells represent a useful tool both for the in vitro study of differentiation into ventral spinal cord neuronal subtypes, and for examining the potential of conditionally immortalized neural stem cells to facilitate functional recovery after spinal cord injury or disease.

Fast and accurate semi-automated segmentation method of spinal cord MR images at 3T applied to the construction of a cervical spinal cord template.

PubMed

El Mendili, Mohamed-Mounir; Chen, Raphaël; Tiret, Brice; Villard, Noémie; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

2015-01-01

To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects' images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template.

The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

PubMed Central

Parker, David

2017-01-01

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury. PMID:29163065

Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

PubMed Central

da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, João Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio

2013-01-01

An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

PubMed

Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

2014-08-15

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

Transverse myelitis-like presentation of methanol intoxication: A case report and review of the literature.

PubMed

Algahtani, Hussein; Shirah, Bader; Ahmad, Raafat; Abobaker, Hind; Hmoud, Mohammed

2018-01-01

Methanol is the simplest member of alcohol family. However, it is an extremely toxic substance to humans upon exposure with severe and detrimental effects that range from visual loss to death. Spinal cord involvement in methanol intoxication is a rare occurrence. In this article, we are reporting a case of methanol intoxication with extensive spinal cord involvement possibly due to necrosis. A literature review yielded only two cases of spinal cord involvement due to methanol intoxication. Our article is the first to discuss the spinal cord involvement specifically including interesting neuroimaging features. We recommend performing MRI of the cervicothoracic spine in every methanol intoxication case to exclude both asymptomatic and symptomatic cases of spinal cord involvement.

Differences in Affect, Life Satisfaction, and Depression between Successfully and Unsuccessfully Rehabilitated Persons with Spinal Cord Injuries

ERIC Educational Resources Information Center

Chapin, Martha H.; Holbert, Donald

2009-01-01

This study assessed whether persons with spinal cord injuries who were successfully rehabilitated differed from those who were not with regard to positive and negative affect, life satisfaction, and depression. An ex post facto research design compared persons with spinal cord injuries who were previously employed with persons with spinal cord…

Intramedullary spinal metastasis of a carcinoid tumor.

PubMed

Kumar, Jay I; Yanamadala, Vijay; Shin, John H

2015-12-01

We report an intramedullary spinal cord metastasis from a bronchial carcinoid, and discuss its mechanisms and management. Intramedullary spinal cord metastases from any cancer are rare, and bronchial carcinoids account for only a small fraction of lung cancers. To our knowledge, an intramedullary spinal cord metastasis from a bronchial carcinoid has been described only once previously. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier

PubMed Central

2013-01-01

Background Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Methods Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Results Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS endothelial cell types can be obtained, and these can be passaged onto large numbers of cell culture inserts for in vitro permeability studies. The passaged brain and spinal cord endothelial cells are pure and express endothelial markers, tight junction proteins and intracellular transport machinery. Further, both models exhibit tight, functional barrier characteristics that are discriminating against large and small molecules in permeability assays and show functional expression of the pharmaceutically important P-gp efflux transporter. Conclusions Our techniques allow the provision of high yields of robust sister cultures of endothelial cells that accurately model the blood-CNS barriers in vitro. These models are ideally suited for use in studying the biology of the blood-brain barrier and blood-spinal cord barrier in vitro and for pre-clinical drug discovery. PMID:23773766

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier.

PubMed

Watson, P Marc D; Paterson, Judy C; Thom, George; Ginman, Ulrika; Lundquist, Stefan; Webster, Carl I

2013-06-18

Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS endothelial cell types can be obtained, and these can be passaged onto large numbers of cell culture inserts for in vitro permeability studies. The passaged brain and spinal cord endothelial cells are pure and express endothelial markers, tight junction proteins and intracellular transport machinery. Further, both models exhibit tight, functional barrier characteristics that are discriminating against large and small molecules in permeability assays and show functional expression of the pharmaceutically important P-gp efflux transporter. Our techniques allow the provision of high yields of robust sister cultures of endothelial cells that accurately model the blood-CNS barriers in vitro. These models are ideally suited for use in studying the biology of the blood-brain barrier and blood-spinal cord barrier in vitro and for pre-clinical drug discovery.

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

PubMed Central

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

2009-01-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, TNF-α transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose-dependently inhibited by the JNK inhibitors SP600125 and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Further, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous excitatory synaptic currents (sEPSCs) but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Taken together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes following JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. PMID:19339605

Nanog interact with CDK6 to regulates astrocyte cells proliferation following spinal cord injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, Jun; Department of Orthopaedics, Xishan People's Hospital, Wuxi, Jiangsu; Ni, Yingjie

2016-01-22

Previous research had reported transcription factors Nanog expressed in pluripotent embryonic stem cells (ESCS) that played an important role in regulating the cell proliferation. Nanog levels are frequently elevated in ESCS, but the role in the spinal cord was not clear. To examine the biological relevance of Nanog, we studied its properties in spinal cord injury model. The expression of Nanog and PCNA was gradually increased and reached a peak at 3 day by western blot analysis. The expression of Nanog was further analyzed by immunohistochemistry. Double immunofluorescent staining uncovered that Nanog can co-labeled with PCNA and GFAP in themore » spinal cord tissue. In vitro, Nanog can promote the proliferation of astrocyte cell by Fluorescence Activating Cell Sorter (FACS) and CCK8. Meanwhile, the cell-cycle protein CDK6 could interact with Nanog in the spinal cord tissue. Taken together, these data suggested that both Nanog may play important roles in spinal cord pathophysiology via interact with CDK6.« less

Minimally Invasive Drainage of a Post-Laminectomy Subfascial Seroma with Cervical Spinal Cord Compression.

PubMed

Kitshoff, Adriaan Mynhardt; Van Goethem, Bart; Cornelis, Ine; Combes, Anais; Dvm, Ingeborgh Polis; Gielen, Ingrid; Vandekerckhove, Peter; de Rooster, Hilde

2016-01-01

A 14 mo old female neutered Doberman pinscher was evaluated for difficulty in rising, a wide based stance, pelvic limb gait abnormalities, and cervical pain of 2 mo duration. Neurologic examination revealed pelvic limb ataxia and cervical spinal hyperesthesia. Spinal reflexes and cranial nerve examination were normal. The pathology was localized to the C1-C5 or C6-T2 spinal cord segments. Computed tomography (CT) findings indicated bony proliferation of the caudal articular processes of C6 and the cranial articular processes of C7, resulting in bilateral dorsolateral spinal cord compression that was more pronounced on the left side. A limited dorsal laminectomy was performed at C6-C7. Due to progressive neurological deterioration, follow-up CT examination was performed 4 days postoperatively. At the level of the laminectomy defect, a subfacial seroma had developed, entering the spinal canal and causing significant spinal cord compression. Under ultrasonographic guidance a closed-suction wound catheter was placed. Drainage of the seroma successfully relieved its compressive effects on the spinal cord and the patient's neurological status improved. CT was a valuable tool in assessing spinal cord compression as a result of a postoperative subfascial seroma. Minimally invasive application of a wound catheter can be successfully used to manage this condition.

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

PubMed Central

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 (P<0.05). MRI 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 positive effects for the regeneration of the white matter. PMID:29201191

Assessment of abdominal muscle function in individuals with motor-complete spinal cord injury above T6 in response to transcranial magnetic stimulation.

PubMed

Bjerkefors, Anna; Squair, Jordan W; Chua, Romeo; Lam, Tania; Chen, Zhen; Carpenter, Mark G

2015-02-01

To use transcranial magnetic stimulation and electromyography to assess the potential for preserved function in the abdominal muscles in individuals classified with motor-complete spinal cord injury above T6. Five individuals with spinal cord injury (C5-T3) and 5 able-bodied individuals. Transcranial magnetic stimulation was delivered over the abdominal region of primary motor cortex during resting and sub-maximal (or attempted) contractions. Surface electromyography was used to record motor-evoked potentials as well as maximal voluntary (or attempted) contractions in the abdominal muscles and the diaphragm. Responses to transcranial magnetic stimulation in the abdominal muscles occurred in all spinal cord injury subjects. Latencies of muscle response onsets were similar in both groups; however, peak-to-peak amplitudes were smaller in the spinal cord injury group. During maximal voluntary (or attempted) contractions all spinal cord injury subjects were able to elicit electromyography activity above resting levels in more than one abdominal muscle across tasks. Individuals with motor-complete spinal cord injury above T6 were able to activate abdominal muscles in response to transcranial magnetic stimulation and during maximal voluntary (or attempted) contractions. The activation was induced directly through corticospinal pathways, and not indirectly by stretch reflex activations of the diaphragm. Transcranial magnetic stimulation and electromyography measurements provide a useful method to assess motor preservation of abdominal muscles in persons with spinal cord injury.

Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury.

PubMed

Hofstetter, Christoph P; Schweinhardt, Petra; Klason, Tomas; Olson, Lars; Spenger, Christian

2003-12-01

Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.

A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate.

PubMed

Nishino, Atsuo; Okamura, Yasushi; Piscopo, Stefania; Brown, Euan R

2010-01-19

Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs). A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis. A reduced preparation of the larva consisting of nerve cord and motor ganglion generates alternating swimming movements. Pharmacological and genetic manipulation of glycine receptors shows that they are implicated in the control of these locomotory movements. Morphological molecular techniques and heterologous expression experiments revealed that glycine receptors are inhibitory and are present on both motoneurones and locomotory muscle while putative glycinergic interneurons were identified in the nerve cord by labeling with an anti-glycine antibody. In Ciona intestinalis, glycine receptors, glycinergic transmission and putative glycinergic interneurons, have a key role in coordinating swimming movements through a simple CPG that is present in the motor ganglion and nerve cord. Thus, the strong association between glycine receptors and vertebrate locomotory networks may now be extended to include the phylum chordata. The results suggest that the basic network for 'spinal-like' locomotion is likely to have existed in the common ancestor of extant chordates some 650 M years ago.

A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate

PubMed Central

2010-01-01

Background Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs). A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis. Results A reduced preparation of the larva consisting of nerve cord and motor ganglion generates alternating swimming movements. Pharmacological and genetic manipulation of glycine receptors shows that they are implicated in the control of these locomotory movements. Morphological molecular techniques and heterologous expression experiments revealed that glycine receptors are inhibitory and are present on both motoneurones and locomotory muscle while putative glycinergic interneurons were identified in the nerve cord by labeling with an anti-glycine antibody. Conclusions In Ciona intestinalis, glycine receptors, glycinergic transmission and putative glycinergic interneurons, have a key role in coordinating swimming movements through a simple CPG that is present in the motor ganglion and nerve cord. Thus, the strong association between glycine receptors and vertebrate locomotory networks may now be extended to include the phylum chordata. The results suggest that the basic network for 'spinal-like' locomotion is likely to have existed in the common ancestor of extant chordates some 650 M years ago. PMID:20085645

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

NASA Astrophysics Data System (ADS)

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 are vulnerable and show significant loss.

Shriners Hospital Spinal Cord Injury Self Care Manual.

ERIC Educational Resources Information Center

Fox, Carol

This manual is intended for young people with spinal cord injuries who are receiving rehabilitation services within the Spinal Cord Injury Unit at Shriners Hospital (San Francisco, California). An introduction describes the rehabilitation program, which includes family conferences, an individualized program, an independent living program,…

Compressive mechanical characterization of non-human primate spinal cord white matter.

PubMed

Jannesar, Shervin; Allen, Mark; Mills, Sarah; Gibbons, Anne; Bresnahan, Jacqueline C; Salegio, Ernesto A; Sparrey, Carolyn J

2018-05-02

The goal of developing computational models of spinal cord injury (SCI) is to better understand the human injury condition. However, finite element models of human SCI have used rodent spinal cord tissue properties due to a lack of experimental data. Central nervous system tissues in non human primates (NHP) closely resemble that of humans and therefore, it is expected that material constitutive models obtained from NHPs will increase the fidelity and the accuracy of human SCI models. Human SCI most often results from compressive loading and spinal cord white matter properties affect FE predicted patterns of injury; therefore, the objectives of this study were to characterize the unconfined compressive response of NHP spinal cord white matter and present an experimentally derived, finite element tractable constitutive model for the tissue. Cervical spinal cords were harvested from nine male adult NHPs (Macaca mulatta). White matter biopsy samples (3 mm in diameter) were taken from both lateral columns of the spinal cord and were divided into four strain rate groups for unconfined dynamic compression and stress relaxation (post-mortem <1-hour). The NHP spinal cord white matter compressive response was sensitive to strain rate and showed substantial stress relaxation confirming the viscoelastic behavior of the material. An Ogden 1st order model best captured the non-linear behavior of NHP white matter in a quasi-linear viscoelastic material model with 4-term Prony series. This study is the first to characterize NHP spinal cord white matter at high (>10/sec) strain rates typical of traumatic injury. The finite element derived material constitutive model of this study will increase the fidelity of SCI computational models and provide important insights for transferring pre-clinical findings to clinical treatments. Spinal cord injury (SCI) finite element (FE) models provide an important tool to bridge the gap between animal studies and human injury, assess injury prevention technologies (e.g. helmets, seatbelts), and provide insight into the mechanisms of injury. Although, FE model outcomes depend on the assumed material constitutive model, there is limited experimental data for fresh spinal cords and all was obtained from rodent, porcine or bovine tissues. Central nervous system tissues in non human primates (NHP) more closely resemble humans. This study characterizes fresh NHP spinal cord material properties at high strains rates and large deformations typical of SCI for the first time. A constitutive model was defined that can be readily implemented in finite strain FE analysis of SCI. Copyright © 2018. Published by Elsevier Ltd.

Pharmacology for the treatment of premature ejaculation.

PubMed

Giuliano, François; Clèment, Pierre

2012-07-01

Male sexual response comprises four phases: excitement, including erection; plateau; ejaculation, usually accompanied by orgasm; and resolution. Ejaculation is a complex sexual response involving a sequential process consisting of two phases: emission and expulsion. Ejaculation, which is basically a spinal reflex, requires a tight coordination between sympathetic, parasympathetic, and somatic efferent pathways originating from different segments and area in the spinal cord and innervating pelvi-perineal anatomical structures. A major relaying and synchronizing role is played by a group of lumbar neurons described as the spinal generator of ejaculation. Excitatory and inhibitory influences from sensory genital and cerebral stimuli are integrated and processed in the spinal cord. Premature ejaculation (PE) can be defined by ≤1-min ejaculatory latency, an inability to delay ejaculation, and negative personal consequences. Because there is no physiological impairment in PE, any pharmacological agent with central or peripheral mechanism of action that is delaying the ejaculation is a drug candidate for the treatment of PE. Ejaculation is centrally mediated by a variety of neurotransmitter systems, involving especially serotonin and serotonergic pathways but also dopaminergic and oxytocinergic systems. Pharmacological delay of ejaculation can be achieved either by inhibiting excitatory or reinforcing inhibitory pathways from the brain or the periphery to the spinal cord. PE can be treated with long-term use of selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. Dapoxetine, a short-acting SSRI, is the first treatment registered for the on-demand treatment of PE. Anesthetics applied on the glans penis have the ability to lengthen the time to ejaculation. Targeting oxytocinergic, neurokinin-1, dopaminergic, and opioid receptors represent future avenues to delaying ejaculation.

[Effect of local hypothermia on H- and M-responses after spinal cord contusion in dogs].

PubMed

Iafarova, G G; Tumakaev, R F; Khazieva, A R; Baltina, T V

2014-01-01

In this study we investigated a motor-neuronal functional state based on H- and M-responses from m. quadratus plantae in dogs before and after experimental spinal cord contusion with and without following local intraoperative hypothermia. H- and M-responses from m. quadratus plantae were recorded during stimulation of the tibial nerve and results were compared between the groups. Our results demonstrate that local hypothermia applied after spinal cord contusion reduces amplitude of both M- and H-responses and also H(max)/M(max) ratio that may indicate depression of motorneurons excitability. After spinal cord contusion without following hypothermia the excitability of the spinal motorneurons during post-traumatic period, in opposite, was significantly increased. These results support a conclusion that intraoperative hypothermia after spinal cord contusion can delay development of functional excitability of the motoneurons and protect from further changes in H- and M-responses.

Magnetic resonance diffusion tensor imaging of cervical spinal cord and lumbosacral enlargement in patients with cervical spondylotic myelopathy.

PubMed

Chen, Xueming; Kong, Chao; Feng, Shiqing; Guan, Hua; Yu, Zhenshan; Cui, Libin; Wang, Yanhui

2016-06-01

To identify the correlations of diffusion tensor imaging (DTI) indices between the cervical spinal cord and lumbosacral enlargement in healthy volunteers and patients with cervical spondylotic myelopathy (CSM). DTI was performed at the cervical spinal cord and lumbosacral enlargement in 10 CSM patients and 10 volunteers at 1.5T. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of were measured and compared between CSM patients and volunteers. DTI indices of different cervical segments in volunteers were compared. DTI indices of the cervical spinal cord were correlated with those of the lumbosacral enlargement. In healthy subjects, DTI indices of different cervical cord sections showed no significant difference (ADC: F = 0.62; P = 0.65; FA: F = 1.228; P = 0.312); there was no correlation between the DTI indices of the cervical spinal cord and those of the lumbosacral enlargement (ADC: r = 0.442, P = 0.201; FA: r = -0.054, P = 0.881). In the CSM patients, the ADC value significantly increased, while the FA value significantly decreased in the cervical spinal cord (ADC: P = 0.002; FA: P < 0.001) and lumbosacral enlargement (ADC: P = 0.003; FA: P < 0.001) compared with the healthy group. Both DTI indices showed no correlation between the cervical spinal cord and those of the lumbosacral enlargement in the CSM group (ADC: r = -0.052, P = 0.887; FA: r = 0.129, P = 0.722). The ADC value of the cervical spinal cord and lumbosacral enlargement in CSM patients showed significant increase compared with healthy volunteers, while the FA value significantly decreased. Both DTI indices of the cervical spinal cord had no linear correlation with those of the lumbosacral enlargement. J. Magn. Reson. Imaging 2016;43:1484-1491. © 2015 Wiley Periodicals, Inc.

Morphology of the caudal spinal cord in Rana (Ranidae) and Xenopus (Pipidae) tadpoles.

PubMed

Nishikawa, K; Wassersug, R

1988-03-08

Using a variety of neuroanatomical and histological techniques, we compare the spinal cord and peripheral nerve distribution in the tails of larvae from Xenopus laevis and three species of Rana. The relatively large, postsacral spinal cord of Xenopus contains abundant motoneurons and their axons. Spinal nerves exit from the spinal cord in a regular array, one nerve per myotome, from the cervical region to near the end of the tail. Somata of motoneurons innervating caudal myotomes are found along the entire length of the tail. In contrast, the caudal cord of Rana is reduced to a filum terminale consisting of little more than an ependymal tube; spinal nerves to all caudal myotomes leave the cord in the sacral region and reach their motor targets via a cauda equina and caudal plexus. Motoneuron cell bodies innervating caudal myotomes are found only in the sacral region. The Rana larval pattern is similar to that of adult frogs and mammals, whereas the Xenopus larval pattern is more like that of salamanders and reptiles. These gross neuroanatomical differences are not due to differences in the size or developmental stage of the tadpoles, but instead are associated with differences in the swimming behavior of the larvae. The presence of motoneurons in the caudal spinal cord of Xenopus may provide local intermyotomal control within the tail; the elongated topography of the cord appears to permit finer, rostral-to-caudal regulation of neuromuscular activity. The Rana spinal cord, on the other hand--with motoneurons clustered anteriorly--may produce concurrent firing of adjacent ipsilateral myotomes, but at the expense of fine intermyotomal regulation. The fact that nerves in the tail of Xenopus enter and exit from the spinal cord locally, as opposed to far anteriorly as in Rana, means that for tadpoles of the same size, reflex arc lengths are many times shorter in Xenopus.

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

NASA Astrophysics Data System (ADS)

Farrar, Matthew John

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

"Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury".

PubMed

Paula, Alecsandra Araujo; Nicolau, Renata Amadei; Lima, Mario de Oliveira; Salgado, Miguel Angel Castillo; Cogo, José Carlos

2014-11-01

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n = 3), control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion + laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery (n = 5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.

Spinal Meninges and Their Role in Spinal Cord Injury: A Neuroanatomical Review.

PubMed

Grassner, Lukas; Grillhösl, Andreas; Griessenauer, Christoph J; Thomé, Claudius; Bühren, Volker; Strowitzki, Martin; Winkler, Peter A

2018-02-01

Current recommendations support early surgical decompression and blood pressure augmentation after traumatic spinal cord injury (SCI). Elevated intraspinal pressure (ISP), however, has probably been underestimated in the pathophysiology of SCI. Recent studies provide some evidence that ISP measurements and durotomy may be beneficial for individuals suffering from SCI. Compression of the spinal cord against the meninges in SCI patients causes a "compartment-like" syndrome. In such cases, intentional durotomy with augmentative duroplasty to reduce ISP and improve spinal cord perfusion pressure (SCPP) may be indicated. Prior to performing these procedures routinely, profound knowledge of the spinal meninges is essential. Here, we provide an in-depth review of relevant literature along with neuroanatomical illustrations and imaging correlates.

Childhood Brain and Spinal Cord Tumors Treatment Overview (PDQ®)—Patient Version

Cancer.gov

Brain and spinal cord tumors may be benign (not cancer) or malignant (cancer). Both types cause signs or symptoms and need treatment. Get information about the many kinds of brain and spinal cord tumors, signs and symptoms, tests to diagnose, and treatment in this expert-reviewed summary.

34 CFR 359.10 - What types of projects are authorized under this program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... rehabilitation services to individuals with spinal cord injuries; and (b) Conduct spinal cord research, including clinical research and the analysis of standardized data in collaboration with other related projects... REHABILITATION RESEARCH: SPECIAL PROJECTS AND DEMONSTRATIONS FOR SPINAL CORD INJURIES What Kinds of Activities...

Microsurgical resection of intramedullary spinal cord hemangioblastoma.

PubMed

McCormick, Paul C

2014-09-01

Spinal cord hemangioblastomas account for about 10% of spinal cord tumors. They usually arise from the dorsolateral pia mater and are characterized by their significant vascularity. The principles and techniques of safe resection are different than those employed for the more commonly occurring intramedullary glial tumors (e.g. ependymoma, astrocytoma) and consist of circumferential detachment of the tumor margin from the surrounding normal pia. This video demonstrates the microsurgical techniques of resection of a thoracic spinal cord hemangioblastoma. The video can be found here: http://youtu.be/yT5KLi4VyAo.

Life satisfaction in patients with and without spinal cord ischemia after advanced endovascular therapy for extensive aortic disease at mid-term follow-up.

PubMed

Mehmedagic, Irma; Santén, Stefan; Jörgensen, Sophie; Acosta, Stefan

2016-11-11

Advanced endovascular aortic repair can be used to treat patients with extensive and complex aortic disease who are at risk of spinal cord ischaemia. The aim of this study was to compare whether life satisfaction differs between patients with and without spinal cord ischaemia at mid-term follow-up. Nested case-control study. Among patients undergoing advanced endovascular aortic repair between 2009 and 2012, 18 patients with spinal cord ischaemia and 33 without were interviewed at home. The Life Satisfaction Questionnaire (LiSat-11) and the Satisfaction With Life Scale (SWLS) were used. LiSat-11 found that patients with spinal cord ischaemia were more dissatisfied with their activities of daily living than were patients without spinal cord ischaemia (p=0.012). Both groups had similar, very low, scores in the sexual life domain; median 2.0 (interquartile range (IQR) 1.5-3.0) and 3.0 (IQR 2.0-4.0), respectively. There was no difference in SWLS between the groups. This study cohort of patients who underwent advanced endovascular aortic repair was rather homo-genous in their rating of life satisfaction and there was little difference between mid-term survivors who had spinal cord ischaemia and those who did not.

Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury.

PubMed

Wang, Lei; Liu, Linjuan; Pan, Zhanpeng; Zeng, Yanjun

2015-11-16

Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

Technique of spinal cord compression induced by inflation of epidural balloon catheter in rabbits (Oryctologus cuniculus): efficient and easy to use model.

PubMed

Fonseca, Antonio F B DA; Scheffer, Jussara P; Coelho, Barbara P; Aiello, Graciane; Guimarães, Arthur G; Gama, Carlos R B; Vescovini, Victor; Cabral, Paula G A; Oliveira, André L A

2016-09-01

The most common cause of spinal cord injury are high impact trauma, which often result in some motor impairment, sensory or autonomic a greater or lesser extent in the distal areas the level of trauma. In terms of survival and complications due to sequelae, veterinary patients have a poor prognosis unfavorable. Therefore justified the study of experimental models of spinal cord injury production that could provide more support to research potential treatments for spinal cord injuries in medicine and veterinary medicine. Preclinical studies of acute spinal cord injury require an experimental animal model easily reproducible. The most common experimental animal model is the rat, and several techniques for producing a spinal cord injury. The objective of this study was to describe and evaluate the effectiveness of acute spinal cord injury production technique through inflation of Fogarty(r) catheter using rabbits as an experimental model because it is a species that has fewer conclusive publications and contemplating. The main requirements of a model as low cost, handling convenience, reproducibility and uniformity. The technique was adequate for performing preclinical studies in neuro-traumatology area, effectively leading to degeneration and necrosis of the nervous tissue fostering the emergence of acute paraplegia.

Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: sexual dimorphism and diergism at the spinal cord level.

PubMed

Nacka-Aleksić, Mirjana; Djikić, Jasmina; Pilipović, Ivan; Stojić-Vukanić, Zorica; Kosec, Duško; Bufan, Biljana; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

2015-10-01

Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-γ+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-γ+:IL-17+IL-10+ cell ratio was shifted towards IL-17+IFN-γ+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1β and IL-6, but downregulated TGF-β mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Early Acute Care on Autonomic Outcomes in SCI: Bedside to Bench and Back

DTIC Science & Technology

2017-12-01

defined as no cord signal abnormality , grade 1 injury was defined as T2 hyperintensity approximately confined to the gray matter, grade 2 injury was...120mcg/kg/min, fentanyl 100mcg/h with Sevoflurane 1.0% (0.5MAC) and an MAP goal of >85 mm Hg was instituted given any concern for MEP integrity in...elicitable MEPs had T2 signal abnormality that involved the entire transverse extent of the spinal cord (BASIC 3 and 4), while nearly all patients

Transverse Myelitis

MedlinePlus

... cord injury to study strategies for replacement or regeneration of spinal cord nerve cells. The knowledge gained from such research should lead ... cord injury to study strategies for replacement or regeneration of spinal cord nerve cells. The knowledge gained from such research should lead ...

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs.

PubMed

Lim, Ji Hey; Byeon, Ye Eun; Ryu, Hak Hyun; Jeong, Yun Hyeok; Lee, Young Won; Kim, Wan Hee; Kang, Kyung Sun; Kweon, Oh Kyeong

2007-09-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCBMSCs isolated from cord blood of canine fetuses were prepared as 10(6) cells/150 microl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

PubMed Central

Lim, Ji-Hey; Byeon, Ye-Eun; Ryu, Hak-Hyun; Jeong, Yun-Hyeok; Lee, Young-Won; Kim, Wan Hee

2007-01-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury. PMID:17679775

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

PubMed Central

Kim, Joong H.; Loy, David N.; Wang, Qing; Budde, Matthew D.; Schmidt, Robert E.; Trinkaus, Kathryn

2010-01-01

Abstract Accurate diagnosis of spinal cord injury (SCI) severity must be achieved before highly aggressive experimental therapies can be tested responsibly in the early phases after trauma. These studies demonstrate for the first time that axial diffusivity (λ||), derived from diffusion tensor imaging (DTI) within 3 h after SCI, accurately predicts long-term locomotor behavioral recovery in mice. Female C57BL/6 mice underwent sham laminectomy or graded contusive spinal cord injuries at the T9 vertebral level (5 groups, n = 8 for each group). In-vivo DTI examinations were performed immediately after SCI. Longitudinal measurements of hindlimb locomotor recovery were obtained using the Basso mouse scale (BMS). Injured and spared regions of ventrolateral white matter (VLWM) were reliably separated in the hyperacute phase by threshold segmentation. Measurements of λ|| were compared with histology in the hyperacute phase and 14 days after injury. The spared normal VLWM determined by hyperacute λ|| and 14-day histology correlated well (r = 0.95). A strong correlation between hindlimb locomotor function recovery and λ||-determined spared normal VLWM was also observed. The odds of significant locomotor recovery increased by 18% with each 1% increase in normal VLWM measured in the hyperacute phase (odds ratio = 1.18, p = 0.037). The capability of measuring subclinical changes in spinal cord physiology and murine genetic advantages offer an early window into the basic mechanisms of SCI that was not previously possible. Although significant obstacles must still be overcome to derive similar data in human patients, the path to clinical translation is foreseeable and achievable. PMID:20001686

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

PubMed

Keeney, Tamra; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Heinemann, Allen W; Charlifue, Susan; Fyffe, Denise C; Marino, Ralph J; Morse, Leslie R; Worobey, Lynn A; Tate, Denise; Rosenblum, David; Zafonte, Ross; Tulsky, David; Jette, Alan M

2018-03-31

To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). Multisite longitudinal (12-mo follow-up) study. Nine SCI Model Systems programs. Adults (N=165) with SCI enrolled in the SCI Model Systems database. Not applicable. SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Thioredoxin-1 Protects Spinal Cord from Demyelination Induced by Methamphetamine through Suppressing Endoplasmic Reticulum Stress and Inflammation

PubMed Central

Yang, Lihua; Guo, Yinli; Huang, Mengbin; Wu, Xiaoli; Li, Xiang; Chen, Guobing; Li, Ye; Bai, Jie

2018-01-01

Methamphetamine (METH) is a psychostimulant abused around the world. Emerging evidence indicates that METH causes brain damage. However, there are very few reports on METH-induced demyelination. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays the roles in protecting neurons from various stresses. However, whether Trx-1 resists demyelination induced by METH has not been reported. In this study, we found that METH-induced thin myelin sheaths in spinal cord, whereas Trx-1 overexpression transgenic (TG) mice restored the myelin sheaths thickness. The expressions of myelin-associated glycoprotein, myelin basic protein, and cyclin-dependent kinase 5 were decreased by METH, whereas these alterations were blocked in Trx-1 TG mice. The expressions of procaspase-12 and procaspase-3 were decreased by METH, the expression of calpain1 was increased by METH, whereas the alterations were suppressed in Trx-1 TG mice. As same as, the expressions of the extracellular signal-regulated kinase, nuclear factor κB, tumor necrosis factor-alpha, and interleukin-1beta were induced by METH, which were suppressed in Trx-1 TG mice. These data suggest that Trx-1 may play a critical role in resisting the METH-mediated demyelination in spinal cord through regulating endoplasmic reticulum stress and inflammation pathways. PMID:29467717

Identification of ghost artifact using texture analysis in pediatric spinal cord diffusion tensor images.

