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Spinal Cord Injury (spinal + cord_injury)
Kinds of Spinal 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] 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] Estrogen as a neuroprotective agent in rat spinal cord injuryJOURNAL OF NEUROCHEMISTRY, Issue 2002N. L. Banik Spinal cord injury (SCI) is a neurological problem affecting approximately 11 000 Americans each year. Several treatment agents have been proposed; however, only methylprednisolone has limited efficacy. Estrogen is a multiactive neuroprotectant with antioxidant and anti-inflammatory properties and attenuates calcium (Ca2+) influx following neuronal injury. To examine the neuroprotective effects of estrogen in SCI, we induced SCI (40 g/cm injury) in rats. Treatment groups were sham (laminectomy only), SCI plus vehicle, and SCI plus estrogen. Injured rats were treated with either 4 mg/kg 17 ,-estradiol (estrogen group) or dimethylsulfoxide (vehicle group) at 15 min and 24 h following injury. All rats were killed at 48 h to analyze SCI segments for calpain content and Bax/Bcl-2 ratio by Western blotting. Tissue was also examined using calcium green-2 to measure intracellular [Ca2+], JC-1 to measure mitochondrial membrane potential, and double immunofluorescence for macrophages and calpain. Calpain content in the lesion penumbra, adjacent to the injury, was higher in vehicle than sham and this increase was attenuated in estrogen treated rats. In the lesion penumbra, the Bax/Bcl-2 ratio was increased in vehicle rats as compared to sham. This increase was attenuated in estrogen treated rats. Estrogen treated rats had less Ca2+ influx, less inflammatory cell infiltration, and increased maintenance of mitochondrial membrane potential compared to vehicle treated rats. Our preliminary data suggest that estrogen may be effective in decreasing Ca2+ influx, inflammatory cell infiltration, and Bax/Bcl-2 ratio following SCI. Acknowledgements:, Supported in part by grants from NIH-NINDS and South Carolina Electric and Gas. [source] GeneChip® analysis after acute spinal cord injury in ratJOURNAL OF NEUROCHEMISTRY, Issue 4 2001Guoqing Song Spinal cord injury (SCI) leads to induction and/or suppression of several genes, the interplay of which governs the neuronal death and subsequent loss of motor function. Using GeneChip®, the present study analyzed changes in the mRNA abundance at 3 and 24 h after SCI in adult rats. SCI was induced at T9 level by the New York University impactor by dropping a 10-g weight from a height of 25 mm. Several transcription factors, immediate early genes, heat-shock proteins, pro-inflammatory genes were up-regulated by 3 h, and persisted at 24 h, after SCI. On the other hand, some neurotransmitter receptors and transporters, ion channels, kinases and structural proteins were down-regulated by 3 h, and persisted at 24 h, after SCI. Several genes that play a role in growth/differentiation, survival and neuroprotection were up-regulated at 24 h after SCI. Using real-time quantitative PCR, the changes observed by GeneChip® were confirmed for seven up-regulated (interleukin-6, heat-shock protein-70, heme oxygenase-1, suppressor of cytokine signaling 2, suppressor of cytokine signaling 3, interferon regulatory factor-1, neuropeptide Y), two down-regulated (vesicular GABA transporter and cholecystokinin precursor) and two unchanged (Cu/Zn-superoxide dismutase and phosphatidyl inositol-3-kinase) genes. The present study shows that inflammation, neurotransmitter dysfunction, increased transcription, ionic imbalance and cytoskeletal damage starts as early as 3 h after SCI. In addition to these effects, 24 h after SCI the repair and regeneration process begins in an attempt to stabilize the injured spinal cord. [source] Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010Eric A. Sribnick Abstract Spinal cord injury (SCI) causes loss of neurological function and, depending on serverity, may cause paralysis. The only recommended pharmacotherapy for the treatment of SCI is high-dose methylprednisolone, and its use is controversial. We have previously shown that estrogen treatment attenuated cell death, axonal and myelin damage, calpain and caspase activities, and inflammation in acute SCI. The aim of this study was to examine whether posttreatment of SCI with estrogen would improve locomotor function by protecting cells and axons and reducing inflammation during the chronic phase following injury. Moderately severe injury (40 g · cm force) was induced in male Sprague-Dawley rats following laminectomy at T10. Three groups of animals were used: sham (laminectomy only), vehicle (dimethyl sulfoxide; DMSO)-treated injury group, and estrogen-treated injury group. Animals were treated with 4 mg/kg estrogen at 15 min and 24 hr postnjury, followed by 2 mg/kg estrogen daily for the next 5 days. After treatment, animals were sacrificed at the end of 6 weeks following injury, and 1-cm segments of spinal cord (lesion, rostral to lesion, and caudal to lesion) were removed