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Sample records for acute spinal-cord ischemia

  1. Acute spinal cord ischemia during aortography treated with intravenous thrombolytic therapy.

    PubMed

    Restrepo, Lucas; Guttin, Jorge F

    2006-01-01

    Acute anterior spinal cord ischemia is a rare but disastrous complication of endovascular aortic procedures. Although intravenous thrombolysis with recombinant tissue plasminogen activator is an effective treatment for acute brain ischemia, its use for the treatment of spinal cord ischemia has not previously been reported. We report the case of a patient who developed anterior spinal cord ischemia during diagnostic aortography He was treated with intravenous recombinant tissue plasminogen activator within 3 hours after the onset of symptoms. The patient had a rapid neurologic improvement and was discharged from the hospital 3 days after thrombolysis, regaining his ability to walk unassisted. We propose that acute spinal cord ischemia can be treated with intravenous recombinant tissue plasminogen activator within 3 hours after the onset of symptoms, as can any other case of acute ischemic stroke.

  2. Acute central cervical spinal cord syndrome.

    PubMed

    Morse, S D

    1982-08-01

    Two cases of the acute central cervical spinal cord syndrome are presented. A 63-year-old diabetic hypertensive man manifested the syndrome as a result of atraumatic ischemia of the cord. A 32-year-old health man developed it after sustaining a hyperextension injury in a baseball game. The pathogenesis and pathophysiology of this entity are reviewed. Knowledge of this entity is of major importance in the analysis and management of head and neck trauma, as well as in the recognition and management of atraumatic neurologic dysfunction due to ischemia, hemorrhage, or thrombosis.

  3. Advance in spinal cord ischemia reperfusion injury: Blood-spinal cord barrier and remote ischemic preconditioning.

    PubMed

    Yu, Qijing; Huang, Jinxiu; Hu, Ji; Zhu, Hongfei

    2016-06-01

    The blood-spinal cord barrier (BSCB) is the physiological and metabolic substance diffusion barrier between blood circulation and spinal cord tissues. This barrier plays a vital role in maintaining the microenvironment stability of the spinal cord. When the spinal cord is subjected to ischemia/reperfusion (I/R) injury, the structure and function of the BSCB is disrupted, further destroying the spinal cord homeostasis and ultimately leading to neurological deficit. Remote ischemic preconditioning (RIPC) is an approach in which interspersed cycles of preconditioning ischemia is followed by reperfusion to tissues/organs to protect the distant target tissues/organs against subsequent lethal ischemic injuries. RIPC is an innovation of the treatment strategies that protect the organ from I/R injury. In this study, we review the morphological structure and function of the BSCB, the injury mechanism of BSCB resulting from spinal cord I/R, and the effect of RIPC on it.

  4. Optical Monitoring and Detection of Spinal Cord Ischemia

    PubMed Central

    Mesquita, Rickson C.; D’Souza, Angela; Bilfinger, Thomas V.; Galler, Robert M.; Emanuel, Asher; Schenkel, Steven S.; Yodh, Arjun G.; Floyd, Thomas F.

    2013-01-01

    Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings. PMID:24358279

  5. The Neuroprotective Effect of Syringic Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats.

    PubMed

    Tokmak, Mehmet; Yuksel, Yasemin; Sehitoglu, Muserref Hilal; Guven, Mustafa; Akman, Tarik; Aras, Adem Bozkurt; Cosar, Murat; Abbed, Khalid M

    2015-10-01

    Acute arterial occlusions via different vascular pathologies are the main causes of spinal cord ischemia. We investigated neuroprotective effects of syringic acid on spinal cord ischemia injury in rats. Rats were divided into four groups: (I) sham-operated control rats, (II) spinal cord ischemia group, (III) spinal cord ischemia group performed syringic acid, and (IV) spinal cord ischemia group performed methylprednisolone intraperitoneally. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. A significant decrease was seen in malondialdehyde levels in group III as compared to group II (P < 0.05). Besides these, nuclear respiratory factor-1 and superoxide dismutase activity of group III were significantly higher than group II (P < 0.05). In histopathological samples, when group III was compared with group II, there was a significant decrease in numbers of apoptotic neurons (P < 0.05). In immunohistochemical staining, BECN1 and caspase-3-immunopositive neurons were significantly decreased in group III compared with group II (P < 0.05). The neurological deficit scores of group III were significantly higher than group II at twenty-fourth hour of ischemia (P < 0.05). Our study revealed that syringic acid pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required for syringic acid to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

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

    PubMed Central

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

    2015-01-01

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

  7. Spinal Cord Stimulation for Chronic Limb Ischemia

    PubMed Central

    Naoum, Joseph J.; Arbid, Elias J.

    2013-01-01

    The treatment of chronic limb ischemia involves the restoration of pulsatile blood flow to the distal extremity. Some patients cannot be treated with endovascular means or with open surgery; some may have medical comorbidities that render them unfit for surgery, while others may have persistent ischemia or pain even in the face of previous attempts at reperfusion. In spinal cord stimulation (SCS), a device with electrodes is implanted in the epidural space to stimulate sensory fibers. This activates cell-signaling molecules that in turn cause the release of vasodilatory molecules, a decrease in vascular resistance, and relaxation of smooth muscle cells. SCS also suppresses sympathetic vasoconstriction and pain transmission. When patient selection is based on microcirculatory parameters, SCS therapy can significantly improve pain relief, halt the progression of ulcers, and potentially achieve limb salvage. PMID:23805343

  8. Critical ischemia time in a model of spinal cord section. A study performed on dogs

    PubMed Central

    Garcia Martinez, David; Rosales Corral, Sergio A.; Flores Soto, Mario E.; Velarde Silva, Gustavo; Portilla de Buen, Eliseo

    2006-01-01

    Vascular changes after acute spinal cord trauma are important factors that predispose quadriplegia, in most cases irreversible. Repair of the spinal blood flow helps the spinal cord recovery. The average time to arrive and perform surgery is 3 h in most cases. It is important to determine the critical ischemia time in order to offer better functional prognosis. A spinal cord section and vascular clamping of the spinal anterior artery at C5–C6 model was used to determine critical ischemia time. The objective was to establish a critical ischemia time in a model of acute spinal cord section. Four groups of dogs were used, anterior approach and vascular clamp of spinal anterior artery with 1, 2, 3, and 4 h of ischemia and posterior hemisection of spinal cord at C5–C6 was performed. Clinical evaluation was made during 12 weeks and morphological evaluation at the end of this period. We obtained a maximal neurological coordination at 23 days average. Two cases showed sequels of right upper limb paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h of ischemia. Morphological examination showed 25% of damaged area. The VIII and IX Rexed’s laminae were the most affected. The critical ischemia time was 3 h. Dogs with 4 h did not exhibit any recovery. PMID:17024402

  9. Targeting the blood-spinal cord barrier: A therapeutic approach to spinal cord protection against ischemia-reperfusion injury.

    PubMed

    Hu, Ji; Yu, Qijing; Xie, Lijie; Zhu, Hongfei

    2016-08-01

    One of the principal functions of physical barriers between the blood and central nervous system protects system (i.e., blood brain barrier and blood-spinal cord barrier) is the protection from toxic and pathogenic agents in the blood. Disruption of blood-spinal cord barrier (BSCB) plays a key role in spinal cord ischemia-reperfusion injury (SCIRI). Following SCIRI, the permeability of the BSCB increases. Maintaining the integrity of the BSCB alleviates the spinal cord injury after spinal cord ischemia. This review summarizes current knowledge of the structure and function of the BSCB and its changes following SCIRI, as well as the prevention and cure of SCIRI and the role of the BSCB.

  10. Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption

    PubMed Central

    Fang, Bo; Li, Xiao-Man; Sun, Xi-Jia; Bao, Na-Ren; Ren, Xiao-Yan; Lv, Huang-Wei; Ma, Hong

    2013-01-01

    Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan’s Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-α (TNF-α) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-α mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-α expression. PMID:23685868

  11. [Pre-hospital care management of acute spinal cord injury].

