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Cord Injury (cord + injury)
Kinds of Cord Injury Selected AbstractsPARTNER OR CARER: ROLE PERCEPTIONS IN THE PRESENCE OF SPINAL CORD INJURYAUSTRALIAN OCCUPATIONAL THERAPY JOURNAL, Issue 4 2004Janet McPherson No abstract is available for this article. [source] Functional Electrical Stimulation-Supported Interval Training Following Sensorimotor-Complete Spinal Cord Injury: A Case SeriesNEUROMODULATION, Issue 3 2009Jack Crosbie PhD ABSTRACT Objective.,To investigate the effect of interval training supported by Functional Electrical Stimulation (FES) on ambulation ability in complete spinal cord injury (SCI). Methods.,We trained four men with sensorimotor-complete (ASIA A) SCI, who achieved gait through FES of the quadriceps femoris, gluteus maximus, and common peroneal nerve on each side on a motorized treadmill. Training involved progressive interval walking exercise, consisting of periods of activity followed by equal periods of rest, repeated until muscle fatigue. We used time to muscle fatigue during continuous treadmill ambulation as the primary outcome measure. We also recorded the patterns of incremental stimulation for all training and testing sessions. Results.,All subjects increased their ambulation capacity; however, the responses varied from subject to subject. Some subjects increased the total distance walked by as much as 300% with progressive improvement over the entire training period; however, others made more modest gains and appeared to reach a performance plateau within a few training sessions. Conclusions.,FES-supported interval training offers a useful and effective strategy for strength-endurance improvement in the large muscle groups of the lower limb in motor-complete SCI. We believe that this training protocol offers a viable alternative to that of continuous walking training in people with SCI using FES to aid ambulation. [source] The Effect of Fatigue on the Timing of Electrical Stimulation-Evoked Muscle Contractions in People with Spinal Cord InjuryNEUROMODULATION, Issue 3 2004Peter J. Sinclair PhD Abstract This study investigated the activation dynamics of electrical stimulation-evoked muscle contractions performed by individuals with spinal cord injury (SCI). The purpose was to determine whether electrical stimulation (ES) firing patterns during cycling exercise should be altered in response to fatigue-induced changes in the time taken for force to rise and fall with ES. Seven individuals with SCI performed isometric contractions and pedaled a motorized cycle ergometer with stimulation applied to the quadriceps muscles. Both exercise conditions were performed for five minutes while the patterns of torque production were recorded. ES-evoked knee extension torque fell by 75% under isometric conditions, and the rate of force rise and decline decreased in proportion to torque (r = 0.91, r = 0.94, respectively). There was no change in the time for torque to rise to 50% of maximum levels. The time for torque to decline did increase slightly, but only during the first minute of exercise. Cycling power output fell approximately 50% during the five minutes of exercise, however, there was no change in the time taken for torque to rise or fall. The magnitude of ES-evoked muscle torques decline substantially with fatigue, however, the overall pattern of torque production remained relatively unchanged. These results suggest there is no need to alter stimulation firing patterns to accommodate fatigue during ES-evoked exercise. [source] Chronic Pain after Spinal Cord Injury: Results of a Long-Term StudyPAIN MEDICINE, Issue 7 2010Ehsan Modirian MD Abstract Objective., Chronic pain after spinal cord injury (SCI) is a common and considerable complication and may continue for a long time. Design., During a 2-year survey, 13.9 ± 3.0 years after injury, a total of 1,295 war-related spinal cord injury survivors were thoroughly examined by physical and rehabilitation specialists and all relevant data, consisting of type and site of pain as well as exacerbating or palliative factors, were recorded. Patients., The mean age of the survivors was 35.9 ± 7.2; 98.5% were male and 1.5% were female. The level of injury was cervical in 9.3%, thoracic in 67%, and lumbosacral in 23.7%, with 8.1% tetraplegic and 89.1% paraplegic. About 89.8% had complete spinal cord injuries and 10.2% had incomplete spinal cord injuries, based on sensory and motor testing. Results., Spinal cord related pain was reported in 64.9% of the subjects; 8.8% reported a history of pain but had no complaint at the time of examination, and 26.3% had never suffered from any pain. Patients suffering from lumbar spinal cord injury reported the highest percent of pain perception, with pain detected in 83.5% of these patients. Common sites of reported pain were the distal lower extremities (46.5%), proximal lower extremities (40.9%), pelvic girdle (24.5%), and upper limbs (5.7%). Conclusion., Spinal cord injury-related pain interferes with daily activities of patients and significantly influences their quality of life. [source] Pain Symptom Profiles in Persons with Spinal Cord InjuryPAIN MEDICINE, Issue 7 2009Yenisel Cruz-Almeida MSPH ABSTRACT Objective., Persistent pain is a common consequence of spinal cord injury. A patient-specific assessment that combines both the identification of pain symptoms and psychosocial factors is needed for a tailored treatment approach. The aim of the study was to define pain symptom profiles and to determine their relationship with