for biochemical analyses. Estrogen treatment reduced COX-2 activity, blocked nuclear factor-,B translocation, prevented glial reactivity, attenuated neuron death, inhibited activation and activity of calpain and caspase-3, decreased axonal damage, reduced myelin loss in the lesion and penumbra, and improved locomotor function compared with vehicle-treated animals. These findings suggest that estrogen may be useful as a promising therapeutic agent for prevention of damage and improvement of locomotor function in chronic SCI. © 2010 Wiley-Liss, Inc. [source] Promoting directional axon growth from neural progenitors grafted into the injured spinal cordJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2010Joseph F. Bonner Abstract Spinal cord injury (SCI) is a devastating condition characterized by disruption of axonal connections, failure of axonal regeneration, and loss of motor and sensory function. The therapeutic promise of neural stem cells has been focused on cell replacement, but many obstacles remain in obtaining neuronal integration following transplantation into the injured CNS. This study investigated the neurotransmitter identity and axonal growth potential of neural progenitors following grafting into adult rats with a dorsal column lesion. We found that using a combination of neuronal and glial restricted progenitors (NRP and GRP) produced graft-derived glutamatergic and GABAergic neurons within the injury site, with minimal axonal extension. Administration of brain-derived neurotrophic factor (BDNF) with the graft promoted modest axonal growth from grafted cells. In contrast, injecting a lentiviral vector expressing BDNF rostral into the injured area generated a neurotrophin gradient and promoted directional growth of axons for up to 9 mm. Animals injected with BDNF lentivirus (at 2.5 and 5.0 mm) showed significantly more axons and significantly longer axons than control animals injected with GFP lentivirus. However, only the 5.0-mm-BDNF group showed a preference for extension in the rostral direction. We concluded that NRP/GRP grafts can be used to produce excitatory and inhibitory neurons, and neurotrophin gradients can guide axonal growth from graft-derived neurons toward putative targets. Together they can serve as a building block for neuronal cell replacement of local circuits and formation of neuronal relays. © 2009 Wiley-Liss, Inc. [source] Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2006Janette Glaser Abstract Spinal cord injury (SCI) is followed by a secondary degenerative process that includes cell death. We have previously demonstrated that the chemokine CXCL10 is up-regulated following SCI and plays a critical role in T-lymphocyte recruitment to sites of injury and inhibition of angiogenesis; antibody-mediated functional blockade of CXCL10 reduced inflammation while enhancing angiogenesis. We hypothesized, based on these findings, that the injury environment established by anti-CXCL10 antibody treatment would support greater survival of neurons and enhance axon sprouting compared with the untreated, injured spinal cord. Here, we document gene array and histopathological data to support our hypothesis. Gene array analysis of treated and untreated tissue from spinal cord-injured animals revealed eight apoptosis-related genes with significant expression changes at 3 days postinjury. In support of these data, quantification of TUNEL-positive cells at 3 days postinjury indicated a 75% reduction in the number of dying cells in treated animals compared with untreated animals. Gene array analysis of treated and untreated tissue also revealed six central nervous system growth-related genes with significant expression changes in the brainstem at 14 days postinjury. In support of these data, quantification of anterograde-labeled corticospinal tract fibers indicated a 60,70% increase in axon sprouting caudal to the injury site in treated animals compared with untreated animals. These findings indicate that anti-CXCL10 antibody treatment provides an environment that reduces apoptosis and increases axon sprouting following injury to the adult spinal cord. © 2006 Wiley-Liss, Inc. [source] Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2005Eric Anthony Sribnick Abstract Spinal cord injury (SCI) is a devastating neurologic injury with functional deficits for which the only currently recommended pharmacotherapy is high-dose methylprednisolone, which has limited efficacy. Estrogen is a multiactive steroid that has shown antiinflammatory and antioxidant effects, and estrogen may modulate intracellular Ca2+ and attenuate apoptosis. For this study, male rats were divided into three groups. Sham group animals received a laminectomy at T12. Injured rats received both laminectomy and 40 g · cm force SCI. Estrogen-group rats received 4 mg/kg 17,-estradiol (estrogen) at 15 min and 24 hr post-injury, and vehicle-group rats received equal volumes of dimethyl sulfoxide (vehicle). Animals were sacrificed at 48 hr post-injury, and 1-cm-long segments of the