PubMed

Alizadeh, Mahdi; Conklin, Chris J; Middleton, Devon M; Shah, Pallav; Saksena, Sona; Krisa, Laura; Finsterbusch, Jürgen; Faro, Scott H; Mulcahey, M J; Mohamed, Feroze B

2018-04-01

Ghost artifacts are a major contributor to degradation of spinal cord diffusion tensor images. A multi-stage post-processing pipeline was designed, implemented and validated to automatically remove ghost artifacts arising from reduced field of view diffusion tensor imaging (DTI) of the pediatric spinal cord. A total of 12 pediatric subjects including 7 healthy subjects (mean age=11.34years) with no evidence of spinal cord injury or pathology and 5 patients (mean age=10.96years) with cervical spinal cord injury were studied. Ghost/true cords, labeled as region of interests (ROIs), in non-diffusion weighted b0 images were segmented automatically using mathematical morphological processing. Initially, 21 texture features were extracted from each segmented ROI including 5 first-order features based on the histogram of the image (mean, variance, skewness, kurtosis and entropy) and 16s-order feature vector elements, incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence matrices in directions of 0°, 45°, 90° and 135°. Next, ten features with a high value of mutual information (MI) relative to the pre-defined target class and within the features were selected as final features which were input to a trained classifier (adaptive neuro-fuzzy interface system) to separate the true cord from the ghost cord. The implemented pipeline was successfully able to separate the ghost artifacts from true cord structures. The results obtained from the classifier showed a sensitivity of 91%, specificity of 79%, and accuracy of 84% in separating the true cord from ghost artifacts. The results show that the proposed method is promising for the automatic detection of ghost cords present in DTI images of the spinal cord. This step is crucial towards development of accurate, automatic DTI spinal cord post processing pipelines. Copyright © 2017 Elsevier Inc. All rights reserved.

Multimodal intraoperative monitoring: an overview and proposal of methodology based on 1,017 cases

PubMed Central

Eggspuehler, Andreas; Muller, Alfred; Dvorak, Jiri

2007-01-01

To describe different currently available tests of multimodal intraoperative monitoring (MIOM) used in spine and spinal cord surgery indicating the technical parameters, application and interpretation as an easy understanding systematic overview to help implementation of MIOM and improve communication between neurophysiologists and spine surgeons. This article aims to give an overview and proposal of the different MIOM-techniques as used daily in spine and spinal cord surgery at our institution. Intensive research in neurophysiology over the past decades has lead to a profound understanding of the spinal cord, nerve functions and their intraoperative functional evaluation in anaesthetised patients. At present, spine surgeons and neurophysiologist are faced with 1,883 publications in PubMed on spinal cord monitoring. The value and the limitations of single monitoring methods are well documented. The diagnostic power of the multimodal approach in a larger study population in spine surgery, as measured with sensitivity and specificity, is dealt with elsewhere in this supplement (Sutter et al. in Eur Spine J Suppl, 2007). This paper aims to give a detailed description of the different modalities used in this study. Description of monitoring techniques of the descending and ascending spinal cord and nerve root pathways by motor evoked potentials of the spinal cord and muscles elicited after transcranial electrical motor cortex, spinal cord, cauda equina and nerve root stimulation, continuous EMG, sensory cortical and spinal evoked potentials, as well as direct spinal cord evoked potentials applied on 1,017 patients. The method of MIOM, continuously adapted according to the site, stage of surgery and potential danger to nerve tissues, proved to be applicable with online results, reliable and furthermore teachable. PMID:17653777

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

PubMed

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

2009-02-01

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

Can the human lumbar posterior columns be stimulated by transcutaneous spinal cord stimulation? A modeling study

PubMed Central

Danner, Simon M.; Hofstoetter, Ursula S.; Ladenbauer, Josef; Rattay, Frank; Minassian, Karen

2014-01-01

Stimulation of different spinal cord segments in humans is a widely developed clinical practice for modification of pain, altered sensation and movement. The human lumbar cord has become a target for modification of motor control by epidural and more recently by transcutaneous spinal cord stimulation. Posterior columns of the lumbar spinal cord represent a vertical system of axons and when activated can add other inputs to the motor control of the spinal cord than stimulated posterior roots. We used a detailed three-dimensional volume conductor model of the torso and the McIntyre-Richard-Grill axon model to calculate the thresholds of axons within the posterior columns in response to transcutaneous lumbar spinal cord stimulation. Superficially located large diameter posterior column fibers with multiple collaterals have a threshold of 45.4 V, three times higher than posterior root fibers (14.1 V). With the stimulation strength needed to activate posterior column axons, posterior root fibers of large and small diameters as well as anterior root fibers are co-activated. The reported results inform on these threshold differences, when stimulation is applied to the posterior structures of the lumbar cord at intensities above the threshold of large-diameter posterior root fibers. PMID:21401670

Involvement of peripheral and spinal tumor necrosis factor α in spinal cord hyperexcitability during knee joint inflammation in rats.

PubMed

König, Christian; Zharsky, Maxim; Möller, Christian; Schaible, Hans-Georg; Ebersberger, Andrea

2014-03-01

Tumor necrosis factor α (TNFα) is produced not only in peripheral tissues, but also in the spinal cord. The purpose of this study was to address the potential of peripheral and spinal TNFα to induce and maintain spinal hyperexcitability, which is a hallmark of pain states in the joints during rheumatoid arthritis and osteoarthritis. In vivo recordings of the responses of spinal cord neurons to nociceptive knee input under normal conditions and in the presence of experimental knee joint inflammation were obtained in anesthetized rats. TNFα, etanercept, or antibodies to TNF receptors were applied to either the knee joint or the spinal cord surface. Injection of TNFα into the knee joint cavity increased the responses of spinal cord neurons to mechanical joint stimulation, and injection of etanercept into the knee joint reduced the inflammation-evoked spinal activity. These spinal effects closely mirrored the induction and reduction of peripheral sensitization. Responses to joint stimulation were also enhanced by spinal application of TNFα, and spinal application of either etanercept or anti-TNF receptor type I significantly attenuated the generation of inflammation-evoked spinal hyperexcitability, which is characterized by widespread pain sensitization beyond the inflamed joint. Spinally applied etanercept did not reduce established hyperexcitability in the acute kaolin/carrageenan model. In antigen-induced arthritis, etanercept decreased spinal responses on day 1, but not on day 3. While peripheral TNFα increases spinal responses to joint stimulation, spinal TNFα supports the generation of the full pattern of spinal hyperexcitability. However, established spinal hyperexcitability may be maintained by downstream mechanisms that are independent of spinal TNFα. Copyright © 2014 by the American College of Rheumatology.

Focal thoracolumbar spinal cord lymphosarcoma in a ferret (Mustela putorius furo)

PubMed Central

Ingrao, Joelle C.; Eshar, David; Vince, Andrew; Lee-Chow, Bridget; Nykamp, Stephanie; DeLay, Josepha; Smith, Dale

2014-01-01

A 6-year-old, castrated male domestic ferret (Mustela putorius furo) was euthanized following progressive hind limb paresis and atonia of the bladder of 1-year duration. Neurological evaluation localized the lesion to the thoracolumbar spinal region, and magnetic resonance imaging showed a focal intramedullary spinal cord lesion. Histopathology revealed an extensive, unencapsulated, poorly demarcated mass within the thoracolumbar spinal cord, diagnosed as lymphosarcoma. PMID:24982519

The Prevalence and Phenotype of Activated Microglia/Macrophages within the Spinal Cord of the Hyperostotic Mouse (twy/twy) Changes in Response to Chronic Progressive Spinal Cord Compression: Implications for Human Cervical Compressive Myelopathy

PubMed Central

Hirai, Takayuki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Takeura, Naoto; Watanabe, Shuji; Sugita, Daisuke; Yoshida, Ai; Johnson, William E. B.; Baba, Hisatoshi

2013-01-01

Background Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease. Methods Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass. Results The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) −2 progressively increased. Conclusions Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. PMID:23717624

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

PubMed Central

D'Amico, Jessica M.; Condliffe, Elizabeth G.; Martins, Karen J. B.; Bennett, David J.; Gorassini, Monica A.

2014-01-01

The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI. PMID:24860447

Retraining walking adaptability following incomplete spinal cord injury.

PubMed

Fox, Emily J; Tester, Nicole J; Butera, Katie A; Howland, Dena R; Spiess, Martina R; Castro-Chapman, Paula L; Behrman, Andrea L

2017-01-01

Functional walking requires the ability to modify one's gait pattern to environmental demands and task goals-gait adaptability. Following incomplete spinal cord injury (ISCI), gait rehabilitation such as locomotor training (Basic-LT) emphasizes intense, repetitive stepping practice. Rehabilitation approaches focusing on practice of gait adaptability tasks have not been established for individuals with ISCIs but may promote recovery of higher level walking skills. The primary purpose of this case series was to describe and determine the feasibility of administering a gait adaptability retraining approach-Adapt-LT-by comparing the dose and intensity of Adapt-LT to Basic-LT. Three individuals with ISCIs (>1 year, AIS C or D) completed three weeks each (15 sessions) of Basic-LT and Adapt-LT. Interventions included practice on a treadmill with body weight support and practice overground (≥30 mins total). Adapt-LT focused on speed changes, obstacle negotiation, and backward walking. Training parameters (step counts, speeds, perceived exertion) were compared and outcomes assessed pre and post interventions. Based on completion of the protocol and similarities in training parameters in the two interventions, it was feasible to administer Adapt-LT with a similar dosage and intensity as Basic-LT. Additionally, the participants demonstrated gains in walking function and balance following each training type. Rehabilitation that includes stepping practice with adaptability tasks is feasible for individuals with ISCIs. Further investigation is needed to determine the efficacy of Adapt-LT.

Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes.

PubMed

Lawrence, Jane M; Stroman, Patrick W; Kollias, Spyros S

2008-03-01

We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements.

Automatic 3D segmentation of spinal cord MRI using propagated deformable models

NASA Astrophysics Data System (ADS)

De Leener, B.; Cohen-Adad, J.; Kadoury, S.

2014-03-01

Spinal cord diseases or injuries can cause dysfunction of the sensory and locomotor systems. Segmentation of the spinal cord provides measures of atrophy and allows group analysis of multi-parametric MRI via inter-subject registration to a template. All these measures were shown to improve diagnostic and surgical intervention. We developed a framework to automatically segment the spinal cord on T2-weighted MR images, based on the propagation of a deformable model. The algorithm is divided into three parts: first, an initialization step detects the spinal cord position and orientation by using the elliptical Hough transform on multiple adjacent axial slices to produce an initial tubular mesh. Second, a low-resolution deformable model is iteratively propagated along the spinal cord. To deal with highly variable contrast levels between the spinal cord and the cerebrospinal fluid, the deformation is coupled with a contrast adaptation at each iteration. Third, a refinement process and a global deformation are applied on the low-resolution mesh to provide an accurate segmentation of the spinal cord. Our method was evaluated against a semi-automatic edge-based snake method implemented in ITK-SNAP (with heavy manual adjustment) by computing the 3D Dice coefficient, mean and maximum distance errors. Accuracy and robustness were assessed from 8 healthy subjects. Each subject had two volumes: one at the cervical and one at the thoracolumbar region. Results show a precision of 0.30 +/- 0.05 mm (mean absolute distance error) in the cervical region and 0.27 +/- 0.06 mm in the thoracolumbar region. The 3D Dice coefficient was of 0.93 for both regions.

Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier.

PubMed

Eve, David J; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V; Garbuzova-Davis, Svitlana

2018-02-13

Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34 + cells (5 × 10 4 , 5 × 10 5 or 1 × 10 6 ) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls' Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34 + cells. The study results provide translational outcomes supporting transplantation of hBM34 + cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients.

The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits.

PubMed

Matsumoto, Satoshi; Matsumoto, Mishiya; Yamashita, Atsuo; Ohtake, Kazunobu; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Sakabe, Takefumi

2003-06-01

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

"My body was my temple": a narrative revealing body image experiences following treatment of a spinal cord injury.

PubMed

Bailey, K Alysse; Gammage, Kimberley L; van Ingen, Cathy; Ditor, David S

2017-09-01

This narrative explores the lived experience of a young woman, Rebecca, and her transitioned body image after sustaining and being treated for a spinal cord injury. Data were collected from a single semi-structured in-depth interview. Rebecca disclosed her transitioned body image experiences after sustaining a spinal cord injury and being treated by medical staff immediately following her injury. Before her injury, she described a holistic body experience and named this experience her "temple". During intensive care in the hospital, she explained her body was treated as an object. The disconnected treatment of her body led to a loss of the private self, as she described her sacred body being stripped away - her "temple" lost and in ruins. Body image may be an overlooked component of health following a spinal cord injury. This narrative emphasizes the importance of unveiling body image experiences after the treatment of a spinal cord injury to medical professionals. Lessons of the importance of considering the transitioned body experiences after a spinal cord injury may help prevent body-related depression and other subsequent health impacts. Recommendations for best practice are provided. Implications for Rehabilitation    Spinal Cord Injury   • A spinal cord injury may drastically change a person's body image, thereby significantly impacting psychological health   • More effective screening for body image within the medical/rehabilitation context is needed to help practitioners recognize distress   • Practitioners should be prepared to refer clients to distress hotlines they may need once released from treatment.

Trident sign trumps Aquaporin-4-IgG ELISA in diagnostic value in a case of longitudinally extensive transverse myelitis.

PubMed

Jolliffe, Evan A; Keegan, B Mark; Flanagan, Eoin P

2018-04-21

Longitudinally-extensive T2-hyperintense spinal cord lesions (≥3 vertebral segments) are associated with neuromyelitis optical spectrum disorder but occur with other disorders including spinal cord sarcoidosis. When linear dorsal subpial enhancement is accompanied by central cord/canal enhancement the axial post-gadolinium sequences may reveal a "trident" pattern that has previously been shown to be strongly suggestive of spinal cord sarcoidosis. We report a case in which the patient was initially diagnosed with neuromyelitis optical spectrum disorder, but where the "trident" sign ultimately led to the correct diagnosis of spinal cord sarcoidosis. Copyright © 2018. Published by Elsevier B.V.

Attachment Style, Social Support, and Coping as Psychosocial Correlates of Happiness in Persons with Spinal Cord Injuries

ERIC Educational Resources Information Center

Wilson, Lisa; Catalano, Denise; Sung, Connie; Phillips, Brian; Chou, Chih-Chin; Chan, Jacob Yui Chung; Chan, Fong

2013-01-01

Objective: To examine the roles of attachment, social support, and coping as psychosocial correlates in predicting happiness in people with spinal cord injuries. Design: Quantitative descriptive research design using multiple regression and correlation techniques. Participants: 274 individuals with spinal cord injuries. Outcome Measures: Happiness…

[Rehabilitation programme using neuromuscular electrical stimulation in spinal cord: epidemiological aspects].

PubMed

Bittar, Cíntia Kelly; Cliquet, Alberto

2011-01-01

To assess epidemiological profile of spinal cord injury outpatients which have been participating of rehabilitation programme using neuromuscular electrical stimulation, in order to implement campaigns for preventing spinal cord trauma. From January to April 2009, 30 patients at the spinal cord injury ambulatory clinic at Hospital das Clínicas of Unicamp were analysed by some epidemiologic characteristics: age, profession, type and level of their paralysis, origin and time of injury. All patients had complete spinal cord injury (ASIA); 24 patients were men and six were women, the mean age was 34.6 years (range, 10-64 years), two patients were children. Twenty-one patients were paraplegic and nine were tetraplegic; causes included automobile accident (12), run over (three), diving (four), bicycle accident (one), motorcycle accident (three), gunshot wound (six), thoracic tuberculosis (one), and lumbar surgery (one). The mean lesion time was 8.2 years (range, 1-15 years). Two patients were retired. The results suggested that spinal cord injury affects mainly young active men. It is necessary to develop incisive actions to prevent accidents, specially directed to traffic security.

'Full dose' reirradiation of human cervical spinal cord.

PubMed

Ryu, S; Gorty, S; Kazee, A M; Bogart, J; Hahn, S S; Dalal, P S; Chung, C T; Sagerman, R H

2000-02-01

With the progress of modern multimodality cancer treatment, retreatment of late recurrences or second tumors became more commonly encountered in management of patients with cancer. Spinal cord retreatment with radiation is a common problem in this regard. Because radiation myelopathy may result in functional deficits, many oncologists are concerned about radiation-induced myelopathy when retreating tumors located within or immediately adjacent to the previous radiation portal. The treatment decision is complicated because it requires a pertinent assessment of prognostic factors with and without reirradiation, radiobiologic estimation of recovery of occult spinal cord damage from the previous treatment, as well as interactions because of multimodality treatment. Recent studies regarding reirradiation of spinal cord in animals using limb paralysis as an endpoint have shown substantial and almost complete recovery of spinal cord injury after a sufficient time after the initial radiotherapy. We report a case of "full" dose reirradiation of the entire cervical spinal cord in a patient who has not developed clinically detectable radiation-induced myelopathy on long-term follow-up of 17 years after the first radiotherapy and 5 years after the second radiotherapy.

Extracellular matrix-derived hydrogels for dental stem cell delivery.

PubMed

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loïc; Leprince, Julian G; Diogenes, Anibal; Shakesheff, Kevin M; White, Lisa J; des Rieux, Anne

2017-01-01

Decellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site-specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017. © 2016 Wiley Periodicals, Inc.

The mechanism of Naringin-enhanced remyelination after spinal cord injury

PubMed Central

Rong, Wei; Pan, Yong-wei; Cai, Xu; Song, Fei; Zhao, Zhe; Xiao, Song-hua; Zhang, Cheng

2017-01-01

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. PMID:28469664

Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion.

PubMed

Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Distribution of syringomyelia along the entire spinal cord in clinically affected Cavalier King Charles Spaniels.

PubMed

Loderstedt, Shenja; Benigni, Livia; Chandler, Kate; Cardwell, Jacqueline M; Rusbridge, Clare; Lamb, Christopher R; Volk, Holger A

2011-12-01

Chiari-like malformation (CM) and syringomyelia (SM) is an important disease complex in the Cavalier King Charles Spaniel (CKCS) but data about the anatomical distribution of SM along the spinal cord are lacking in veterinary medicine. The objective of this study was to define the anatomic distribution of SM in CKCS clinically affected by CM/SM. Magnetic resonance imaging (MRI) of the brain and the entire spinal cord of 49 dogs was performed and different morphological parameters compared. Syrinx formation was present in the C1-C4 region and in other parts of the spinal cord. The maximal dorsoventral syrinx size can occur in any region of the spinal cord and the total syrinx size was positively correlated with age. Seventy-six per cent of CKCS with a cranial cervical syrinx also have a syrinx affecting more caudal spinal cord regions. MRI restricted to the cervical region may underestimate the extent of SM and the severity of the disease process in the majority of dogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG.

PubMed

Kim, C-Yoon; Hwang, In-Kyu; Kim, Hana; Jang, Se-Woong; Kim, Hong Seog; Lee, Won-Young

2016-01-01

A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs.

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.

PubMed

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.: Four weeks after injection, the retrograde delivery of the LacZ marker gene was identified in cervical spinal neurons and some glial cells, including oligodendrocytes in the white matter of the spinal cord, in both the twy/twy mouse and the heterozygous Institute of Cancer Research mouse (+/twy). In the compressed spinal cord of twy/twy mouse, AdV-BDNF gene transfection resulted in a significant decrease in the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells present in the spinal cord and a downregulation in the caspase apoptotic pathway compared with AdV-LacZ (control) gene transfection. There was a marked and significant increase in the areas of the spinal cord of AdV-BDNF-injected mice that were NF- and NG2-immunopositive compared with AdV-LacZ-injected mice, indicating the increased presence of neurons and oligodendrocytes in response to BDNF transfection. Our results demonstrate that targeted retrograde BDNF gene delivery suppresses apoptosis in neurons and oligodendrocytes in the chronically compressed spinal cord of twy/twy mouse. Further work is required to establish whether this method of gene delivery may provide neuroprotective effects in other situations of compressive spinal cord injury.

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

PubMed

Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

2016-04-01

Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat.

PubMed

Kalderon, N; Xu, S; Koutcher, J A; Fuks, Z

2001-06-22

Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.

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

PubMed

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 (P<0.05). This recovery was accompanied by increased numbers of surviving neuron and neurofilament-positive fibers in 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 (P<0.05). Transplanted MSCs survived for 8 weeks and reduced IL-6 and COX-2 levels, which may have promoted neuronal regeneration in 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.

Age, gender and normalization covariates for spinal cord gray matter and total cross-sectional areas at cervical and thoracic levels: A 2D phase sensitive inversion recovery imaging study.

PubMed

Papinutto, Nico; Schlaeger, Regina; Panara, Valentina; Zhu, Alyssa H; Caverzasi, Eduardo; Stern, William A; Hauser, Stephen L; Henry, Roland G

2015-01-01

The source of inter-subject variability and the influence of age and gender on morphometric characteristics of the spinal cord, such as the total cross-sectional area (TCA), the gray matter (GM) and white matter (WM) areas, currently remain under investigation. Understanding the effect of covariates such as age, gender, brain volumes, and skull- and vertebra-derived metrics on cervical and thoracic spinal cord TCA and GM areas in healthy subjects would be fundamental for exploring compartment specific changes in neurological diseases affecting the spinal cord. Using Magnetic Resonance Imaging at 3T we investigated 32 healthy subjects using a 2D phase sensitive inversion recovery sequence and we measured TCA, GM and WM areas at 4 cervical and thoracic levels of the spinal cord. We assessed age and gender relationships of cord measures and explored associations between cord measures and a) brain volumes and b) skull- and vertebra-derived metrics. Age and gender had a significant effect on TCA, WM and GM areas (with women and elderly having smaller values than men and younger people respectively), but not on the GM area/TCA ratio. The total intracranial volume and C3 vertebra dimensions showed the highest correlations with cord measures. When used in multi-regression models, they reduced cord areas group variability by approximately a third. Age and gender influences on cord measures and normalization strategies here presented might be of use in the study of compartment specific changes in various neurological diseases affecting the spinal cord.

The pathway of subarachnoid CSF moving into the spinal parenchyma and the role of astrocytic aquaporin-4 in this process.

PubMed

Wei, Fang; Zhang, Cui; Xue, Rong; Shan, Lidong; Gong, Shan; Wang, Guoqing; Tao, Jin; Xu, Guangyin; Zhang, Guoxing; Wang, Linhui

2017-08-01

It has been proved that cerebrospinal fluid (CSF) in the subarachnoid space could reenter the brain parenchyma via the perivascular space. The present study was designed to explore the pathway of subarachnoid CSF flux into the spinal cord and the potential role of aquaporin-4 (AQP4) in this process. Fluorescently tagged cadaverine, for the first time, was used to study CSF movement in mice. Following intracisternal infusion of CSF tracers, the cervical spinal cord was sliced and prepared for fluorescence imaging. Some sections were subject with immunostaining in order to observe tracer distribution and AQP4 expression. Fluorescently tagged cadaverine rapidly entered the spinal cord. Tracer influx into the spinal parenchyma was time dependent. At 10min post-infusion, cadaverine was largely distributed in the superficial tissue adjacent to the pial surface. At 70min post-infusion, cadaverine was distributed in the whole cord and especially concentrated in the gray matter. Furthermore, fluorescent tracer could enter the spinal parenchyma either along the perivascular space or across the pial surface. AQP4 was observed highly expressed in the astrocytic endfeet surrounding blood vessels and the pial surface. Blocking AQP4 by its specific inhibitor TGN-020 strikingly reduced the inflow of CSF tracers into the spinal cord. Subarachnoid CSF could flow into the spinal cord along the perivascular space or across the pial surface, in which AQP4 is involved. Our observation provides a basis for the study on CSF movement in the spinal cord when some neurological diseases occur. Copyright © 2017 Elsevier Inc. All rights reserved.

Different patterns of longitudinal brain and spinal cord changes and their associations with disability progression in NMO and MS.

PubMed

Liu, Yaou; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Liu, Zheng; Dong, Huiqing; Weiler, Florian; Hahn, Horst K; Shi, Fu-Dong; Butzkueven, Helmut; Barkhof, Frederik; Li, Kuncheng

2018-01-01

To investigate the longitudinal spinal cord and brain changes in neuromyelitis optica (NMO) and multiple sclerosis (MS) and their associations with disability progression. We recruited 28 NMO, 22 MS, and 20 healthy controls (HC), who underwent both spinal cord and brain MRI at baseline. Twenty-five NMO and 20 MS completed 1-year follow-up. Baseline spinal cord and brain lesion loads, mean upper cervical cord area (MUCCA), brain, and thalamus volume and their changes during a 1-year follow-up were measured and compared between groups. All the measurements were also compared between progressive and non-progressive groups in NMO and MS. MUCCA decreased significantly during the 1-year follow-up in NMO not in MS. Percentage brain volume changes (PBVC) and thalamus volume changes in MS were significantly higher than NMO. MUCCA changes were significantly different between progressive and non-progressive groups in NMO, while baseline brain lesion volume and PBVC were associated with disability progression in MS. MUCCA changes during 1-year follow-up showed association with clinical disability in NMO. Spinal cord atrophy changes were associated with disability progression in NMO, while baseline brain lesion load and whole brain atrophy changes were related to disability progression in MS. • Spinal cord atrophy progression was observed in NMO. • Spinal cord atrophy changes were associated with disability progression in NMO. • Brain lesion and atrophy were related to disability progression in MS.

The changing nature of admissions to a spinal cord injury center: violence on the rise.

PubMed

Farmer, J C; Vaccaro, A R; Balderston, R A; Albert, T J; Cotler, J

1998-10-01

The purpose of this study was to analyze changing etiologies for admission to a spinal cord injury center. This study was designed to retrospectively analyze the etiology of admissions to a spinal cord injury center during a 15-year period, specifically gunshot versus nongunshot wound injuries. Gunshot wounds are a well-recognized cause of spinal cord injury. In some centers, up to 52% of admissions are due to this, and these trends are believed to be increasing. All patients with spinal cord injury admitted to our center between 1979 and 1993 were analyzed. Frequencies of specific etiologies were determined and then comparisons were made between gunshot wound and nongunshot wound groups. Factors analyzed included age, male/female ratio, ethnic make-up, marital status, employment status, level of injury, and neurologic status. One thousand eight hundred seventeen patients were included. Overall, gunshot wound spinal cord injuries compromised 16.9% of injuries. A clear trend of increasing numbers of admissions was seen between 1984 and 1993 because of this. Gunshot wounds and nongunshot wounds differed dramatically in terms of age, ethnic make-up, marital status, employment status, and neurologic status. Cost attributed to treating gunshot wound injuries at our center for 1993 was 5.4 million dollars. Gunshot wounds as a cause of spinal cord injury are increasing at an alarming rate. The demographics of the gunshot wounds and nongunshot wound spine cord injuries differ significantly.

The experience of attempting to return to work following spinal cord injury: a systematic review of the qualitative literature.

PubMed

Hilton, Gillean; Unsworth, Carolyn; Murphy, Gregory

2018-07-01

This review sought to answer the question "What are the barriers and facilitators influencing people's experience of return to work following spinal cord injury?" Studies that met the selection criteria were identified, presented and critically appraised using National Institute for Health and Care Excellence guidelines. Thematic synthesis was completed with studies possessing strong methodological rigor. Synthesis and interpretation involved three stages; coding of primary data; development of descriptive themes reflective of the primary data; and establishment of analytical themes to answer the review question. Data from nine papers were included in the thematic synthesis. Several descriptive themes and three analytical themes were drawn from the data to answer the research question. Analytical themes included: a matrix of personal and environmental factors exists requiring complex navigation in order to create possibilities and opportunities for postinjury employment; the process of seeking or gaining employment shares a reciprocal relationship with the temporal nature of adjustment to spinal cord injury; and there is an intrinsic need for occupational engagement through paid employment. Returning to or gaining employment after spinal cord injury is a fundamentally difficult experience for people. Multiple strategies are required to support the navigation of the process. There is, however, a need in people with spinal cord injury, to be a worker, and with that comes the inherent benefits of being employed. Implications for rehabilitation Returning to work should be a significant focus of spinal cord injury rehabilitation. Employment is both possible and health promoting following spinal cord injury. Multiple strategies are required to support people to navigate the return to work process. It is important to be cognizant of the individual motivations for being a worker and the complexity of the adjustment process. Spinal cord injury centers can provide a consistent and supportive framework and culture of positivity about employment after spinal cord injury.

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

NASA Astrophysics Data System (ADS)

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).