    PubMed

    Hess, Thorsten; Hirschfeld, Sven; Thietje, Roland; Lönnecker, Stefan; Kerner, Thoralf; Stuhr, Markus

    2016-04-01

    Acute injury to the spine and spinal cord can occur both in isolation as also in the context of multiple injuries. Whereas a few decades ago, the cause of paraplegia was almost exclusively traumatic, the ratio of traumatic to non-traumatic causes in Germany is currently almost equivalent. In acute treatment of spinal cord injury, restoration and maintenance of vital functions, selective control of circulation parameters, and avoidance of positioning or transport-related additional damage are in the foreground. This article provides information on the guideline for emergency treatment of patients with acute injury of the spine and spinal cord in the preclinical phase. PMID:27070515

  12. Acute complications of spinal cord injuries

    PubMed Central

    Hagen, Ellen Merete

    2015-01-01

    The aim of this paper is to give an overview of acute complications of spinal cord injury (SCI). Along with motor and sensory deficits, instabilities of the cardiovascular, thermoregulatory and broncho-pulmonary system are common after a SCI. Disturbances of the urinary and gastrointestinal systems are typical as well as sexual dysfunction. Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature control and disturbance of sweating, vasodilatation and autonomic dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic response, elicited by stimuli below the level of injury. The symptoms may be mild like skin rash or slight headache, but can cause severe hypertension, cerebral haemorrhage and death. All personnel caring for the patient should be able to recognize the symptoms and be able to intervene promptly. Disturbance of respiratory function are frequent in tetraplegia and a primary cause of both short and long-term morbidity and mortality is pulmonary complications. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent complications which need to be addressed. The psychological stress associated with SCI may lead to anxiety and depression. Knowledge of possible complications during the acute phase is important because they may be life threatening and/ or may lead to prolonged rehabilitation. PMID:25621207

  13. [SCS (spinal cord stimulation) in severe ischemia of the legs].

    PubMed

    Polisca, R; Domenichini, M; Signoretti, P; Marchi, P

    1992-01-01

    Spinal cord stimulation (SCS) of the low thoracic spinal epidural space was carried out in 11 patients with pain from peripheral arterial disease of the lower limbs. Conservative treatment or vasoactive drugs also failed. Results are reported relating to pain, exercise endurance on the bicycle ergometer, trophic lesion changes and TCpO2. After a mean postimulation follow-up period of 15 months, substantial pain relief was preoperative non healing skin ulcerations, but gangrenous conditions were not benefited. Exercise tolerance as measured on a bicycle ergometer increased by 40%. It is concluded that SCS is vary promising in severe limb ischemia where reconstruction surgery is not possible or has been unsuccessful.

  14. Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injury

    PubMed Central

    Wang, Baogang; Zhu, Qingsan; Man, Xiaxia; Guo, Li; Hao, Liming

    2014-01-01

    Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-dependently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reperfusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression. PMID:25374589

  15. [Spinal cord ischemia following subrenal aortic clamping].

    PubMed

    Battisti, G; Marigliani, M; Stio, F; Iavarone, C

    1990-01-01

    The paraplegia caused by an aortic clamping just below the Renal artery is a rare but very complication in aortic surgery. Such a complication is even rarer if we consider the few cases reported in literature following a reconstructive surgery for occlusive chronic diseases of aortiliac axes. The authors have studied the case of a patient bearing the syndrome of Leriche; this one had an aortic clamping below the kidney and soon after developed an acute ischaemic syndrome below the spinal medulla with flaccid paraparesis, anal and vesical sphincteric diseases and persistence of deep tactile sensibility. After a reconstruction of vascular anatomy of the medulla they emphasize the importance, in such a disease, of the "arteria radicularis magna" of Adamkievicz and its place of origin. After they discuss the severe physioopathologic moments that are connected: with the direct ischaemia following aortic clamping in the cases where the arteria radicularis magna rises at a level lower than the clamping itself; with the embolism or thrombosis caused by surgical manipulation peroperatively (it might be the cause of paraplegia more frequent in aneurysmectomia surgery); with the severe hypotension per- and post operatively for the existence of arteriosclerotic disease of the lumbar arteries. Finally they analyses preoperatively diagnostic possibilities and per operatively methods used in preventing this sort of complication.

  16. Imaging of Spinal Cord Injury: Acute Cervical Spinal Cord Injury, Cervical Spondylotic Myelopathy, and Cord Herniation.

    PubMed

    Talekar, Kiran; Poplawski, Michael; Hegde, Rahul; Cox, Mougnyan; Flanders, Adam

    2016-10-01

    We review the pathophysiology and imaging findings of acute traumatic spinal cord injury (SCI), cervical spondylotic myelopathy, and briefly review the much less common cord herniation as a unique cause of myelopathy. Acute traumatic SCI is devastating to the patient and the costs to society are staggering. There are currently no "cures" for SCI and the only accepted pharmacologic treatment regimen for traumatic SCI is currently being questioned. Evaluation and prognostication of SCI is a demanding area with significant deficiencies, including lack of biomarkers. Accurate classification of SCI is heavily dependent on a good clinical examination, the results of which can vary substantially based upon the patient׳s condition or comorbidities and the skills of the examiner. Moreover, the full extent of a patients׳ neurologic injury may not become apparent for days after injury; by then, therapeutic response may be limited. Although magnetic resonance imaging (MRI) is the best imaging modality for the evaluation of spinal cord parenchyma, conventional MR techniques do not appear to differentiate edema from axonal injury. Recently, it is proposed that in addition to characterizing the anatomic extent of injury, metrics derived from conventional MRI and diffusion tensor imaging, in conjunction with the neurological examination, can serve as a reliable objective biomarker for determination of the extent of neurologic injury and early identification of patients who would benefit from treatment. Cervical spondylosis is a common disorder affecting predominantly the elderly with a potential to narrow the spinal canal and thereby impinge or compress upon the neural elements leading to cervical spondylotic myelopathy and radiculopathy. It is the commonest nontraumatic cause of spinal cord disorder in adults. Imaging plays an important role in grading the severity of spondylosis and detecting cord abnormalities suggesting myelopathy.

  17. Imaging of Spinal Cord Injury: Acute Cervical Spinal Cord Injury, Cervical Spondylotic Myelopathy, and Cord Herniation.

    PubMed

    Talekar, Kiran; Poplawski, Michael; Hegde, Rahul; Cox, Mougnyan; Flanders, Adam

    2016-10-01

    We review the pathophysiology and imaging findings of acute traumatic spinal cord injury (SCI), cervical spondylotic myelopathy, and briefly review the much less common cord herniation as a unique cause of myelopathy. Acute traumatic SCI is devastating to the patient and the costs to society are staggering. There are currently no "cures" for SCI and the only accepted pharmacologic treatment regimen for traumatic SCI is currently being questioned. Evaluation and prognostication of SCI is a demanding area with significant deficiencies, including lack of biomarkers. Accurate classification of SCI is heavily dependent on a good clinical examination, the results of which can vary substantially based upon the patient׳s condition or comorbidities and the skills of the examiner. Moreover, the full extent of a patients׳ neurologic injury may not become apparent for days after injury; by then, therapeutic response may be limited. Although magnetic resonance imaging (MRI) is the best imaging modality for the evaluation of spinal cord parenchyma, conventional MR techniques do not appear to differentiate edema from axonal injury. Recently, it is proposed that in addition to characterizing the anatomic extent of injury, metrics derived from conventional MRI and diffusion tensor imaging, in conjunction with the neurological examination, can serve as a reliable objective biomarker for determination of the extent of neurologic injury and early identification of patients who would benefit from treatment. Cervical spondylosis is a common disorder affecting predominantly the elderly with a potential to narrow the spinal canal and thereby impinge or compress upon the neural elements leading to cervical spondylotic myelopathy and radiculopathy. It is the commonest nontraumatic cause of spinal cord disorder in adults. Imaging plays an important role in grading the severity of spondylosis and detecting cord abnormalities suggesting myelopathy. PMID:27616315

  18. Hyperbaric oxygen preconditioning attenuates early apoptosis after spinal cord ischemia in rats.

    PubMed

    Wang, Liping; Li, Wenxian; Kang, Zhimin; Liu, Yun; Deng, Xiaoming; Tao, Hengyi; Xu, Weigang; Li, Runping; Sun, Xuejun; Zhang, John H