lesion, rostral penumbra, and caudal penumbra were excised. Inflammation was assessed by examining tissue edema, infiltration of macrophages/microglia, and levels of cytosolic and nuclear NF,B and inhibitor of kappa B (I,B,). Myelin integrity was examined using Luxol fast blue staining. When compared to sham, vehicle-treated animals revealed increased tissue edema, increased infiltration of inflammatory cells, decreased cytosolic levels of NF,B and I,B,, increased levels of nuclear NF,B, and increased myelin loss. Treatment of SCI rats with estrogen reduced edema and decreased inflammation and myelin loss in the lesion and penumbral areas, suggesting its potential as a therapeutic agent. Further work needs to be done, however, to elucidate the neuroprotective mechanism of estrogen. © 2005 Wiley-Liss, Inc. [source] Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscleMUSCLE AND NERVE, Issue 4 2008Micah J. Drummond PhD Abstract Spinal cord injury reduces the rate of skeletal muscle protein synthesis and increases protein breakdown, resulting in rapid muscle loss. The purpose of this study was to determine whether long-term paraplegia would eventually result in a downregulation of muscle mRNA and protein expression associated with both protein synthesis and breakdown. After 10 weeks of spinal cord transection, soleus muscle from 12 rats (6 sham-control, 6 paraplegic) was studied for mRNAs and proteins associated with protein synthesis and breakdown using real-time polymerase chain reaction and immunoblotting techniques. Protein kinase B (PKB/Akt), ribosomal S6 kinase 1 (S6K1), and myogenin mRNA were downregulated, whereas muscle ring finger 1 (MuRF1) and phospho-forkhead transcription factor 4 (FoxO4) protein were increased in paraplegic rats. We conclude that gene and protein expression of pathways associated with protein synthesis are reduced, whereas some markers of protein breakdown remain elevated following chronic paraplegia. Clinical interventions designed to increase muscle protein synthesis may be helpful in preventing excessive muscle loss during long-term paraplegia. Muscle Nerve, 2008 [source] Single muscle fiber size and contractility after spinal cord injury in ratsMUSCLE AND NERVE, Issue 1 2006Walter R. Frontera MD Abstract Spinal cord injury (SCI) results in muscle weakness but the degree of impairment at the level of single fibers is not known. The purpose of this study was to examine the effects of T9,level SCI on single muscle fibers from the tibialis anterior of rats. Significant decreases in cross-sectional area (CSA), maximal force (Po), and specific force (SF = Po/CSA) were noted at 2 weeks. Atrophy and force-generating capacity were reversed at 4 weeks, but SF remained impaired. Maximum shortening velocity (Vo) did not change after injury. SCI thus appears to affect various contractile properties of single muscle fibers differently. Normal cage activity may partially restore function but new interventions are needed to restore muscle fiber quality. Muscle Nerve, 2006 [source] Assessment of spinal cord pathology following trauma using early changes in the spinal cord evoked potentials: A pharmacological and morphological study in the ratMUSCLE AND NERVE, Issue S11 2002Hari Shanker Sharma PhD Abstract The possibility that spinal cord pathology following trauma can be assessed with early changes in the spinal cord evoked potentials (SCEPs) was examined in a rat model. Spinal cord injury (SCI) was produced in Equithesin-anesthetized (3 ml/kg, i.p.) rats through a longitudinal incision into the right dorsal horn at the T10,11 segments. The SCEPs were recorded with epidural electrodes placed over the T9 (rostral) segment of the cord. The SCEPs consisted of a small positive amplitude and a broad and high negative amplitude (NA). SCI resulted in an instant depression of the rostral NA that lasted for 1 h. However, the latency of NA continued to increase over time. At 5 h, spinal cord blood flow declined by 30% in the T9 segment, whereas the spinal cord water content and the permeability of the blood,spinal cord barrier (BSCB) were markedly increased. Damage to the nerve cells, glial cells, and myelin was quite common in the spinal cord, as seen by light and electron microscopy. Pretreatment with p -chlorophenylalanine, indomethacin, ibuprofen, and nimodipine attenuated the SCEP changes immediately after trauma and resulted in a marked reduction in edema formation, BSCB permeability, and blood flow changes at 5 h. However, pretreatment with cyproheptadine, dexamethasone, phentolamine, and propranolol failed to attenuate the SCEP changes after SCI and did not reduce the cord pathology. These observations suggest that early changes in SCEP reflect secondary injury-induced alterations in the cord microenvironment. Obviously, these changes are crucial in determining the ultimate magnitude and severity of cord pathology. © 2002 Wiley Periodicals, Inc. Muscle Nerve Supplement 11: S83,S91, 2002 [source] Changes in afferent activity after spinal cord injury,NEUROUROLOGY AND URODYNAMICS, Issue 1 2010William C. de Groat Abstract 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 (A,) 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. Neurourol. Urodynam. 