psychosocial factors in persons with spinal cord injury. Design., Face-to-face interview and examination. Setting., VA Medical Center and Miami Project to Cure Paralysis, Miami, Florida. Patients., Persons with spinal cord injury (135 men and 21 women) provided detailed descriptions of 330 neuropathic pains. Outcome Measures., The American Spinal Injury Impairment Scale, pain history and measures of pain interference, life satisfaction, locus of control, social support and depression. Results., The exploratory factor analyses and regression analyses revealed three distinct symptom profiles: 1) aching, throbbing pain, aggravated by cold weather and constipation predicted by a combination of chance locus of control and lower levels of life satisfaction; 2) stabbing, penetrating, and constant pain of high intensity predicted by a combination of pain interference, localized pain, powerful others locus of control and depressed mood; and 3) burning, electric, and stinging pain aggravated by touch and muscle spasms predicted by pain interference. Conclusions., Although these results need to be replicated in other spinal cord injury samples, our findings suggest that pain symptom profiles may be a useful way to further characterize pain in a comprehensive assessment strategy. [source] Indorenate Improves Motor Function in Rats with Chronic Spinal Cord InjuryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2007Guadalupe Bravo Four months after a ninth thoracic vertebrae spinal cord contusion, 29 rats were randomly allocated into two groups: saline solution and indorenate-treated animals with daily doses incremented at weekly intervals. The locomotor performance of all rats was measured by the Basso, Beattie, and Bresnahan (BBB) rating scale. The results showed that at the end of the treatment, the motor activity of indorenate group was significantly better than that presented by saline solution group. The 80% of indorenate, (against 15% of saline solution) did not show detriment on motor activity. When we analysed the motor activity of rats with basal BBB lower than 10, a significant improvement of motor recovery in indorenate-treated animals was observed. The benefits observed in locomotor function at low doses followed by increasing doses could be associated with pharmacological treatment by indorenate, a well-known 5-HT1A receptor agonist. Our results suggest a potential mechanism by which serotonergic agents may improve motor function in rats with chronic spinal cord injury. [source] Cytoplasmic Extracts from Adipose Tissue Stromal Cells Alleviates Secondary Damage by Modulating Apoptosis and Promotes Functional Recovery Following Spinal Cord InjuryBRAIN PATHOLOGY, Issue 3 2007Soo Kyung Kang Spinal cord injury (SCI) typically results from sustained trauma to the spinal cord, resulting in loss of neurologic function at the level of the injury. However, activation of various physiological mechanisms secondary to the initial trauma including edema, inflammation, excito-toxicity, excessive cytokine release and apoptosis may exacerbate the injury and/or retard natural repair mechanisms. Herein, we demonstrate that cytoplasmic extracts prepared from adipose tissue stromal cells (ATSCs) inhibits H2O2 -mediated apoptosis of cultured spinal cord-derived neural progenitor cells (NPCs) resulting in increased cell survival. The ATSC extracts mediated this effect by decreasing caspase-3 and c-Jun,NH2-terminal kinase (SAPK/JNK) activity, inhibiting cytochrome c release from mitochondria and reducing Bax expression levels in cells. Direct injection of ATSC extracts mixed with Matrigel into the spinal cord immediately after SCI also resulted in reduced apoptotic cell death, astrogliosis and hypo-myelination but did not reduce the extent of microglia infiltration. Moreover, animals injected with the ATSC extract showed significant functional improvement of hind limbs as measured by the BBB (Basso, Beattie and Bresnahan) scale. Collectively, these studies show a prominent therapeutic effect of ATSC cytoplasmic extracts on SCI principally caused by an inhibition of apoptosis-mediated cell death, which spares white matter, oligodendrocytes and neurons at the site of injury. The ability of ATSC extracts to prevent secondary pathological events and improve neurologic function after SCI suggests that extracts prepared from autologous cells harvested from SCI patients may have clinical utility. [source] Histological and Ultrastructural Analysis of White Matter Damage after Naturally-occurring Spinal Cord InjuryBRAIN PATHOLOGY, Issue 2 2006Peter M. Smith Detailed analysis of the structural changes that follow human clinical spinal cord injury is limited by difficulties in achieving adequate tissue fixation. This study bypasses this obstacle by examining the spinal cord from paraplegic domestic animals, enabling us to document the ultrastructural changes at different times following injury. In all but one case, injury resulted from a combination of contusion and compression. There was infarction and hemorrhage, followed by gray matter destruction and the rapid development of a variety of white matter changes including axon swelling and myelin degeneration. Axons greater than 5 µm in diameter were more susceptible to degenerative changes, whereas smaller axons, particularly those in the subpial region, were relatively well preserved. Demyelinated axons were seen within 2 weeks after injury and, at later time points, both Schwann cell and oligodendrocyte remyelination was common. More subtle white matter abnormalities