    2009-01-01

    This study tested the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning (HBO-PC) is mediated by inhibition of early apoptosis. Male Sprague-Dawley rats were preconditioned with consecutive 4 cycles of 1-h HBO exposures (2.5 atmospheres absolute [ATA], 100% O(2)) at a 12-h interval. At 24 h after the last HBO pretreatment, rats underwent 9 min of spinal cord ischemia induced by occlusion of the descending thoracic aorta in combination with systemic hypotension (40 mmHg). Spinal cord ischemia produced marked neuronal death and neurological dysfunction in animals. HBO-PC enhanced activities of Mn-superoxide dismutase (Mn-SOD) and catalase, as well as the expression of Bcl-2 in the mitochondria in the normal spinal cord at 24 h after the last pretreatment (before spinal cord ischemia), and retained higher levels throughout the early reperfusion in the ischemic spinal cord. In parallel, superoxide and hydrogen peroxide levels in mitochondria were decreased, cytochrome c release into the cytosol was reduced at 1 h after reperfusion, and activation of caspase-3 and -9 was subsequently attenuated. HBO-PC improved neurobehavioral scores and reduced neuronal apoptosis in the anterior, intermediate, and dorsal gray matter of lumbar segment at 24 h after spinal cord ischemia. HBO-PC increased nitric oxide (NO) production. L-nitroarginine-methyl-ester (L-NAME; 10 mg/kg), a nonselective NO synthase (NOS) inhibitor, applied before each HBO-PC protocol abolished these beneficial effects of HBO-PC. We conclude that HBO-PC reduced spinal cord ischemia-reperfusion injury by increasing Mn-SOD, catalase, and Bcl-2, and by suppressing mitochondrial apoptosis pathway. NO may be involved in this neuroprotection. PMID:19196076

  19. Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits.

    PubMed

    Liu, Bingbing; Huang, Weihua; Xiao, Xiaoshan; Xu, Yao; Ma, Songmei; Xia, Zhengyuan

    2015-01-01

    Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties.

  20. Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

    PubMed Central

    Liu, Bingbing; Huang, Weihua; Xiao, Xiaoshan; Xu, Yao; Ma, Songmei; Xia, Zhengyuan

    2015-01-01

    Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties. PMID:26161241

  1. Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

    PubMed Central

    Zhang, Nannan; Ding, Shinghua

    2015-01-01

    Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy. PMID:26274772

  2. Adenine nucleotide levels and regional distribution of ATP in rabbit spinal cord after ischemia and recirculation.

    PubMed

    Danielisová, V; Chavko, M; Kehr, J

    1987-03-01

    Rabbit spinal cords were subjected to 10 to 40 minutes of ischemia with and without 4 days of recirculation and L-4 segment was analyzed for adenylates and ATP-induced bioluminiscence. ATP level and energy charge was progressively reduced by increasing durations of ischemia. Regional evaluation of ATP-induced bioluminiscence after 10 and 20 minutes of ischemia revealed ATP depletion mainly in the gray matter of spinal cord. Forty minutes of ischemia resulted in complete reduction of ATP bioluminiscence in both gray and white matter. Within 4 days of recirculation following all periods of ischemia studied, only partial metabolic recovery occurred. Restitution of ATP-induced bioluminiscence was regionally heterogeneous, reduced predominantly in the anterior horns of gray matter.

  3. Current concepts in the immediate management of acute spinal cord injuries.

    PubMed Central

    Tator, C H; Rowed, D W

    1979-01-01

    The management of acute spinal cord injuries has changed considerably during the past 10 years owing to new information about the pathophysiology of cord trauma and new diagnostic and treatment methods. It is now known that the cord suffers not only from the immediate physical effects of trauma, but also from secondary pathologic processes, such as ischemia and edema, which are treatable in the first few hours after injury. New neuroradiologic and neurophysiological techniques, such as the recording of the somatosensory evoked potential, increase the accuracy of diagnosis and prognosis in the acute phase. Current immediate treatment includes the administration of steroids and mannitol, with careful attention to respiratory and cardiovascular homeostasis, to overcome post-traumatic ischemia and edema, and immobilization of the spine with devices such as the halo. New surgical procedures are used in selected cases to improve neurologic recovery, to provide rigid immobilization of the spine or to allow earlier mobilization of the patient. The care of spinal cord injuries in the acute phase is facilitated by multidisciplinary units. Images FIG. 1A FIG. 1B FIG. 3 PMID:117894

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

    PubMed Central

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

    2016-01-01

    Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care. PMID:27482201

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

    PubMed

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

    2016-06-01

    Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care. PMID:27482201

  6. Ischemia-reperfusion model in rat spinal cord: cell viability and apoptosis signaling study

    PubMed Central

    de Lavor, Mário Sérgio Lima; Binda, Nancy Scardua; Fukushima, Fabíola Bono; Caldeira, Fátima Maria Caetano; da Silva, Juliana Figueira; Silva, Carla Maria Osório; de Oliveira, Karen Maciel; Martins, Bernardo de Caro; Torres, Bruno Benetti Junta; Rosado, Isabel Rodrigues; Gomez, Renato Santiago; Gomez, Marcus Vinícius; de Melo, Eliane Gonçalves

    2015-01-01

    This work aimed at determining the ideal ischemia time in an in vitro ischemia-reperfusion model of spinal cord injury. Rat spinal cord slices were prepared and then exposed or not to oxygen deprivation and low glucose (ODLG) for 30, 45, 60, 75 and 90 minutes. Cell viability was assessed by triphenyltetrazolium (TTC), lactate dehydrogenase (LDH) release, and fluorochrome dyes specific for cell dead (ethidium homodimer) using the apotome system. Glutamate release was enzymatically measured by a fluorescent method. Gene expression of apoptotic factors was assessed by real time RT-PCR. Whereas spinal cord slices exposed to ODLG exhibited mild increase in fluorescence for 30 minutes after the insult, the 45, 60, 75 and 90 minutes caused a 2-fold increase. ODLG exposure for 45, 60, 75 or 90 minutes, glutamate and LDH release were significantly elevated. nNOS mRNA expression was overexpressed for 45 minutes and moderately increased for 60 minutes in ODLG groups. Bax/bcl-xl ratio, caspase 9 and caspase 3 mRNA expressions were significantly increased for 45 minutes of ODLG, but not for 30, 60, 75 and 90 minutes. Results showed that cell viability reduction in the spinal cord was dependent on ischemic time, resulting in glutamate and LDH release. ODLG for 45 minutes was adequate for gene expression evaluation of proteins and proteases involved in apoptosis pathways. PMID:26617703

  7. Epidural spinal cord stimulation in chronic non-reconstructible limb ischemia.

    PubMed

    Neuhauser; Greiner; Kofler; Perkmann

    2004-04-01

    For patients with chronic non-reconstructible limb ischemia (chronic CLI), spinal-cord stimulation (SCS) has been advocated for the treatment of ischemic pain and prevention of amputation. The present clinical report was performed to evaluate the long-term effects of SCS on limb survival. A retrospective review was performed of 21 patients who had undergone SCS between December 1997 and July 2002 due to chronic CLI. The impulse generator used was the Itrel device (Medtronic, Inc). All conventional methods for revascularization and improvement of microcirculatory blood flow had been performed prior to SCS treatment. Patient selection was performed by clinical examination, pulse volume records, Doppler ankle/brachial measurements, angiography, and thoracic spine and lumbar spine x-ray. Since July 2000, additional TcpO2 measurements at the dorsum of the foot have been performed. SCS implantation was performed as a one-stage procedure in all cases. Patients are followed up to 57 months. Of 21 patients with chronic CLI, 20 (95%) were available for follow-up investigations. Four patients died one to fifteen months after implantation due to acute renal failure or myocardial infarction (19%). Major amputation could be avoided in 15 (71%) of 21 patients. Two electrode dislocation, one pulse-generator dislocation, and one wire disconnection occurred; no other complications were observed. SCS represents a safe and effective therapy for patients with chronic non-reconstructible critical limb ischemia.

  8. Sponge-mediated Lentivirus Delivery to Acute and Chronic Spinal Cord Injuries

    PubMed Central

    Thomas, Aline M.; Palma, Jaime L.; Shea, Lonnie D.

    2015-01-01

    The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are have are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration. PMID:25724274

  9. Sponge-mediated lentivirus delivery to acute and chronic spinal cord injuries.

    PubMed

    Thomas, Aline M; Palma, Jaime L; Shea, Lonnie D

    2015-04-28

    The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration.