Impact Depth and the Interaction with Impact Speed Affect the Severity of Contusion Spinal Cord Injury in Rats

PubMed Central

Lam, Cameron J.; Assinck, Peggy; Liu, Jie; Tetzlaff, Wolfram

2014-01-01

Abstract Spinal cord injury (SCI) biomechanics suggest that the mechanical factors of impact depth and speed affect the severity of contusion injury, but their interaction is not well understood. The primary aim of this work was to examine both the individual and combined effects of impact depth and speed in contusion SCI on the cervical spinal cord. Spinal cord contusions between C5 and C6 were produced in anesthetized rats at impact speeds of 8, 80, or 800 mm/s with displacements of 0.9 or 1.5 mm (n=8/group). After 7 days postinjury, rats were assessed for open-field behavior, euthanized, and spinal cords were harvested. Spinal cord tissue sections were stained for demyelination (myelin-based protein) and tissue sparing (Luxol fast blue). In parallel, a finite element model of rat spinal cord was used to examine the resulting maximum principal strain in the spinal cord during impact. Increasing impact depth from 0.9 to 1.5 mm reduced open-field scores (p<0.01) above 80 mm/s, reduced gray (GM) and white matter (WM) sparing (p<0.01), and increased the amount of demyelination (p<0.01). Increasing impact speed showed similar results at the 1.5-mm impact depth, but not the 0.9-mm impact depth. Linear correlation analysis with finite element analysis strain showed correlations (p<0.001) with nerve fiber damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with WM (R2=0.90) and GM (R2=0.76) sparing. The results demonstrate that impact depth is more important in determining the severity of SCI and that threshold interactions exist between impact depth and speed. PMID:24945364

Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells

PubMed Central

Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

2016-01-01

Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2/3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2/3+ cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2/3+ neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

Characteristics of AMPA receptor-mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1-4

PubMed Central

Dai, Wei-Min; Egebjerg, Jan; Lambert, John D C

2001-01-01

Electrophysiological recordings have been used to characterize responses mediated by AMPA receptors expressed by cultured rat cortical and spinal cord neurones. The EC50 values for AMPA were 17 and 11 μM, respectively.Responses of cortical neurones to AMPA were inhibited competitively by NBQX (pKi=6.6). Lower concentrations of NBQX (⩽1 μM) also potentiated the plateau responses of spinal cord neurones to AMPA, which could be attributed to a depression of desensitization to AMPA.GYKI 52466 inhibited responses of spinal cord neurones to AMPA to about twice the extent of responses of cortical neurones.Blockade of AMPA receptor desensitization by cyclothiazide (CTZ) potentiated responses of spinal cord neurones (6.8 fold) significantly more than responses of cortical neurones (4.8 fold). Responses of cortical neurones to KA were potentiated 3.5 fold by CTZ, while responses of spinal cord neurones were unaffected.Ultra-fast applications of AMPA to outside-out patches showed responses of spinal cord neurones desensitized by 97.5% and exhibit marked inward rectification, whereas cortical neurones desensitized by 91% and exhibited slight outward rectification. The time constants of deactivation and desensitization were about twice as fast in spinal cord than cortical neurones.In cortical neurones, single-cell RT – PCR showed GluR2 and GluR1 accounted for 91% of all subunits and were expressed together in 67% of neurones, predominantly as the flip variants (78%). GluR2 was detected alone in 24% of neurones. GluR3 and GluR4 were present in only 14 and 29% of neurones, respectively. For spinal cord neurones, GluR4o was detected in 81% of neurones, whereas predominantly flop versions of GluR1, 2 and 3 were detected in 38, 13 and 13% of neurones, respectively. These expression patterns are related to the respective pharmacological and mechanistic properties. PMID:11309259

Fast and Accurate Semi-Automated Segmentation Method of Spinal Cord MR Images at 3T Applied to the Construction of a Cervical Spinal Cord Template

PubMed Central

El Mendili, Mohamed-Mounir; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

2015-01-01

Objective To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. Materials and Methods A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects’ images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Results Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. Conclusion A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template. PMID:25816143

Making sense out of spinal cord somatosensory development

PubMed Central

Seal, Rebecca P.

2016-01-01

The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits. PMID:27702783

Idiopathic thoracic transdural intravertebral spinal cord herniation

PubMed Central

Turel, Mazda K; Wewel, Joshua T; Kerolus, Mena G; O'Toole, John E

2017-01-01

Idiopathic spinal cord herniation is a rare and often missed cause of thoracic myelopathy. The clinical presentation and radiological appearance is inconsistent and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed entity. While ventral spinal cord herniation through a dural defect has been previously described, intravertebral herniation is a distinct entity and extremely rare. We present the case of a 70-year old man with idiopathic thoracic transdural intravertebral spinal cord herniation and discuss the clinico-radiological presentation, pathophysiology and operative management along with a review the literature of this unusual entity. PMID:29021685

Reduce, reuse, recycle - Developmental signals in spinal cord regeneration.

PubMed

Cardozo, Marcos Julian; Mysiak, Karolina S; Becker, Thomas; Becker, Catherina G

2017-12-01

Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord tissue after injury, generating new neurons that mature and integrate into the spinal circuitry. Elucidating the molecular signals that promote this regeneration is a fundamental question in regeneration research. Model systems, such as salamanders and larval and adult zebrafish are used to analyse successful regeneration. This shows that many developmental signals, such as Notch, Hedgehog (Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF), Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and activate resident spinal progenitor cells. Here we compare the roles of these signals in spinal cord development and regeneration of the much larger and fully patterned adult spinal cord. Understanding how developmental signalling systems are reactivated in successfully regenerating species may ultimately lead to ways to reactivate similar systems in mammalian progenitor cells, which do not show neurogenesis after spinal injury. Copyright © 2017. Published by Elsevier Inc.

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

PubMed

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

2009-04-01

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

Repair of spinal cord injury with neuronal relays: From fetal grafts to neural stem cells.

PubMed

Bonner, Joseph F; Steward, Oswald

2015-09-04

Spinal cord injury (SCI) disrupts the long axonal tracts of the spinal cord leading to devastating loss of function. Cell transplantation in the injured spinal cord has the potential to lead to recovery after SCI via a variety of mechanisms. One such strategy is the formation of neuronal relays between injured long tract axons and denervated neurons. The idea of creating a neuronal relay was first proposed over 25 years ago when fetal tissue was first successfully transplanted into the injured rodent spinal cord. Advances in labeling of grafted cells and the development of neural stem cell culturing techniques have improved the ability to create and refine such relays. Several recent studies have examined the ability to create a novel neuronal circuit between injured axons and denervated targets. This approach is an alternative to long-distance regeneration of damaged axons that may provide a meaningful degree of recovery without direct recreation of lost pathways. This brief review will examine the contribution of fetal grafting to current advances in neuronal grafting. Of particular interest will be the ability of transplanted neurons derived from fetal grafts, neural precursor cells and neural stem cells to reconnect long distance motor and sensory pathways of the injured spinal cord. This article is part of a Special Issue entitled SI: Spinal cord injury. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2018-01-01

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

[Exoskeletons for rehabilitation of patients with spinal cord injuries. Options and limitations].

PubMed

Aach, M; Meindl, R C; Geßmann, J; Schildhauer, T A; Citak, M; Cruciger, O

2015-02-01

Mobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries. This article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries. The different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials. Although exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.

Building Infrastructure to Accelerate Transfer of Basic Research in Spinal Cord Injury (SCI) to Clinical Practice: North American Clinical Trials Network

DTIC Science & Technology

2013-08-01

RISCIS trial. 2. Participation by NACTN sites in the Novartis clinical trial of the monoclonal antibody to Nogo. Martin Schwab, PhD...Martha Horn and Simone Hirsch at Traumacenter, Murnau; Kristin Lorenz and Petra Schatz at Hohe Warte, Bayreuth. 8 Neurorehabilitation and Neural Repair

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

2000-01-01

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

Phantom sensations in people with complete spinal cord lesions: a grounded theory perspective.

PubMed

Drysdale, Daren G; Shem, Kazuko; Walbom, Agnes; Miner, Maureen D; Maclachlan, Malcolm

2009-01-01

Phantom sensations are somatic phenomena arising from denervated parts of the body. There is very little research, and much diagnostic confusion, regarding such experiences in people with spinal cord injuries. In the case of 'complete' spinal cord lesions, phantom experiences may challenge, and indeed, contradict, the understanding that both clinicians and patients have of such injuries. This paper seeks to provide a better understanding of such 'phantom' sensations in spinal cord injury. We used grounded theory methods to explore 'phantom' sensations as experienced by individuals with complete (ASIA A) spinal lesions. Eight people with complete lesions, who were selected through theoretical sampling, participated in a semi-structured interview. Emergent themes included injury context, sensations experienced, the meaning of sensations, body connectivity, attitude and communication about sensations. Our results provide an enhanced understanding of the embodied experience of phantom sensations, and important insights regarding self-construction and rehabilitative processes in people with spinal cord injury who experience such anomalous sensations.

[Attempts at management of experimental spinal cord hemisection by complete immobilization of the spine in dogs].

PubMed

Renard, C

1980-06-01

This animal experimentation shows the results of a method aiming at proving the possibilities of medullar reconstruction, if the medullar surfaces are in firm contact ant if medullar tension is neutralized. After hemitransection of the spinal cord, a total spinal immobilization in extension is obtained by using an original orthopaedic prosthesis. Thus, we operated on five dogs, one of which, the reference dog, underwent hemitransection of the spinal cord but no spine immobilization. From a clinical point of view, this dog developed a spastic crural monoplegia, whereas recuperation of motricity by the other dogs was surprising. Histological studies allowed us to observe a certain re-establishment of the spinal cord continuity, suggesting the beginning of an organization of a regeneration mechanism. These statements show the harmful influence of intra-medullar tension for spinal cord reconstruction. In practice, tractions on the spine must be abandoned for they increase the intramedullar tension very much and compromise any eventual "recuperation" after a medullar traumatism.

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

PubMed

Conrad, Benjamin N; Barry, Robert L; Rogers, Baxter P; Maki, Satoshi; Mishra, Arabinda; Thukral, Saakshi; Sriram, Subramaniam; Bhatia, Aashim; Pawate, Siddharama; Gore, John C; Smith, Seth A

2018-06-01

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology.

PubMed

Buchanan, J T

2001-03-01

Among the advantages offered by the lamprey brainstem and spinal cord for studies of the structure and function of the nervous system is the unique identifiability of several pairs of reticulospinal neurons in the brainstem. These neurons have been exploited in investigations of the patterns of sensory input to these cells and the patterns of their outputs to spinal neurons, but no doubt these cells could be used much more effectively in exploring their roles in descending control of the spinal cord. The variability of cell positions of neurons in the spinal cord has precluded the recognition of unique spinal neurons. However, classes of nerve cells can be readily defined and characterized within the lamprey spinal cord and this has led to progress in understanding the cellular and synaptic mechanisms of locomotor activity. In addition, both the identifiable reticulospinal cells and the various spinal nerve cell classes and their known synaptic interactions have been used to demonstrate the degree and specificity of regeneration within the lamprey nervous system. The lack of uniquely identifiable cells within the lamprey spinal cord has hampered progress in these areas, especially in gaining a full understanding of the locomotor network and how neuromodulation of the network is accomplished.

Measurement Structure of the Trait Hope Scale in Persons with Spinal Cord Injury: A Confirmatory Factor Analysis

ERIC Educational Resources Information Center

Smedema, Susan Miller; Pfaller, Joseph; Moser, Erin; Tu, Wei-Mo; Chan, Fong

2013-01-01

Objective: To evaluate the measurement structure of the Trait Hope Scale (THS) among individuals with spinal cord injury. Design: Confirmatory factor analysis and reliability and validity analyses were performed. Participants: 242 individuals with spinal cord injury. Results: Results support the two-factor measurement model for the THS with agency…

Religiosity and Spirituality among Persons with Spinal Cord Injury: Attitudes, Beliefs, and Practices

ERIC Educational Resources Information Center

Marini, Irmo; Glover-Graf, Noreen M.

2011-01-01

A total of 157 persons with spinal cord injury completed the "Spirituality and Spinal Cord Injury Survey" in relation to their spiritual and/or religious attitudes, beliefs, and practices in terms of adapting to their disability. Factor analysis accounting for 69% of the variance revealed four factors related to Spiritual Help and Improvement…

Body composition of active persons with spinal cord injury and with poliomyelitis

USDA-ARS?s Scientific Manuscript database

This study sought to evaluate the body composition of subjects with active spinal cord injuries and polio. Two groups of males and females, active, free-living, of similar ages and body mass index (BMI), were distributed according to the source of deficiency: SCI – low spinal cord injury (T5-T12) an...

Ex Vivo Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

PubMed Central

Jirjis, Michael B.; Kurpad, Shekar N.

2013-01-01

Abstract The aim of this study was to characterize magnetic resonance diffusion tensor imaging (DTI) in proximal regions of the spinal cord following a thoracic spinal cord injury (SCI). Sprague–Dawley rats (n=40) were administered a control, mild, moderate, or severe contusion injury at the T8 vertebral level. Six direction diffusion weighted images (DWIs) were collected ex vivo along the length of the spinal cord, with an echo/repetition time of 31.6 ms/14 sec and b=500 sec/mm2. Diffusion metrics were correlated to hindlimb motor function. Significant differences were found for whole cord region of interest (ROI) drawings for fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusion coefficient (LD), and radial diffusion coefficient (RD) at each of the cervical levels (p<0.01). Motor function correlated with MD in the cervical segments of the spinal cord (r2=0.80). The diffusivity of water significantly decreased throughout “uninjured” portions of the spinal cord following a contusion injury (p<0.05). Diffusivity metrics were found to be altered following SCI in both white and gray matter regions. Injury severity was associated with diffusion changes over the entire length of the cord. This study demonstrates that DTI is sensitive to SCI in regions remote from injury, suggesting that the diffusion metrics may be used as a biomarker for severity of injury. PMID:23782233

Immunological cross-reactivity between acid extracts of myelin, liver and neoplastic tissues: studies in immunized guinea-pigs.

PubMed Central

Flavell, D. J.; Goepel, J.; Wilson, A. P.; Potter, C. W.

1979-01-01

Groups of 4 guinea-pigs were immunized with acid extracts prepared from bovine myelin (EF), normal human liver tissue and malignant or benign neoplastic tissues in Freund's complete adjuvant (FCA1. The animals were weighed daily and examined for clinical signs of experimental allergic encephalomyelitis (EAE). All the animals immunized with EF developed clinical symptoms of EAE within 21 days of the initial immunization, whilst some of the animals immunized with certain tumour extracts developed symptoms which closely resembled those of EAE. Control animals immunized with FCA only remained asymptomatic. Cellular immunity to the various extracts in immunized animals was assessed 20 days after immunization by i.d. skin testing, and upon killing at Day 21 with the direct peritoneal-exudate macrophage migration inhibition (MMI) test. Brains and spinal cords were removed at killing, fixed in formalin and processed for histological examination. I.d. skin testing was shown to be most consistent in demonstrating positive delayed hypersensitivity, whilst the MMI test frequently gave negative results in the presence of pronounced skin responses to specific extracts. Thus it was shown that 3/4 animals immunized with basic proteins extracted from an adenocarcinoma of the lung or related hepatic metastases, and 1/2 animals immunized with an extract of a carcinoma of the breast, gave intense erythema and induration responses 5 mm in diameter 24 h after i.d. challenge with EF. No such response was obtained in animals immunized with basic proteins extracted from normal human liver, any of the other neoplastic tissues, or in control animals immunized with FCA only. Examination of brains and spinal cords from animals immunized with EF revealed dense infiltration by mononuclear cells in the ependyma and choroid plexus of levels in the spinal cord. Examination of brains and spinal cords from animals immunized with the lung-tumour extract or related hepatic metastases which showed demonstrable immunological cross-reactivity with EF in immunized animals, revealed a number of inflammatory changes characterized by dense infiltrates of mononuclear cells sub-ependymally, and perivascular cuffing in the cortex. However, no significant lesions were seen in the spinal cords of these animals. Polyacrylamide-gel electrophoresis of the 2 tumour extracts exerting this apparent encephalitogenic effect did not reveal proteins within the mol. wt range of EF. Thus the observed pathological effects and cross-reactivity with EF were probably not due to contamination with nervous-tissue components. It is suggested that these tumour extracts may have contained a component or components other than EF, immunologically cross-reactive with EF, and capable of inducing the observed encephalitis. Images Fig. 2 Fig. 3a, b Fig. 3c, d PMID:92328

Enrichment of spinal cord cell cultures with motoneurons

PubMed Central

1978-01-01

Spinal cord cell cultures contain several types of neurons. Two methods are described for enriching such cultures with motoneurons (defined here simply as cholinergic cells that are capable of innervating muscle). In the first method, 7-day embryonic chick spinal cord neurons were separated according to size by 1 g velocity sedimentation. It is assumed that cholinergic motoneurons are among the largest cells present at this stage. The spinal cords were dissociated vigorously so that 95-98% of the cells in the initial suspension were isolated from one another. Cells in leading fractions (large cell fractions: LCFs) contain about seven times as much choline acetyltransferase (CAT) activity per unit cytoplasm as do cells in trailing fractions (small cell fractions: SCFs). Muscle cultures seeded with LCFs develop 10-70 times as much CAT as cultures seeded with SCFs and six times as much CAT as cultures seeded with control (unfractionated) spinal cord cells. More than 20% of the large neurons in LCF-muscle cultures innervate nearby myotubes. In the second method, neurons were gently dissociated from 4-day embryonic spinal cords and maintained in vitro. This approach is based on earlier observations that cholinergic neurons are among the first cells to withdraw form the mitotic cycle in the developing chick embryo (Hamburger, V. 1948. J. Comp. Neurol. 88:221- 283; and Levi-Montalcini, R. 1950. J. Morphol. 86:253-283). 4-Day spinal cord-muscle cultures develop three times as much CAT as do 7-day spinal cord-muscle plates, prepared in the same (gentle) manner. More than 50% of the relatively large 4-day neurons innervate nearby myotubes. Thus, both methods are useful first steps toward the complete isolation of motoneurons. Both methods should facilitate study of the development of cholinergic neurons and of nerve-muscle synapse formation. PMID:566275

Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein.

PubMed

Son, Marjatta; Leary, Scot C; Romain, Nadine; Pierrel, Fabien; Winge, Dennis R; Haller, Ronald G; Elliott, Jeffrey L

2008-05-02

G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.

PubMed

Chaudhry, Rajeev; Madden-Fuentes, Ramiro J; Ortiz, Tara K; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S; Ross, Sherry S; Seed, Patrick C

2014-05-01

Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The impact of pain on spiritual well-being in people with a spinal cord injury.

PubMed

Siddall, P J; McIndoe, L; Austin, P; Wrigley, P J

2017-01-01

The study uses a cross-sectional, group comparison, questionnaire-based design. To determine whether spinal cord injury and pain have an impact on spiritual well-being and whether there is an association between spiritual well-being and measures of pain and psychological function. University teaching hospital in Sydney, New South Wales, Australia. Questionnaires evaluating pain, psychological and spiritual well-being were administered to a group of people with a spinal cord injury (n=53) and a group without spinal cord injury (n=37). Spiritual well-being was assessed using the Functional Assessment of Chronic Illness and Therapy - Spirituality Extended Scale (FACIT-Sp-Ex). Pain and psychological function were also assessed using standard, validated measures of pain intensity, pain interference, mood and cognition. Levels of spiritual well-being in people with a spinal cord injury were significantly lower when compared with people without a spinal cord injury. In addition, there was a moderate but significant negative correlation between spiritual well-being and pain intensity. There was also a strong and significant negative correlation between depression and spiritual well-being and a strong and significant positive correlation between spiritual well-being and both pain self-efficacy and satisfaction with life. Consequences of a spinal cord injury include increased levels of spiritual distress, which is associated, with higher levels of pain and depression and lower levels of pain self-efficacy and satisfaction with life. These findings indicate the importance of addressing spiritual well-being as an important component in the long-term rehabilitation of any person following spinal cord injury. This study was supported by grant funding from the Australian and New Zealand College of Anaesthetists, and the National Health and Medical Research Council of Australia.

Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).

PubMed

Mehta, Prachi; Premkumar, Brian; Morris, Renée

2016-08-03

The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats

PubMed Central

Yang, Xiao-Hua; Ding, Ying; Li, Wen; Zhang, Rong-Yi; Wu, Jin-Lang; Ling, Eng-Ang; Wu, Wutian

2017-01-01

Objectives In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether ‘Governor Vessel’ (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. Methods Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. Results EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. Conclusions The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination. PMID:27841975

Preexisting severe cervical spinal cord compression is a significant risk factor for severe paralysis development in patients with traumatic cervical spinal cord injury without bone injury: a retrospective cohort study.

PubMed

Oichi, Takeshi; Oshima, Yasushi; Okazaki, Rentaro; Azuma, Seiichi

2016-01-01

The objective of this study is to investigate whether preexisting severe cervical spinal cord compression affects the severity of paralysis once patients develop traumatic cervical spinal cord injury (CSCI) without bone injury. We retrospectively investigated 122 consecutive patients with traumatic CSCI without bone injury. The severity of paralysis on admission was assessed by the American Spinal Injury Association impairment scale (AIS). The degree of preexisting cervical spinal cord compression was evaluated by the maximum spinal cord compression (MSCC) and was divided into three categories: minor compression (MSCC ≤ 20 %), moderate compression (20 % < MSCC ≤ 40 %), and severe compression (40 % < MSCC). We investigated soft-tissue damage on magnetic resonance imaging to estimate the external force applied. Other potential risk factors, including age, sex, fused vertebra, and ossification of longitudinal ligament, were also reviewed. A multivariate logistic regression analysis was performed to investigate the risk factors for developing severe paralysis (AIS A-C) on admission. Our study included 103 males and 19 females with mean age of 65 years. Sixty-one patients showed severe paralysis (AIS A-C) on admission. The average MSCC was 22 %. Moderate compression was observed in 41, and severe in 20. Soft-tissue damage was observed in 91. A multivariate analysis showed that severe cervical spinal cord compression significantly affected the severity of paralysis at the time of injury, whereas both mild and moderate compression did not affect it. Soft-tissue damage was also significantly associated with severe paralysis on admission. Preexisting severe cervical cord compression is an independent risk factor for severe paralysis once patients develop traumatic CSCI without bone injury.

Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.

PubMed

Ogita, Shogo; Endo, Toshiki; Sugiyama, Shinichiro; Saito, Ryuta; Inoue, Tomoo; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji

2017-05-01

Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord.

PubMed

Zhu, J; Jhamandas, K; Yang, H Y

1992-10-02

Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord.

Cycling exercise and fetal spinal cord transplantation act synergistically on atrophied muscle following chronic spinal cord injury in rats.

PubMed

Peterson, C A; Murphy, R J; Dupont-Versteegden, E E; Houlé, J D

2000-01-01

The potential of two interventions, alone or in combination, to restore chronic spinal cord transection-induced changes in skeletal muscles of adult Sprague-Dawley rats was studied. Hind limb skeletal muscles were examined in the following groups of animals: rats with a complete spinal cord transection (Tx) for 8 weeks; Tx with a 4-week delay before initiation of a 4-week motor-assisted cycling exercise (Ex) program; Tx with a 4-week delay before transplantation (Tp) of fetal spinal cord tissue into the lesion cavity; Tx with a 4-week delay before Tp and Ex; and uninjured control animals. Muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas were significantly reduced 8 weeks after transection. Whereas transplantation of fetal spinal cord tissue did not reverse this atrophy and exercise alone had only a modest effect in restoring lost muscle mass, the combination of exercise and transplantation significantly increased muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas in both soleus and plantaris muscles. Spinal cord injury (SCI) also caused changes in myosin heavy chain (MyHC) expression toward faster isoforms in both soleus and plantaris and increased soleus myofiber succinate dehydrogenase (SDH) activity. Combined exercise and transplantation led to a change in the expression of the fastest MyHC isoform in soleus but had no effect in the plantaris. Exercise alone and in combination with transplantation reduced SDH activity to control levels in the soleus. These results suggest a synergistic action of exercise and transplantation of fetal spinal cord tissue on skeletal muscle properties following SCI, even after an extended post-injury period before intervention.

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

PubMed Central

Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

1994-01-01

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7529113

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

PubMed

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.

Spinal cord lesions in Bangladesh: an epidemiological study 1994 - 1995.

PubMed

Hoque, M F; Grangeon, C; Reed, K

1999-12-01

Spinal Cord Lesions are a major public health problem in Bangladesh. This epidemiological study was undertaken in order to identify the causes of spinal cord lesions and thus to allow prevention and control programs to be developed. The records of 247 patients with spinal cord lesions admitted to The Centre for the Rehabilitation of the Paralysed (CRP), Savar, Dhaka from January 1994 to June 1995 were reviewed retrospectively. Comparisons were made with the reports of studies from other countries, both developing and developed. The most common cause of traumatic lesions was a fall from a height followed by falling when carrying a heavy weight on the head and road traffic accidents. Most of the patients were between 20 - 40 years old and the overall age group ranged from 10 - 70 years. The male:female ratio was 7.5 : 1.0. Among the traumatic spinal cord lesions, 60% were paraplegics and 40% tetraplegics. Among the non-traumatic spinal cord lesions cases 84% were paraplegics and 16% tetraplegics. The leading cause of death resulted from respiratory complications and these deaths occurred in the very early period of admission. From the results it can be deduced that the high incidence of spinal cord lesion as a result from falls from a height, and from falling when carrying a heavy weight on the head, can be explained by the mainly agricultural based economy of Bangladesh. The most common age group (10 - 40 years) of patients reflects the socio-economic conditions of Bangladesh. The male:female ratio (7.5 : 1.0) of patients with a spinal cord lesion is due to the socio-economic status and to the traditional culture of the society.

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

PubMed

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

2017-10-01

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

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

PubMed Central

Kim, Jae Young; Mun, Chin Hee; Suh, Minah

2017-01-01

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype. PMID:29093636

Spinal cord ischemia after simultaneous and sequential treatment of multilevel aortic disease.

PubMed

Piffaretti, Gabriele; Bonardelli, Stefano; Bellosta, Raffaello; Mariscalco, Giovanni; Lomazzi, Chiara; Tolenaar, Jip L; Zanotti, Camilla; Guadrini, Cristina; Sarcina, Antonio; Castelli, Patrizio; Trimarchi, Santi

2014-10-01

The aim of the present study is to report a risk analysis for spinal cord injury in a recent cohort of patients with simultaneous and sequential treatment of multilevel aortic disease. We performed a multicenter study with a retrospective data analysis. Simultaneous treatment refers to descending thoracic and infrarenal aortic lesions treated during the same operation, and sequential treatment refers to separate operations. All descending replacements were managed with endovascular repair. Of 4320 patients, multilevel aortic disease was detected in 77 (1.8%). Simultaneous repair was performed in 32 patients (41.5%), and a sequential repair was performed in 45 patients (58.4%). Postoperative spinal cord injury developed in 6 patients (7.8%). At multivariable analysis, the distance of the distal aortic neck from the celiac trunk was the only independent predictor of postoperative spinal cord injury (odds ratio, 0.75; 95% confidence interval, 0.56-0.99; P=.046); open surgical repair of the abdominal aortic disease was associated with a higher risk of spinal cord injury but did not reach statistical significance (odds ratio, 0.16; 95% confidence interval, 0.02-1.06; P=.057). Actuarial survival estimates at 1, 2, and 5 years after the procedure were 80%±5%, 68%±6%, and 63%±7%, respectively. Spinal cord injury did not impair survival (P=.885). In our experience, the risk of spinal cord injury is still substantial at 8% in patients with multilevel aortic disease. The distance of the distal landing zone from the celiac trunk is a significant predictor of spinal cord ischemia. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

GDNF and NGF family members and receptors in human fetal and adult spinal cord and dorsal root ganglia.

PubMed

Josephson, A; Widenfalk, J; Trifunovski, A; Widmer, H R; Olson, L; Spenger, C

2001-11-12

We describe the expression of mRNA encoding ligands and receptors of members of the GDNF family and members of the neurotrophin family in the adult human spinal cord and dorsal root ganglia (DRG). Fetal human spinal cord and ganglia were investigated for the presence of ligands and receptors of the neurotrophin family. Tissues were collected from human organ donors and after routine elective abortions. Messenger RNA was found encoding RET, GFR alpha-1, BDNF, trkB, and trkC in the adult human spinal cord and BDNF, NT-3, p75, trkB, and trkC in the fetal human spinal cord. The percentage of adult human DRG cells expressing p75, trkA, trkB, or trkC was 57, 46, 29, and 24%, respectively, and that of DRG cells expressing RET, GFR alpha-1, GFR alpha-2, or GFR alpha-3 was 79, 20, 51, and 32%, respectively. GFR alpha-2 was expressed selectively in small, GFR alpha-3 principally in small and GFR alpha-1 and RET in both large and small adult human DRG neurons. p75 and trkB were expressed by a wide range of DRG neurons while trkA was expressed in most small diameter and trkC primarily in large DRG neurons. Fetal DRG cells were positive for the same probes as adult DRG cells except for NT-3, which was only found in fetal DRG cells. Messenger RNA species only expressed at detectable levels in fetal but not adult spinal cord tissues included GDNF, GFR alpha-2, NT-3, and p75. Notably, GFR alpha-2, which is expressed in the adult rat spinal cord, was not found in the adult human spinal cord. Copyright 2001 Wiley-Liss, Inc.

Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker

PubMed Central

Kolind, Shannon; Seddigh, Arshia; Combes, Anna; Russell-Schulz, Bretta; Tam, Roger; Yogendrakumar, Vignan; Deoni, Sean; Sibtain, Naomi A.; Traboulsee, Anthony; Williams, Steven C.R.; Barker, Gareth J.; Brex, Peter A.

2015-01-01

Objectives Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). Methods Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. Results Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (− 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: − 11%, p = 0.01; spine: − 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). Interpretation In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability. PMID:26594633

Altered spinal cord activity during sexual stimulation in women with SCI: a pilot fMRI study.

PubMed

Alexander, Marcalee; Kozyrev, Natalie; Figley, Chase R; Richards, J Scott

2017-01-01

The objective of this study was to assess the feasibility of the use of functional magnetic resonance imaging (fMRI) to evaluate the spinal activation during sexual response of the thoracic, lumbar and sacral spinal cord. This is a laboratory-based pilot study in human females at a University-based medical center in the United States. In three healthy spinal cord injury (SCI) females, spinal cord activations during sexual audiovisual stimulation (alone), genital self-stimulation (alone) and simultaneous audiovisual and genital self-stimulation (combined) were assessed and then compared with each subjects' remaining sensory and motor function. Spinal fMRI responses of the intermediolateral columns were found during audiovisual stimulation in both subjects with incomplete injuries, but they were not observed in the subject with a complete injury. Moreover, sacral responses to combined stimulation differed greatly between the subjects with complete and incomplete injuries. These results not only provide the first in vivo documentation of spinal fMRI responses associated with sexual arousal in women with SCIs, but also suggest that spinal cord fMRI is capable of distinguishing between injury subtypes. Therefore, although there are certain limitations associated with fMRI during sexual stimulation (for example, movement artifacts, an artificially controlled environment and so), these findings demonstrate the potential utility of incorporating spinal cord fMRI in future research to evaluate the impact of specific patterns of SCI on sexual responses and/or the effects of treatment.

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI).