were identified by examining sagittal sections, including focal accumulation of organelles in the axoplasm and partial and paranodal myelin abnormalities. These observations serve to validate observations from experimental models of spinal contusion but also highlight the complexity of naturally occurring (ie, clinical) spinal injury. They also raise the possibility that focal abnormalities such as paranodal demyelination may contribute to early axonal dysfunction and possibly to progressive tissue damage. [source] Diffusion tensor magnetic resonance imaging in spinal cord injuryCONCEPTS IN MAGNETIC RESONANCE, Issue 3 2008Benjamin M. Ellingson Abstract Noninvasive assessment of spinal cord integrity following injury is critical for precise diagnosis, prognosis, and surgical intervention strategies. Diffusion weighted imaging and diffusion tensor imaging are more sensitive to the underlying spinal cord microstructure than traditional imaging techniques. As a result, diffusion imaging is emerging as the clinical technique for imaging the spinal cord after trauma, surgery or during progressive degenerative diseases. This review describes the basic physics of diffusion imaging using magnetic resonance, techniques used to visualize diffusion measurements, and expected changes in diffusion measurements following spinal cord injury. © 2008 Wiley Periodicals, Inc.Concepts Magn Reson Part A 32A: 219,237, 2008. [source] Cervical spinal cord injury following cephalic presentation and delivery by Caesarean sectionDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2001C Morgan MD MRCP MRCPCH We describe a term infant with an acute spinal cord injury following emergency Caesarean section. Foetal movements were normal on the day that the mother was admitted for postterm induction of labour. Caesarean section was performed because of foetal distress and failure to progress during labour. The initial clinical picture suggested acute birth asphyxia. The presence of a high cervical spine injury became more obvious as the clinical picture evolved over the next 7 days. A discontinuity of the cervical spinal cord at C4,5 was confirmed on MRI. Spontaneous respiration failed to develop and intensive care was withdrawn on day 15. No evidence of trauma, or a vascular, neurological, or congenital anomaly of the cervical spinal cord was found at post mortem. The absence of a similar case following cephalic presentation and Caesarean section made bereavement couselling of the parents especially difficult. [source] Mixed primary culture and clonal analysis provide evidence that NG2 proteoglycan-expressing cells after spinal cord injury are glial progenitorsDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2007Soonmoon Yoo Abstract NG2+ cells in the adult rat spinal cord proliferate after spinal cord injury (SCI) and are postulated to differentiate into mature glia to replace some of those lost to injury. To further study these putative endogenous precursors, tissue at 3 days after SCI or from uninjured adults was dissociated, myelin partially removed and replicate cultures grown in serum-containing or serum-free medium with or without growth factors for up to 7 days in vitro (DIV). Cell yield after SCI was 5,6 times higher than from the normal adult. Most cells were OX42+ microglia/macrophages but there were also more than twice the normal number of NG2+ cells. Most of these coexpressed A2B5 or nestin, as would be expected for glial progenitors. Few cells initially expressed mature astrocyte (GFAP) or oligodendrocyte (CC1) markers, but more did at 7 DIV, suggesting differentiation of glial precursors in vitro. To test the hypothesis that NG2+ cells after SCI express progenitor-like properties, we prepared free-floating sphere and single cell cultures from purified suspension of NG2+ cells from injured spinal cord. We found that sphere cultures could be passaged in free-floating subcultures, and upon attachment the spheres clonally derived from an acutely purified single cell differentiated into oligodendrocytes and rarely astrocytes. Taken together, these data support the hypothesis that SCI stimulates proliferation of NG2+ cells that are glial progenitor cells. Better understanding the intrinsic properties of the NG2+ cells stimulated by SCI may permit future therapeutic manipulations to improve recovery after SCI. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] L1, ,1 integrin, and cadherins mediate axonal regeneration in the embryonic spinal cordDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2006Murray Blackmore Abstract Embryonic birds and mammals are capable of axon regeneration after spinal cord injury, but this ability is lost during a discrete developmental transition. We recently showed that changes within maturing neurons, as opposed to changes solely in the spinal cord environment, significantly restrict axon regeneration during development. The developmental changes within neurons that limit axon regeneration remain unclear. One gap in knowledge is the identity of the adhesive receptors that embryonic neurons use to extend axons in the spinal cord. Here we test the roles of L1/NgCAM, ,1 integrin, and cadherins, using a coculture system in which embryonic chick brainstem neurons regenerate axons into an explant of embryonic spinal cord. By in vivo and in vitro methods, we found that brainstem neurons reduce axonal expression of L1 as they mature. Disrupting either L1 or ,1 integrin function individually in our coculture system partially inhibited growth of brainstem axons in spinal cords, while disrupting cadherin function alone had no effect. However, when all three adhesive receptors were blocked simultaneously, axon growth in the spinal cord was reduced by 90%. Using immunohistochemistry and in situ hybridization we show that during the period when neurons lose their regenerative capacity they reduce expression of mRNA for N-cadherin, and reduce axonal L1/NgCAM protein through a post-transcriptional mechanism. These data show that embryonic neurons use L1/NgCAM, ,1 integrin, and cadherin receptors for axon regeneration in the embryonic spinal cord, and raise the possibility that a reduced expression of these essential receptors may contribute to the low-regenerative capacity of older neurons. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Induction of endogenous neural precursors in mouse models of spinal cord injury and diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2005M. F. Azari Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin-positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord. [source] Neuropathic pain in spinal cord injury: significance of clinical and electrophysiological measuresEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Susanne Wydenkeller Abstract A large percentage of spinal cord-injured subjects suffer from neuropathic pain below the level of the lesion (bNP). The neural mechanisms underlying this condition are not clear. The aim of this study was to elucidate the general effects of spinal deafferentiation and of bNP on electroencephalographic (EEG) activity. In addition, the relationship between the presence of bNP and impaired function of the spinothalamic tract was studied. Measurements were performed in complete and incomplete spinal cord-injured subjects with and without bNP as well as in a healthy control group. Spinothalamic tract function, assessed by contact heat evoked potentials, did not differ between subjects with and without bNP; nevertheless, it was impaired in 94% of subjects suffering from bNP. In the EEG recordings, the degree of deafferentiation was reflected in a slowing of EEG peak frequency in the 6,12-Hz band. Taking into account this unspecific effect, spinal cord-injured subjects with bNP showed significantly slower EEG activity than subjects without bNP. A discrimination analysis in the subjects with spinothalamic tract dysfunction correctly classified 84% of subjects as belonging to either the group with bNP or the group without bNP, according to their EEG peak frequency. These findings could be helpful for both the development of an objective diagnosis of bNP and for testing the effectiveness of new therapeutic agents. [source] Involvement of mitochondrial signaling pathways in the mechanism of Fas-mediated apoptosis after spinal cord injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Wen Ru Yu Abstract Activation of the Fas receptor has been recently linked to apoptotic cell death after spinal cord injury (SCI). Although it is generally considered that Fas activation mediates apoptosis predominantly through the extrinsic pathway, we hypothesized that intrinsic mitochondrial signaling could be involved in the underlying mechanism of Fas-induced apoptosis after SCI. In the present study, we utilized the FejotaTM clip compression model of SCI at T5,6 in C57BL/6 Fas-deficient (lpr) and wild-type mice. Complementary studies were conducted using an in vitro model of trauma or a Fas-activating antibody to induce apoptosis in primary neuronal,glial mixed spinal cord cultures. After in vivo SCI, lpr mice, in comparison with wild-type mice, exhibited reduced numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells at the lesion, reduced expression of truncation of Bid (tBid), apoptosis-inducing factor, activated caspase-9 and activated caspase-3, and increased expression of the antiapoptotic proteins Bcl-2 and Bcl-xL. After in vitro neurotrauma or the induction of Fas signaling by the Jo2 activating antibody, lpr spinal cord cultures showed an increased proportion of cells retaining mitochondrial membrane integrity and a reduction of tBid expression, caspase-9 and caspase-3 activation, and TUNEL-positive cells as compared to wild-type spinal cord cultures. The neutralization of Fas ligand (FasL) protected against traumatically induced or Fas-mediated caspase-3 activation and the loss of mitochondrial membrane potential and tBid expression in wild-type spinal cord cultures. However, in lpr spinal cord cultures, FasL neutralization had no protective effects. In summary, these data provide direct evidence for the induction of intrinsic mitochondrial signaling pathways following Fas activation after SCI. [source] Glial cell loss, proliferation and replacement in the contused murine spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Judith M. Lytle Abstract Studies in the rat have shown that contusive spinal cord injury (SCI) results in devastating pathology, including significant loss of mature oligodendrocytes and astrocytes even in spared white matter. Subsequently, there is increased proliferation of endogenous NG2+ cells, postulated to contribute to replacement of mature glia chronically, which is important for functional recovery. Studies of mechanisms that stimulate endogenous progenitor cells would be facilitated by using mouse models with naturally occurring and genetically engineered mutations. To determine whether the murine response is similar to that in the rat, we performed contusive SCI on adult female C57Bl/6 mice at the T8,9 level. Animals received