  10. Time representation of mitochondrial morphology and function after acute spinal cord injury.

    PubMed

    Jia, Zhi-Qiang; Li, Gang; Zhang, Zhen-Yu; Li, Hao-Tian; Wang, Ji-Quan; Fan, Zhong-Kai; Lv, Gang

    2016-01-01

    Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2-24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2-24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na(+)-K(+)-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.

  11. Time representation of mitochondrial morphology and function after acute spinal cord injury

    PubMed Central

    Jia, Zhi-qiang; Li, Gang; Zhang, Zhen-yu; Li, Hao-tian; Wang, Ji-quan; Fan, Zhong-kai; Lv, Gang

    2016-01-01

    Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged. PMID:26981103

  12. Coronary slow flow and acute coronary syndrome in a patient with spinal cord injury.

    PubMed

    Aktoz, Meryem; Tatli, Ersan; Barutcu, Ahmet; Ozkalayci, Flora; Umit, Elif; Altun, Armagan

    2011-01-01

    We report the case of a 55-year-old man who presented with acute coronary syndrome due to coronary slow flow after spinal cord injury. Data regarding the causes and clinical manifestations of coronary slow flow are inconclusive, but the autonomic nervous system is believed to be at least a contributing factor. The predominant vagal activity causes vasodilation and hemostasis, which can lead to acute coronary syndrome. We hereby call attention to hyperactive parasympathetic tonicity, which can lead to coronary slow flow and acute coronary syndrome in acute spinal cord injury patients. PMID:21841878

  13. Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia.

    PubMed

    Garbuzova-Davis, Svitlana; Haller, Edward; Tajiri, Naoki; Thomson, Avery; Barretta, Jennifer; Williams, Stephanie N; Haim, Eithan D; Qin, Hua; Frisina-Deyo, Aric; Abraham, Jerry V; Sanberg, Paul R; Van Loveren, Harry; Borlongan, Cesario V

    2016-07-01

    We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction. PMID:27283328

  14. 1H-MRS in spinal cord injury: acute and chronic metabolite alterations in rat brain and lumbar spinal cord

    PubMed Central

    Erschbamer, Matthias; Öberg, Johanna; Westman, Eric; Sitnikov, Rouslan; Olson, Lars; Spenger, Christian

    2011-01-01

    A variety of tests of sensorimotor function are used to characterize outcome after experimental spinal cord injury (SCI). These tests typically do not provide information about chemical and metabolic processes in the injured CNS. Here, we used 1H-magnetic resonance spectroscopy (MRS) to monitor long-term and short-term chemical changes in the CNS in vivo following SCI. The investigated areas were cortex, thalamus/striatum and the spinal cord distal to injury. In cortex, glutamate (Glu) decreased 1 day after SCI and slowly returned towards normal levels. The combined glutamine (Gln) and Glu signal was similarly decreased in cortex, but increased in the distal spinal cord, suggesting opposite changes of the Glu/Gln metabolites in cortex and distal spinal cord. In lumbar spinal cord, a marked increase of myo-inositol was found 3 days, 14 days and 4 months after SCI. Changes in metabolite concentrations in the spinal cord were also found for choline and N-acetylaspartate. No significant changes in metabolite concentrations were found in thalamus/striatum. Multivariate data analysis allowed separation between rats with SCI and controls for spectra acquired in cortex and spinal cord, but not in thalamus/striatum. Our findings suggest MRS could become a helpful tool to monitor spatial and temporal alterations of metabolic conditions in vivo in the brain and spinal cord after SCI. We provide evidence for dynamic temporal changes at both ends of the neuraxis, cortex cerebri and distal spinal cord, while deep brain areas appear less affected. PMID:21251091

  15. Cell elimination as a strategy for repair in acute spinal cord injury.

    PubMed

    Kalderon, Nurit

    2005-01-01

    Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later stages of wound healing (the third week after injury) triggering chronic inflammation and progressive tissue decay that is the characteristic pathology of spinal cord injury. Specific cell elimination within a critical time window after injury can lead to repair in the acutely injured spinal cord. Cell proliferation events can be manipulated/modified by x-irradiation. Clinically, numerous radiation protocols (i.e., radiation therapy) have been developed that specifically eliminate the rapidly dividing cells without causing any noticeable/significant damage to the tissue as a whole. Radiation therapy when applied within the critical time window after injury prevents the onset of chronic inflammation thus leading to repair of structure and function. Various aspects of the development of this cell-elimination strategy for repair in acute spinal cord injury by utilizing radiation therapy are being reviewed. Topics reviewed here: identifying the window of opportunity; and the beneficial repair effects of radiation therapy in a transection injury model and in a model relevant to human injury, the contusion injury model. The possible involvement of cellular components of the blood-spinal cord barrier as the trigger of chronic inflammation and/or target of the radiation therapy is discussed. PMID:15853680

  16. Intravenous infusion of magnesium chloride improves epicenter blood flow during the acute stage of contusive spinal cord injury in rats.

    PubMed

    Muradov, Johongir M; Hagg, Theo

    2013-05-15

    Vasospasm, hemorrhage, and loss of microvessels at the site of contusive or compressive spinal cord injury lead to infarction and initiate secondary degeneration. Here, we used intravenous injection of endothelial-binding lectin followed by histology to show that the number of perfused microvessels at the injury site is decreased by 80-90% as early as 20 min following a moderate T9 contusion in adult female rats. Hemorrhage within the spinal cord also was maximal at 20 min, consistent with its vasoconstrictive actions in the central nervous system (CNS). Microvascular blood flow recovered to up to 50% of normal volume in the injury penumbra by 6 h, but not at the epicenter. A comparison with an endothelial cell marker suggested that many microvessels fail to be reperfused up to 48 h post-injury. The ischemia was probably caused by vasospasm of vessels penetrating the parenchyma, because repeated Doppler measurements over the spinal cord showed a doubling of total blood flow over the first 12 h. Moreover, intravenous infusion of magnesium chloride, used clinically to treat CNS vasospasm, greatly improved the number of perfused microvessels at 24 and 48 h. The magnesium treatment seemed safe as it did not increase hemorrhage, despite the improved parenchymal blood flow. However, the treatment did not reduce acute microvessel, motor neuron or oligodendrocyte loss, and when infused for 7 days did not affect functional recovery or spared epicenter white matter over a 4 week period. These data suggest that microvascular blood flow can be restored with a clinically relevant treatment following spinal cord injury.

  17. Role of autophagy in the bimodal stage after spinal cord ischemia reperfusion injury in rats.

    PubMed

    Fang, Bo; Li, Xiao-Qian; Bao, Na-Ren; Tan, Wen-Fei; Chen, Feng-Shou; Pi, Xiao-Li; Zhang, Ying; Ma, Hong

    2016-07-22

    Autophagy plays an important role in spinal cord ischemia reperfusion (I/R) injury, but its neuroprotective or neurodegenerative role remains controversial. The extent and persistence of autophagy activation may be the critical factor to explain the opposing effects. In this study, the different roles and action mechanisms of autophagy in the early and later stages after I/R injury were investigated in rats. Thespinal cord I/R injury was induced by 14-min occlusion of the aortic arch, after which rats were treated with autophagic inhibitor (3-methyladenine, 3-MA) or agonist (rapamycin) immediately or 48h following the injury. Autophagy markers, microtubule-associated protein light chain 3-II (LC3-II) and Beclin 1 increased and peaked at the early stage (8h) and the later stage (72h) after spinal cord I/R injury. Beclin 1 was mostly expressed in neurons, but was also expressed to an extent in astrocytes, microglia and vascular endothelial cells. 8h after injury, rats treated with 3-MA showed a decrease in the hind-limb Basso-Beattie-Bresnahan (BBB) motor function scores, surviving motor neurons, and B-cell lymphoma-2 (Bcl-2) expression, and increase in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, Bcl-2-associated X protein (Bax), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) expression, and activation of microglia, while those treated with rapamycin showed opposing effects. However, 72h after injury, rats treated with 3-MA improved the BBB scores, and the surviving motor neurons, and reduced the autophagic cell death, while those treated with rapamycin had adverse effects. These findings provide the first evidence that early activated autophagy alleviates spinal cord I/R injury via inhibiting apoptosis and inflammation; however later excessively elevated autophagy aggravates I/R injury through inducing autophagic cell death. PMID:27109922