29: 63,76, 2010. © 2009 Wiley-Liss, Inc. [source] Histomorphometric and Densitometric Changes in the Femora of Spinal Cord Transected MiceTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2008Sylvain Picard Abstract Spinal cord injury (SCI) leads generally to significant bone tissue loss within a few months to a few years post,trauma. Although, increasing data from rat models are available to study the underlying mechanisms of SCI-associated bone loss, little is known about the extent and rapidity of bone tissue changes in mouse models of SCI. The objectives are to characterize and describe quantitatively femoral bone tissue changes during 1 month in adult paraplegic mice. Histomorphometric and densitometric measurements were performed in 3- to 4-month-old CD1 mice spinal cord transected at the low-thoracic level (Th9/10). We found a general decrease in bone volume (,22%), trabecular thickness (,10%), and trabecular number (,14%) within 30 days post-transection. Dual-energy X-ray absorptiometric measurements revealed no change in bone mineral density but a significant reduction (,14%) in bone mineral content. These results show large structural changes occurring within only a few weeks post,spinal cord transection in the femora of adult mice. Given the increasing availability of genetic and molecular research tools for research in mice, this murine model may be useful to study further the cellular and molecular mechanisms of demineralization associated with SCI. Anat Rec, 291:303,307, 2008. © 2008 Wiley-Liss, Inc. [source] Erectile function and male reproduction in men with spinal cord injury: a reviewANDROLOGIA, Issue 3 2010F. Dimitriadis Summary Spinal cord injury (SCI) in men results in defects in erectile function, ejaculatory process and male reproductive potential. There are alterations in the capacity of men with SCI to achieve reflexogenic, psychogenic and nocturnal erections. The sexual function in different stages after SCI and the types of erections depend mainly on the completeness of the injury and the level of neurological damage. Furthermore, most of the SCI men demonstrate defects concerning the entrance of semen into the posterior urethra and the expulsion of the semen through the penile urethra and the urethral orifice. In addition, SCI men develop defects in the secretory function of the Leydig cells, Sertoli cells and the male accessory genital glands. The overall result is a decreased quality of the semen is recovered either with penile vibratory stimulation (PVS) or with electroejaculation. Nowadays the therapeutic andrological approach of SCI men focuses on achievement of erectile function, recovery of spermatozoa and assisted reproductive technology. The first line of therapy recommended for infertility in SCI men is collection of semen via PVS with concomitant evaluation of total motile sperm yields for assisted conception which may include intravaginal insemination, intrauterine insemination, or in vitro fertilisation/intracytoplasmic sperm injection. Patients failing PVS may be referred for electroejaculation or surgical sperm retrieval. [source] Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured ratsANNALS OF NEUROLOGY, Issue 1 2010Roman R. Gonzenbach MD Objective Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions. Methods and Results Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti,Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms. Interpretation The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect. ANN NEUROL 2010;68:48,57 [source] Protective role of aquaporin-4 water channels after contusion spinal cord injuryANNALS OF NEUROLOGY, Issue 6 2010Atsushi Kimura MD Objective Spinal cord injury (SCI) is accompanied by disruption of the blood-spinal cord barrier and subsequent extravasation of fluid and proteins, which results in edema (increased water content) at the site of injury. However, the mechanisms that control edema and the extent to which edema impacts outcome after SCI are not well elucidated. Methods Here, we examined the role of aquaporin-4 (AQP4) water channels after experimental contusion injury in mice, a clinically relevant animal model of SCI. Results Mice lacking AQP4 (AQP4,/, mice) exhibited significantly impaired locomotor function and prolonged bladder dysfunction compared with wild-type (WT) littermates after contusion SCI. Consistent with a greater extent of functional deterioration, AQP4,/, mice showed greater neuronal loss and demyelination, with prominent cyst formation, which is generally absent in mouse SCI. The extent of spinal cord edema, as expressed by percentage water content, was persistently increased above control levels in AQP4,/, mice but not WT mice at 14 and 28 days after injury. Immunohistochemical analysis indicated that blood vessels in the vicinity of the lesion core had incomplete barrier function