bromodeoxyuridine injections in the first week following injury and were killed at 1, 3, 4, 7 or 28 days postinjury (DPI). The overall loss of macroglia and the temporal,spatial response of NG2+ cells after SCI in the (C57Bl/6) mouse was very similar to that in the (Sprague,Dawley) rat. By 24 h after SCI nearly half of the macroglia in spared ventral white matter had been lost. Cell proliferation was increased at 1,7 DPI, peaking at 3,4 DPI. Dividing cells included NG2+ cells and Cd11b+ macrophages and microglia. Furthermore, cells dividing in the first week expressed markers of mature glia at 28 DPI. The similarities in endogenous progenitor cell response to SCI in the mouse and rat suggest that this is a fundamental injury response, and that transgenic mouse models may be used to further probe how this cellular response to SCI might be enhanced to improve recovery after SCI. [source] Macrophages and neurons are targets of retinoic acid signaling after spinal cord contusion injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Kirsten Schrage Abstract The physiological reactions after spinal cord injury are accompanied by local synthesis of the transcriptional activator retinoic acid (RA). RA exerts its effects by binding to retinoic acid receptors (RAR) which heterodimerize with retinoid X receptors (RXR) and then act as ligand-activated transcription factors. To identify possible cellular targets of RA we investigated protein levels and cellular distribution of retinoid receptors in the rat spinal cord at 4, 7, 14 and 21 days after a contusion injury. In the nonlesioned spinal cord, immunoreactivity for RAR,, RXR,, RXR, and RXR, was localized in the cytosol of neurons, that of RXR, and RXR, in astrocytes and that of RAR,, RXR, and RXR, in some oligodendrocytes. After contusion injury RAR, and all RXRs appeared in the cell nuclei of reactive microglia and macrophages. This nuclear staining began at 4 days, was most prominent at 7 and 14 days and had decreased at 21 days after injury. A similar nuclear translocation was also observed for the RAR,, RXR, and RXR, staining in neurons situated around the border of the contusion. These observations suggest that RA participates as a signal for the physiological responses of microglia and neurons after CNS injury. [source] The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2004Lowell T. McPhail Abstract Myelin-derived molecules inhibit axonal regeneration in the CNS. The Long,Evans Shaker rat is a naturally occurring dysmyelinated mutant, which although able to express the components of myelin lacks functional myelin in adulthood. Given that myelin breakdown exposes axons to molecules that are inhibitory to regeneration, we sought to determine whether injured dorsal column axons in a Shaker rat would exhibit a regenerative response absent in normally myelinated Long,Evans (control) rats. Although Shaker rat axons did not regenerate beyond the lesion, they remained at the caudal end of the crush site. Control rat axons, in contrast, retracted and died back from the edge of the crush. The absence of retraction/dieback in Shaker rats was associated with a reduced phagocytic reaction to dorsal column crush around the caudal edge of the lesion. Systemic injection of minocycline, a tetracycline derivative, in control rats reduced both the macrophage response and axonal retraction/dieback following dorsal column injury. In contrast, increasing macrophage activation by spinal injection of the yeast particulate zymosan had no effect on axonal retraction/dieback in Shaker rats. Schwann cell invasion was reduced in minocycline-treated control rats compared with untreated control rats, and was almost undetectable in Shaker rats, suggesting that like axonal retraction/dieback, spinal Schwann cell infiltration is dependent upon macrophage-mediated myelin degeneration. These results indicate that following spinal cord injury the phagocyte-mediated degeneration of myelin and subsequent exposure of inhibitory molecules to the injured axons contributes to their retraction/dieback. [source] Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2004Katharina Pfeifer Abstract Adult neural progenitor cells (NPC) are an attractive source for cell transplantation and neural tissue replacement after central nervous system (CNS) injury. Following transplantation of NPC cell suspensions into the acutely injured rat spinal cord, NPC survive; however, they migrate away from the lesion site and are unable to replace the injury-induced lesion cavity. In the present study we examined (i) whether NPC can be retained within the lesion site after co-transplantation with primary fibroblasts, and (ii) whether NPC promote axonal regeneration following spinal cord injury. Co-cultivation of NPC with fibroblasts demonstrated that NPC adhere to fibroblasts and the extracellular matrix produced by fibroblasts. In the presence of fibroblasts, the differentiation pattern of co-cultivated NPC was shifted towards glial differentiation. Three weeks after transplantation of adult spinal-cord-derived NPC with primary fibroblasts as mixed cell suspensions into the acutely injured cervical spinal cord in adult rats, the lesion cavity was completely replaced. NPC survived throughout the graft and differentiated exclusively into glial cells. Quantification of neurofilament-labeled axons and anterogradely labeled corticospinal axons indicated that NPC co-grafted with fibroblasts significantly enhanced axonal regeneration. Both neurofilament-labeled axons and corticospinal axons aligned longitudinally