  18. Role of autophagy in the bimodal stage after spinal cord ischemia reperfusion injury in rats.

    PubMed

    Fang, Bo; Li, Xiao-Qian; Bao, Na-Ren; Tan, Wen-Fei; Chen, Feng-Shou; Pi, Xiao-Li; Zhang, Ying; Ma, Hong

    2016-07-22

    Autophagy plays an important role in spinal cord ischemia reperfusion (I/R) injury, but its neuroprotective or neurodegenerative role remains controversial. The extent and persistence of autophagy activation may be the critical factor to explain the opposing effects. In this study, the different roles and action mechanisms of autophagy in the early and later stages after I/R injury were investigated in rats. Thespinal cord I/R injury was induced by 14-min occlusion of the aortic arch, after which rats were treated with autophagic inhibitor (3-methyladenine, 3-MA) or agonist (rapamycin) immediately or 48h following the injury. Autophagy markers, microtubule-associated protein light chain 3-II (LC3-II) and Beclin 1 increased and peaked at the early stage (8h) and the later stage (72h) after spinal cord I/R injury. Beclin 1 was mostly expressed in neurons, but was also expressed to an extent in astrocytes, microglia and vascular endothelial cells. 8h after injury, rats treated with 3-MA showed a decrease in the hind-limb Basso-Beattie-Bresnahan (BBB) motor function scores, surviving motor neurons, and B-cell lymphoma-2 (Bcl-2) expression, and increase in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, Bcl-2-associated X protein (Bax), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) expression, and activation of microglia, while those treated with rapamycin showed opposing effects. However, 72h after injury, rats treated with 3-MA improved the BBB scores, and the surviving motor neurons, and reduced the autophagic cell death, while those treated with rapamycin had adverse effects. These findings provide the first evidence that early activated autophagy alleviates spinal cord I/R injury via inhibiting apoptosis and inflammation; however later excessively elevated autophagy aggravates I/R injury through inducing autophagic cell death.

  19. Electroacupuncture attenuates cervical spinal cord injury following cerebral ischemia/reperfusion in stroke-prone renovascular hypertensive rats

    PubMed Central

    TAN, FENG; CHEN, JIE; LIANG, YANGUI; GU, MINHUA; LI, YANPING; WANG, XUEWEN; MENG, DI

    2014-01-01

    Cerebral ischemia induces injury, not only in the ischemic core and surrounding penumbra tissues, but also in remote areas such as the cervical spinal cord. The aim of the present study was to determine the effects of electroacupuncture (EA) on cervical spinal cord injury following cerebral ischemia/reperfusion in stroke-prone renovascular hypertensive (RHRSP) rats. The results demonstrated that neuronal loss, which was assayed by Nissl staining in the cervical spinal cords of RHRSP rats subjected to transient middle cerebral artery occlusion (MCAO), was markedly decreased by EA stimulation at the GV20 (Baihui) and GV14 (Dazhui) acupoints compared with that in rats undergoing sham stimulation. Quantitative polymerase chain reaction and western blot analysis demonstrated that EA stimulation blocked the MCAO-induced elevated protein expression levels of glial fibrillary acidic protein and amyloid precursor protein in the cervical spinal cord at days 24 and 48. To further investigate the mechanism underlying the neuroprotective role of EA stimulation, the protein expression levels of Nogo-A and Nogo-66 receptor-1 (NgR1), two key regulatory molecules for neurite growth, were recorded in each group. The results revealed that EA stimulation reduced the MCAO-induced elevation of Nogo-A and NgR1 protein levels at day 14 and 28 in RHRSP rats. Therefore, the results demonstrated that EA reduced cervical spinal cord injury following cerebral ischemia in RHRSP rats, indicating that EA has the potential to be developed as a therapeutic treatment agent for cervical spinal cord injury following stroke. PMID:24926338

  20. Quantifying the internal deformation of the rodent spinal cord during acute spinal cord injury - the validation of a method.

    PubMed

    Bhatnagar, Tim; Liu, Jie; Yung, Andrew; Cripton, Peter; Kozlowski, Piotr; Tetzlaff, Wolfram; Oxland, Thomas

    2016-01-01

    Visualization and analysis of the rodent spinal cord subject to experimental spinal cord injury (SCI) has almost completely been limited to naked-eye observations, and a single measure of gross spinal cord motion due to injury. This study introduces a novel method which utilizes MRI to quantify the deformation of the rodent spinal cord due to imposed, clinically-relevant injuries - specifically, cervical contusion and dislocation mechanisms. The image registration methods were developed using the Advanced Normalization Tools package, which incorporate rigid, affine and deformable registration steps. The proposed method is validated against a fiducial-based, 'gold-standard' measure of spinal cord tissue motion. The validation analysis yielded accuracy (and precision) values of 62 μm (49 μm), 73 μm (79 μm) and 112 μm (110 μm), for the medio-lateral, dorso-ventral and cranio-caudal directions, respectively. The internal morphological change of the spinal cord has never before been quantified, experimentally. This study demonstrates the capability of this method and its potential for future application to in vivo rodent models of SCI.

  1. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure. PMID:25687701

  2. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure.

  3. Spinal cord stimulation for patients with inoperable chronic critical leg ischemia

    PubMed Central

    Chen, Xiao-pei; Fu, Wei-min; Gu, Wei

    2011-01-01

    BACKGROUND: Because of the prevalence of diabetes, the treatment of diabetic foot is still challenging. Even an exactly proved effective and practical method can’t be listed except vascular surgery which is not a long-term way for it. Spinal cord stimulation (SCS) is a very promising option in the treatment algorithm of inoperable chronic critical leg ischemia (CLI). DATA SOURCES: We searched Pubmed database with key words or terms such as “spinal cord stimulation”, “ischemic pain” and “limb ischemia” appeared in the last five years. RESULTS: The mechanism of SCS is unclear. Two theories have emerged to interpret the benefits of SCS. Pain relief from SCS can be confirmed by a majority of the studies, while limb salvage and other more ambitious improvements have not come to an agreement. The complications of SCS are not fatal, but most of them are lead migration, lead connection failure, and local infection. CONCLUSIONS: SCS is a safe, promising treatment for patients with inoperable CLI. It is effective in pain reduction compared with traditional medical treatment. PMID:25215020

  4. Beneficial effect of the oxygen free radical scavenger amifostine (WR-2721) on spinal cord ischemia/reperfusion injury in rabbits

    PubMed Central

    Chronidou, Fany; Apostolakis, Efstratios; Papapostolou, Ioannis; Grintzalis, Konstantinos; Georgiou, Christos D; Koletsis, Efstratios N; Karanikolas, Menelaos; Papathanasopoulos, Panagiotis; Dougenis, Dimitrios

    2009-01-01

    Background Paraplegia is the most devastating complication of thoracic or thoraco-abdominal aortic surgery. During these operations, an ischemia-reperfusion process is inevitable and the produced radical oxygen species cause severe oxidative stress for the spinal cord. In this study we examined the influence of Amifostine, a triphosphate free oxygen scavenger, on oxidative stress of spinal cord ischemia-reperfusion in rabbits. Methods Eighteen male, New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by temporary occlusion of the descending thoracic aorta by a coronary artery balloon catheter, advanced through the femoral artery. The animals were randomly divided in 3 groups. Group I functioned as control. In group II the descending aorta was occluded for 30 minutes and then reperfused for 75 min. In group III, 500 mg Amifostine was infused into the distal aorta during the second half-time of ischemia period. At the end of reperfusion all animals were sacrificed and spinal cord specimens were examined for superoxide radicals by an ultra sensitive fluorescent assay. Results Superoxide radical levels ranged, in group I between 1.52 and 1.76 (1.64 ± 0.10), in group II between 1.96 and 2.50 (2.10 ± 0.23), and in group III (amifostine) between 1.21 and 1.60 (1.40 ± 0.19) (p = 0.00), showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker measurement ranged, in group I between 0.278 and 0.305 (0.296 ± 0.013), in group II between 0.427 and 0.497 (0.463 ± 0.025), and in group III (amifostine) between 0.343 and 0.357 (0.350 ± 0.007) (p < 0.00), showing a decrease of 38% after Amifostine administration. Conclusion By direct and indirect methods of measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is suggested that intra-aortic Amifostine infusion during spinal cord ischemia phase, significantly attenuated the spinal cord oxidative injury in rabbits. PMID:19758462