because of sparse tight junctions. Interpretation These results suggest that AQP4 plays a protective role after contusion SCI by facilitating the clearance of excess water, and that targeting edema after SCI may be a novel therapeutic strategy. ANN NEUROL 2010;67:794,801 [source] Oral administration of a tri-therapy for central pattern generator activation in paraplegic mice: Proof-of-concept of efficacyBIOTECHNOLOGY JOURNAL, Issue 4 2010Pierre A. Guertin Dr. Abstract Spinal cord injury (SCI) is a neurological condition, for which no cure exists, typically leading to an immediate and irreversible loss of sensory and voluntary motor functions accompanied by significant health problems. We conducted proof-of-concept experiments aimed at assessing efficacy upon oral administration of a novel combination therapy for central pattern generator (CPG) activation and corresponding locomotor movement generation in completely paraplegic animals. Co-administration orally (by gavage) of buspirone, levodopa and carbidopa was found to dose-dependently induce episodes of steady weight-bearing stepping in low-thoracic (Th9/10) spinal cord-transected (Tx) mice (with no other form of assistance or training). Robust hindlimb stepping with weight-bearing capabilities was induced with the tri-therapy but not with clinically relevant doses of these compounds administered separately. These results provide evidence suggesting that this drug combination may be ideally suited to constitute a first-in-class therapy (CPG activator) for locomotor activity induction in chronic SCI individuals, given that efficacy was shown using commercially available brain-permeable small molecules, already known as safe for the treatment of various neurological indications. [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] Assessing the burden of injury in six European countriesCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 4 2007Richard Reading Assessing the burden of injury in six European countries . PolinderS, MeerdingWJ, MulderS, PetridouE, Van BeeckE, and EUROCOST Reference Group . ( 2007 ) Bulletin of the World Health Organization , 85 , 27 , 34 . Objective To assess injury-related mortality, disability and disability-adjusted life years (DALYs) in six European countries. Methods Epidemiological data (hospital discharge registers, emergency department registers, mortality databases) were obtained for Austria, Denmark, Ireland, Netherlands, Norway and the United Kingdom (England and Wales). For each country, the burden of injury was estimated in years lost due to premature mortality (YLL), years lived with disability (YLD), and DALYs (per 1000 persons). Findings We observed marked differences in the burden of injury between countries. Austria lost the largest number of DALYs (25 per 1000 persons), followed by Denmark, Norway and Ireland (17,20 per 1000 persons). In the Netherlands and the United Kingdom, the total burden due to injuries was relatively low (12 per 1000 persons). The variation between countries was attributable to a high variation in premature mortality (YLL varied from 9 to 17 per 1000 persons) and disability (YLD varied from 2 to 8 per 1000 persons). In all countries, males aged 25,44 years represented one-third of the total injury burden, mainly due to traffic and intentional injuries. Spinal cord injury and skull,brain injury resulted in the highest burden due to permanent disability. Conclusion The burden of injury varies considerably among the six participating European countries, but males aged 15,24 years are responsible for a disproportionate share of the assessed burden of injury in all countries. Consistent injury control policy is supported by high-quality summary measures of population health. There is an urgent need for standardized data on the incidence and functional consequences of injury. [source] Spinal cord injury at birth: a hidden causative factorACTA PAEDIATRICA, Issue 6 2008Jesper Fenger-Gron Abstract A case of perinatally acquired spinal cord injury (SCI) is presented. The foetus was vigorous until birth, the breech presented and delivery was performed by a non-traumatic Caesarean section. The infant displayed symptoms of severe SCI but diagnosis was delayed due to severe co-morbidity. Diagnostic considerations are briefly reviewed. Ventilatory support was withdrawn at the age of 20 days when the infant had still not exhibited any respiratory effort or spontaneous movements. Autopsy revealed a serious congenital malalignment of the upper cervical vertebrae and at the histological examination extensive reactive changes were observed in the same area. To our knowledge such findings have not been published previously. Conclusion: In cases of serious perinatally acquired SCI, claim of malpractice is often apparent. In this case a hidden congenital malformation of the cervical vertebrae was revealed, highlighting the need of careful postmortem examinations in such cases. [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] | |||||||||||||||||||||||||||||||||||||