PubMed

Fyffe, Denise; Kalpakjian, Claire Z; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C; Tulsky, David S; Jette, Alan M

2016-09-01

To provide validation of functional ability levels for the Spinal Cord Injury - Functional Index (SCI-FI). Cross-sectional. Inpatient rehabilitation hospital and community settings. A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Not Applicable. Spinal Cord Injury-Functional Index (SCI-FI). Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed.

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

PubMed

Gonzalez-Piña, Rigoberto; Nuño-Licona, Alberto

2007-01-01

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

Thoracic arachnoid cyst resection.

PubMed

Deutsch, Harel

2014-09-01

Arachnoid cysts in the spinal cord may be asymptomatic. In some cases arachnoid cysts may exert mass effect on the thoracic spinal cord and lead to pain and myelopathy symptoms. Arachnoid cysts may be difficult to visualize on an MRI scan because the thin walled arachnoid may not be visible. Focal displacement of the thoracic spinal cord and effacement of the spinal cord with apparent widening of the cerebrospinal fluid space is seen. This video demonstrates surgical techniques to remove a dorsal arachnoid cyst causing spinal cord compression. The surgery involves a thoracic laminectomy. The dura is opened sharply with care taken not to open the arachnoid so that the cyst can be well visualized. The thickened arachnoid walls of the cyst are removed to alleviate the compression caused by the arachnoid cyst. The video can be found here: http://youtu.be/pgUrl9xvsD0.

Modeling the neuroanatomic propagation of ALS in the spinal cord

NASA Astrophysics Data System (ADS)

Drawert, Brian; Thakore, Nimish; Mitchell, Brian; Pioro, Erik; Ravits, John; Petzold, Linda R.

2017-07-01

Recent hypotheses of amyotrophic lateral sclerosis (ALS) progression have posited a point-source origin of motor neuron death with neuroanatomic propagation either contiguously to adjacent regions, or along networks via axonal and synaptic connections. Although the molecular mechanisms of propagation are unknown, one leading hypothesis is a "prion-like" spread of misfolded and aggregated proteins, including SOD1 and TDP-43. We have developed a mathematical model representing cellular and molecular spread of ALS in the human spinal cord. Our model is based on the stochastic reaction-diffusion master equation approach using a tetrahedral discretized space to capture the complex geometry of the spinal cord. Domain dimension and shape was obtained by reconstructing human spinal cord from high-resolution magnetic resonance (MR) images and known gross and histological neuroanatomy. Our preliminary results qualitatively recapitulate the clinically observed pattern of spread of ALS thorough the spinal cord.

Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patient.

PubMed

Bernal-Cano, F; Joseph, J T; Koralnik, I J

2007-10-01

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. This disease is caused by a reactivation of the polyomavirus JC (JCV). Clinical presentation can be variable from patient to patient as lesions can occur anywhere in the CNS white matter; however, they appear to spare the optic nerves and the spinal cord. The authors present a case of PML in the setting of acquired immunodeficiency syndrome (AIDS) who developed PML lesions in the spinal cord, discovered during the postmortem examination. This finding is significant because PML has recently been diagnosed in patients with multiple sclerosis (MS) treated with the novel immunomodulatory medication natalizumab. Indeed, spinal cord lesions are frequent in MS. Therefore clinicians should be aware that in addition to the brain, PML may also affect the spinal cord white matter.

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

PubMed

Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

2017-06-01

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

Percutaneous Radiofrequency Ablation of Painful Spinal Tumors Adjacent to the Spinal Cord with Real-Time Monitoring of Spinal Canal Temperature: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakatsuka, Atsuhiro, E-mail: nakatuka@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki

2009-01-15

PurposeTo prospectively evaluate the feasibility, safety, and clinical utility of bone radiofrequency (RF) ablation with real-time monitoring of the spinal canal temperature for the treatment of spinal tumors adjacent to the spinal cord.Materials and MethodsOur Institutional Review Board approved this study. Patients gave informed consent. The inclusion criteria were (a) a painful spinal metastasis and (b) a distance of 1 cm or less between the metastasis and the spinal cord. The thermocouple was placed in the spinal canal under CT fluoroscopic guidance. When the spinal canal temperature reached 45{sup o}C, RF application was immediately stopped. RF ablation was considered technicallymore » successful when the procedure was performed without major complications. Clinical success was defined as a fall in the visual analogue scale score of at least 2 points.ResultsTen patients with spinal tumors measuring 3-8 cm (mean, 4.9 {+-} 1.5 cm) were enrolled. The distance between the tumor and the spinal cord was 1-6 mm (mean, 2.4 {+-} 1.6 mm). All procedures were judged technically successful (100%). The spinal canal temperature did not exceed 45{sup o}C in 9 of the 10 patients (90%). In the remaining patient, the temperature rose to 48{sup o}C, resulting in transient neural damage, although RF application was immediately stopped when the temperature reached 45{sup o}C. Clinical success was achieved within 1 week in all patients (100%).ConclusionBone RF ablation with real-time monitoring of the spinal canal temperature is feasible, safe, and clinically useful for the treatment of painful spinal metastases adjacent to the spinal cord.« less

Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

PubMed

Kimura, S; Gomibuchi, F; Shimoda, H; Ikezawa, Y; Segawa, H; Kaneko, F; Uchiyama, S; Homma, T

2000-04-01

Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model.

PubMed

Weirich, S D; Cotler, H B; Narayana, P A; Hazle, J D; Jackson, E F; Coupe, K J; McDonald, C L; Langford, L A; Harris, J H

1990-07-01

Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.

Neuromodulation of lower limb motor control in restorative neurology.

PubMed

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-06-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuromodulation of lower limb motor control in restorative neurology

PubMed Central

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-01-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. PMID:22464657

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

PubMed

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 compression in two related Ursus arctos horribilis.

PubMed

Thomovsky, Stephanie A; Chen, Annie V; Roberts, Greg R; Schmidt, Carrie E; Layton, Arthur W

2012-09-01

Two 15-yr-old grizzly bear littermates were evaluated within 9 mo of each other with the symptom of acute onset of progressive paraparesis and proprioceptive ataxia. The most significant clinical examination finding was pelvic limb paresis in both bears. Magnetic resonance examinations of both bears showed cranial thoracic spinal cord compression. The first bear had left-sided extradural, dorsolateral spinal cord compression at T3-T4. Vertebral canal stenosis was also observed at T2-T3. Images of the second bear showed lateral spinal cord compression from T2-T3 to T4-T5. Intervertebral disk disease and associated spinal cord compression was also observed at T2-T3 and T3-T4. One grizzly bear continued to deteriorate despite reduced exercise, steroid, and antibiotic therapy. The bear was euthanized, and a necropsy was performed. The postmortem showed a spinal ganglion cyst that caused spinal cord compression at the level of T3-T4. Wallerian-like degeneration was observed from C3-T6. The second bear was prescribed treatment that consisted of a combination of reduced exercise and steroid therapy. He continued to deteriorate with these medical therapies and was euthanized 4 mo after diagnosis. A necropsy showed hypertrophy and protrusion of the dorsal longitudinal ligament at T2-T3 and T3-T4, with resulting spinal cord compression in this region. Wallerian-like degeneration was observed from C2-L1. This is one of few case reports that describes paresis in bears. It is the only case report, to the authors' knowledge, that describes spinal magnetic resonance imaging findings in a grizzly bear and also the only report that describes a cranial thoracic myelopathy in two related grizzly bears with neurologic signs.

Management of Lower Extremity Long-bone Fractures in Spinal Cord Injury Patients.

PubMed

Schulte, Leah M; Scully, Ryan D; Kappa, Jason E

2017-09-01

The AO classification system, used as a guide for modern fracture care and fixation, follows a basic philosophy of care that emphasizes early mobility and return to function. Lower extremity long-bone fractures in patients with spinal cord injury often are pathologic injuries that present unique challenges, to which the AO principles may not be entirely applicable. Optimal treatment achieves healing without affecting the functional level of the patient. These injuries often result from low-energy mechanisms in nonambulatory patients with osteopenic bone and a thin, insensate soft-tissue envelope. The complication rate can be high, and the outcomes can be catastrophic without proper care. Satisfactory results can be obtained through various methods of immobilization. Less frequently, internal fixation is applied. In certain cases, after discussion with the patient, amputation may be suitable. Prevention strategies aim to minimize bone loss and muscle atrophy.

Cholinergic mechanisms in spinal locomotion—potential target for rehabilitation approaches

PubMed Central

Jordan, Larry M.; McVagh, J. R.; Noga, B. R.; Cabaj, A. M.; Majczyński, H.; Sławińska, Urszula; Provencher, J.; Leblond, H.; Rossignol, Serge

2014-01-01

Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments. PMID:25414645

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

PubMed

Paquin, M-Ê; El Mendili, M M; Gros, C; Dupont, S M; Cohen-Adad, J; Pradat, P-F

2018-01-01

There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls ( P = .004) compared with spinal cord atrophy ( P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline ( R = 0.56 for gray matter and R = 0.55 for spinal cord; P < .01). Prediction at 1 year with clinical scores ( R 2 = 0.54) was improved when including a combination of gray matter and white matter cross-sectional areas ( R 2 = 0.74). Although improvements over spinal cord cross-sectional areas were modest, this study suggests the potential use of gray matter cross-sectional areas as an MR imaging structural biomarker to monitor the evolution of amyotrophic lateral sclerosis. © 2018 by American Journal of Neuroradiology.

Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain

PubMed Central

Klaw, Michelle C; Xu, Chen; Tom, Veronica J

2013-01-01

In the vast majority of studies utilizing adeno-associated virus (AAV) in central nervous system applications, including those published with spinal cord injury (SCI) models, AAV has been administered at the level of the cell body of neurons targeted for genetic modification, resulting in transduction of neurons in the vicinity of the injection site. However, as SCI interrupts many axon tracts, it may be more beneficial to transduce a diverse pool of supraspinal neurons. We determined if descending axons severed by SCI are capable of retrogradely transporting AAV to remotely transduce a variety of brain regions. Different AAV serotypes encoding the reporter green fluorescent protein (GFP) were injected into gray and white matter immediately rostral to a spinal transection site. This resulted in the transduction of thousands of neurons within the spinal cord and in multiple regions within the brainstem that project to spinal cord. In addition, we established that different serotypes had disparate regional specificity and that AAV5 transduced the most brain and spinal cord neurons. This is the first demonstration that retrograde transport of AAV by axons severed by SCI is an effective means to transduce a collection of supraspinal neurons. Thus, we identify a novel, minimally invasive means to transduce a variety of neuronal populations within both the spinal cord and the brain following SCI. This paradigm to broadly distribute viral vectors has the potential to be an important component of a combinatorial strategy to promote functional axonal regeneration. PMID:23881451

Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors.

PubMed

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

2017-08-23

When new motor learning changes the spinal cord, old behaviors are not impaired; their key features are preserved by additional compensatory plasticity. To explore the mechanisms responsible for this compensatory plasticity, we transected the spinal dorsal ascending tract before or after female rats acquired a new behavior-operantly conditioned increase or decrease in the right soleus H-reflex-and examined an old behavior-locomotion. Neither spinal dorsal ascending tract transection nor H-reflex conditioning alone impaired locomotion. Nevertheless, when spinal dorsal ascending tract transection and H-reflex conditioning were combined, the rats developed a limp and a tilted posture that correlated in direction and magnitude with the H-reflex change. When the right H-reflex was increased by conditioning, the right step lasted longer than the left and the right hip was higher than the left; when the right H-reflex was decreased by conditioning, the opposite occurred. These results indicate that ascending sensory input guides the compensatory plasticity that normally prevents the plasticity underlying H-reflex change from impairing locomotion. They support the concept of the state of the spinal cord as a negotiated equilibrium that reflects the concurrent influences of all the behaviors in an individual's repertoire; and they support the new therapeutic strategies this concept introduces. SIGNIFICANCE STATEMENT The spinal cord provides a reliable final common pathway for motor behaviors throughout life. Until recently, its reliability was explained by the assumption that it is hardwired; but it is now clear that the spinal cord changes continually as new behaviors are acquired. Nevertheless, old behaviors are preserved. This study shows that their preservation depends on sensory feedback from the spinal cord to the brain: if feedback is removed, the acquisition of a new behavior may disrupt an old behavior. In sum, when a new behavior changes the spinal cord, sensory feedback to the brain guides further change that preserves old behaviors. This finding contributes to a new understanding of spinal cord function and to development of new rehabilitation therapies. Copyright © 2017 the authors 0270-6474/17/378198-09$15.00/0.

The Role of Core Self-Evaluations in the Relationship between Stress and Depression in Persons with Spinal Cord Injury

ERIC Educational Resources Information Center

DeAngelis, Jesse B.; Yaghmaian, Rana; Smedema, Susan Miller

2016-01-01

Purpose: To investigate the role of core self-evaluations (CSE) in the relationship between perceived stress and depression in persons with spinal cord injury. Method: Two hundred forty-seven adults with spinal cord injury completed an online survey measuring perceived stress, CSE, and depressive symptoms. Results: A multiple regression analysis…

Frequency Mapping of Rat Spinal Cord at 7T

NASA Astrophysics Data System (ADS)

Chen, Evan; Rauscher, Alexander; Kozlowski, Piotr; Yung, Andrew

2012-10-01

The spinal cord is an integral part of the nervous system responsible for sensory, motor, and reflex control crucial to all bodily function. Due to its non-invasive nature, MRI is well matched for characterizing and imaging of spinal cord, and is used extensively for clinical applications. Recent developments in magnetic resonance imaging (MRI) at high field (7T) using phase represents a new approach of characterizing spinal cord myelin. Theory suggests that microstructure differences in myelinated white matter (WM) and non-myelinated gray matter (GM) affect MR phase, measurable frequency shifts. Data from pilot experiments using a multi-gradient echo (MGE) sequence to image rat spinal cords placed parallel to main magnetic field B0 has shown frequency shifts between not only between WM and GM, but also between specific WM tracts of the dorsal column, including the fasciculus gracilis, fasciculus cuneatus, and corticospinal tract. Using MGE, frequency maps at multiple echo times (TE) between 4ms and 22ms show a non-linear relationship between WM frequency, contrary to what was previously expected. These results demonstrate the effectiveness of MGE in revealing new information about spinal cord tissue microstructure, and lays important groundwork for in-vivo and human studies.

Sexuality and sexual life in women with spinal cord injury: a controlled study.

PubMed

Kreuter, Margareta; Siösteen, Agneta; Biering-Sørensen, Fin

2008-01-01

To describe sexual life in women with spinal cord injury. Controlled cross-sectional, questionnaire. Women, 18-65 years, treated at spinal cord centres in Sweden, Denmark, Norway, Finland and Iceland. 545 women (57%) completed the questionnaires. The age-matched control group consisted of 507 women. The 104-item Spinal Cord Injury Women Questionnaire, was designed to assess different dimensions of sexuality. 80% of the women with spinal cord injury had engaged in sex after the injury. Reasons for not wanting or not having the courage to be intimate and sexual were physical problems, low sexual desire, low self-esteem and feelings of being unattractive. The motivations of both the women with spinal cord injury and controls to engage in sexual activity were intimacy-based rather than primarily sexual. Being in the right mood both before and during sex to become receptive to sexual stimulation was important. For women who are able to overcome the physical restrictions and mental obstacles due to injury, it is possible to regain an active and positive sexual life together with a partner. Sexual information and counselling should be available both during initial rehabilitation and later when the women have returned to their homes.

Dynamic membrane depolarization is an early regulator of ependymoglial cell response to spinal cord injury in axolotl

PubMed Central

Sabin, Keith; Santos-Ferreira, Tiago; Essig, Jaclyn; Rudasill, Sarah; Echeverri, Karen

2016-01-01

Salamanders, such as the Mexican axolotl, are some of the few vertebrates fortunate in their ability to regenerate diverse structures after injury. Unlike mammals they are able to regenerate a fully functional spinal cord after injury. However, the molecular circuitry required to initiate a pro-regenerative response after spinal cord injury is not well understood. To address this question we developed a spinal cord injury model in axolotls and used in vivo imaging of labeled ependymoglial cells to characterize the response of these cells to injury. Using in vivo imaging of ion sensitive dyes we identified that spinal cord injury induces a rapid and dynamic change in the resting membrane potential of ependymoglial cells. Prolonged depolarization of ependymoglial cells after injury inhibits ependymoglial cell proliferation and subsequent axon regeneration. Using transcriptional profiling we identified c-Fos as a key voltage sensitive early response gene that is expressed specifically in the ependymoglial cells after injury. This data establishes that dynamic changes in the membrane potential after injury are essential for regulating the specific spatiotemporal expression of c-Fos that is critical for promoting faithful spinal cord regeneration in axolotl. PMID:26477559

Real-time PCR quantification of gene expression in embryonic mouse tissue.

PubMed

Villalon, Eric; Schulz, David J; Waters, Samuel T

2014-01-01

The Gbx family of transcription factors consists of two closely related proteins GBX1 and GBX2. A defining feature of the GBX family is a highly conserved 60 amino acid DNA-binding domain, which differs by just two amino acids. Gbx1 and Gbx2 are co-expressed in several areas of the developing central nervous system including the forebrain, anterior hindbrain, and spinal cord, suggesting the potential for genetic redundancy. However, there is a spatiotemporal difference in expression of Gbx1 and Gbx2 in the forebrain and spinal cord. Gbx2 has been shown to play a critical role in positioning the midbrain/hindbrain boundary and developing anterior hindbrain, whereas gene-targeting experiments in mice have revealed an essential function for Gbx1 in the spinal cord for normal locomotion. To determine if Gbx2 could potentially compensate for a loss of Gbx1 in the developing spinal cord, we performed real-time PCR to examine levels of Gbx2 expression in Gbx1(-/-) spinal cord at embryonic day (E) 13.5, a developmental stage when Gbx2 is rapidly downregulated. We demonstrate that Gbx2 expression is elevated in the spinal cord of Gbx1(-/-) embryos.

Site-specific gene transfer into the rat spinal cord by photomechanical waves

NASA Astrophysics Data System (ADS)

Ando, Takahiro; Sato, Shunichi; Toyooka, Terushige; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Obara, Minoru

2011-10-01

Nonviral, site-specific gene delivery to deep tissue is required for gene therapy of a spinal cord injury. However, an efficient method satisfying these requirements has not been established. This study demonstrates efficient and targeted gene transfer into the spinal cord by using photomechanical waves (PMWs), which were generated by irradiating a black laser absorbing rubber with 532-nm nanosecond Nd:YAG laser pulses. After a solution of plasmid DNA coding for enhanced green fluorescent protein (EGFP) or luciferase was intraparenchymally injected into the spinal cord, PMWs were applied to the target site. In the PMW application group, we observed significant EGFP gene expression in the white matter and remarkably high luciferase activity only in the spinal cord segment exposed to the PMWs. We also assessed hind limb movements 24 h after the application of PMWs based on the Basso-Beattie-Bresnahan (BBB) score to evaluate the noninvasiveness of this method. Locomotor evaluation showed no significant decrease in BBB score under optimum laser irradiation conditions. These findings demonstrated that exogenous genes can be efficiently and site-selectively delivered into the spinal cord by applying PMWs without significant locomotive damage.

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

PubMed

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

1985-03-01

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

Microsurgical resection of intramedullary spinal cord ependymoma.

PubMed

McCormick, Paul C

2014-09-01

Ependymomas are the most commonly occurring intramedullary spinal cord tumor in adults. With few exceptions these tumors are histologically benign, although they exhibit some biologic variability with respect to growth rate. While unencapsulated, spinal ependymomas are non-infiltrative and present a clear margin of demarcation from the surrounding spinal cord that serves as an effective dissection plane. This video demonstrates the technique of microsurgical resection of an intramedullary ependymoma through a posterior midline myelotomy. The video can be found here: http://youtu.be/lcHhymSvSqU.

[Spinal cord injury due to penetrating missiles].

PubMed

Ohry, Avi

2003-10-01

Gunshot wound of the spine is a major cause of spinal cord injury among US civilian population, members of the military armed conflict personnel, or civilians injured in terrorists attacks. The bullet fragments cause damage to the spinal cord even without penetrating the spinal canal. Concussive effects, heat, fractures or vascular injury may cause the neurological damage. Unfortunately, bullet or shrapnel removal or laminectomy do not change the prognosis. In this article we review the historical background, the Israeli experience, ballistic-forensic considerations, complications, treatment and prognosis.

An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

PubMed

Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

2014-11-25

Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury.

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

PubMed

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 in partially lesioned cord of monkeys. Copyright © 2013 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Jianzhong; Cao, Yong; Wu, Tianding

2014-10-15

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

Scissors stab wound to the cervical spinal cord at the craniocervical junction.

PubMed

Zhang, Xiao-Yong; Yang, Ying-Ming

2016-06-01

Stab wounds resulting in spinal cord injury of the craniocervical junction are rare. A scissors stab wound to the cervical spinal cord has been reported only once in the literature. This paper aimed to report a case of Brown-Séquard-plus syndrome in an 8-year-old boy secondary to a scissors stab wound at the craniocervical junction. Case report and review of the literature. Case report of an 8-year-old boy accidentally stabbed in the neck by scissors, which were thrown as a dart. The case study of an 8-year-old boy who was hospitalized because of a scissors stab wound at the craniocervical junction. The patient developed Brown-Séquard-plus syndrome on the left side of the body. Magnetic resonance imaging revealed a laceration of the spinal cord at the craniocervical junction with cerebrospinal fluid leakage. Careful cleansing and interrupted sutures of the wounds were performed to prevent cerebrospinal fluid leakage. Rehabilitation therapy was performed 2 days later. A follow-up examination revealed complete recovery of the neurologic deficit 8 months post-injury. Treatment of scissors stab wounds to the cervical spinal cord, whether conservative management or thorough surgical exploration, should be individualized based on history, examination, and imaging. As shown in this case report, despite conservative management, complete recovery, which was unexpected, was attributed to the initial mild laceration of the spinal cord and ipsilateral spinal cord functional compensation. Copyright © 2016 Elsevier Inc. All rights reserved.

Cannabis use in persons with traumatic spinal cord injury in Denmark.

PubMed

Andresen, Sven R; Biering-Sørensen, Fin; Hagen, Ellen Merete; Nielsen, Jørgen F; Bach, Flemming W; Finnerup, Nanna B

2017-01-31

To evaluate recreational and medical cannabis use in individuals with traumatic spinal cord injury, including reasons and predictors for use, perceived benefits and negative consequences. Cross-sectional survey in Denmark. A 35-item questionnaire was sent to 1,101 patients with spinal cord injury who had been in contact with a rehabilitation centre between 1990 and 2012. A total of 537 participants completed the questionnaire. Of these, 36% had tried cannabis at least once and 9% were current users. Of current users, 79% had started to use cannabis before their spinal cord injury. The main reason for use was pleasure, but 65% used cannabis partly for spinal cord injury-related consequences and 59% reported at least good effect on pain and spasticity. Negative consequences of use were primarily inertia and feeling quiet/subdued. Lower age, living in rural areas/larger cities, tobacco-smoking, high alcohol intake and higher muscle stiffness were significantly associated with cannabis use. Those who had never tried cannabis reported that they would mainly use cannabis to alleviate pain and spasticity if it were legalized. Cannabis use is more frequent among individuals with spinal cord injury in Denmark than among the general population. High muscle stiffness and various demographic characteristics (lower age, living in rural areas/larger cities, tobacco-smoking and high alcohol intake) were associated with cannabis use. Most participants had started using cannabis before their spinal cord injury. There was considerable overlap between recreational and disability-related use.

Spinal Cord Diseases

MedlinePlus

... spinal muscular atrophy Symptoms vary but might include pain, numbness, loss of sensation and muscle weakness. These symptoms can occur around the spinal cord, and also in other areas such as your arms and legs. Treatments often include medicines and surgery.

Nonlinear Viscoelastic Characterization of the Porcine Spinal Cord

PubMed Central

Shetye, Snehal; Troyer, Kevin; Streijger, Femke; Lee, Jae H. T.; Kwon, Brian K.; Cripton, Peter; Puttlitz, Christian M.

2014-01-01

Although quasi-static and quasi-linear viscoelastic properties of the spinal cord have been reported previously, there are no published studies that have investigated the fully (strain-dependent) nonlinear viscoelastic properties of the spinal cord. In this study, stress relaxation experiments and dynamic cycling were performed on six fresh porcine lumbar cord specimens to examine their viscoelastic mechanical properties. The stress relaxation data were fitted to a modified superposition formulation and a novel finite ramp time correction technique was applied. The parameters obtained from this fitting methodology were used to predict the average dynamic cyclic viscoelastic behavior of the porcine cord. The data indicate that the porcine spinal cord exhibited fully nonlinear viscoelastic behavior. The average weighted RMSE for a Heaviside ramp fit was 2.8kPa, which was significantly greater (p < 0.001) than that of the nonlinear (comprehensive viscoelastic characterization (CVC) method) fit (0.365kPa). Further, the nonlinear mechanical parameters obtained were able to accurately predict the dynamic behavior, thus exemplifying the reliability of the obtained nonlinear parameters. These parameters will be important for future studies investigating various damage mechanisms of the spinal cord and studies developing high resolution finite elements models of the spine. PMID:24211612

The rat corticospinal system is functionally and anatomically segregated.

PubMed

Olivares-Moreno, Rafael; Moreno-Lopez, Yunuen; Concha, Luis; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2017-12-01

The descending corticospinal (CS) projection has been considered a key element for motor control, which results from direct and indirect modulation of spinal cord pre-motor interneurons in the intermediate gray matter of the spinal cord, which, in turn, influences motoneurons in the ventral horn. The CS tract (CST) is also involved in a selective and complex modulation of sensory information in the dorsal horn. However, little is known about the spinal network engaged by the CST and the organization of CS projections that may encode different cortical outputs to the spinal cord. This study addresses the issue of whether the CS system exerts parallel control on different spinal networks, which together participate in sensorimotor integration. Here, we show that in the adult rat, two different and partially intermingled CS neurons in the sensorimotor cortex activate, with different time latencies, distinct spinal cord neurons located in the dorsal horn and intermediate zone of the same segment. The fact that different populations of CS neurons project in a segregated manner suggests that CST is composed of subsystems controlling different spinal cord circuits that modulate motor outputs and sensory inputs in a coordinated manner.

Spinal cord ischemia following thoracotomy without epidural anesthesia.

PubMed

Raz, Aeyal; Avramovich, Aharon; Saraf-Lavi, Efrat; Saute, Milton; Eidelman, Leonid A

2006-06-01

Paraplegia is an uncommon yet devastating complication following thoracotomy, usually caused by compression or ischemia of the spinal cord. Ischemia without compression may be a result of global ischemia, vascular injury and other causes. Epidural anesthesia has been implicated as a major cause. This report highlights the fact that perioperative cord ischemia and paraplegia may be unrelated to epidural intervention. A 71-yr-old woman was admitted for a left upper lobectomy for resection of a non-small cell carcinoma of the lung. The patient refused epidural catheter placement and underwent a left T5-6 thoracotomy under general anesthesia. During surgery, she was hemodynamically stable and good oxygen saturation was maintained. Several hours following surgery the patient complained of loss of sensation in her legs. Neurological examination disclosed a complete motor and sensory block at the T5-6 level. Magnetic resonance imaging (MRI) revealed spinal cord ischemia. The patient received iv steroid treatment, but remained paraplegic. Five months following the surgery there was only partial improvement in her motor symptoms. A follow-up MRI study was consistent with a diagnosis of spinal cord ischemia. In this case of paraplegia following thoracic surgery for lung resection, epidural anesthesia/analgesia was not used. The MRI demonstrated evidence of spinal cord ischemia, and no evidence of cord compression. This case highlights that etiologies other than epidural intervention, such as injury to the spinal segmental arteries during thoracotomy, should be considered as potential causes of cord ischemia and resultant paraplegia in this surgical population.

Psychometric Validation of the World Health Organization Disability Assessment Schedule 2.0-Twelve-Item Version in Persons with Spinal Cord Injuries

ERIC Educational Resources Information Center

Smedema, Susan Miller; Ruiz, Derek; Mohr, Michael J.

2017-01-01

Purpose: To evaluate the factorial and concurrent validity and internal consistency reliability of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item version in persons with spinal cord injuries. Method: Two hundred forty-seven adults with spinal cord injuries completed an online survey consisting of the WHODAS…

Experiences of Living with Pain after a Spinal Cord Injury

DTIC Science & Technology

2013-09-01

AD_________________ Award Number: W81XWH-12-1-0465 TITLE: Experiences of Living with Pain after a...COVERED 01 September 2012 – 31 August 2013 4. TITLE AND SUBTITLE Experiences of Living with Pain after a Spinal Cord Injury 5a. CONTRACT NUMBER...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Persistent chronic pain is prevalent after a spinal cord injury (SCI), with

Employment among Spinal Cord Injured Patients Living in Turkey: A Cross-Sectional Study

ERIC Educational Resources Information Center

Gunduz, Berrin; Erhan, Belgin; Bardak, Ayse Nur

2010-01-01

The aim of this study was to determine the rate of employment and to establish the factors affecting vocational status in spinal cord injured patients living in Turkey. One hundred and fifty-two traumatic spinal cord injured patients older than 18 years with injury duration of at least 1 year and living in the community were included in the study;…

Cardio Respiratory Adaptations with Long Term Personalized Exercise Program in a T12 Spinal Cord Injured Person

ERIC Educational Resources Information Center

Vasiliadis, Angelo; Christoulas, Kosmas; Evaggelinou, Christina; Vrabas, Ioannis

2009-01-01

The purpose of this study was to investigate the physiological adaptations in cardio respiratory endurance with a personalized exercise program with arm-cranking exercise in a paraplegic person (incomplete T12 spinal cord injury). A 32 year-old man with spinal cord injury (T12) participated in the present study performing 30 minutes arm cranking…

Evaluation of normal appearing spinal cord by diffusion tensor imaging, fiber tracking, fractional anisotropy, and apparent diffusion coefficient measurement in 13 dogs

PubMed Central

2013-01-01

Background Functional magnetic resonance (fMR) imaging offers plenty of new opportunities in the diagnosis of central nervous system diseases. Diffusion tensor imaging (DTI) is a technique sensitive to the random motion of water providing information about tissue architecture. We applied DTI to normal appearing spinal cords of 13 dogs of different breeds and body weights in a 3.0 T magnetic resonance (MR) scanner. The aim was to study fiber tracking (FT) patterns by tractography and the variations of the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) observed in the spinal cords of dogs with different sizes and at different locations (cervical and thoracolumbar). For that reason we added a DTI sequence to the standard clinical MR protocol. The values of FA and ADC were calculated by means of three regions of interest defined on the cervical or the thoracolumbar spinal cord (ROI 1, 2, and 3). Results The shape of the spinal cord fiber tracts was well illustrated following tractography and the exiting nerve roots could be differentiated from the spinal cord fiber tracts. Routine MR scanning times were extended for 8 to 12 min, depending on the size of the field of view (FOV), the slice thickness, and the size of the interslice gaps. In small breed dogs (< 15 kg body weight) the fibers could be tracked over a length of approximately 10 vertebral bodies with scanning times of about 8 min, whereas in large breed dogs (> 25 kg body weight) the traceable fiber length was about 5 vertebral bodies which took 10 to 12 min scanning time. FA and ADC values showed mean values of 0.447 (FA), and 0.560 × 10-3 mm2/s (ADC), respectively without any differences detected with regard to different dog sizes and spinal cord 45 segments examined. Conclusion FT is suitable for the graphical depiction of the canine spinal cord and the exiting nerve roots. The FA and ADC values offer an objective measure for evaluation of the spinal cord fiber integrity in dogs. PMID:23618404

p53 participates in the protective effects of ischemic post-conditioning against OGD-reperfusion injury in primary cultured spinal cord neurons.