  5. Intrathecally Transplanting Mesenchymal Stem Cells (MSCs) Activates ERK1/2 in Spinal Cords of Ischemia-Reperfusion Injury Rats and Improves Nerve Function

    PubMed Central

    Wang, Yonghong; Liu, He; Ma, Hong

    2016-01-01

    Background We investigated whether an intrathecal transplantation of mesenchymal stem cells (MSCs) activates extracellular adjusting protein kinase1 and 2(ERK1/2) in the spinal cords of rats following an ischemia-reperfusion injury, resulting in improved spinal cord function and inhibition of apoptosis. Material/Methods We observed the relationship between the activation of ERK1/2 in the rat spinal cord and intrathecal transplantation of MSCs, as well as the effect of U0126, a MEK1/2 (upstream protein of ERK1/2) inhibitor, on a spinal cord ischemia-reperfusion injury model in rats using Basso Beattie Bresnahan (BBB) scoring, somatosensory evoked potentials (SSEPs), immunohistochemistry, and Western blot analysis. Results After transplantation of MSCs, the lower limb motor function score increased, and the incubation period of SSEPs and amplitude were improved. Moreover, following transplantation of MSCs, Bcl2 expression increased, whereas Bax expression decreased after reperfusion. Transplantation of MSCs significantly enhanced pERK1/2 expression in the spinal cord, as well as pERK1/2 in immunoreactive cells located in the grey matter of the L4/5 levels of the spinal cord, following ischemia reperfusion injury in rats. The effective dose of U0126 required to inhibit pERK1/2 expression was 200 μg/kg. Bcl-2 decreased and the level of Bax expression increased in the spinal cord after ischemia reperfusion injury, and the protective effects of MSCs were attenuated. Conclusions Our findings suggest that intrathecal transplantation of MSCs activates ERK1/2 in the spinal cord following ischemia reperfusion injury, partially improves spinal cord function, and inhibits apoptosis in rats. PMID:27135658

  6. Intrathecally Transplanting Mesenchymal Stem Cells (MSCs) Activates ERK1/2 in Spinal Cords of Ischemia-Reperfusion Injury Rats and Improves Nerve Function.

    PubMed

    Wang, Yonghong; Liu, He; Ma, Hong

    2016-01-01

    BACKGROUND We investigated whether an intrathecal transplantation of mesenchymal stem cells (MSCs) activates extracellular adjusting protein kinase1 and 2(ERK1/2) in the spinal cords of rats following an ischemia-reperfusion injury, resulting in improved spinal cord function and inhibition of apoptosis. MATERIAL AND METHODS We observed the relationship between the activation of ERK1/2 in the rat spinal cord and intrathecal transplantation of MSCs, as well as the effect of U0126, a MEK1/2 (upstream protein of ERK1/2) inhibitor, on a spinal cord ischemia-reperfusion injury model in rats using Basso Beattie Bresnahan (BBB) scoring, somatosensory evoked potentials (SSEPs), immunohistochemistry, and Western blot analysis. RESULTS After transplantation of MSCs, the lower limb motor function score increased, and the incubation period of SSEPs and amplitude were improved. Moreover, following transplantation of MSCs, Bcl2 expression increased, whereas Bax expression decreased after reperfusion. Transplantation of MSCs significantly enhanced pERK1/2 expression in the spinal cord, as well as pERK1/2 in immunoreactive cells located in the grey matter of the L4/5 levels of the spinal cord, following ischemia reperfusion injury in rats. The effective dose of U0126 required to inhibit pERK1/2 expression was 200 µg/kg. Bcl-2 decreased and the level of Bax expression increased in the spinal cord after ischemia reperfusion injury, and the protective effects of MSCs were attenuated. CONCLUSIONS Our findings suggest that intrathecal transplantation of MSCs activates ERK1/2 in the spinal cord following ischemia reperfusion injury, partially improves spinal cord function, and inhibits apoptosis in rats. PMID:27135658

  7. Characteristics of mRNA dynamic expression related to spinal cord ischemia/reperfusion injury: a transcriptomics study.

    PubMed

    Qi, Zhi-Ping; Xia, Peng; Hou, Ting-Ting; Li, Ding-Yang; Zheng, Chang-Jun; Yang, Xiao-Yu

    2016-03-01

    Following spinal cord ischemia/reperfusion injury, an endogenous damage system is immediately activated and participates in a cascade reaction. It is difficult to interpret dynamic changes in these pathways, but the examination of the transcriptome may provide some information. The transcriptome reflects highly dynamic genomic and genetic information and can be seen as a precursor for the proteome. We used DNA microarrays to measure the expression levels of dynamic evolution-related mRNA after spinal cord ischemia/reperfusion injury in rats. The abdominal aorta was blocked with a vascular clamp for 90 minutes and underwent reperfusion for 24 and 48 hours. The simple ischemia group and sham group served as controls. After rats had regained consciousness, hindlimbs showed varying degrees of functional impairment, and gradually improved with prolonged reperfusion in spinal cord ischemia/reperfusion injury groups. Hematoxylin-eosin staining demonstrated that neuronal injury and tissue edema were most severe in the 24-hour reperfusion group, and mitigated in the 48-hour reperfusion group. There were 8,242 differentially expressed mRNAs obtained by Multi-Class Dif in the simple ischemia group, 24-hour and 48-hour reperfusion groups. Sixteen mRNA dynamic expression patterns were obtained by Serial Test Cluster. Of them, five patterns were significant. In the No. 28 pattern, all differential genes were detected in the 24-hour reperfusion group, and their expressions showed a trend in up-regulation. No. 11 pattern showed a decreasing trend in mRNA whereas No. 40 pattern showed an increasing trend in mRNA from ischemia to 48 hours of reperfusion, and peaked at 48 hours. In the No. 25 and No. 27 patterns, differential expression appeared only in the 24-hour and 48-hour reperfusion groups. Among the five mRNA dynamic expression patterns, No. 11 and No. 40 patterns could distinguish normal spinal cord from pathological tissue. No. 25 and No. 27 patterns could distinguish simple

  8. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

    SciTech Connect

    Hao, J.X.; Xu, X.J.; Aldskogius, H.; Seiger, A.; Wiesenfeld-Hallin, Z. )

    1991-08-01

    Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord.

  9. Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats.

    PubMed

    Liu, Shiyao; Yang, Yanwei; Jin, Mu; Hou, Siyu; Dong, Xiuhua; Lu, Jiakai; Cheng, Weiping

    2016-09-15

    Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling

  10. Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats.

    PubMed

    Liu, Shiyao; Yang, Yanwei; Jin, Mu; Hou, Siyu; Dong, Xiuhua; Lu, Jiakai; Cheng, Weiping

    2016-09-15

    Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling

  11. Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis.

    PubMed

    Gökce, Emre Cemal; Kahveci, Ramazan; Gökce, Aysun; Cemil, Berker; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Kısa, Üçler; Erdoğan, Bülent; Güvenç, Yahya; Alagöz, Fatih; Kahveci, Ozan

    2016-06-01

    OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the

  12. In Vivo Neuroprotective Effect of Histidine-Tryptophan-Ketoglutarate Solution in an Ischemia/Reperfusion Spinal Cord Injury Animal Model

    PubMed Central

    Kang, Shin Kwang; Kang, Min-Woong; Rhee, Youn Ju; Kim, Cuk-Seong; Jeon, Byeong Hwa; Han, Sung Joon; Cho, Hyun Jin; Na, Myung Hoon; Yu, Jae-Hyeon

    2016-01-01

    Background Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. Methods Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. Results The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, 1.17±0.75 in the IR group, 1.33±1.03 in the saline group, and 2.67±0.81 in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. Conclusion Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats. PMID:27525231

  13. Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis.

    PubMed

    Gökce, Emre Cemal; Kahveci, Ramazan; Gökce, Aysun; Cemil, Berker; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Kısa, Üçler; Erdoğan, Bülent; Güvenç, Yahya; Alagöz, Fatih; Kahveci, Ozan

    2016-06-01

    OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the

  14. Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury.