along GFAP-expressing NPC-derived cells, which displayed a bipolar morphology reminiscent of immature astroglia. Thus, grafted astroglial differentiated NPC promote axon regrowth following spinal cord injury by means of cellular guidance. [source] Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Ehud Hauben Abstract Immune cells have been shown to contribute to spontaneous recovery from central nervous system (CNS) injury. Here we show that adult female rats and mice recover significantly better than their male littermates from incomplete spinal cord injury (ISCI). This sexual dimorphism is wiped out and recovery is worse in adult mice deprived of mature T cells. After spinal cord contusion in adult rats, functional recovery (measured by locomotor scores in an open field) was significantly worse in females treated with dihydrotestosterone prior to the injury than in placebo-treated controls, and significantly better in castrated males than in their noncastrated male littermates. Post-traumatic administration of the testosterone receptor antagonist flutamide promoted the functional recovery in adult male rats. These results, in line with the known inhibitory effect of testosterone on cell-mediated immunity, suggest that androgen-mediated immunosuppression plays a role in ISCI-related immune dysfunction and can therefore partly explain the worse outcome of ISCI in males than in female. We suggest that females, which are more prone to develop autoimmune response than males, benefit from this response in cases of CNS insults. [source] Assessment of behavioural recovery following spinal cord injury in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000Gillian D. Muir Abstract Behavioural recovery is one of the primary goals of therapeutic intervention in animal models of disease. It is necessary, therefore, to have the means with which to quantify pertinent behavioural changes in experimental animals. Nevertheless, the number and diversity of behavioural measures which have been used to assess recovery after experimental interventions often makes it difficult to compare results between studies. The present review attempts to integrate and categorize the wide variety of behavioural assessments used to measure recovery in spinal-injured rats. These categories include endpoint measures, kinematic measures, kinetic measurements, and electrophysiological measurements. Within this categorization, we discuss the advantages and disadvantages of each type of measurement. Finally, we make some recommendations regarding the principles for a comprehensive behavioural analysis after experimental spinal cord injury in rats. [source] Acupuncture greatly improves recovery from spinal cord injury compared with standard care aloneFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 3 2003Article first published online: 14 JUN 2010 [source] Time Controlled Protein Release from Layer-by-Layer Assembled Multilayer Functionalized Agarose HydrogelsADVANCED FUNCTIONAL MATERIALS, Issue 2 2010Sumit Mehrotra Abstract Axons of the adult central nervous system exhibit an extremely limited ability to regenerate after spinal cord injury. Experimentally generated patterns of axon growth are typically disorganized and randomly oriented. Support of linear axonal growth into spinal cord lesion sites has been demonstrated using arrays of uniaxial channels, templated with agarose hydrogel, and containing genetically engineered cells that secrete brain-derived neurotrophic factor (BDNF). However, immobilizing neurotrophic factors secreting cells within a scaffold is relatively cumbersome, and alternative strategies are needed to provide sustained release of BDNF from templated agarose scaffolds. Existing methods of loading the drug or protein into hydrogels cannot provide sustained release from templated agarose hydrogels. Alternatively, here it is shown that pH-responsive H-bonded poly(ethylene glycol)(PEG)/poly(acrylic acid)(PAA)/protein hybrid layer-by-layer (LbL) thin films, when prepared over agarose, provided sustained release of protein under physiological conditions for more than four weeks. Lysozyme, a protein similar in size and isoelectric point to BDNF, is released from the multilayers on the agarose and is biologically active during the earlier time points, with decreasing activity at later time points. This is the first demonstration of month-long sustained protein release from an agarose hydrogel, whereby the drug/protein is loaded separately from the agarose hydrogel fabrication process. [source] Triptolide promotes spinal cord repair by inhibiting astrogliosis and inflammationGLIA, Issue 8 2010Zhida Su Abstract Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Traumatic SCI directly damages the cell bodies and/or processes of neurons and triggers a series of endogenous processes, including neuroinflammatory response and reactive astrogliosis. In this study, we found that triptolide, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis and inflammation and promoted spinal cord repair. Triptolide was shown to prevent astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced in injured spinal cord treated with triptolide. Triptolide treatment was also shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion site. Using neurofilament staining and anterograde tracing, a significantly greater number of regenerative axons were observed in the triptolide-treated rats. Importantly, behavioral tests revealed that injured rats receiving triptolide had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These