PubMed

Li, Jinquan; Chen, Gong; Gao, Xinjie; Shen, Chao; Zhou, Ping; Wu, Xing; Che, Xiaoming; Xie, Rong

2017-01-18

Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Psychometric properties of the International Classification of Functioning, Disability and Health set for spinal cord injury nursing based on Rasch analysis.

PubMed

Li, Kun; Yan, Tiebin; You, Liming; Xie, Sumei; Li, Yun; Tang, Jie; Wang, Yingmin; Gao, Yan

2018-02-01

To examine the psychometric properties of the International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing (ICF-SCIN) using Rasch analysis. A total of 140 spinal cord injury patients were recruited between December 2013 and March 2014 through convenience sampling. Nurses used the components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF-SCIN to rate the patients' functioning. Rasch analysis was performed using RUMM 2030 software. In each component, categories were rescored from 01234 to 01112 because of reversed thresholds. Nine testlets were created to overcome local dependency. Four categories which fit to the Rasch model poorly were deleted. After modification, the components BF, BS, and AP showed good fit to the Rasch model with a Bonferroni-adjusted significant level (χ 2  =   86.29, p = 0.006; χ 2  =   22.44, p = 0.130; χ 2  =   39.92, p = 0.159). The person separation indices (PSIs) for the three components were 0.80, 0.54, and 0.97, respectively. No differential item functioning (DIF) was detected across age, gender, or educational level. The fit properties of the ICF set were satisfactory after modifications. The ICF-SCIN has the potential as a nursing assessment instrument for measuring the functioning of patients with spinal cord injury. Implications for rehabilitation The International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing contains a group of categories which can reflect the functioning of spinal cord injury patients from the perspective of nurses. The components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF set for spinal cord injury achieved the fit to the Rasch model through rescoring, generating testlets, and deleting categories with poor fit. The ICF set for spinal cord injury nursing (ICF-SCIN) has the potential to be used as a clinical nursing assessment tool in measuring the functioning of patients with spinal cord injury.

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

PubMed

Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

1994-09-01

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors. 6. Effects of individual peptidase inhibitors on the enzymatic degradation of SP and NKA by synaptic membrane fractions were examined. Thiorphan, actinonin and captopril inhibited SP degradation, while thiorphan and actinonin, but not captopril, inhibited NKA degradation. The potency of the inhibition of each peptidase inhibitor was lower than that of the mixture.7. The present results suggest that enzymatic degradation is involved in the inactivation of tachykinin neurotransmitters in the spinal cord of the neonatal rat.

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

PubMed

Wang, Fangyong; Yuan, Yuan; Li, Jianjun

2015-12-01

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

Review of cross-cultural issues related to quality of life after spinal cord injury.

PubMed

Tate, Denise; Forchheimer, Martin

2014-01-01

Quality of life (QOL) is a dynamic concept that means different things to different people, both in the general public and within the research community. Because of this, a common definition of QOL has been hard to achieve. This article reviews cross-cultural issues related to QOL research in spinal cord injury (SCI). Many factors influence QOL for persons with SCI, including observable and objective indicators and subjective self-report ones. The World Health Organization's International Classification of Function, Disability and Health is used in this article as a framework to better understand how these factors may influence QOL. A number of important steps are summarized with respect to measurement issues in QOL. A comparison between data from 2 countries (United States and Brazil) using the International SCI QOL Basic Data Set shows similarities in scores and good reliability in the Brazilian sample. Substantial, significant correlations were observed among the SCI QOL Basic Data Set items and the WHOQOL-BREF within the US sample. The article ends with a set of recommendations for the development of cross-cultural measures of QOL for use in the SCI population.

Early Versus Delayed Surgical Decompression of Spinal Cord after Traumatic Cervical Spinal Cord Injury: A Cost-Utility Analysis.

PubMed

Furlan, Julio C; Craven, B Catharine; Massicotte, Eric M; Fehlings, Michael G

2016-04-01

This cost-utility analysis was undertaken to compare early (≤24 hours since trauma) versus delayed surgical decompression of spinal cord to determine which approach is more cost effective in the management of patients with acute traumatic cervical spinal cord injury (SCI). This study includes the patients enrolled into the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) and admitted at Toronto Western Hospital. Cases were grouped into patients with motor complete SCI and individuals with motor incomplete SCI. A cost-utility analysis was performed for each group of patients by the use of data for the first 6 months after SCI. The perspective of a public health care insurer was adopted. Costs were estimated in 2014 U.S. dollars. Utilities were estimated from the STASCIS. The baseline analysis indicates early spinal decompression is more cost-effective approach compared with the delayed spinal decompression. When we considered the delayed spinal decompression as the baseline strategy, the incremental cost-effectiveness ratio analysis revealed a saving of US$ 58,368,024.12 per quality-adjusted life years gained for patients with complete SCI and a saving of US$ 536,217.33 per quality-adjusted life years gained in patients with incomplete SCI for the early spinal decompression. The probabilistic analysis confirmed the early-decompression strategy as more cost effective than the delayed-decompression approach, even though there is no clearly dominant strategy. The results of this economic analysis suggests that early decompression of spinal cord was more cost effective than delayed surgical decompression in the management of patients with motor complete and incomplete SCI, even though no strategy was clearly dominant. Copyright © 2016 Elsevier Inc. All rights reserved.

Zebrafish transgenic constructs label specific neurons in Xenopus laevis spinal cord and identify frog V0v spinal neurons.

PubMed

Juárez-Morales, José L; Martinez-De Luna, Reyna I; Zuber, Michael E; Roberts, Alan; Lewis, Katharine E

2017-09-01

A correctly functioning spinal cord is crucial for locomotion and communication between body and brain but there are fundamental gaps in our knowledge of how spinal neuronal circuitry is established and functions. To understand the genetic program that regulates specification and functions of this circuitry, we need to connect neuronal molecular phenotypes with physiological analyses. Studies using Xenopus laevis tadpoles have increased our understanding of spinal cord neuronal physiology and function, particularly in locomotor circuitry. However, the X. laevis tetraploid genome and long generation time make it difficult to investigate how neurons are specified. The opacity of X. laevis embryos also makes it hard to connect functional classes of neurons and the genes that they express. We demonstrate here that Tol2 transgenic constructs using zebrafish enhancers that drive expression in specific zebrafish spinal neurons label equivalent neurons in X. laevis and that the incorporation of a Gal4:UAS amplification cassette enables cells to be observed in live X. laevis tadpoles. This technique should enable the molecular phenotypes, morphologies and physiologies of distinct X. laevis spinal neurons to be examined together in vivo. We have used an islet1 enhancer to label Rohon-Beard sensory neurons and evx enhancers to identify V0v neurons, for the first time, in X. laevis spinal cord. Our work demonstrates the homology of spinal cord circuitry in zebrafish and X. laevis, suggesting that future work could combine their relative strengths to elucidate a more complete picture of how vertebrate spinal cord neurons are specified, and function to generate behavior. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1007-1020, 2017. © 2017 Wiley Periodicals, Inc.

Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord.

PubMed

Elliott Donaghue, Irja; Tator, Charles H; Shoichet, Molly S

2015-01-01

Spinal cord injury is a debilitating condition that currently lacks effective clinical treatment. Neurotrophin-3 (NT-3) has been demonstrated in experimental animal models to induce axonal regeneration and functional improvements, yet its local delivery remains challenging. For ultimate clinical translation, a drug delivery system is required for localized, sustained, and minimally invasive release. Here, an injectable composite drug delivery system (DDS) composed of biodegradable polymeric nanoparticles dispersed in a hyaluronan/methyl cellulose hydrogel was injected into the intrathecal space to achieve acute local delivery to the spinal cord after a thoracic clip compression injury. NT-3 was encapsulated in the DDS and released in vitro for up to 50 d. With a single injection of the DDS into the intrathecal space of the injured spinal cord, NT-3 diffused ventrally through the cord and was detectable in the spinal cord for at least 28 d therein. Delivery of NT-3 resulted in significant axon growth with no effect on the astroglial response to injury in comparison with vehicle and injury controls. NT-3 treatment promoted functional improvements at 21 d according to the Basso Beattie Bresnahan locomotor scale in comparison with the DDS alone. The sustained delivery of bioactive NT-3 to the injured spinal cord achieved in this study demonstrates the promise of this DDS for central nervous system repair.

Thoracic Unilateral Spinal Cord Injury After Spinal Anaesthesia for Total Hip Replacement: Fate or Mistake?

PubMed Central

Fabio, Costa; Romualdo, Del Buono; Eugenio, Agrò Felice; Vittoradolfo, Tambone; Massimiliano, Vitali Andrea; Giovanna, Ricci

2017-01-01

Spinal anaesthesia is the most preffered anesthesia technique for total hip replacement, and its complications range from low entity (insignificant) to life threatening. The incidence of neurologic complications after neuraxial anaesthesia is not perfectly clear, although there are several described cases of spinal cord ischaemia. We present a case of unilateral T8–T11 spinal cord ischaemia following L2–L3 spinal anaesthesia for total hip replacement. Magnetic resonance imaging showed a hyperintense T8–T11 signal alteration on the leftside of paramedian spinal cord. A temporal epidemiologic linkage between the damage and the surgery seems to be present. The injury occurred without anatomical proximity between the injury site and the spinal needle entry site. This may be due to multiple contributing factors, each of them is probably not enough to determine the damage by itself; however, acting simultaneously, they could have been responsible for the complication. The result was unpredictable and unavoidable and was caused by unforeseeable circumstances and not by inadequate medical practice. PMID:28439446

Observational study of the effectiveness of spinal cord injury rehabilitation using the Spinal Cord Injury-Ability Realization Measurement Index.

PubMed

Scivoletto, G; Bonavita, J; Torre, M; Baroncini, I; Tiberti, S; Maietti, E; Laurenza, L; China, S; Corallo, V; Guerra, F; Buscaroli, L; Candeloro, C; Brunelli, E; Catz, A; Molinari, M

2016-06-01

Retrospective observational study. The objective of this study was to determine the rehabilitation potential and the extent to which it is realized in a cohort of spinal cord injury patients using the Spinal Cord Injury-Ability Realization Measurement Index (SCI-ARMI) and to study the clinical factors that influence this realization. Two spinal units in Italy. Consecutive patients were assessed at the end of an in-patient rehabilitation program using the Spinal Cord Independence Measure and the International Standards for Neurological Classification of Spinal Cord Injury. On the basis of these data and of the age and gender of the patients, we calculated the SCI-ARMI score. Regression analyses were performed to study the relationship between clinical factors and the extent to which rehabilitation potential is realized. We examined the data for 306 patients. Most patients were discharged without having reached their rehabilitation potential, with an SCI-ARMI score <80%. SCI-ARMI scores at discharge were positively influenced by etiology and the lesion level and correlated negatively with lesion severity and the presence of complications during rehabilitation. The SCI-ARMI is an effective tool that can be used to measure the achievement of rehabilitation potential in SCI patients and to identify groups of patients who are at risk of not meeting their rehabilitative potential.

Expression of the repulsive guidance molecule RGM and it receptor Neogenin after spinal cord injury in sea lamprey

PubMed Central

Shifman, Michael I.; Yumul, Rae Eden; Laramore, Cindy; Selzer, Michael E.

2009-01-01

The sea lamprey recovers normal-appearing locomotion after spinal cord transection and its spinal axons regenerate selectively in their correct paths. However, among identified reticulospinal neurons some are consistently bad regenerators and only about 50% of severed reticulospinal axons regenerate through the site of injury. We previously suggested (Shifman and Selzer, 2000) that selective chemorepulsion might explain why some neurons are bad regenerators and others not. To explore the role of additional chemorepulsive axonal guidance molecules during regeneration, we examined the expression of the repulsive guidance molecule (RGM) and its receptor neogenin by in situ hybridization and quantitative PCR. RGM mRNA was expressed in the spinal cord, primarily in neurons of the lateral gray matter and in dorsal cells. Following spinal cord transection, RGM message was downregulated in neurons close (within 10 mm) to the transection at 2 and 4 weeks, although it was upregulated in reactive microglia at 2 weeks post-transection. Neogenin mRNA expression was unchanged in the brainstem after spinal cord transection, and among the identified reticulospinal neurons, was detected only in “bad regenerators, Neurons that are known to regenerate well never expressed neogenin. The downregulation of RGM expression in neurons near the transection may increase the probability that regenerating axons will regenerate through the site of injury and entered caudal spinal cord. PMID:19268666

Peripheral ionotropic glutamate receptors contribute to Fos expression increase in the spinal cord through antidromic electrical stimulation of sensory nerves.

PubMed

Li, Jia-Heng; He, Pei-Yao; Fan, Dan-Ni; Alemujiang, Dilinapa; Huo, Fu-Quan; Zhao, Yan; Cao, Dong-Yuan

2018-06-21

Previous studies have shown that peripheral ionotropic glutamate receptors are involved in the increase in sensitivity of a cutaneous branch of spinal dorsal ramus (CBDR) through antidromic electrical stimulation (ADES) of another CBDR in the adjacent segment. CBDR in the thoracic segments run parallel to each other and no synaptic contact at the periphery is reported. The present study investigated whether the increased sensitivity of peripheral sensory nerves via ADES of a CBDR induced Fos expression changes in the adjacent segments of the spinal cord. Fos expression increased in the T8 - T12 segments of the spinal cord evoked by ADES of the T10 CBDR in rats. The increased Fos expression in the T11 and T12, but not T8 - T10 spinal cord segments, was significantly blocked by local application of either N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine maleate (MK-801) or non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the receptive field of T11 CBDR. The results suggest that endogenous glutamate released by ADES of sensory nerve may bind to peripheral ionotropic glutamate receptors and activate adjacent sensory nerve endings to increase the sensitivity of the spinal cord. These data reveal the potential mechanisms of neuron activation in the spinal cord evoked by peripheral sensitization. Copyright © 2018 Elsevier B.V. All rights reserved.

In vitro and in vivo analysis and characterization of engineered spinal neural implants (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shor, Erez; Shoham, Shy; Levenberg, Shulamit

2016-03-01

Spinal cord injury is a devastating medical condition. Recent developments in pre-clinical and clinical research have started to yield neural implants inducing functional recovery after spinal cord transection injury. However, the functional performance of the transplants was assessed using histology and behavioral experiments which are unable to study cell dynamics and the therapeutic response. Here, we use neurophotonic tools and optogenetic probes to investigate cellular level morphology and activity characteristics of neural implants over time at the cellular level. These methods were used in-vitro and in-vivo, in a mouse spinal cord injury implant model. Following previous attempts to induce recovery after spinal cord injury, we engineered a pre-vascularized implant to obtain better functional performance. To image network activity of a construct implanted in a mouse spinal cord, we transfected the implant to express GCaMP6 calcium activity indicators and implanted these constructs under a spinal cord chamber enabling 2-photon chronic in vivo neural activity imaging. Activity and morphology analysis image processing software was developed to automatically quantify the behavior of the neural and vascular networks. Our experimental results and analyses demonstrate that vascularized and non-vascularized constructs exhibit very different morphologic and activity patterns at the cellular level. This work enables further optimization of neural implants and also provides valuable tools for continuous cellular level monitoring and evaluation of transplants designed for various neurodegenerative disease models.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Boike, Thomas P.

Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat hasmore » demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.« less

[Neuronal control of posture and locomotion in decerebrated and spinalized animals].

PubMed

Musienko, P E; Gorskiĭ, O V; Kilimnik, V A; Kozlovskaia, I B; Courtine, G; Edgerton, V R; Gerasimenko, Iu P

2013-03-01

We have found that the brainstem-spinal cord circuitry of decerebrated cats actively maintain the equilibrium during standing, walking and imposed mechanical perturbations similar to that observed in intact animals. The corrective hindlimb motor responses during standing included redistribution of the extensor activity ipsilateral and contralateral to perturbation. The postural corrections in walking cats were due to considerable modification of EMG pattern in the limbs as well as changing of the swing-stance phases of the step cycle and ground reaction forces depending of perturbation side. Thus the basic mechanisms for balance control of decerebrated animals in these two forms of motor behavior are different. Balance-related adjustments relied entirely on the integration of somatosensory information arising from the moving hindquarters because of the suppression of vestibular, visual, and head-neck-trunk sensory input. We propose that the somatosensory input from the hindquarters in concert with the lumbosacral spinal circuitry can control the dynamics of the hindquarters sufficient to sustain balance. We found that, after isolation from the brainstem or forebrain, lumbosacral circuits receiving tonic epidural electrical stimulation can effectively control equilibrium during standing and stepping. Detailed analyses of the relationships among muscle activity, trunk kinematics, and limb kinetics indicate that spinal motor systems utilize a combination of feedback and feedforward strategies to maintain dynamic equilibrium during walking. The unexpected ability of spinal circuitries to exert efficient postural control in the presence of epidural electrical stimulation in decerebrated and spinal cats have significant implications for the potential of humans with a severe spinal cord injury to regain a significant level of functional standing and walking capacities.

Verminous (Strongylus vulgaris) myelitis in a donkey.

PubMed

Mayhew, I G; Brewer, B D; Reinhard, M K; Greiner, E C

1984-01-01

A fifth stage Strongylus vulgaris migrated through the spinal cord of a 2-year-old, male donkey resulting in progressive paraparesis and then tetraplegia. A profound neutrophilic pleocytosis was detected on analysis of cerebrospinal fluid. The parasite appeared to have entered the mid-lumbar spinal cord, migrated to the cranial thoracic segments, exited, then re-entered the spinal cord a few segments craniad. It then traveled further cranially and was found in the third cervical spinal cord segment. Some parts of the lesion were remarkably free from tissue necrosis, hemorrhage and inflammation. Severe granulomatous myelitis with hemorrhage and necrosis were seen at other sites. The latter were quite similar to lesions seen in equine protozoal myeloencephalitis.

Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury

PubMed Central

Vigani, Barbara; Rossi, Silvia; Sandri, Giuseppina; Bonferoni, Maria Cristina; Ferrari, Franca

2017-01-01

The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the polymers more investigated in the production of neural fibrous scaffolds is also provided. PMID:29239316

Favourable outcome of posterior decompression and stabilization in lordosis for cervical spondylotic myelopathy: the spinal cord "back shift" concept.

PubMed

Denaro, Vincenzo; Longo, Umile Giuseppe; Berton, Alessandra; Salvatore, Giuseppe; Denaro, Luca

2015-11-01

Surgical management of patients with multilevel CSM aims to decompress the spinal cord and restore the normal sagittal alignment. The literature lacks of high level evidences about the best surgical approach. Posterior decompression and stabilization in lordosis allows spinal cord back shift, leading to indirect decompression of the anterior spinal cord. The purpose of this study was to investigate the efficacy of posterior decompression and stabilization in lordosis for multilevel CSM. 36 out of 40 patients were clinically assessed at a mean follow-up of 5, 7 years. Outcome measures included EMS, mJOA Score, NDI and SF-12. Patients were asked whether surgery met their expectations and if they would undergo the same surgery again. Bone graft fusion, instrumental failure and cervical curvature were evaluated. Spinal cord back shift was measured and correlation with EMS and mJOA score recovery rate was analyzed. All scores showed a significative improvement (p < 0.001), except the SF12-MCS (p > 0.05). Ninety percent of patients would undergo the same surgery again. There was no deterioration of the cervical alignment, posterior grafted bones had completely fused and there were no instrument failures. The mean spinal cord back shift was 3.9 mm (range 2.5-4.5 mm). EMS and mJOA recovery rates were significantly correlated with the postoperative posterior cord migration (P < 0.05). Posterior decompression and stabilization in lordosis is a valuable procedure for patients affected by multilevel CSM, leading to significant clinical improvement thanks to the spinal cord back shift. Postoperative lordotic alignment of the cervical spine is a key factor for successful treatment.

A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

PubMed Central

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-01-01

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury. PMID:27830790

The development of spinal cord anatomy.

PubMed

Pearce, J M S

2008-01-01

A panel illustrating spinal cord injury in The Dying Lioness in the British Museum dates to 650 BC. This paper outlines the subsequent progression of knowledge of the anatomy of the spinal cord. The animal dissections of Galen are considered because his deductions persisted through the Dark Ages until the late 18th century. Anatomy advanced gradually to yield discoveries of the complex tracts and grey matter elements of the cord and their functions. Amongst many distinguished exponents, the works of Blasius, Huber, Vicq d'Azyr and Stilling are emphasised. (c) 2008 S. Karger AG, Basel

Sexual counseling with spinal cord-injured clients.

PubMed

Miller, D K

1975-01-01

Spinal cord-injured clients have many fears and misapprehension about their sexual functioning. Common beliefs include: (a) disabled men cannot sexually satisfy able-bodied women; and (b) cord-injured persons cannot have sexual intercourse. Such misapprehensions can be helped by the counselor's willingness to discuss sexual issues openly. Clients need a clear and accurate picture of the facts, as well as encouragement and support to help them rediscover their sexuality. Spinal cord injury does not mean sexual incapacity. Given a knowing and patient partner, most clients can enjoy a satisfying sex life.

Comparison of alpha-synuclein immunoreactivity in the spinal cord between the adult and aged beagle dog

PubMed Central

Ahn, Ji-Hyeon; Choi, Jung-Hoon; Park, Joon-Ha; Yan, Bing-Chun; Kim, In-Hye; Lee, Jae-Chul; Lee, Dae-Hwan; Kim, Jin-Sang

2012-01-01

Alpha-synuclein (α-syn) is a presynaptic protein that is richly expressed in the central and peripheral nervous systems of mammals, and it is related to the pathogenesis of Parkinson's disease and other neurodegenerative disorders. In the present study, we compared the distribution of the immunoreactivity of α-syn and its related gliosis in the spinal cord of young adult (2-3 years) and aged (10-12 years) beagle dogs. We discovered that α-syn immunoreactivity was present in many neurons in the thoracic level of the aged spinal cord, however, its protein level was not distinct inform that of the adult spinal cord. In addition, ionized calcium-binding adapter molecule-1 (a marker for microglia) immunoreactivity, and not glial fibrillary acidic protein (a marker for astrocytes) immunoreactivity, was somewhat increased in the aged group compared to the adult group. These results indicate that α-syn immunoreactivity was not dramatically changed in the dog spinal cord during aging. PMID:23091516

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI)

PubMed Central

Fyffe, Denise; Kalpakjian, Claire Z.; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C.; Tulsky, David S.; Jette, Alan M.

2016-01-01

Objective: To provide validation of functional ability levels for the Spinal Cord Injury – Functional Index (SCI-FI). Design: Cross-sectional. Setting: Inpatient rehabilitation hospital and community settings. Participants: A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Interventions: Not Applicable. Main Outcome Measures: Spinal Cord Injury-Functional Index (SCI-FI). Results: Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. Conclusions: These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed. PMID:26781769

Acute electroacupuncture inhibits nitric oxide synthase expression in the spinal cord of neuropathic rats.

PubMed

Cha, Myeoung Hoon; Bai, Sun Joon; Lee, Kyung Hee; Cho, Zang Hee; Kim, Young-Bo; Lee, Hye-Jung; Lee, Bae Hwan

2010-02-01

To examine the effects of electroacupuncture stimulation on behavioral changes and neuronal nitric oxide synthase expression in the rat spinal cord after nerve injury. Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the left tibial and sural nerves. Behavioral responses to mechanical stimulation were tested for 2 weeks post-operatively. At the end of behavioral testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9 (Eumleungcheon) acupoints. Immunocytochemical staining was performed to investigate changes in the expression of neuronal nitric oxide synthase-immunoreactive neurons in the L4-5 spinal cord. Mechanical allodynia was observed by nerve injury. The mechanical allodynia was decreased after electroacupuncture stimulation. Neuronal nitric oxide synthase expression was also decreased in L4-5 spinal cord by electroacupuncture treatment. These results suggest that electroacupuncture relieves mechanical allodynia in the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase expression in the spinal cord.

Therapeutic horse back riding of a spinal cord injured veteran: a case study.

PubMed

Asselin, Glennys; Penning, Julius H; Ramanujam, Savithri; Neri, Rebecca; Ward, Constance

2012-01-01

To determine an incomplete spinal cord injured veteran's experience following participation in a therapeutic horseback riding program. Following the establishment of a nationwide therapeutic riding program for America's wounded service veterans in 2007, a Certified Rehabilitation Registered Nurse from the Michael E. DeBakey Veteran Affairs Medical Center worked with an incomplete spinal cord injured veteran who participated in the Horses for Heroes program. This program resulted in many benefits for the veteran, including an increase in balance, muscle strength, and self-esteem. A physical, psychological, and psychosocial benefit of therapeutic horseback riding is shown to have positive results for the spinal cord injured. Therapeutic riding is an emerging field where the horse is used as a tool for physical therapy, emotional growth, and learning. Veterans returning from the Iraq/Afghanistan war with traumatic brain injuries, blast injuries, depression, traumatic amputations, and spinal cord injuries may benefit from this nurse-assisted therapy involving the horse. © 2012 Association of Rehabilitation Nurses.

Anaplastic astrocytoma in the spinal cord of an African pygmy hedgehog (Atelerix albiventris).

PubMed

Gibson, C J; Parry, N M A; Jakowski, R M; Eshar, D

2008-11-01

A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100.

Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

DTIC Science & Technology

2016-12-01

respiratory pathways following spinal cord injury. J Appl Physiol. 94(2):795-810. Raineteau O and Schwab ME (2001). Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci. 2(4):262-73. APPENDICES : None

Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

PubMed

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

2017-08-15

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

Spinal Reflexes and Windup In Vitro: Effects of Analgesics and Anesthetics.

PubMed

Rivera-Arconada, Ivan; Roza, Carolina; Lopez-Garcia, Jose A

2016-02-01

The spinal cord is the first relay center for nociceptive information. Following peripheral injury, the spinal cord sensitizes. A sign of spinal sensitization is the hyper-reflexia which develops shortly after injury and can be detected in the isolated spinal cord as a "memory of pain." In this context, it is easy to understand that many analgesic compounds target spinally located sites of action to attain analgesia. In vitro isolated spinal cord preparations have been used for a number of years, and experience on the effects of compounds of diverse pharmacological families on spinal function has accumulated. Recently, we have proposed that the detailed study of spinal segmental reflexes in vitro may produce data relevant to the evaluation of the analgesic potential of novel compounds. In this review, we describe the main features of segmental reflexes obtained in vitro and discuss the effects of compounds of diverse chemical nature and pharmacological properties on such reflexes. Our aim was to compare the different profiles of action of the compounds on segmental reflexes in order to extract clues that may be helpful for pharmacological characterization of novel analgesics. © 2015 John Wiley & Sons Ltd.

Effects of Enhanced Oxygen Delivery by Perfluorocarbons in Spinal Cord Injury

DTIC Science & Technology

2013-10-01

been established, linking post- traumatic ischemia to axonal dysfunction.8 Decreased oxygen level in severe traumatic injuries appears to be implicated...rodent weight drop traumatic spinal cord injury model; ( 2 ) determine if enhanced oxygen delivery in spinal cord injury spares cellular elements, white...shown that ischemia /hypoxia play crucial role in the devastating effects of the secondary injury following SCI which translates into worse neurological

Muscle activity and mood state during simulated plant factory work in individuals with cervical spinal cord injury

PubMed Central

Okahara, Satoshi; Kataoka, Masataka; Okuda, Kuniharu; Shima, Masato; Miyagaki, Keiko; Ohara, Hitoshi

2016-01-01

[Purpose] The present study investigated the physical and mental effects of plant factory work in individuals with cervical spinal cord injury and the use of a newly developed agricultural working environment. [Subjects] Six males with C5–C8 spinal cord injuries and 10 healthy volunteers participated. [Methods] Plant factory work involved three simulated repetitive tasks: sowing, transplantation, and harvesting. Surface electromyography was performed in the dominant upper arm, upper trapezius, anterior deltoid, and biceps brachii muscles. Subjects’ moods were monitored using the Profile of Mood States. [Results] Five males with C6–C8 injuries performed the same tasks as healthy persons; a male with a C5 injury performed fewer repetitions of tasks because it took longer. Regarding muscle activity during transplantation and harvesting, subjects with spinal cord injury had higher values for the upper trapezius and anterior deltoid muscles compared with healthy persons. The Profile of Mood States vigor scores were significantly higher after tasks in subjects with spinal cord injury. [Conclusion] Individuals with cervical spinal cord injury completed the plant factory work, though it required increased time and muscle activity. For individuals with C5–C8 injuries, it is necessary to develop an appropriate environment and assistive devices to facilitate their work. PMID:27134377

2-Decenoic acid ethyl ester, a derivative of unsaturated medium-chain fatty acids, facilitates functional recovery of locomotor activity after spinal cord injury.