    PubMed

    Cemil, Berker; Gokce, Emre Cemal; Kahveci, Ramazan; Gokce, Aysun; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Erdogan, Bulent; Kosem, Bahadir

    2016-06-01

    Garlic has been used as a food as well as a component of traditional medicine. Aged garlic extract (AGE) is claimed to promote human health through antioxidant/anti-inflammatory activities with neuroprotective effects. We evaluated the possible beneficial effect of AGE neurologically, pathologically, ultrastructurally, and biochemically in a spinal cord ischemia-reperfusion (I/R) model of rats. Twenty-four Sprague-Dawley rats were divided into three groups: sham (no I/R), I/R, and AGE (I/R+AGE); each group consisted of eight animals. Animals were evaluated neurologically with the Basso, Beattie, and Bresnahan (BBB) scoring system. The spinal cord tissue samples were harvested for pathological and ultrastructural examinations. Oxidative products (Malondialdehyde, nitric oxide), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), inflammatory cytokines (tissue tumor necrosis factor alpha, interleukin-1), and caspase-3 activity were analyzed. The AGE group had significantly higher BBB scores than the I/R group. Pathologically, AGE group revealed reduced degree of ischemia and spinal cord edema. Ultrastructural results also showed preservation of tissue structure in the AGE group. Oxidative product levels of the I/R group were significantly higher than both the other groups, and antioxidant enzyme levels of AGE group were significantly higher than the I/R group. There was also significant difference between the sham and AGE groups in terms of total antioxidant enzyme levels. Furthermore, AGE treatment significantly reduced the inflammatory cytokines and caspase-3 activity than the I/R group. This study demonstrates the considerable neuroprotective effect of AGE on the neurological, pathological, ultrastructural, and biochemical status of rats with I/R-induced spinal cord injury.

  15. Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury.

    PubMed

    Cemil, Berker; Gokce, Emre Cemal; Kahveci, Ramazan; Gokce, Aysun; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Erdogan, Bulent; Kosem, Bahadir

    2016-06-01

    Garlic has been used as a food as well as a component of traditional medicine. Aged garlic extract (AGE) is claimed to promote human health through antioxidant/anti-inflammatory activities with neuroprotective effects. We evaluated the possible beneficial effect of AGE neurologically, pathologically, ultrastructurally, and biochemically in a spinal cord ischemia-reperfusion (I/R) model of rats. Twenty-four Sprague-Dawley rats were divided into three groups: sham (no I/R), I/R, and AGE (I/R+AGE); each group consisted of eight animals. Animals were evaluated neurologically with the Basso, Beattie, and Bresnahan (BBB) scoring system. The spinal cord tissue samples were harvested for pathological and ultrastructural examinations. Oxidative products (Malondialdehyde, nitric oxide), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), inflammatory cytokines (tissue tumor necrosis factor alpha, interleukin-1), and caspase-3 activity were analyzed. The AGE group had significantly higher BBB scores than the I/R group. Pathologically, AGE group revealed reduced degree of ischemia and spinal cord edema. Ultrastructural results also showed preservation of tissue structure in the AGE group. Oxidative product levels of the I/R group were significantly higher than both the other groups, and antioxidant enzyme levels of AGE group were significantly higher than the I/R group. There was also significant difference between the sham and AGE groups in terms of total antioxidant enzyme levels. Furthermore, AGE treatment significantly reduced the inflammatory cytokines and caspase-3 activity than the I/R group. This study demonstrates the considerable neuroprotective effect of AGE on the neurological, pathological, ultrastructural, and biochemical status of rats with I/R-induced spinal cord injury. PMID:27183321

  16. Unilateral microinjection of acrolein into thoracic spinal cord produces acute and chronic injury and functional deficits.

    PubMed

    Gianaris, Alexander; Liu, Nai-Kui; Wang, Xiao-Fei; Oakes, Eddie; Brenia, John; Gianaris, Thomas; Ruan, Yiwen; Deng, Ling-Xiao; Goetz, Maria; Vega-Alvarez, Sasha; Lu, Qing-Bo; Shi, Riyi; Xu, Xiao-Ming

    2016-06-21

    Although lipid peroxidation has long been associated with spinal cord injury (SCI), the specific role of lipid peroxidation-derived byproducts such as acrolein in mediating damage remains to be fully understood. Acrolein, an α-β unsaturated aldehyde, is highly reactive with proteins, DNA, and phospholipids and is considered as a second toxic messenger that disseminates and augments initial free radical events. Previously, we showed that acrolein increased following traumatic SCI and injection of acrolein induced tissue damage. Here, we demonstrate that microinjection of acrolein into the thoracic spinal cord of adult rats resulted in dose-dependent tissue damage and functional deficits. At 24h (acute) after the microinjection, tissue damage, motoneuron loss, and spinal cord swelling were observed on sections stained with Cresyl Violet. Luxol fast blue staining further showed that acrolein injection resulted in dose-dependent demyelination. At 8weeks (chronic) after the microinjection, cord shrinkage, astrocyte activation, and macrophage infiltration were observed along with tissue damage, neuron loss, and demyelination. These pathological changes resulted in behavioral impairments as measured by both the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and grid walking analysis. Electron microscopy further demonstrated that acrolein induced axonal degeneration, demyelination, and macrophage infiltration. These results, combined with our previous reports, strongly suggest that acrolein may play a critical causal role in the pathogenesis of SCI and that targeting acrolein could be an attractive strategy for repair after SCI. PMID:27058147

  17. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  18. Effect of noradrenalin and EGb 761 pretreatment on the ischemia-reperfusion injured spinal cord neurons in rabbits.

    PubMed

    Mechírová, Eva; Domoráková, Iveta; Danková, Marianna; Danielisová, Viera; Burda, Jozef

    2009-09-01

    Short term sublethal ischemia or ischemic preconditioning gives protection to the neurons against subsequent lethal ischemic attack. This so-called ischemic tolerance can also be provided by certain drugs. We examined the effect of noradrenalin and EGb 761 on the spinal cord neurons injured by 30 min occlusion of abdominal aorta in rabbits. The animals survived 48 and 72 h. Degenerated neurons were visualized by Fluoro Jade B method, viable neurons were demonstrated immunohistochemically with NeuN and ubiquitin antibodies. The rabbits with noradrenalin administration 48 h before 30 min of ischemia and 48/72 h of reperfusion, showed significant increase of degenerated Fluoro Jade B labeled neurons. Animals of both groups were paraplegic. Rabbits pretreated 7 days with EGb 761 prior to 30 min of ischemia and with 48/72 h of reperfusion revealed significant decrease of Fluoro Jade B-positive neurons when compared with the groups with 30 min of ischemia followed by 48/72 h of reperfusion. In the NeuN sections, the number of viable neurons was moderately decreased. These animals showed no paraplegia. Ubiquitin aggregates occurred in the cytoplasm of degenerated neurons in the sections of rabbits preconditioned with noradrenalin 48 h prior to 30 min of ischemia and followed by 48 h of reperfusion while after 72 h of reperfusion, shrunk light shadows without ubiquitin reaction were visible. Our results indicate that EGb 761 could be involved in protection of spinal cord neurons against ischemic injury while effect of noradrenalin is not unambiguous.

  19. Hypoxic preconditioning increases the protective effect of bone marrow mesenchymal stem cells on spinal cord ischemia/reperfusion injury.

    PubMed

    Wang, Zhilin; Fang, Bo; Tan, Zhibin; Zhang, Dong; Ma, Hong

    2016-03-01

    Transplantation of bone marrow mesenchymal stem cells (BMSCs) protect against spinal cord ischemia/reperfusion injury (SCIRI). However, a large number of transplanted BMSCs often undergo apoptosis, which severely affects the treatment outcome. Previous studies have demonstrated that hypoxic preconditioning effectively increases the survival rate of BMSCs following transplantation, and increases their protective effect on injured tissues. However, there have been few reports regarding roles of hypoxic preconditioning in SCIRI. The present study isolated rat BMSCs and separately transplanted hypoxia‑ and non‑hypoxia‑preconditioned BMSCs into the spinal cord tissues of rats with SCIRI. The role of hypoxic preconditioning in the promotion of the protective effect of BMSCs on SCIRI was investigated using neurological function scores, Evans blue staining, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. In addition, reverse transcription‑quantitative polymerase chain reaction and western blotting were used to detect the expression levels of hypoxia‑inducible factor 1α (HIF‑1α), and to investigate its possible underlying mechanism of action. The results indicated that hypoxic preconditioning effectively increased the protective effects of BMSCs on neurological function, blood spinal cord barrier and tissue damage following SCIRI, and inhibited apoptosis. Furthermore, hypoxic preconditioned BMSCs upregulated the expression of HIF‑1α in spinal cord tissues. Therefore, hypoxic preconditioning effectively increased the protective effect of BMSCs on SCIRI and may be associated with upregulation of the expression of HIF‑1α. Hypoxic preconditioning may serve as an effective means of increasing the protective effect of BMSCs on SCIRI.