results suggested that triptolide promoted axon regeneration and locomotor recovery by attenuating glial scaring and inflammation, and shed light on the potential therapeutic benefit for SCI. © 2010 Wiley-Liss, Inc. [source] Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytesGLIA, Issue 13 2008Wei-Lin Liu Abstract Reactive gliosis caused by post-traumatic injury often results in marked expression of chondroitin sulfate proteoglycan (CSPG), which inhibits neurite outgrowth and regeneration. Methylprednisolone (MP), a synthetic glucocorticoid, has been shown to have neuroprotective and anti-inflammatory effects for the treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG expression in reactive glial cells remains unclear. In our study, we induced astrocyte reactivation using ,-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and cyclothiazide to mimic the excitotoxic stimuli of SCI. The expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivation, and CSPG neurocan and phosphacan were significantly elevated by AMPA treatment. The conditioned media from AMPA-treated astrocytes strongly inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG expression in adult rats with SCI. Additionally, both the glucocorticoid receptor (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression. Taken together, these results suggest that MP may improve neuronal repair and promote neurite outgrowth after excitotoxic insult via GR-mediated downregulation of astrocyte reactivation and inhibition of CSPG expression. © 2008 Wiley-Liss, Inc. [source] Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferationGLIA, Issue 1 2005Jaime Struve Abstract Astrocyte proliferation is tightly controlled during development and in the adult nervous system. In the present study, we find that a high-molecular-weight (MW) form of the glycosaminoglycan hyaluronan (HA) is found in rat spinal cord tissue and becomes degraded soon after traumatic spinal cord injury. Newly synthesized HA accumulates in injured spinal cord as gliosis proceeds, such that high-MW HA becomes overabundant in the extracellular matrix surrounding glial scars after 1 month. Injection of hyaluronidase, which degrades HA, into normal spinal cord tissue results in increased numbers of glial fibrillary acidic protein (GFAP)-positive cells that also express the nuclear proliferation marker Ki-67, suggesting that HA degradation promotes astrocyte proliferation. In agreement with this observation, adding high- but not low-MW HA to proliferating astrocytes in vitro inhibits cell growth, while treating confluent, quiescent astrocyte cultures with hyaluronidase induces astrocyte proliferation. Collectively, these data indicate that high-MW HA maintains astrocytes in a state of quiescence, and that degradation of HA following CNS injury relieves growth inhibition, resulting in increased astrocyte proliferation. © 2005 Wiley-Liss, Inc. [source] Cortical and subcortical correlates of functional electrical stimulation of wrist extensor and flexor muscles revealed by fMRIHUMAN BRAIN MAPPING, Issue 3 2009Armin Blickenstorfer Abstract The main scope of this study was to test the feasibility and reliability of FES in a MR-environment. Functional Electrical Stimulation (FES) is used in the rehabilitation therapy of patients after stroke or spinal cord injury to improve their motor abilities. Its principle lies in applying repeated electrical stimulation to the relevant nerves or muscles for eliciting either isometric or concentric contractions of the treated muscles. In this study we report cerebral activation patterns in healthy subjects undergoing fMRI during FES stimulation. We stimulated the wrist extensor and flexor muscles in an alternating pattern while BOLD-fMRI was recorded. We used both block and event-related designs to demonstrate their feasibility for recording FES activation in the same cortical and subcortical areas. Six out of fifteen subjects repeated the experiment three times within the same session to control intraindividual variance. In both block and event-related design, the analysis revealed an activation pattern comprising the contralateral primary motor cortex, primary somatosensory cortex and premotor cortex; the ipsilateral cerebellum; bilateral secondary somatosensory cortex, the supplementary motor area and anterior cingulate cortex. Within the same subjects we observed a consistent replication of the activation pattern shown in overlapping regions centered on the peak of activation. Similar time course within these regions were demonstrated in the event-related design. Thus, both techniques demonstrate reliable activation of the sensorimotor network and eventually can be used for assessing plastic changes associated with FES rehabilitation treatment. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source] Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2002JENS SØNKSEN Summary The purpose of this review is to present the current understanding of penile vibratory stimulation (PVS) and electroejaculation (EEJ) procedures and its clinical use in men with ejaculatory dysfunction. Unfortunately, the record of treating such individuals has been quite poor, but within recent years development and refinement of PVS and EEJ in men with spinal cord injury (SCI) has significantly enhanced the prospects for treatment of ejaculatory dysfunction. The majority of spinal cord injured men are not able to produce antegrade ejaculation by masturbation or sexual stimulation. However, approximately 80% of all spinal cord injured men with an intact ejaculatory reflex arc (above T10) can obtain antegrade ejaculation with PVS. Electroejaculation may be successful in obtaining ejaculate from men with all types of SCI, including men who do not have major components of the ejaculatory reflex arc. Because vibratory stimulation is very simple in use, non-invasive, it does not require anaesthesia and is preferred by the patients when compared with EEJ, PVS is recommended to be the first choice of treatment in spinal cord injured men. Furthermore, EEJ has been successfully used to induce ejaculation in men with multiple sclerosis and diabetic neuropathy. Any other conditions which affect the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully with EEJ. Finally, for sperm retrieval and sperm cryopreservation before intensive anticancer therapy in pubertal boys, PVS and EEJ have been successfully performed in patients who failed to obtain ejaculation by masturbation. Nearly all data concerning semen characteristics in men with ejaculatory dysfuntion originate from spinal cord injured men. Semen analyses demonstrate low sperm motility rates in the majority of spinal cord injured men. The data give evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few weeks) an acute SCI. Furthermore, it is suggested that some factors in the seminal plasma and/or disordered storage of spermatozoa in the seminal vesicles are mainly responsible for the impaired semen profiles in men with chronic SCI. Home insemination with semen obtained by penile vibratory and introduced intravaginally in order to achieve successful pregnancies may be an option for some spinal cord injured men and their partners. The majority of men will further enhance their fertility potential when using either penile vibratory or EEJ combined with assisted reproduction techniques such as intrauterine insemination or in-vitro fertilization with or without intracytoplasmic sperm injection. [source] Usefulness of a malleable penile prosthesis in patients with a spinal cord injuryINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2008Young Dong Kim Objectives: The usefulness of a malleable penile prosthesis was evaluated in patients with spinal cord injury (SCI) by investigating the complications and the patients' satisfaction. Methods: A total of 48 patients with a SCI, who underwent malleable penile prosthesis (AMS 600) insertion from 1990 to 2004 were evaluated by reviewing the patients' medical records and interviewing them via questionnaires. The mean patients age was 58.9 years, and the mean follow-up period was 11.7 years. In 23 patients, penile prosthesis implantation was carried out to improve urinary management and to treat erectile dysfunction (ED). Results: Complications occurred in eight patients (16.7%). Wound infections in four (8.3%). Two patients were treated with conservative management, and two were managed through prostheses removal. Other complications were erosion in two patients (4.2%), uncontrolled penile pain owing to excessive prosthesis length in one patient (2.1%), and supersonic transporter (SST) deformity in one patient (2.1%). The overall patient satisfaction rate was 79.2%. The dissatisfaction was mainly due to the complications that resulted in the removal of the prosthesis, or partner's unnatural sensation. All of the prostheses that were implanted in the patients for the improvement of their urinary management gave them the benefit of convenient urinary management, except for two patients, whose prostheses were removed. Conclusions: The insertion of malleable penile prostheses in patients with SCI is associated with low complication rates and good patient satisfaction. It is therefore still an attractive option. [source] Intrathecal glutamate promotes glycinergic neuronal activity and inhibits the micturition reflex in urethane-anesthetized ratsINTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2006KATSUHIRO ASHITOMI Objectives: In order to clarify the role of glutamate in the micturition reflex and in glutamatergic and glycinergic neuronal activity, we examined the effects of intrathecal (IT) injection of glutamate or MK-801 (an N- methyl-D-aspartate receptor antagonist) on bladder activity and on the glutamate and glycine levels in the lumbosacral cord of female rats with or without acute lower thoracic spinal cord injury (SCI). Methods: Under urethane anesthesia, isovolumetric cystometry was performed in rats with or without SCI before and after IT injection of glutamate or MK-801 at the lumbosacral cord level. The glutamate and glycine levels of the whole lumbosacral cord were measured after IT injection of glutamate or MK-801 in both groups. Results: In intact rats, IT glutamate (100 µg) prolonged the interval between bladder contractions and decreased the amplitude of contractions. IT MK-801 (3,100 µg) also prolonged the interval between bladder contractions and decreased the amplitude in intact rats. In SCI rats, cystometry demonstrated the disappearance of bladder contractions, and the glycine level in the lumbosacral cord was elevated. In intact rats, IT glutamate (0.3,100 µg) increased the glycine level in the lumbosacral cord. On the other hand, IT MK-801 (3,100 µg) decreased both glutamate and glycine levels in intact and SCI rats. Conclusions: These results suggest that glutamatergic neurons have stimulatory projections to both glutamatergic and glycinergic neurons in the lumbosacral cord, and that glutamatergic neurons inhibit the micturition reflex by stimulating glycinergic neurons. [source] |