PubMed

Hirakawa, A; Shimizu, K; Fukumitsu, H; Soumiya, H; Iinuma, M; Furukawa, S

2010-12-29

There is increasing evidence that omega-3 polyunsaturated fatty acids (PUFAs) have therapeutic potential in various animal models of neuronal injury. However, very few studies have examined the effect of medium-chain fatty acids (MCFAs) on neuronal injury. So in the present study we synthesized various MCFAs and their derivatives, and found that exposure to trans-2-decenoic acid ethyl ester (DAEE) markedly activated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured cortical neurons. Therefore, we examined the effect of DAEE treatment on a rat model of spinal cord injury. DAEE (150 μg/kg body weight) administered after hemisection of the spinal cord resulted in improved functional recovery, decreased the lesion size, increased the activation of ERK1/2, and enhanced the expression of bcl-2 and brain-derived neurotrophic factor (BDNF) mRNA in the injury site of the spinal cord. Furthermore, it also increased neuronal survival after spinal cord injury. These results indicate that the possibility that DAEE will become a promising tool for reducing the secondary damage observed following primary physical injury to the spinal cord. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

PubMed

Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

Automated quantitative gait analysis during overground locomotion in the rat: its application to spinal cord contusion and transection injuries.

PubMed

Hamers, F P; Lankhorst, A J; van Laar, T J; Veldhuis, W B; Gispen, W H

2001-02-01

Analysis of locomotion is an important tool in the study of peripheral and central nervous system damage. Most locomotor scoring systems in rodents are based either upon open field locomotion assessment, for example, the BBB score or upon foot print analysis. The former yields a semiquantitative description of locomotion as a whole, whereas the latter generates quantitative data on several selected gait parameters. In this paper, we describe the use of a newly developed gait analysis method that allows easy quantitation of a large number of locomotion parameters during walkway crossing. We were able to extract data on interlimb coordination, swing duration, paw print areas (total over stance, and at 20-msec time resolution), stride length, and base of support: Similar data can not be gathered by any single previously described method. We compare changes in gait parameters induced by two different models of spinal cord injury in rats, transection of the dorsal half of the spinal cord and spinal cord contusion injury induced by the NYU or MASCIS device. Although we applied this method to rats with spinal cord injury, the usefulness of this method is not limited to rats or to the investigation of spinal cord injuries alone.

Multilevel thoracic hemangioma with spinal cord compression in a pediatric patient: case report and review of the literature.

PubMed

Cherian, Jacob; Sayama, Christina M; Adesina, Adekunle M; Lam, Sandi K; Luerssen, Thomas G; Jea, Andrew

2014-09-01

Vertebral hemangiomas are common benign vascular tumors of the spine. It is very rare for these lesions to symptomatically compress neural elements. If spinal cord compression does occur, it usually involves only a single level. Multilevel vertebral hemangiomas causing symptomatic spinal cord compression have never been reported in the pediatric population to the best of our knowledge. We report the case of a 15-year-old boy presenting with progressive paraparesis due to thoracic spinal cord compression from a multilevel thoracic hemangioma (T5-T10) with epidural extension. Because of his progressive neurological deficit, he was initially treated with urgent multilevel decompressive laminectomies from T4 to T11. This was to be followed by radiotherapy for residual tumor, but the patient was unfortunately lost to follow-up. He re-presented 3 years later with recurrent paraparesis and progressive disease. This was treated with urgent radiotherapy with good response. As of 6 months follow-up, he has made an excellent neurological recovery. In this report, we present the first case of a child with multilevel vertebral hemangiomas causing symptomatic spinal cord compression and review the literature to detail the pathophysiology, management, and treatment of other cases of spinal cord compression by vertebral hemangiomas.

Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia

PubMed Central

Haller, Edward; Tajiri, Naoki; Thomson, Avery; Barretta, Jennifer; Williams, Stephanie N.; Haim, Eithan D.; Qin, Hua; Frisina-Deyo, Aric; Abraham, Jerry V.; Sanberg, Paul R.; Van Loveren, Harry; Borlongan, Cesario V.

2016-01-01

We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction. PMID:27283328

Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate-Induced Excitotoxicity.

PubMed

Liu, Dongfei; Chen, Jian; Jiang, Tao; Li, Wei; Huang, Yao; Lu, Xiyi; Liu, Zehua; Zhang, Weixia; Zhou, Zheng; Ding, Qirui; Santos, Hélder A; Yin, Guoyong; Fan, Jin

2018-04-01

New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (≈7.2 µm in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl-2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inflammatory myofibroblastic tumour of the spinal cord: case report and review of the literature.

PubMed

Despeyroux-Ewers, M; Catalaâ, I; Collin, L; Cognard, C; Loubes-Lacroix, F; Manelfe, C

2003-11-01

Inflammatory myofibroblastic tumours (IMT), also called inflammatory pseudotumours, nodular lymphoid hyperplasia, plasma-cell granuloma and fibrous xanthoma, are rare soft-tissue lesions characterised by inflammatory cells and a fibrous stroma. Clinically and radiologically, they may look like malignant tumours. They rarely affect the central nervous system and are very rare in the spinal cord. We report an IMT of the spinal cord in a 22-year-old woman presenting with spinal cord compression and a cauda equina syndrome. MRI showed a lesion at T9 with extramedullary and intramedullary components giving low signal on T2-weighted images and enhancing homogeneously. Pial lesions on the lumbar enlargement and thoracic spinal were present 11 months after surgery, when the lesion recurred. We present the radiological, operative and pathological findings and review the literature.

Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats

PubMed Central

2014-01-01

Background Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes. Results The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol. Conclusions These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue. PMID:24739121

Activation of p38 MAP Kinase is Involved in Central Neuropathic Pain Following Spinal Cord Injury

PubMed Central

Crown, Eric D; Gwak, Young Seob; Ye, Zaiming; Johnson, Kathia M; Hulsebosch, Claire E

2008-01-01

Recent work regarding chronic central neuropathic pain (CNP) following spinal cord injury (SCI) suggests that activation of key signaling molecules such as members of the mitogen activated protein kinase (MAPK) family play a role in the expression of at-level mechanical allodynia. Specifically, Crown and colleagues (2005, 2006) have shown that the development of at-level CNP following moderate spinal cord injury is correlated with increased expression of the activated (and thus phosphorylated) forms of the MAPKs extracellular signal related kinase and p38 MAPK. The current study extends this work by directly examining the role of p38 MAPK in the maintenance of at-level CNP following spinal cord injury. Using a combination of behavioral, immunocytochemical, and electrophysiological measures we demonstrate that increased activation of p38 MAPK occurs in the spinal cord just rostral to the site of injury in rats that develop at-level mechanical allodynia after moderate SCI. Immunocytochemical analyses indicate that the increases in p38 MAPK activation occurred in astrocytes, microglia, and dorsal horn neurons in the spinal cord rostral to the site of injury. Inhibiting the enzymatic activity of p38 MAPK dose dependently reverses the behavioral expression of at-level mechanical allodynia and also decreases the hyperexcitability seen in thoracic dorsal horn neurons after moderate SCI. Taken together, these novel data are the first to demonstrate causality that increased activation of p38 MAPK in multiple cell types play an important role in the maintenance of at-level CNP following spinal cord injury. PMID:18590729

Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies.

PubMed

Oliveira, J Miguel; Carvalho, Luisa; Silva-Correia, Joana; Vieira, Sílvia; Majchrzak, Malgorzata; Lukomska, Barbara; Stanaszek, Luiza; Strymecka, Paulina; Malysz-Cymborska, Izabela; Golubczyk, Dominika; Kalkowski, Lukasz; Reis, Rui L; Janowski, Miroslaw; Walczak, Piotr

2018-01-01

The prospects for cell replacement in spinal cord diseases are impeded by inefficient stem cell delivery. The deep location of the spinal cord and complex surgical access, as well as densely packed vital structures, question the feasibility of the widespread use of multiple spinal cord punctures to inject stem cells. Disorders characterized by disseminated pathology are particularly appealing for the distribution of cells globally throughout the spinal cord in a minimally invasive fashion. The intrathecal space, with access to a relatively large surface area along the spinal cord, is an attractive route for global stem cell delivery, and, indeed, is highly promising, but the success of this approach relies on the ability of cells (1) to survive in the cerebrospinal fluid (CSF), (2) to adhere to the spinal cord surface, and (3) to migrate, ultimately, into the parenchyma. Intrathecal infusion of cell suspension, however, has been insufficient and we postulate that embedding transplanted cells within hydrogel scaffolds will facilitate reaching these goals. In this review, we focus on practical considerations that render the intrathecal approach clinically viable, and then discuss the characteristics of various biomaterials that are suitable to serve as scaffolds. We also propose strategies to modulate the local microenvironment with nanoparticle carriers to improve the functionality of cellular grafts. Finally, we provide an overview of imaging modalities for in vivo monitoring and characterization of biomaterials and stem cells. This comprehensive review should serve as a guide for those planning preclinical and clinical studies on intrathecal stem cell transplantation.

Individualization of a Manualized Pressure Ulcer Prevention Program: Targeting Risky Life Circumstances Through a Community-Based Intervention for People with Spinal Cord Injury

PubMed Central

Vaishampayan, Ashwini; Clark, Florence; Carlson, Mike; Blanche, Erna Imperatore

2012-01-01

Purpose To sensitize practitioners working with individuals with spinal cord injury to the complex life circumstances that are implicated in the development of pressure ulcers, and to document the ways that interventions can be adapted to target individual needs. Methods Content analysis of weekly fidelity/ quality control meetings that were undertaken as part of a lifestyle intervention for pressure ulcer prevention in community-dwelling adults with spinal cord injury. Results Four types of lifestyle-relevant challenges to ulcer prevention were identified: risk-elevating life circumstances, communication difficulties, equipment problems, and individual personality issues. Intervention flexibility was achieved by changing the order of treatment modules, altering the intervention content or delivery approach, or going beyond the stipulated content. Conclusion Attention to recurrent types of individual needs, along with explicit strategies for tailoring manualized interventions, has potential to enhance pressure ulcer prevention efforts for adults with spinal cord injury. Target audience This continuing education article is intended for practitioners interested in learning about a comprehensive, context-sensitive, community-based pressure ulcer prevention program for people with spinal cord injury. Objectives After reading this article, the reader should be able to: Describe some of the contextual factors that increase pressure ulcer risk in people with spinal cord injury living in the community.Distinguish between tailored and individualized intervention approaches.Identify the issues that must be taken into account to design context-sensitive, community-based pressure ulcer prevention programs for people with spinal cord injury.Describe approaches that can be used to individualize manualized interventions. PMID:21586911

MiR-137 inhibited inflammatory response and apoptosis after spinal cord injury via targeting of MK2.

PubMed

Gao, Lin; Dai, Chenfei; Feng, Zhiping; Zhang, Lixin; Zhang, Zhiqiang

2018-04-01

Spinal cord injuries are common and troublesome disorder, which is mediated by various signal pathways and mechanisms. MK2 is also involved in numerous inflammatory diseases including spinal cord injury. The role of microRNA-137 (miR-137) and its detailed working mechanism in spinal cord injuries remain unclear. In the present study, we found that an elevated MK2 but a decreased miR-137 was expressed in serum specimens of patients with spinal cord injury and in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Meanwhile, we suggested that upregulation of miR-137 could inhibit the expression of TNF-α and IL-6, two markers of inflammatory response after SCI, and apoptosis in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Furthermore, we verified that MK2 was a direct target of miR-137 thorough a constructed luciferase assay. Even further, we elucidated that miR-137 could suppress the inflammatory response and apoptosis via negative regulation of MK2. Finally, through an animal model trial performed using mice, we demonstrated the protective effect of how miR-137 works on inflammatory response and apoptosis after spinal cord injury. Considering all the forementioned, our findings revealed that miR-137 inhibited inflammatory response and apoptosis after spinal cord injury via the targeting of MK2. The outcomes of the present study might indicate a new target in molecular treatment of SCI. © 2017 Wiley Periodicals, Inc.

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

PubMed

Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

2016-10-01

This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

Fertility and sexuality in the spinal cord injury patient.

PubMed

Stoffel, J T; Van der Aa, F; Wittmann, D; Yande, S; Elliott, S

2018-06-14

After a spinal cord injury, patients have different perceptions of sexuality, sexual function, and potential for fertility. These changes can greatly impact quality of life over a lifetime. The purpose of this workgroup was to identify common evidence based or expert opinion themes and recommendations regarding treatment of sexuality, sexual function and fertility in the spinal cord injury population. As part of the SIU-ICUD joint consultation of Urologic Management of the Spinal Cord Injury (SCI), a workgroup and comprehensive literature search of English language manuscripts regarding fertility and sexuality in the spinal cord injury patient were formed. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for levels of evidence (LOEs) and grades of recommendation (GORs). Genital arousal, ejaculation, and orgasm are significantly impacted after spinal cord injury in both male and female SCI patients. This may have a more significant impact on potential for fertility in male spinal cord injury patients, particularly regarding ability of generate erection, semen quantity and quality. Female patients should be consulted that pregnancy is still possible after injury and a woman should expect resumption of normal reproductive function. As a result, sexual health teaching should be continued in women despite injury. Pregnancy in a SCI may cause complications such as autonomic dysreflexia, so this group should be carefully followed during pregnancy. By understanding physiologic changes after injury, patients and care teams can work together to achieve goals and maximize sexual quality of life after the injury.

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

PubMed

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.

The Effectiveness and Safety of Exoskeletons as Assistive and Rehabilitation Devices in the Treatment of Neurologic Gait Disorders in Patients with Spinal Cord Injury: A Systematic Review

PubMed Central

Fisahn, Christian; Aach, Mirko; Jansen, Oliver; Moisi, Marc; Mayadev, Angeli; Pagarigan, Krystle T.; Dettori, Joseph R.; Schildhauer, Thomas A.

2016-01-01

Study Design Systematic review. Clinical Questions (1) When used as an assistive device, do wearable exoskeletons improve lower extremity function or gait compared with knee-ankle-foot orthoses (KAFOs) in patients with complete or incomplete spinal cord injury? (2) When used as a rehabilitation device, do wearable exoskeletons improve lower extremity function or gait compared with other rehabilitation strategies in patients with complete or incomplete spinal cord injury? (3) When used as an assistive or rehabilitation device, are wearable exoskeletons safe compared with KAFO for assistance or other rehabilitation strategies for rehabilitation in patients with complete or incomplete spinal cord injury? Methods PubMed, Cochrane, and Embase databases and reference lists of key articles were searched from database inception to May 2, 2016, to identify studies evaluating the effectiveness of wearable exoskeletons used as assistive or rehabilitative devices in patients with incomplete or complete spinal cord injury. Results No comparison studies were found evaluating exoskeletons as an assistive device. Nine comparison studies (11 publications) evaluated the use of exoskeletons as a rehabilitative device. The 10-meter walk test velocity and Spinal Cord Independence Measure scores showed no difference in change from baseline among patients undergoing exoskeleton training compared with various comparator therapies. The remaining primary outcome measures of 6-minute walk test distance and Walking Index for Spinal Cord Injury I and II and Functional Independence Measure–Locomotor scores showed mixed results, with some studies indicating no difference in change from baseline between exoskeleton training and comparator therapies, some indicating benefit of exoskeleton over comparator therapies, and some indicating benefit of comparator therapies over exoskeleton. Conclusion There is no data to compare locomotion assistance with exoskeleton versus conventional KAFOs. There is no consistent benefit from rehabilitation using an exoskeleton versus a variety of conventional methods in patients with chronic spinal cord injury. Trials comparing later-generation exoskeletons are needed. PMID:27853668

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

PubMed

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.

Therapeutic potential of spinal cord stimulation for gastrointestinal motility disorders: a preliminary rodent study.

PubMed

Song, G-Q; Sun, Y; Foreman, R D; Chen, J D Z

2014-03-01

Spinal cord electrical stimulation (SCS) has been applied for the management of chronic pain. Most of studies have revealed a decrease in sympathetic activity with SCS. The aim of this study was to investigate the effects and mechanisms of SCS on gastrointestinal (GI) motility in healthy and diabetic rats. Male rats chronically implanted with a unipolar electrode at T9/T10 were studied. The study included four experiments to assess the effects of SCS on (1) gastric tone; (2) gastric emptying of liquids and intestinal transit; (3) gastric emptying of solids; and (4) sympathovagal balance in healthy rats and/or in Streptozotocin (STZ)-induced diabetic rat. (1) Spinal cord stimulation intensity dependently increased gastric tone in healthy rats. The gastric volume was 0.97 ± 0.15 mL at baseline, and decreased to 0.92 ± 0.16 mL with SCS of the 30% motor threshold (MT; p = 0.13 vs baseline), 0.86 ± 0.14 mL with 60% MT (p = 0.045 vs baseline), and 0.46 ± 0.19 mL with 90% MT (p = 0.0050 vs baseline). (2) Spinal cord stimulation increased gastric emptying of liquids by about 17% and accelerated small intestinal transit by about 20% in healthy rats (p < 0.001). (3) Spinal cord stimulation accelerated gastric emptying of solids by about 24% in healthy rats and by about 78% in diabetic rats. (4) Spinal cord stimulation decreased sympathetic activity (1.13 ± 0.18 vs 0.68 ± 0.09, p < 0.04) and sympathovagal balance (0.51 ± 0.036 vs 0.40 ± 0.029, p = 0.028). Spinal cord stimulation accelerates gastric emptying of liquids and solids, and intestinal transit, probably by inhibiting the sympathetic activity. Spinal cord stimulation may have a therapeutic potential for treating GI motility disorders. © 2013 John Wiley & Sons Ltd.

Using peer mentoring for people with spinal cord injury to enhance self-efficacy beliefs and prevent medical complications.

PubMed

Ljungberg, Inger; Kroll, Thilo; Libin, Alexander; Gordon, Samuel

2011-02-01

Individuals with spinal cord injury/disease are faced with a myriad of psychosocial adjustment challenges. This article describes the implementation of a peer-mentoring programme designed to support this adjustment process for people with SCI/disease and the programme's believed impact on self-efficacy and prevention of medical complications. With shorter length of stay in acute inpatient rehabilitation after spinal cord injury/disease, peer mentor programmes are becoming an important component to assist with education and community re-integration. Quasi-experimental non-controlled pretest/post-test. Patients with newly acquired spinal cord injury/disease participated in a one-year spinal cord injury peer-mentoring programme. Peer mentors met with their assigned participants regularly during inpatient care and on discharge to track medical complications and assist with adjusting to life after spinal cord injury/disease. In all, of 37 mentees enrolled, 24 successfully completed the programme. Sixty-seven per cent showed improved self-efficacy score between the two time points. Medical complications and doctor visits all decreased significantly between 0-6 months and 7-12 months. Our findings indicate that the older an individual is, the lower the likelihood of having a urinary tract infection (p = 0.006). The programme was well received by all mentees who felt they could connect well with their peer mentor. Peer mentoring in a rehabilitation setting enhances the understanding of challenges that patients and medical staff deal with on a day-to-day basis. Our findings suggest it is important to monitor and educate individuals with spinal cord injury/disease at the acute stage to improve medical outcomes. Caution is advised in the interpretation of these results as they were obtained in a small non-random sample using self-report data. Peer mentors play an increasingly important role in nurse-delivered education in the spinal cord injury/disease population. © 2011 Blackwell Publishing Ltd.

Examining the relationship between post-traumatic stress disorder and social participation among Veterans with spinal cord injuries and disorders.

PubMed

Etingen, Bella; Locatelli, Sara M; Miskevics, Scott; LaVela, Sherri L

2017-07-26

The objectives of this study were to examine differences in social participation among Veterans with spinal cord injuries/disorders with and without post-traumatic stress disorder, and determine if lower social participation was independently associated with having post-traumatic stress disorder. A cross-sectional mailed national survey was sent to a national sample of Veterans with spinal cord injuries/disorders who received prior-year Veterans Affairs healthcare. Surveys provided data on: demographics, health conditions, injury characteristics, and social participation. Analyses included bivariate comparisons, and multivariate logistic regression to determine if lower social participation was independently associated with post-traumatic stress disorder. Veterans with (vs. without) post-traumatic stress disorder (n = 896) reported lower social participation (40.2 vs. 43.9, p < 0.0001). Multivariate analyses showed that longer duration of injury (OR = 0.98, 95% CI: 0.97-1.00, p = 0.04) and white race (OR = 0.62, 95% CI: 0.38-1.01, p = 0.05) were associated with lower odds of post-traumatic stress disorder, while a greater number of health conditions (OR = 1.43, 95% CI: 1.25-1.64, p < 0.0001) was associated with greater odds. When controlling for covariates, lower social participation was independently associated with post-traumatic stress disorder (OR = 0.94, 95% CI: 0.90-0.98, p = 0.003). Results indicate post-traumatic stress disorder is associated with lower social participation in Veterans with spinal cord injuries/disorders, independent of other factors that may impact participation. Efforts to screen for and treat post-traumatic stress disorder among persons with spinal cord injuries/disorders, regardless of injury-specific factors, are needed to improve participation. Implications for Rehabilitation Individuals with spinal cord injuries/disorders often have post-traumatic stress disorder; in Veterans with spinal cord injuries/disorders this may be compounded by trauma incurred through military experiences. Social participation, an important aspect of rehabilitation and community integration following spinal cord injury or disorder, may be hindered by symptoms of post-traumatic stress disorder. Our data show that post-traumatic stress disorder is associated with lower social participation in Veterans with spinal cord injuries/disorders, independent of other factors that may impact participation. These results indicate that efforts to screen for and treat post-traumatic stress disorder among persons with spinal cord injuries/disorders, regardless of injury-specific factors, are needed to improve participation in this patient population.

Spinal sensory circuits in motion.

PubMed

Böhm, Urs Lucas; Wyart, Claire

2016-12-01

The role of sensory feedback in shaping locomotion has been long debated. Recent advances in genetics and behavior analysis revealed the importance of proprioceptive pathways in spinal circuits. The mechanisms underlying peripheral mechanosensation enabled to unravel the networks that feedback to spinal circuits in order to modulate locomotion. Sensory inputs to the vertebrate spinal cord were long thought to originate from the periphery. Recent studies challenge this view: GABAergic sensory neurons located within the spinal cord have been shown to relay mechanical and chemical information from the cerebrospinal fluid to motor circuits. Innovative approaches combining genetics, quantitative analysis of behavior and optogenetics now allow probing the contribution of these sensory feedback pathways to locomotion and recovery following spinal cord injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relative shortening and functional tethering of spinal cord in adolescent scoliosis - Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE.

PubMed

Chu, Winnie Cw; Lam, Wynnie Mw; Ng, Bobby Kw; Tze-Ping, Lam; Lee, Kwong-Man; Guo, Xia; Cheng, Jack Cy; Burwell, R Geoffrey; Dangerfield, Peter H; Jaspan, Tim

2008-06-27

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowth and biomechanical growth modulation may also contribute to AIS pathogenesis.

In-vivo spinal nerve sensing in MISS using Raman spectroscopy

NASA Astrophysics Data System (ADS)

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.

Basic science of pain.

PubMed

DeLeo, Joyce A

2006-04-01

The origin of the theory that the transmission of pain is through a single channel from the skin to the brain can be traced to the philosopher and scientist René Descartes. This simplified scheme of the reflex was the beginning of the development of the modern doctrine of reflexes. Unfortunately, Descartes' reflex theory directed both the study and treatment of pain for more than 330 years. It is still described in physiology and neuroscience textbooks as fact rather than theory. The gate control theory proposed by Melzack and Wall in 1965 rejuvenated the field of pain study and led to further investigation into the phenomena of spinal sensitization and central nervous system plasticity, which are the potential pathophysiologic correlates of chronic pain. The processing of pain takes place in an integrated matrix throughout the neuroaxis and occurs on at least three levels-at peripheral, spinal, and supraspinal sites. Basic strategies of pain control monopolize on this concept of integration by attenuation or blockade of pain through intervention at the periphery, by activation of inhibitory processes that gate pain at the spinal cord and brain, and by interference with the perception of pain. This article discusses each level of pain modulation and reviews the mechanisms of action of opioids and potential new analgesics. A brief description of animal models frames a discussion about recent advances regarding the role of glial cells and central nervous system neuroimmune activation and innate immunity in the etiology of chronic pain states. Future investigation into the discovery and development of novel, nonopioid drug therapy may provide needed options for the millions of patients who suffer from chronic pain syndromes, including syndromes in which the pain originates from peripheral nerve, nerve root, spinal cord, bone, muscle, and disc.

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

PubMed

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

2015-12-29

This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P < 0.05 for each). Thus, edaravone can enhance the survival and differentiation of NSCs in injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

Inhibitory descending rhombencephalic projections in larval sea lamprey.

PubMed

Valle-Maroto, S M; Fernández-López, B; Villar-Cerviño, V; Barreiro-Iglesias, A; Anadón, R; Rodicio, M Celina

2011-10-27

Lampreys are jawless vertebrates, the most basal group of extant vertebrates. This phylogenetic position makes them invaluable models in comparative studies of the vertebrate central nervous system. Lampreys have been used as vertebrate models to study the neuronal circuits underlying locomotion control and axonal regeneration after spinal cord injury. Inhibitory inputs are key elements in the networks controlling locomotor behaviour, but very little is known about the descending inhibitory projections in lampreys. The aim of this study was to investigate the presence of brain-spinal descending inhibitory pathways in larval stages of the sea lamprey Petromyzon marinus by means of tract-tracing with neurobiotin, combined with immunofluorescence triple-labeling methods. Neurobiotin was applied in the rostral spinal cord at the level of the third gill, and inhibitory populations were identified by the use of cocktails of antibodies raised against glycine and GABA. Glycine-immunoreactive (-ir) neurons that project to the spinal cord were observed in three rhombencephalic reticular nuclei: anterior, middle and posterior. Spinal-projecting GABA-ir neurons were observed in the anterior and posterior reticular nuclei. Double glycine-ir/GABA-ir spinal cord-projecting neurons were only observed in the posterior reticular nucleus, and most glycine-ir neurons did not display GABA immunoreactivity. The present results reveal the existence of inhibitory descending projections from brainstem reticular neurons to the spinal cord, which were analyzed in comparative and functional contexts. Further studies should investigate which spinal cord circuits are affected by these descending inhibitory projections. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Surfer’s Myelopathy: A Radiologic Study of 23 Cases

PubMed Central

Nakamoto, B.K.; Siu, A.M.; Hashiba, K.A.; Sinclair, B.T.; Baker, B.J.; Gerber, M.S.; McMurtray, A.M.; Pearce, A.M.; Pearce, J.W.

2015-01-01

BACKGROUND AND PURPOSE Surfing is an uncommon cause of an acute nontraumatic myelopathy. This study describes the MR imaging characteristics and clinical correlates in 23 subjects with surfer’s myelopathy. MATERIALS AND METHODS This was a retrospective review of 23 cases of surfer’s myelopathy from 2003–2012. Spinal cord MR imaging characteristics and neurologic examinations with the use of the American Spinal Injury Association scale were reviewed. Logistic regression was used to determine associations between MR imaging characteristics, American Spinal Injury Association scale, and clinical improvement. RESULTS All subjects (19 male, 4 female; mean age, 26.3 ± 7.4 years) demonstrated “pencil-like,” central T2-hyperintense signal abnormalities in the spinal cord extending from the midthoracic region to the conus with associated cord expansion and varying degrees of conus enlargement on spinal cord MR imaging within 24 hours of symptom onset. T1 signal was normal. Faint gadolinium enhancement was present in a minority. Although there was a strong correlation between initial American Spinal Injury Association score and clinical improvement (P = .0032), MR imaging characteristics were not associated with American Spinal Injury Association score or clinical improvement. CONCLUSIONS Surfer’s myelopathy should be considered in the radiographic differential diagnosis of a longitudinally extensive T2-hyperintense spinal cord lesion. MR imaging characteristics do not appear to be associated with severity on examination or clinical improvement. PMID:23828111

The neuropathological foundations for the restorative neurology of spinal cord injury.

PubMed

Kakulas, Byron A; Kaelan, Cahyono

2015-02-01

An appreciation of the neuropathology of human spinal cord injury (SCI) is a basic requirement for all concerned with the medical treatment of patients with SCI as well as for the many neuroscientists devoted to finding a "cure". An understanding of the neuropathology of SCI is a necessary guide to those concerned at all levels of treatment, whether they are doctors or other health professionals. The underlying changes in the spinal cord are especially relevant to the restorative neurology (RN) of SCI. The new discipline of RN seeks to enhance the function of residual spinal cord elements which have survived the injury and so improve the patient's rehabilitative status. This is in contrast to the conventional approach in rehabilitation which works around the clinical neurological deficiencies. Following the injury a series of changes take place in the spinal cord and surrounding tissues which continue to evolve throughout the life of the patient. In flexion and extension injuries resulting from motor vehicle trauma, diving and sporting accidents the spinal cord is compressed and disrupted but usually with some continuity remaining in the white matter columns. The brunt of the injury is usually centrally placed where there is bleeding into the disrupted grey matter involving one two segments, usually cervical. The loss of central grey matter is nowhere near as important as is the tearing apart of the white matter tracts in determining the patient's clinical state. The central grey matter supplies one two overlapping segmental myotomes and sensory fields. In contrast loss of continuity in the long white matter tracts is catastrophic because all functions below the level of injury are affected, autonomic or voluntary either by paralysis or anaesthesia, usually both. It is important to determine the exact nature of the injury in every patient as a preliminary to treatment by RN. This assessment is both clinical and neurophysiological with special attention given to any part of the long white matter tracts which may have escaped the initial injury. It is these residual nerve fibres which provide the opportunity to improve the patient's neurological state by being re-activated, modulated and enhanced by stimulation or by other RN methods. The conversion of a clinically complete SCI patient to being incomplete and ambulant is a tremendous improvement in the patient's status. It is the purpose of this article to provide the reader with the essential neuropathology of SCI as a beginning point in planning treatment whether it is medical or ancillary, as well as to inform the neuroscientist about the condition being addressed in his or her research. © 2015 Elsevier B.V. All rights reserved.

Subarachnoid Hemorrhage due to Spinal Cord Schwannoma Presenting Findings Mimicking Meningitis.

PubMed

Zhang, Hong-Mei; Zhang, Yin-Xi; Zhang, Qing; Song, Shui-Jiang; Liu, Zhi-Rong

2016-08-01

Subarachnoid hemorrhage (SAH) of spinal origin is uncommon in clinical practice, and spinal schwannomas associated with SAH are even more rarely reported. We report an unusual case of spinal SAH mimicking meningitis with normal brain computed tomography (CT)/magnetic resonance imaging (MRI) and negative CT angiography. Cerebrospinal fluid examination results were consistent with the manifestation of SAH. Spinal MRI performed subsequently showed an intradural extramedullary mass. The patient received surgery and was finally diagnosed with spinal cord schwannoma. A retrospective chart review of the patient was performed. We describe a case of SAH due to spinal cord schwannoma. Our case highlights the importance of careful history taking and complete evaluation. We emphasize that spinal causes should always be ruled out in patients with angionegative SAH and that schwannoma should be considered in the differential diagnosis of SAH etiologies even though rare. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Shock Wave Treatment Protects From Neuronal Degeneration via a Toll-Like Receptor 3 Dependent Mechanism: Implications of a First-Ever Causal Treatment for Ischemic Spinal Cord Injury.

PubMed

Lobenwein, Daniela; Tepeköylü, Can; Kozaryn, Radoslaw; Pechriggl, Elisabeth J; Bitsche, Mario; Graber, Michael; Fritsch, Helga; Semsroth, Severin; Stefanova, Nadia; Paulus, Patrick; Czerny, Martin; Grimm, Michael; Holfeld, Johannes

2015-10-27

Paraplegia following spinal cord ischemia represents a devastating complication of both aortic surgery and endovascular aortic repair. Shock wave treatment was shown to induce angiogenesis and regeneration in ischemic tissue by modulation of early inflammatory response via Toll-like receptor (TLR) 3 signaling. In preclinical and clinical studies, shock wave treatment had a favorable effect on ischemic myocardium. We hypothesized that shock wave treatment also may have a beneficial effect on spinal cord ischemia. A spinal cord ischemia model in mice and spinal slice cultures ex vivo were performed. Treatment groups received immediate shock wave therapy, which resulted in decreased neuronal degeneration and improved motor function. In spinal slice cultures, the activation of TLR3 could be observed. Shock wave effects were abolished in spinal slice cultures from TLR3(-/-) mice, whereas the effect was still present in TLR4(-/-) mice. TLR4 protein was found to be downregulated parallel to TLR3 signaling. Shock wave-treated animals showed significantly better functional outcome and survival. The protective effect on neurons could be reproduced in human spinal slices. Shock wave treatment protects from neuronal degeneration via TLR3 signaling and subsequent TLR4 downregulation. Consequently, it represents a promising treatment option for the devastating complication of spinal cord ischemia after aortic repair. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Release and repair of a ventral thoracic spinal cord herniation.

PubMed

McCormick, Paul C

2014-09-01

Ventral thoracic spinal cord herniation is a rare but increasingly recognized cause of progressive myelopathy. This video demonstrates the imaging characteristics and surgical techniques for release and reduction of the spinal cord herniation as well as primary repair and reinforcement of the ventral dural hernia defect through an extended posterior approach. An instrumented fusion was concomitantly performed. The video can be found here: http://youtu.be/6Pcokep6Tug.

Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

DTIC Science & Technology

2012-10-01

ABSTRACT: This grant will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Rigorous...Surgical Technique) will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Aim 2 (Graft...connected to a rigid needle of the same gauge as the floating cannula one – Figure 7) using the maximum volume/number of injections could result in

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2015-10-01

demonstrated locomotor recovery in mice receiving 40mg/kg DFA up to 3 hours following spinal cord injury -We demonstrated improved locomotor recovery...health, as evaluated by body weight -We identified no added locomotor recovery due to multiple, successive doses of DFA. Moreover, additional doses...bladder function Significance: We have identified robust locomotor recovery in both mild and severe spinal cord injured mice that received DFA up

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

DTIC Science & Technology

2016-07-01

Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12...subjected to spinal cord impact with a custom-made controlled spinal cord impactor and balloon compression. Neurological function was assessed for

Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

DTIC Science & Technology

2013-10-01

2   INTRODUCTION: The magnitude of acute post- traumatic hemorrhagic necrosis (PHN) is an early prognostic indicator of long-term...Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury PRINCIPAL INVESTIGATOR: J. Marc Simard...Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury 5b. GRANT NUMBER W81XWH-10-1-0898 5c. PROGRAM ELEMENT NUMBER 6

Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

DTIC Science & Technology

2013-10-01

collection in underway. 15. SUBJECT TERMS Spinal Cord Injury, Immunogenetics, Chronic pain, Opioids 16. SECURITY CLASSIFICATION OF: 17...prototypic opioid , morphine, is capable of TLR4-mediated proinflammation6-8 . As such, exposure to morphine at the time of injury may result in...fashion to the spinal cord injury and/or to experience inflammation in response to opioid exposure. Critically, this genetic variability may

Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

DTIC Science & Technology

2014-10-01

collection in underway. 15. SUBJECT TERMS Spinal Cord Injury, Immunogenetics, Chronic pain, Opioids 16. SECURITY CLASSIFICATION OF: 17...The prototypic opioid , morphine, is capable of TLR4-mediated proinflammation6-8. As such, exposure to morphine at the time of injury may result in...proinflammatory fashion to the spinal cord injury, and/or to experience inflammation in response to opioid exposure. Critically, this genetic variability

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

PubMed

Gallagher, Gina; Bell, Alison

2016-01-01

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

Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron.

PubMed

Rivera-Oliver, Marla; Moreno, Estefanía; Álvarez-Bagnarol, Yocasta; Ayala-Santiago, Christian; Cruz-Reyes, Nicole; Molina-Castro, Gian Carlo; Clemens, Stefan; Canela, Enric I; Ferré, Sergi; Casadó, Vicent; Díaz-Ríos, Manuel

2018-05-24

While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A 1 -dopamine D 1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D 1 receptor-mediated signaling. A 1 -D 1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

Inflammatory cascades mediate synapse elimination in spinal cord compression

PubMed Central

2014-01-01

Background Cervical compressive myelopathy (CCM) is caused by chronic spinal cord compression due to spondylosis, a degenerative disc disease, and ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported to be an ideal animal model for CCM-related neuronal dysfunction, because they develop spontaneous spinal cord compression without any artificial manipulation. Previous histological studies showed that neurons are lost due to apoptosis in CCM, but the mechanism underlying this neurodegeneration was not fully elucidated. The purpose of this study was to investigate the pathophysiology of CCM by evaluating the global gene expression of the compressed spinal cord and comparing the transcriptome analysis with the physical and histological findings in twy mice. Methods Twenty-week-old twy mice were divided into two groups according to the magnetic resonance imaging (MRI) findings: a severe compression (S) group and a mild compression (M) group. The transcriptome was analyzed by microarray and RT-PCR. The cellular pathophysiology was examined by immunohistological analysis and immuno-electron microscopy. Motor function was assessed by Rotarod treadmill latency and stride-length tests. Results Severe cervical calcification caused spinal canal stenosis and low functional capacity in twy mice. The microarray analysis revealed 215 genes that showed significantly different expression levels between the S and the M groups. Pathway analysis revealed that genes expressed at higher levels in the S group were enriched for terms related to the regulation of inflammation in the compressed spinal cord. M1 macrophage-dominant inflammation was present in the S group, and cysteine-rich protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in these spinal cords. Furthermore, C1q, which initiates the classical complement cascade, was more upregulated in the S group than in the M group. The confocal and electron microscopy observations indicated that classically activated microglia/macrophages had migrated to the compressed spinal cord and eliminated synaptic terminals. Conclusions We revealed the detailed pathophysiology of the inflammatory response in an animal model of chronic spinal cord compression. Our findings suggest that complement-mediated synapse elimination is a central mechanism underlying the neurodegeneration in CCM. PMID:24589419

Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

PubMed

Hofstoetter, Ursula S; Krenn, Matthias; Danner, Simon M; Hofer, Christian; Kern, Helmut; McKay, William B; Mayr, Winfried; Minassian, Karen

2015-10-01

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Changes in Level of the Conus after Corrective Surgery for Scoliosis: MRI-Based Preliminary Study in 31 Patients

PubMed Central

Hong, Jae-Young; Park, Jung-Ho; Hur, Chang-Yong; Hong, Suk-Joo; Modi, Hitesh N

2011-01-01

Background Detection of postoperative spinal cord level change can provide basic information about the spinal cord status, and electrophysiological studies regarding this point should be conducted in the future. Methods To determine the changes in the spinal cord level postoperatively and the possible associated factors, we prospectively studied 31 patients with scoliosis. All the patients underwent correction and posterior fusion using pedicle screws and rods between January 2008 and March 2009. The pre- and postoperative conus medullaris levels were determined by matching the axial magnetic resonance image to the sagittal scout image. The patients were divided according to the change in the postoperative conus medullaris level. The change group was defined as the patients who showed a change of more than one divided section in the vertebral column postoperatively, and the parameters of the change and non-change groups were compared. Results The mean pre- and postoperative Cobb's angle of the coronal curve was 76.80° ± 17.19° and 33.23° ± 14.39°, respectively. Eleven of 31 patients showed a lower conus medullaris level postoperatively. There were no differences in the pre- and postoperative magnitude of the coronal curve, lordosis and kyphosis between the groups. However, the postoperative degrees of correction of the coronal curve and lumbar lordosis were higher in the change group. There were also differences in the disease entities between the groups. A higher percentage of patients with Duchene muscular dystrophy had a change in level compared to that of the patients with cerebral palsy (83.3% vs. 45.5%, respectively). Conclusions The conus medullaris level changed postoperatively in the patients with severe scoliosis. Overall, the postoperative degree of correction of the coronal curve was higher in the change group than that in the non-change group. The degrees of correction of the coronal curve and lumbar lordosis were related to the spinal cord level change after scoliosis correction. PMID:21369475

Zebrafish: an exciting model for investigating the spatio-temporal pattern of enteric nervous system development.

PubMed

Doodnath, Reshma; Dervan, Adrian; Wride, Michael A; Puri, Prem

2010-12-01

Recently, the zebrafish (Danio rerio) has been shown to be an excellent model for human paediatric research. Advantages over other models include its small size, externally visually accessible development and ease of experimental manipulation. The enteric nervous system (ENS) consists of neurons and enteric glia. Glial cells permit cell bodies and processes of neurons to be arranged and maintained in a proper spatial arrangement, and are essential in the maintenance of basic physiological functions of neurons. Glial fibrillary acidic protein (GFAP) is expressed in astrocytes, but also expressed outside of the central nervous system. The aim of this study was to investigate the spatio-temporal pattern of GFAP expression in developing zebrafish ENS from 24 h post-fertilization (hpf), using transgenic fish that express green fluorescent protein (GFP). Zebrafish embryos were collected from transgenic GFP Tg(GFAP:GFP)(mi2001) adult zebrafish from 24 to 120 hpf, fixed and processed for whole mount immunohistochemistry. Antibodies to Phox2b were used to identify enteric neurons. Specimens were mounted on slides and imaging was performed using a fluorescent laser confocal microscope. GFAP:GFP labelling outside the spinal cord was identified in embryos from 48 hpf. The patterning was intracellular and consisted of elongated profiles that appeared to migrate away from the spinal cord into the periphery. At 72 and 96 hpf, GFAP:GFP was expressed dorsally and ventrally to the intestinal tract. At 120 hpf, GFAP:GFP was expressed throughout the intestinal wall, and clusters of enteric neurons were identified using Phox2b immunofluorescence along the pathway of GFAP:GFP positive processes, indicative of a migratory pathway of ENS precursors from the spinal cord into the intestine. The pattern of migration of GFAP:GFP expressing cells outside the spinal cord suggests an organized, early developing migratory pathway to the ENS. This shows for the first time that Tg(GFAP:GFP)(mi2001) zebrafish model is an ideal one to study spatio-temporal patterning of early ENS development.

Correlation of nitric oxide levels in the cerebellum and spinal cord of experimental autoimmune encephalomyelitis rats with clinical symptoms.

PubMed

Ljubisavljevic, Srdjan; Stojanovic, Ivana; Pavlovic, Dusica; Milojkovic, Maja; Vojinovic, Slobodan; Sokolovic, Dusan; Stevanovic, Ivana

2012-01-01

Experimental autoimmune encephalomyelitis (EAE) is a well-established cell-mediated autoimmune inflammatory disease of the CNS, which has been used as a model of the human demyelinating disease. EAE is characterized by infiltration of the CNS by lymphocytes and mononuclear cells, microglial and astrocytic hypertrophy, and demyelination which cumulatively contribute to clinical expression of the disease. EAE was induced in female Sprague-Dawley rats, 3 months old (300 g ± 20 g), by immunization with myelin basic protein (MBP) in combination with Complete Freund's adjuvant (CFA). The animals were divided into 7 groups: control, EAE, CFA, EAE + aminoguanidine (AG), AG, EAE + N-acetyl-L-cysteine (NAC) and NAC. The animals were sacrificed 15 days after EAE induction, and the level of nitric oxide (NO(·)) production was determined by measuring nitrite and nitrate concentrations in 10% homogenate of cerebellum and spinal cord. Obtained results showed that the level of NO(·) was significantly increased in all examined tissues of the EAE rats compared to the control and CFA groups. Also, AG and NAC treatment decreased the level of NO(·) in all tissues compared to the EAE group. The level of NO(·) is increased significantly in the spinal cord compared to the cerebellum. The clinical course of the EAE was significantly decreased in the EAE groups treated with AG and NAC during the development of the disease compared to EAE group and its correlates with the NO(·) level in cerebellum and spinal cord. The findings of our work suggest that NO(·) and its derivatives play an important role in multiple sclerosis (MS). It may be the best target for new therapies in human demyelinating disease and recommend the new therapeutic approaches based on a decreased level of NO(·) during the course of MS.

Vgf is a novel biomarker associated with muscle weakness in amyotrophic lateral sclerosis (ALS), with a potential role in disease pathogenesis

PubMed Central

Zhao, Zhong; Lange, Dale J.; Ho, Lap; Bonini, Sara; Shao, Belinda; Salton, Stephen R.; Thomas, Sunil; Pasinetti, Giulio Maria

2008-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Previous proteomic evidence revealed that the content of certain peptide fragments including Vgf-derived peptide aa 398-411 (Vgf398-411) of the precursor Vgf protein in the cerebral spinal fluid (CSF) correctly identified patients with ALS from normal and disease controls. Using quantitative ELISA immunoassay we found that the CSF levels of Vgf decreases with muscle weakness in patients with ALS. In SOD1 G93A transgenic mice, loss of full-length Vgf content in CSF, serum and in SMI-32 immunopositive spinal cord motor neurons is noted in asymptomatic animals (approximately 75 days old) and continues to show a progressive decline as animals weaken. In vitro studies show that viral-mediated exogenous Vgf expression in primary mixed spinal cord neuron cultures attenuates excitotoxic injury. Thus, while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS, restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injury. PMID:18432310

Vgf is a novel biomarker associated with muscle weakness in amyotrophic lateral sclerosis (ALS), with a potential role in disease pathogenesis.

PubMed

Zhao, Zhong; Lange, Dale J; Ho, Lap; Bonini, Sara; Shao, Belinda; Salton, Stephen R; Thomas, Sunil; Pasinetti, Giulio Maria

2008-04-15

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Previous proteomic evidence revealed that the content of certain peptide fragments including Vgf-derived peptide aa 398-411 (Vgf(398-411)) of the precursor Vgf protein in the cerebral spinal fluid (CSF) correctly identified patients with ALS from normal and disease controls. Using quantitative ELISA immunoassay we found that the CSF levels of Vgf decreases with muscle weakness in patients with ALS. In SOD1 G93A transgenic mice, loss of full-length Vgf content in CSF, serum and in SMI-32 immunopositive spinal cord motor neurons is noted in asymptomatic animals (approximately 75 days old) and continues to show a progressive decline as animals weaken. In vitro studies show that viral-mediated exogenous Vgf expression in primary mixed spinal cord neuron cultures attenuates excitotoxic injury. Thus, while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS, restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injury.

Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury

PubMed Central

Gómez-Soriano, Julio; Goiriena, Eider; Taylor, Julian

2010-01-01

For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threatening withdrawal syndrome present serious problems for its management. Now, in an experimental model of spinal cord injury spasticity, AMPA receptor blockade with NGX424 (Tezampanel) has been shown to reduce stretch reflex activity alone and during tolerance to intrathecal baclofen therapy. These results stem from the observation that GluA1 receptors are overexpressed on reactive astrocytes following experimental ischaemic spinal cord injury. Although further validation is required, the appropriate choice of AMPA receptor antagonists for treatment of stretch hyperreflexia based on our recent understanding of reactive astrocyte neurobiology following spinal cord injury may lead to the development of a better adjunct clinical therapy for spasticity without the side effects of intrathecal baclofen therapy. LINKED ARTICLE This article is a commentary on Oshiro et al., pp. 976–985 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2010.00954.x PMID:20662840

Spinally projecting neurons of the dorsal column nucleus in a reptile: locus of origin and trajectory of termination.

PubMed

Pritz, M B

1996-01-01

Interconnections between the dorsal column nucleus and the spinal cord were investigated in a reptile, Caiman crocodilus. After placement of an anterograde tracer into the dorsal column nucleus, descending fibers are seen to leave this nucleus to enter the dorsal funiculus where they course ventrally to terminate in lamina V of the spinal cord as far caudally as C2. Placement of a retrograde tracer into cut fibers of the cervical spinal cord identified the relay cells of the dorsal column nucleus that project to the spinal cord. These neurons were mainly clustered in a caudal and ventral part of this nucleus. The soma of these spinally projecting cells were small and were generally round or oval in shape. A number of these neurons had the long axis of their soma oriented dorsoventrally, with a primary dendrite extending dorsally. Fibers in the dorsal funiculus that originated from the spinal cord enter the caudal part of the dorsal column nucleus and turn ventral. In the dorsal column nucleus, these axons run parallel to the vertically oriented dendrites of these spinally projecting cells before termination in close relation to the cell bodies of these neurons. Quantitative observations (mean +/- standard error) were made on well labeled neurons and included several measurements: area, perimeter, and degree of eccentricity (greatest width/greatest length) in both the transverse as well as the sagittal plane. These spinally projecting neurons in Caiman are located in the dorsal column nucleus in a position similar to that of spinally projecting cells in cats.

Spinal cord compression in a patient with a pain pump for failed back syndrome: a chalk-like precipitate mimicking a spinal cord neoplasm: case report.

PubMed

Wadhwa, Rishi K; Shaya, Mark R; Nanda, Anil

2006-02-01

The use of intrathecal morphine has been effective with few complications for chronic intractable pain of both benign and malignant origins. A rare but serious problem that exists is the formation of an inflammatory mass at the catheter tip of the pain pump. We report the case of a 67-year-old female patient with failed back syndrome who presented with sensory complaints and back pain. Magnetic resonance imaging revealed impingement on the thoracic cord by a mass. The mass was originally thought to be a spinal cord tumor; however, operation and chemical analysis of the mass showed that it was a bupivacaine precipitate at the tip of the catheter of the pain pump. This is the first such case, to our knowledge, of a bupivacaine precipitate mimicking a spinal cord tumor.

Paralysis recovery in humans and model systems

NASA Technical Reports Server (NTRS)

Edgerton, V. Reggie; Roy, Roland R.

2002-01-01

Considerable evidence now demonstrates that extensive functional and anatomical reorganization following spinal cord injury occurs in centers of the brain that have some input into spinal motor pools. This is very encouraging, given the accumulating evidence that new connections formed across spinal lesions may not be initially functionally useful. The second area of advancement in the field of paralysis recovery is in the development of effective interventions to counter axonal growth inhibition. A third area of significant progress is the development of robotic devices to quantify the performance level of motor tasks following spinal cord injury and to 'teach' the spinal cord to step and stand. Advances are being made with robotic devices for mice, rats and humans.

Descending motor pathways and the spinal motor system - Limbic and non-limbic components

NASA Technical Reports Server (NTRS)

Holstege, Gert

1991-01-01

Research on descending motor pathways to caudal brainstem and spinal cord in the spinal motor system is reviewed. Particular attention is given to somatic and autonomic motoneurons in the spinal cord and brainstem, local projections to motoneurons, bulbospinal interneurons projecting to motoneurons, descending pathways of somatic motor control systems, and descending pathways involved in limbic motor control systems.

Analysis of scientific output by spine surgeons from Japan: January 2000 to December 2013.

PubMed

Kawaguchi, Yoshiharu; Guarise da Silva, Pedro; Quadros, Francine Wurzius; Merlin, Luiz Henrique; Radaelli, Lucas; Guyot, Juan Pablo; Dozza, Diego; Martins, Délio; Scheverin, Nicolas; Riew, Daniel K; Kimura, Tomoatsu; Falavigna, Asdrubal

2016-01-01

Over the last decade, the growing body of work on spine pathology has led to developments and refinements in the areas of basic science, diagnosis and treatment of a variety of spine conditions. Scientific publications have a global impact on the international scientific community as they share vital information that can be applied by physicians worldwide to solve their everyday medical problems. The historical background of scientific publication in journals in Japan on the subject of spine is unclear. We performed a literature search for publications by Japanese spine surgeons regarding spine or spinal cord topics using an online database: Pubmed.gov (http://www.ncbi.nlm.nih.gov/pubmed/). The results were stored and analyzed at the Laboratory of Clinical Studies and Basic Models of Spinal Disorders of the University of Caxias do Sul. Results were limited to articles published from January 2000 to December 2013. The search terms used were "Japan" AND ("spine" OR "spinal diseases" OR "spinal cord" OR "spinal cord diseases" OR "vertebroplasty" OR "arthrodesis" OR "discectomy" OR "foraminotomy" OR "laminectomy" OR "denervation" OR "back injuries"). Japanese spine surgeons were defined as spine surgeons from orthopedic or neurosurgical specialties where the publication was affiliated with Japanese services. A total of 16,140 articles were identified by the Medline search. Most of the articles were excluded based on information provided in the title and abstract as they were not related to spine surgery. This study comprised 1768 articles published in the Medline database by Japanese spine surgeons from 2000 to 2013. The number of publications rose in a linear fashion, with the number of papers published increasing by 5.4 per year (p = 0.038). In recent years the publications were increasingly performed in conjunction with the neurosurgery and orthopedics specialties. This study showed a clear increase in publications (on Medline) by Japanese spine surgeons over the last 14 years. While this is a positive development, there is also cause for concern as there is some evidence that the number of young scientists is declining in Japan. Special attention to educating researchers and improving resources for research is crucial to further increase the number and quality of Japanese publications. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2014-10-01

doses of DFA, male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level (mild...detect the absence of L-selectin on leukocytes 1 day post-SCI. Male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal...subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level. DFA (40mg/kg) or vehicle was administered

Histaminergic Receptors Modulate Spinal Cord Injury-Induced Neuronal Nitric Oxide Synthase Upregulation and Cord Pathology: New Roles of Nanowired Drug Delivery for Neuroprotection.

PubMed

Sharma, Hari S; Patnaik, Ranjana; Muresanu, Dafin F; Lafuente, José V; Ozkizilcik, Asya; Tian, Z Ryan; Nozari, Ala; Sharma, Aruna

2017-01-01

The possibility that histamine influences the spinal cord pathophysiology following trauma through specific receptor-mediated upregulation of neuronal nitric oxide synthase (nNOS) was examined in a rat model. A focal spinal cord injury (SCI) was inflicted by a longitudinal incision into the right dorsal horn of the T10-11 segments. The animals were allowed to survive 5h. The SCI significantly induced breakdown of the blood-spinal cord barrier to protein tracers, reduced the spinal cord blood flow at 5h, and increased the edema formation and massive upregulation of nNOS expression. Pretreatment with histamine H1 receptor antagonist mepyramine (1mg, 5mg, and 10mg/kg, i.p., 30min before injury) failed to attenuate nNOS expression and spinal cord pathology following SCI. On the other hand, blockade of histamine H2 receptors with cimetidine or ranitidine (1mg, 5mg, or 10mg/kg) significantly reduced these early pathophysiological events and attenuated nNOS expression in a dose-dependent manner. Interestingly, TiO 2 -naowire delivery of cimetidine or ranitidine (5mg doses) exerted superior neuroprotective effects on SCI-induced nNOS expression and cord pathology. It appears that effects of ranitidine were far superior than cimetidine at identical doses in SCI. On the other hand, pretreatment with histamine H3 receptor agonist α-methylhistamine (1mg, 2mg, or 5mg/kg, i.p.) that inhibits histamine synthesis and release in the central nervous system thwarted the spinal cord pathophysiology and nNOS expression when used in lower doses. Interestingly, histamine H3 receptor antagonist thioperamide (1mg, 2mg, or 5mg/kg, i.p.) exacerbated nNOS expression and cord pathology after SCI. These novel observations suggest that blockade of histamine H2 receptors or stimulation of histamine H3 receptors attenuates nNOS expression and induces neuroprotection in SCI. Taken together, our results are the first to demonstrate that histamine-induced pathophysiology of SCI is mediated via nNOS expression involving specific histamine receptors. © 2017 Elsevier Inc. All rights reserved.

Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling

PubMed Central

Pearcey, Gregory E. P.; Noble, Steven A.; Munro, Bridget; Zehr, E. Paul

2017-01-01

Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation (CONTROL + STIM), sprints with sensory stimulation (SPRINT + STIM) and sprints without stimulation (SPRINT). Seven participants also performed a fourth session (CONTROL), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM, participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM, participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared to sprints without stimulation. These results demonstrate that sensory stimulation can substantially mitigate the fatiguing effects of sprints. PMID:29326570

Magnetic Resonance Imaging of the Codman Microsensor Transducer Used for Intraspinal Pressure Monitoring: Findings From the Injured Spinal Cord Pressure Evaluation Study.

PubMed

Phang, Isaac; Mada, Marius; Kolias, Angelos G; Newcombe, Virginia F J; Trivedi, Rikin A; Carpenter, Adrian; Hawkes, Rob C; Papadopoulos, Marios C

2016-05-01

Laboratory and human study. To test the Codman Microsensor Transducer (CMT) in a cervical gel phantom. To test the CMT inserted to monitor intraspinal pressure in a patient with spinal cord injury. We recently introduced the technique of intraspinal pressure monitoring using the CMT to guide management of traumatic spinal cord injury [Werndle et al. Crit Care Med 2014;42:646]. This is analogous to intracranial pressure monitoring to guide management of patients with traumatic brain injury. It is unclear whether magnetic resonance imaging (MRI) of patients with spinal cord injury is safe with the intraspinal pressure CMT in situ. We measured the heating produced by the CMT placed in a gel phantom in various configurations. A 3-T MRI system was used with the body transmit coil and the spine array receive coil. A CMT was then inserted subdurally at the injury site in a patient who had traumatic spinal cord injury and MRI was performed at 1.5 T. In the gel phantom, heating of up to 5°C occurred with the transducer wire placed straight through the magnet bore. The heating was abolished when the CMT wire was coiled and passed away from the bore. We then tested the CMT in a patient with an American Spinal Injuries Association grade C cervical cord injury. The CMT wire was placed in the configuration that abolished heating in the gel phantom. Good-quality T1 and T2 images of the cord were obtained without neurological deterioration. The transducer remained functional after the MRI. Our data suggest that the CMT is MR conditional when used in the spinal configuration in humans. Data from a large patient group are required to confirm these findings. N/A.

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

PubMed

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.

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

PubMed

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development of less invasive neuromuscular electrical stimulation model for motor therapy in rodents

PubMed Central

Kanchiku, Tsukasa; Kato, Yoshihiko; Suzuki, Hidenori; Imajo, Yasuaki; Yoshida, Yuichiro; Moriya, Atsushi; Taguchi, Toshihiko; Jung, Ranu

2012-01-01

Background Combination therapy is essential for functional repairs of the spinal cord. Rehabilitative therapy can be considered as the key for reorganizing the nervous system after spinal cord regeneration therapy. Functional electrical stimulation has been used as a neuroprosthesis in quadriplegia and can be used for providing rehabilitative therapy to tap the capability for central nervous system reorganization after spinal cord regeneration therapy. Objective To develop a less invasive muscular electrical stimulation model capable of being combined with spinal cord regeneration therapy especially for motor therapy in the acute stage after spinal cord injury. Methods The tibialis anterior and gastrocnemius motor points were identified in intact anesthetized adult female Fischer rats, and stimulation needle electrodes were percutaneously inserted into these points. Threshold currents for visual twitches were obtained upon stimulation using pulses of 75 or 8 kHz for 200 ms. Biphasic pulse widths of 20, 40, 80, 100, 300, and 500 µs per phase were used to determine strength–duration curves. Using these parameters and previously obtained locomotor electromyogram data, stimulations were performed on bilateral joint muscle pairs to produce reciprocal flexion/extension movements of the ankle for 15 minutes while three-dimensional joint kinematics were assessed. Results Rhythmic muscular electrical stimulation with needle electrodes was successfully done, but decreased range of motion (ROM) over time. High-frequency and high-amplitude stimulation was also shown to be effective in alleviating decreases in ROM due to muscle fatigue. Conclusions This model will be useful for investigating the ability of rhythmic muscular electrical stimulation therapy to promote motor recovery, in addition to the efficacy of combining treatments with spinal cord regeneration therapy after spinal cord injuries. PMID:22507026

Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling.

PubMed

Pearcey, Gregory E P; Noble, Steven A; Munro, Bridget; Zehr, E Paul

2017-01-01

Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation ( CONTROL + STIM ), sprints with sensory stimulation ( SPRINT + STIM ) and sprints without stimulation ( SPRINT ). Seven participants also performed a fourth session ( CONTROL ), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM , participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM , participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared to sprints without stimulation. These results demonstrate that sensory stimulation can substantially mitigate the fatiguing effects of sprints.

Pathology of radiation injury to the canine spinal cord.

PubMed

Powers, B E; Beck, E R; Gillette, E L; Gould, D H; LeCouter, R A

1992-01-01

The histopathologic response of the canine spinal cord to fractionated doses of radiation was investigated. Forty-two dogs received 0, 44, 52, 60, or 68 Gy in 4 Gy fractions to the thoracic spinal cord. Dogs were evaluated for neurologic signs and were observed for 1 or 2 years after irradiation. Six major lesion types were observed; five in the irradiated spinal cord and one in irradiated dorsal root ganglia. The three most severe spinal cord lesions were white matter necrosis, massive hemorrhage, and segmental parenchymal atrophy which had an ED50 of 56.9 Gy (51.3-63.3 Gy 95% CI) in 4 Gy fractions. These lesions were consistently associated with abnormal neurologic signs. Radiation damage to the vasculature was the most likely cause of these three lesions. The two less severe spinal cord lesions were focal fiber loss, which had an ED50 of 49.5 Gy (44.8-53.6 Gy 95% CI) in 4 gy fractions and scattered white matter vacuolation that occurred at all doses. These less severe lesions were not consistently associated with neurologic signs and indicated the presence of residual damage that may occur after lower doses of radiation. Radiation damage to glial cells, axons, and/or vasculature were possible causes of these lesions. In the irradiated dorsal root ganglia, affected sensory neurons contained large intracytoplasmic vacuoles, and there was loss of neurons and satellite cells. Such alterations could affect sensory function. The dog is a good model for spinal cord irradiation studies as tolerance doses for lesions causing clinical signs are close to the estimated tolerance doses for humans, and studies involving volume and long-term observation can be done.

Factors predicting publication of spinal cord injury trials registered on www.ClinicalTrials. gov.

PubMed

DePasse, J Mason; Park, Sara; Eltorai, Adam E M; Daniels, Alan H

2018-02-06

Treatment options for spinal cord injuries are currently limited, but multiple clinical trials are underway for a variety of interventions, drugs, and devices. The Food and Drug Administration website www.ClinicalTrials.gov catalogues these trials and includes information on the status of the trial, date of initiation and completion, source of funding, and region. This investigation assesses the factors associated with publication and the publication rate of spinal cord injury trials. Retrospective analysis of publically available data on www.ClinicalTrials.gov. The www.ClinicalTrials.gov was queried for all trials on patients with spinal cord injury, and these trials were assessed for status, type of intervention, source of funding, and region. Multiple literature searches were performed on all completed trials to determine publication status. There were 626 studies identified concerning the treatment of patients with spinal cord injury, of which 250 (39.9%) were completed. Of these, only 119 (47.6%) were published. There was no significant difference in the rate of publication between regions (p> 0.16) or by study type (p> 0.29). However, trials that were funded by the NIH were more likely to be published than trials funded by industry (p= 0.01). The current publication rate of spinal cord injury trials is only 47.6%, though this rate is similar to the publication rate for trials in other fields. NIH-funded trials are significantly more likely to become published than industry-funded trials, which could indicate that some trials remain unpublished due to undesirable results. However, it is also likely that many trials on spinal cord injury yield negative results, as treatments are often ineffective.

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

PubMed

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

2017-10-01

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

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

PubMed Central

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

The Epidemiology of Back-Related Hospitalizations Among U.S. Navy Personnel

DTIC Science & Technology

1988-06-21

Sacroiliac Joint (12.5%), and Fracture/Fracture- Dislocation of Vertebral Column Without Spinal Cord Lesion (12.0%). Table 1 Demographic Summary of Navy...Other or Unspecified 2,302 17.6 Back Part Sprain/Strain Sacroiliac Joint 1,636 12.5 Fracture/Fracture-Dislocation of 1,575 12.0 Vertebral Column...Without Spinal Cord Lesion Affection of Sacroiliac Joint 197 1.5 Fracture/Fracture-Dislocation of 115 .9 Vertebral Column With Spinal Cord Lesion Open

The Process of Adjustment among Caregivers of Individuals with Spinal Cord Injury: A Qualitative Study

DTIC Science & Technology

2015-10-01

Paralyzed Veterans of America Summit highlighting caregiver quality of life and social support. 10 What was the...1 AWARD NUMBER: W81XWH-14-1-0621 TITLE: The Process of Adjustment among Caregivers of Individuals with Spinal Cord Injury: A Qualitative Study...among Caregivers of Individuals with Spinal Cord Injury: A Qualitative Study 5b. GRANT NUMBER W81XWH-14-1-0621 5c. PROGRAM ELEMENT NUMBER 6

Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0618 TITLE: Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury...Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience 5a. CONTRACT NUMBER...military and veterans. All persons with SCI are at increased risk of pressure ulcer development which remains one of the most significant secondary

Efficacy of chitosan and sodium alginate scaffolds for repair of spinal cord injury in rats

PubMed Central

Yao, Zi-ang; Chen, Feng-jia; Cui, Hong-li; Lin, Tong; Guo, Na; Wu, Hai-ge

2018-01-01

Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats. Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells (regenerating nerve fibers) and less glial fibrillary acidic protein-immunoreactive cells (astrocytic scar tissue) were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue, and as such, is more suitable to help the repair of spinal cord injury. PMID:29623937

Return to work following spinal cord injury: a review.

PubMed

Lidal, Ingeborg Beate; Huynh, Tuan Khai; Biering-Sørensen, Fin

2007-09-15

To review literature on return to work (RTW) and employment in persons with spinal cord injury (SCI), and present employment rates, factors influencing employment, and interventions aimed at helping people with SCI to obtain and sustain productive work. A systematic review for 2000 - 2006 was carried out in PubMed/Medline, AMED, (ISI) Web of Science, EMBASE, CINAHL, PsycInfo and Sociological abstracts database. The keywords 'spinal cord injuries', 'spinal cord disorder', 'spinal cord lesion' or 'spinal cord disease' were cross-indexed with 'employment', 'return to work', 'occupation' or 'vocational'. Out of approximately 270 hits, 110 references were used, plus 13 more found elsewhere. Among individuals with SCI working at the time of injury 21 - 67% returned to work after injury. RTW was higher in persons injured at a younger age, had less severe injuries and higher functional independence. Employment rate improved with time after SCI. Persons with SCI employed ranged from 11.5% to 74%. Individuals who sustained SCI during childhood or adolescence had higher adult employment rates. Most common reported barriers to employment were problems with transportation, health and physical limitations, lack of work experience, education or training, physical or architectural barriers, discrimination by employers, and loss of benefits. Individuals with SCI discontinue working at younger age. This review confirmed low employment rates after SCI. Future research should explore interventions aimed at helping people with SCI to obtain and sustain productive work.

Exploring Facilitators of Post-traumatic Growth in Patients with Spinal Cord Injury: A Qualitative Study

PubMed Central

Khanjani, Mohammad Saeed; Younesi, Seyed Jalal; Khankeh, Hamid Reza; Azkhosh, Manouchehr

2017-01-01

Introduction There is increasing evidence regarding people’s reactions to life stressors in which people also may show positive experiences following a traumatic event. The aim of the present study was to explain the facilitators of post-traumatic growth based on the experiences of patients with a spinal cord injury. Methods This was a qualitative study conducted on 16 Iranian patients with a spinal cord injury using semistructured, in-depth interviews, and content analysis in 2015. These participants, despite their spinal cord injury, were successful in their lives and were considered successful members of society. A purposive sampling method was used until reaching data saturation, and then the collected data were analyzed using a content analysis method. Results The study revealed several factors as facilitators of post-traumatic growth in the patients. The extracted facilitators were put into seven categories of main concepts, including existence of support resources, contact with spinal cord injury associations, spiritual beliefs, positive attitude toward injury, access to proper facilities, enhancement of knowledge and awareness, and active presence in society. Conclusion Different factors may facilitate post-traumatic growth in patients with a spinal cord injury. Understanding these facilitators may help us in designing educational, support, and consulting programs for patients and their families as well as to the correct the support programs. PMID:28243405

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Serotonergic neuron system in the spinal cord of the gar Lepisosteus oculatus (Lepisosteiformes, Osteichthyes) with special regard to the juxtameningeal serotonergic plexus as a paracrine site.

PubMed

Chiba, Akira

2007-02-08

Immunohistochemical and electron microscopic studies were carried out to elucidate the structure of the serotonergic neuron system in the spinal cord of the spotted gar, Lepisosteus oculatus, a nonteleost actinopterygian. Serotonin-immunoreactive (5HT-IR) cell bodies and fibers were widely distributed in the spinal cord, constituting an intrinsic neuron system. This system comprised three anatomical cell groups in different portions of the spinal cord, i.e., the rostromedial cell group, the paired ventrolateral cell groups, and the ventral superficial cell group. The rostromedial cell group included cerebrospinal fluid-contacting neurons with intraventricular processes. The immunostained fibers projecting from all three of these cell groups ran in various directions, mainly ventrally and ventrolaterally, and partly gave rise to a dense plexus at the ventrolateral surface of the spinal cord. Immunoelectron microscopy of the relevant portion demonstrated many varicose fibers containing 5HT-immunopositive vesicles. Conventional electron microscopy of the plexus showed that the constituent varicose fibers were unmyelinated and frequently made a direct contact with the basement membrane contiguous to the leptomeniges (meninx primitiva). There, exocytotic figures of cytoplasmic vesicles were demonstrated, suggesting that 5HT may be secreted, in a paracrine way, into the extraspinal space. This specialized area in the gar spinal cord may be referred to as the juxtameningeal serotonergic plexus.

A rare case of multifocal intramedullary germinoma in cervical spinal cord.

PubMed

Wang, R; Fan, X; Zhang, B

2014-06-01

Case report. We present for the first time a patient with multifocal intramedullary cervical spinal cord germ cell tumors with elevated serum alpha-fetoprotein (AFP). Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. A 19-year-old girl experienced numbness in her right leg 10 months before diagnosis. The numbness gradually became severe and extended up to the thorax. Magnetic resonance imaging (MRI) visualized several intramedullary masses with intensive enhancement and extensive peritumoral edema in the spinal cord at the C3-T1 vertebral body levels. Administration of methylprednisolone caused no treatment effect. The largest mass, which was located at the T1 level inside the normal spinal cord and confirmed by naked eye observation, was completely extracted under a microscope. Postoperative pathological examination demonstrated the so-called 'two-cell pattern,' which is typical of germinoma with placental alkaline phosphatase expression. The serum level of AFP was 64.50 ng ml(-1) (normal range: 0-5 ng ml(-1)). The residual tumor was eliminated through radiation therapy (local 30 Gy) following surgery. Afterward, the patient's neurological deficits were improved but not resolved. Six years after surgery, no recurrence was encountered and the patient remained stable. Radiotherapy is the salvage therapy for spinal cord germinoma. Steroids were of no therapeutic value in the treatment of intramedullary spinal cord germinoma.

Effect of thalidomide on signal transduction pathways and secondary damage in experimental spinal cord trauma.

PubMed

Genovese, Tiziana; Mazzon, Emanuela; Esposito, Emanuela; Di Paola, Rosanna; Caminiti, Rocco; Meli, Rosaria; Bramanti, Placido; Cuzzocrea, Salvatore

2008-09-01

TNF-alpha seems to play a central role in the inflammatory process of spinal cord injury. We tested the neuroprotective effects of thalidomide, an immunomodulatory agent that inhibits TNF-alpha production, which have not been investigated so far. The aim of our study was to evaluate the therapeutic efficacy of thalidomide in an experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a 4-level T5 to T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production that is followed by recruitment of other inflammatory cells, production of a range of inflammation mediators, tissue damage, apoptosis, and disease. Thalidomide treatment significantly reduced the degree of: 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3) iNOS, nitrotyrosine, lipid peroxidation, and cytokine expression (TNF-alpha and IL-1beta); 4) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and Bax and Bcl-2 expression); and 5) nuclear factor-kappaB activation. In a separate set of experiments, we have also clearly demonstrated that thalidomide significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with thalidomide reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Co-Ultramicronized Palmitoylethanolamide/Luteolin Promotes Neuronal Regeneration after Spinal Cord Injury

PubMed Central

Crupi, Rosalia; Impellizzeri, Daniela; Bruschetta, Giuseppe; Cordaro, Marika; Paterniti, Irene; Siracusa, Rosalba; Cuzzocrea, Salvatore; Esposito, Emanuela

2016-01-01

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-ultraPEALut in an estabished murine model of SCI. A vascular clip was applied to the spinal cord dura at T5–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. PMID:27014061

Evaluating diagnosis-based risk-adjustment methods in a population with spinal cord dysfunction.

PubMed

Warner, Grace; Hoenig, Helen; Montez, Maria; Wang, Fei; Rosen, Amy

2004-02-01

To examine performance of models in predicting health care utilization for individuals with spinal cord dysfunction. Regression models compared 2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs) and diagnostic cost groups (DCGs). To improve prediction, we added to our model: (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in self-care function, and (3) both 1 and 2. Models were replicated in 3 populations. Samples from 3 populations: (1) 40% of veterans using Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803), (2) veteran sample with spinal cord dysfunction identified by codes from the International Statistical Classification of Diseases, 9th Revision, Clinical Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs Spinal Cord Dysfunction Registry (N=5888). Not applicable. Inpatient, outpatient, and total days of care in FY97. The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2) range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic information improved prediction more in the ACG model than in the DCG model (R(2) range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care function slightly improved performance (R(2) range increased from 0 to.04). The DCG risk-adjustment models predicted health care utilization better than ACG models. ACG model prediction was improved by adding information.

Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

PubMed Central

Zhang, Yu-Ting; Jin, Hui; Wang, Jun-Hua; Wen, Lan-Yu; Yang, Yang; Ruan, Jing-Wen; Zhang, Shu-Xin; Ling, Eng-Ang

2017-01-01

Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy. PMID:28744378

Anatomical study of blood supply to the cervical spinal cord in the guinea pig.

PubMed

Mazensky, David; Danko, Jan; Petrovova, Eva; Flesarova, Slavka; Supuka, Peter; Supukova, Anna; Luptakova, Lenka; Purzyc, Halina

2015-06-01

The aim of this study was to describe the arterial arrangement of the cervical spinal cord in the guinea pig. The study was carried out on 20 adult English self guinea pigs using corrosion and dissection technique. Batson's corrosion casting kit no. 17(©) was used as a casting medium. The origin of the ventral spinal artery from the left vertebral artery was found on average in 35% of the cases and from the right vertebral artery on average in 40% of the cases. The ventral spinal artery with origin from the anastomosis of two medial branches was found on average in 25% of the cases. The presence of ventral radicular branches of rami spinales entering the ventral spinal artery in the cervical region was observed in 42% of the cases on the right side and in 58% of the cases on the left side. The presence of dorsal radicular branches of rami spinales that reached the spinal cord was observed in 63% of the cases on the left side and in 37% of the cases on the right side. The number of radicular branches supplying the spinal cord is greater in guinea pig than in humans. © 2014 Japanese Society of Animal Science.

Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

1988-01-01

Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

Association of head trauma with cervical spine injury, spinal cord injury, or both.

PubMed

Iida, H; Tachibana, S; Kitahara, T; Horiike, S; Ohwada, T; Fujii, K

1999-03-01

Links between cervical spine and/or spinal cord injuries and head trauma have not been reported in detail. 188 patients with cervical spine and/or spinal cord injury were divided into two groups, i.e., with upper cervical and mid-lower cervical injury, and compared for head injury. Associated head trauma was investigated in 188 patients with cervical spine and/or spinal cord injuries; 35% had moderate or severe injuries. Brain damage was more frequently observed in patients with upper cervical injury than in those with mid to lower cervical injury. Those patients with upper cervical injury appeared to have an elevated risk of suffering skull base fractures, traumatic subarachnoid hemorrhage, and contusional hemotoma. Approximately one third of patients with cervical spine and/or spinal cord injuries had moderate or severe head injuries. Brain damage was more frequently associated with upper cervical injury. Those patients with upper cervical injury are at greater risk of suffering from skull base fractures and severe intracranial hematomas than those with mid to lower cervical injury.

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

NASA Astrophysics Data System (ADS)

Prasad, Abhishek; Sahin, Mesut

2006-12-01

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

Clinical Response of 277 Patients with Spinal Cord Injury to Stem Cell Therapy in Iraq

PubMed Central

Hammadi, Abdulmajeed Alwan; Marino, Andolina; Farhan, Saad

2012-01-01

Background and Objectives: Spinal cord injury is a common neurological problem secondary to car accidents, war injuries and other causes, it may lead to varying degrees of neurological disablement, and apart from physiotherapy there is no available treatment to regain neurological function loss. Our aim is to find a new method using autologous hematopoietic stem cells to gain some of the neurologic functions lost after spinal cord injury. Methods and Results: 277 patients suffering from spinal cord injury were submitted to an intrathecally treatment with peripheral stem cells. The cells were harvested from the peripheral blood after a treatment with G-CSF and then concentrated to 4∼ 6 ml. 43% of the patients improved; ASIA score shifted from A to B in 88 and from A to C in 32. The best results were achieved in patients treated within one year from the injury. Conclusions: Since mesenchymal cells increase in the peripheral blood after G-CSF stimulation, a peripheral blood harvest seems easier and cheaper than mesenchymal cell cultivation prior to injection. It seems reasonable treatment for spinal cord injury. PMID:24298358

Opioid administration following spinal cord injury: Implications for pain and locomotor recovery

PubMed Central

Woller, Sarah A.; Hook, Michelle A.

2013-01-01

Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries. PMID:23501709

Longitudinal study of bone loss in chronic spinal cord injury patients

PubMed Central

Karapolat, Inanc; Karapolat, Hale Uzumcugil; Kirazli, Yesim; Capaci, Kazim; Akkoc, Yesim; Kumanlioglu, Kamil

2015-01-01

[Purpose] This prospective longitudinal study evaluated the changes in bone metabolism markers and bone mineral density of spinal cord injury patients over 3 years. We also assessed the relationships among the bone mineral density, bone metabolism, and clinical data of spinal cord injury patients. [Subjects and Methods] We assessed the clinical data (i.e., immobilization due to surgery, neurological status, neurological level, and extent of lesion) in 20 spinal cord injury patients. Bone mineral density, and hormonal and biochemical markers of the patients were measured at 0, 6, 12, and 36 months. [Results] Femoral neck T score decreased significantly at 36 months (p < 0.05). Among the hormonal markers, parathyroid hormone and vitamin D were significantly elevated, while bone turnover markers (i.e., deoxypyridinoline and osteocalcin) were significantly decreased at 12 and 36 months (p < 0.05). [Conclusion] Bone mineral density of the femoral neck decreases significantly during the long-term follow-up of patients with spinal cord injury due to osteoporosis. This could be due to changes in hormonal and bone turnover markers. PMID:26157234

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

PubMed Central

Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

2015-01-01

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. PMID:26630262

ARTERIAL HYPERTENSION AND IRRADIATION DAMAGE TO THE NERVOUS SYSTEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asscher, A.W.; Anson, S.G.

1962-12-29

On the basis of previous studies it appeared that irradiation damage to the nervous system might be more severe and more easily produced in hypertensive than in normotensive subjects. This hypothesis was investigated by studying the frequency of neurological complications and vascular lesions in the spinal cord after x irradiation of the cord in hypertensive and normotensive rats. Two weeks before irradiation of the spinal cord, a clip was applied to the right renal artery of the animals to produce hypertension. Single doses of 1500, 2000, or 3000 r were administered to the spinal cord in the cervical and uppermore » thoracic region of hypertensive rats (systolic blood pressure higher than 145 mm Hg) and normotensive rats. After 1500 r to spinal cord, no abnormalities were noted in the normotensive controls during the period of observation. Some hypertensive animaIs showed transient abnormalities of gait, and during the following week died suddenly. Those remaining died unexpectedly 35-259 days after irradiation without apparent preceding neurological manifestations, although acute vascular lesions were found in the irradiated regions of the spinal cord. The normotensive controls of the 2000-r group showed no abnormalities of gait or of tail sensation, but the hypertensive rats died 67-243 days after irradiation, and ntaxic episodes preceding these unexpected deaths in one animal. Ristologically, the irradiated segments of the cords showed multiple focal acute vascular necrosis. The smaller arteries in irradiated segments of the cords showed hyaline thickening; some of the smaller vessels were widely dilated and filled with blood, and their walls were necrotic. The white matter of the irradiated parts of these cords showed numerous holes (status spongiosus) in the lateral and dorsal columns. The anterior-horn cells in the irradiated zones were swollen, their nuclei pyknotic and cytoplasm devoid of Nissl granules. No abnormalities, besides thickening of the meninges in the irradiated areas, were found in the cords of the normotensive controls. After 3000 r the normotensive animals of this group showed no abnormalities of gait and Survived normally; no vascular lesions were found in their spinal cords. The hypentensive animals died suddenly 43-70 days after irradiation of the cord, and in all, death was preceded by ataxic episodes. Postmortem, numerous foci of acute vascular necrosis were found in the irradiated cord. These experiments suggest that moderate arterial hypertension seriously modifies the effect of x irradiation of the spinal cord. The transience of the ataxia in irradiated hypertensive rats suggests a possible origin in reversible vasoconstriction. When such episodes were followed by sudden death, arterial necrosis was invariably present in the irradiated region of the cord. Moreover, in hypertensive animals in which paraplegia developed, there was widespread necrosis of nerve tissue as well as organized vascular necrosis. A search of hospital records revealed three cases in which high blood pressure was recorded along with necrosis of the brain or spinal cord following therapeutic irradiation. In two of these, large doses of irradiation had been administered, and the necrosis might have been due to irradiation alone. In the third case, however, necrosis of the spinal cord occurred artd one factor which may have determined this individual sensitivity was high blood pressure. (BBB)« less

Endovascular thoracic aortic repair and previous or concomitant abdominal aortic repair: is the increased risk of spinal cord ischemia real?

PubMed

Baril, Donald T; Carroccio, Alfio; Ellozy, Sharif H; Palchik, Eugene; Addis, Michael D; Jacobs, Tikva S; Teodorescu, Victoria; Marin, Michael L

2006-03-01

Spinal cord ischemia after endovascular thoracic aortic repair remains a significant risk. Previous or concomitant abdominal aortic repair may increase this risk. This investigation reviews the occurrence of spinal cord ischemia after endovascular repair of the descending thoracic aorta in patients with previous or concomitant abdominal aortic repair. Over an 8-year period, 125 patients underwent endovascular exclusion of the thoracic aorta at the Mount Sinai Medical Center. Twenty-eight of these patients had previous or concomitant abdominal aortic repair. The 27 patients who underwent staged repairs all had cerebrospinal fluid (CSF) drainage during and following repair. This population was analyzed for the complication of spinal cord ischemia and factors related to its occurrence. Mean follow-up was 19.3 months (range 1-61). Spinal cord ischemia developed in four of the 28 patients (14.3%) who underwent endovascular thoracic aortic repair with previous or concomitant abdominal aortic repair, while one of 97 patients (1.0%) developed ischemia among the remaining thoracic endograft population. One patient with concomitant abdominal aortic repair developed cord ischemia that manifested 12 hr following the procedure. The remaining three patients with previous abdominal aortic repair developed more delayed-onset paralysis ranging from the third postoperative day to 7 weeks following repair. Irreversible cord ischemia occurred in three patients, with full recovery in one patient. Major complications from CSF drainage occurred in one patient (3.7%). Spinal cord ischemia occurred at a markedly higher rate in patients with previous or concomitant abdominal aortic repair. This risk continued beyond the immediate postoperative period. The benefit of perioperative and salvage CSF drainage remains to be determined.

CSF smear

MedlinePlus

... this page: //medlineplus.gov/ency/article/003768.htm CSF smear To use the sharing features on this ... around the spinal cord and brain. Cerebrospinal fluid (CSF) protects the brain and spinal cord from injury. ...

Anatomical evidence for red nucleus projections to motoneuronal cell groups in the spinal cord of the monkey

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.; Ralston, Diane Daly

1988-01-01

In four rhesus monkeys wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections were made in the mesencephalic tegmentum. In three cases with injections involving the red nucleus (RN), rubrospinal fibers descended mainly contralaterally to terminate in laminae V, VI and dorsal VII of the spinal cord and in the lateral motoneuronal cell groups at the level of the cervical and lumbosacral enlargements. In all four cases the area of the interstitial nucleus of Cajal (INC) was injected, which resulted in labeled interstitiospinal fibers in the medial part of the ipsilateral ventral funiculus of the spinal cord. The results indicate that there is no major qualitative difference between the mesencephalic (RN and INC) and motor cortical projections to the spinal cord.

Enzymatic inactivation of tachykinin neurotransmitters in the isolated spinal cord of the newborn rat.

PubMed

Yanagisawa, M; Yoshioka, K; Kurihara, T; Saito, K; Seno, N; Suzuki, H; Hosoki, R; Otsuka, M

1992-12-01

A mixture of peptidase inhibitors increased the magnitude of the saphenous nerve-evoked slow depolarization of a lumbar ventral root and prolonged the similarly evoked inhibition of monosynaptic reflex (MSR) in the isolated spinal cord of the newborn rat in the presence of naloxone. The saphenous nerve-evoked MSR inhibition was curtailed by a tachykinin antagonist, GR71251, and after the treatment with GR71251, the peptidase inhibitor mixture no more prolonged the MSR inhibition. The present results suggest that enzymatic degradation plays a role in the termination of action of tachykinins released from primary afferents in the newborn rat spinal cord. The results provide a further support for the notion that tachykinins serve as neurotransmitters in the spinal cord of the newborn rat.

Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury.

PubMed

Feitosa, Matheus Levi Tajra; Sarmento, Carlos Alberto Palmeira; Bocabello, Renato Zonzini; Beltrão-Braga, Patrícia Cristina Baleeiro; Pignatari, Graciela Conceição; Giglio, Robson Fortes; Miglino, Maria Angelica; Orlandin, Jéssica Rodrigues; Ambrósio, Carlos Eduardo

2017-07-01

To investigate the therapeutic potential of human immature dental pulp stem cells in the treatment of chronic spinal cord injury in dogs. Three dogs of different breeds with chronic SCI were presented as animal clinical cases. Human immature dental pulp stem cells were injected at three points into the spinal cord, and the animals were evaluated by limb function and magnetic resonance imaging (MRI) pre and post-operative. There was significant improvement from the limb function evaluated by Olby Scale, though it was not supported by the imaging data provided by MRI and clinical sign and evaluation. Human dental pulp stem cell therapy presents promising clinical results in dogs with chronic spinal cord injuries, if used in association with physical therapy.

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

PubMed Central

Chen, Wenling; Marvizón, Juan Carlos G.

2009-01-01

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

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

PubMed

Chen, W; Marvizón, J C G

2009-06-16

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

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

PubMed Central

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

2017-01-01

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

[Diagnostic imaging of spinal diseases].

PubMed

Miyasaka, Kazuo

2005-11-01

With the advent of magnetic resonance imaging, diagnostic accuracy of spinal disorders has been much improved regarding their localization and histological prediction. The location of herniated disc materials is well appreciated on MR images without using contrast materials. MRI can predict the posterior longitudinal ligament is perforated or not. Kinematics of the spinal axis and CSF flow movement is evaluated on MRI with fast imaging. MR angiography with 3D reconstruction depicts the Adamkiewicz's artery and anterior spinal artery. Neuritis and neuropathy can be diagnosed by post-contrast T1 weighted image since inflammatory nerves are thick and enhance. Some intramedullary deseases tend to involve the peripheral area of the spinal cord; others are central. Edema extends longitudinally within the spinal cord by sparing the peripheral margin of the spinal cord and it is well appreciated with the T2- and proton- weighted images. The lateral and posterior funiculi are more frequently involved in multiple sclerosis.

Inhibitory effects of eugenol on putative nociceptive response in spinal cord preparation isolated from neonatal rats.

PubMed

Yagura, Saki; Onimaru, Hiroshi; Kanzaki, Koji; Izumizaki, Masahiko

2018-06-01

Eugenol is contained in several plants including clove and is thought to exert an analgesic effect. It has been suggested that the slow ventral root potential induced by ipsilateral dorsal root stimulation in the isolated (typically lumbar) spinal cord of newborn rats reflects the nociceptive response, and this in vitro experimental model is useful to assess the actions of analgesics. To further elucidate neuronal mechanisms of eugenol-induced analgesia, we examined the effects of extracellularly applied eugenol on the nociceptive spinal reflex response. To evaluate the effects of eugenol on putative nociceptive responses, the ipsilateral fifth lumbar (L5) dorsal root was stimulated using a glass suction electrode, and the induced reflex responses were recorded from the L5 and twelfth thoracic (Th12) ventral roots in spinal cord preparations (Th10-L5) from newborn rats (postnatal day 0-3). We found that eugenol (0.25-1.0 mM) caused dose-dependent attenuation of the reflex response and also depressed spontaneous ventral root activity. We also found that the slow ventral root potential was further divided into two components: initial and late components. A lower concentration of eugenol selectively depressed the late component. The inhibitory effects by 1.0 mM eugenol were not reversed by 10 µM capsazepine (TRPV1 antagonist) or 40 µM HC-030031 (TRPA1 antagonist). The depressive effect of eugenol on the reflex response was also confirmed by optical recordings using voltage-sensitive dye. Our report provides additional evidence on the basic neuronal mechanisms of eugenol to support its clinical use as a potential analgesic treatment.

Spinal cord stimulation: a review of the safety literature and proposal for perioperative evaluation and management.

PubMed

Walsh, Kevin M; Machado, Andre G; Krishnaney, Ajit A

2015-08-01

There is currently no consensus on appropriate perioperative management of patients with spinal cord stimulator implants. Magnetic resonance imaging (MRI) is considered safe under strict labeling conditions. Electrocautery is generally not recommended in these patients but sometimes used despite known risks. The aim was to discuss the perioperative evaluation and management of patients with spinal cord stimulator implants. A literature review, summary of device labeling, and editorial were performed, regarding the safety of spinal cord stimulator devices in the perioperative setting. A literature review was performed, and the labeling of each Food and Drug Administration (FDA)-approved spinal cord stimulation system was reviewed. The literature review was performed using PubMed and the FDA website (www.fda.gov). Magnetic resonance imaging safety recommendations vary between the models. Certain systems allow for MRI of the brain to be performed, and only one system allows for MRI of the body to be performed, both under strict labeling conditions. Before an MRI is performed, it is imperative to ascertain that the system is intact, without any lead breaks or low impedances, as these can result in heating of the spinal cord stimulation (SCS) and injury to the patient. Monopolar electrocautery is generally not recommended for patients with SCS; however, in some circumstances, it is used when deemed required by the surgeon. When cautery is necessary, bipolar electrocautery is recommended. Modern electrocautery units are to be used with caution as there remains a risk of thermal injury to the tissue in contact with the SCS. As with MRI, electrocautery usage in patients with SCS systems with suspected breaks or abnormal impedances is unsafe and may cause injury to the patient. Spinal cord stimulation is increasingly used in patients with pain of spinal origin, particularly to manage postlaminectomy syndrome. Knowledge of the safety concerns of SCS and appropriate perioperative evaluation and management of the SCS system can reduce risks and improve surgical planning. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasticity in reflex pathways to the lower urinary tract following spinal cord injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2013-01-01

The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs. PMID:21596038

Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

2016-11-01

Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.