  20. Intrathecal Injection of 3-Methyladenine Reduces Neuronal Damage and Promotes Functional Recovery via Autophagy Attenuation after Spinal Cord Ischemia/Reperfusion Injury in Rats.

    PubMed

    Wei, Xing; Zhou, Zhentao; Li, Lingyun; Gu, Jun; Wang, Chen; Xu, Fuqi; Dong, Qirong; Zhou, Xiaozhong

    2016-01-01

    The present study aimed to determine the occurrence of autophagy following ischemia/reperfusion (I/R) injury in the rat spinal cord and whether autophagy inhibition contributes to neural tissue damage and locomotor impairment. A spinal cord I/R model was induced via descending thoracic aorta occlusion for 10 min using systemic hypotension (40 mmHg) in adult male Sprague-Dawley rats. Then, 600 nmol 3-methyladenine (3-MA) or vehicle was intrathecally administered. Ultrastructural spinal cord changes were observed via transmission electron microscopy (TEM) and immunofluorescent double-labeling. Western blots were used to determine the protein expression of microtubule-associated protein light chain 3 (LC3) and Beclin 1. Autophagy was activated after spinal cord I/R injury as demonstrated by significantly increased LC3 and Beclin 1 expression at 3-48 h after injury. Furthermore, TEM images indicated the presence of autophagosomes and autolysosomes in the injured spinal cord. 3-MA significantly decreased LC3 and Beclin 1 expression and the number of LC3-positive cells in spinal cord of I/R versus vehicle groups. Moreover, the 3-MA-treated rats exhibited better neurobehavioral scores compared with control rats. These findings suggest activation of autophagy leading to neuronal cell death in the I/R injured spinal cord. These effects were significantly inhibited by intrathecal 3-MA administration. Thus intrathecal 3-MA administration may represent a novel treatment target following spinal cord I/R injury. PMID:27150140

  1. Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury.

    PubMed

    Thakore, Nakul P; Samantaray, Supriti; Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A; Cox, April; Krause, James; Banik, Naren L

    2016-02-01

    To clarify the molecular changes of sublesional muscle in the acute phase of spinal cord injury (SCI), a moderately severe injury (40 g cm) was induced in the spinal cord (T10 vertebral level) of adult male Sprague-Dawley rats (injury) and compared with sham (laminectomy only). Rats were sacrificed at 48 h (acute) post injury, and gastrocnemius muscles were excised. Morphological examination revealed no significant changes in the muscle fiber diameter between the sham and injury rats. Western blot analyses performed on the visibly red, central portion of the gastrocnemius muscle showed significantly higher expression of muscle specific E3 ubiquitin ligases (muscle ring finger-1 and muscle atrophy f-box) and significantly lower expression of phosphorylated Akt-1/2/3 in the injury group compared to the sham group. Cyclooxygenase 2, tumor necrosis factor alpha (TNF-α), and caspase-1, also had a significantly higher expression in the injury group; although, the mRNA levels of TNF-α and IL-6 did not show any significant difference between the sham and injury groups. These results suggest activation of protein degradation, deactivation of protein synthesis, and development of inflammatory reaction occurring in the sublesional muscles in the acute phase of SCI before overt muscle atrophy is seen. PMID:26290268

  2. Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice.

    PubMed

    Heeman, Jacqueline H; Zhang, Yangmiao; Shirachi, Donald Y; Quock, Raymond M

    2013-12-01

    Earlier research has demonstrated that treatment with hyperbaric oxygen (HBO2) can elicit an antinociceptive response in models of acute pain. We have demonstrated that this antinociceptive effect is centrally-mediated and is dependent on opioid receptors. The purpose of the present study was to examine the role of endogenous opioid peptides and opioid receptors specifically in the spinal cord in the acute antinociceptive effect of HBO2 in mice. Male NIH Swiss mice were exposed to HBO2 (100% oxygen at 3.5atm absolute) for 11min and their antinociceptive responsiveness was determined using the glacial acetic acid-induced abdominal constriction test. HBO2-induced antinociception was sensitive to antagonism by intrathecal (i.t.) pretreatment with the κ- and μ-selective opioid antagonists norbinaltorphimine and β-funaltrexamine, respectively, but not the δ-selective antagonist naltrindole. The antinociceptive effect of HBO2 was also significantly attenuated by i.t. pretreatment with a rabbit antiserum against rat dynorphin1-13 but not antisera against β-endorphin or methionine-enkephalin. Based on these experimental findings, the acute antinociceptive effect of HBO2 appears to involve neuronal release of dynorphin and activation of κ- and μ-opioid receptors in the spinal cord. PMID:24113418

  3. [Spinal cord infarction].

    PubMed

    Naumann, N; Shariat, K; Ulmer, S; Stippich, C; Ahlhelm, F J

    2012-05-01

    Infarction of the spinal cord can cause a variety of symptoms and neurological deficits because of the complex vascular supply of the myelon. The most common leading symptom is distal paresis ranging from paraparesis to tetraplegia caused by arterial ischemia or infarction of the myelon. Venous infarction, however, cannot always be distinguished from arterial infarction based on the symptoms alone.Modern imaging techniques, such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) assist in preoperative planning of aortic operations to reliably identify not only the most important vascular structure supplying the spinal cord, the artery of Adamkiewicz, but also other pathologies such as tumors or infectious disorders. In contrast to CT, MRI can reliably depict infarction of the spinal cord.

  4. Intraoperative Targeted Temperature Management in Acute Brain and Spinal Cord Injury.

    PubMed

    Kraft, Jacqueline; Karpenko, Anna; Rincon, Fred

    2016-02-01

    Acute brain and spinal cord injuries affect hundreds of thousands of people worldwide. Though advances in pre-hospital and emergency and neurocritical care have improved the survival of some to these devastating diseases, very few clinical trials of potential neuro-protective strategies have produced promising results. Medical therapies such as targeted temperature management (TTM) have been trialed in traumatic brain injury (TBI), spinal cord injury (SCI), acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), and intracranial hemorrhage (ICH), but in no study has a meaningful effect on outcome been demonstrated. To this end, patient selection for potential neuro-protective therapies such as TTM may be the most important factor to effectively demonstrate efficacy in clinical trials. The use of TTM as a strategy to treat and prevent secondary neuronal damage in the intraoperative setting is an area of ongoing investigation. In this review we will discuss recent and ongoing studies that address the role of TTM in combination with surgical approaches for different types of brain injury. PMID:26759319

  5. Preoperative prediction of spinal cord ischemia after thoracic endovascular aortic repair

    PubMed Central

    Scali, Salvatore T.; Wang, S. Keisin; Feezor, Robert J.; Huber, Thomas S.; Martin, Tomas D.; Klodell, Charles T.; Beaver, Thomas M.; Beck, Adam W.

    2014-01-01

    Objective Spinal cord ischemia (SCI) is a devastating, but potentially preventable, complication of thoracic endovascular aortic repair (TEVAR). The purpose of this analysis was to determine what factors predict SCI after TEVAR. Methods All TEVAR procedures at a single institution were reviewed for patient characteristics, prior aortic repair history, aortic centerline of flow analysis, and procedural characteristics. SCI was defined as any lower extremity neurologic deficit that was not attributable to an intracranial process or peripheral neuropathy. Forty-three patient and procedural variables were evaluated individually for association with SCI. Those with the strongest relationships to SCI (P < .1) were included in a multivariable logistic regression model, and a stepwise variable elimination algorithm was bootstrapped to derive a best subset of predictors from this model. Results From 2002–13, 741 patients underwent TEVAR for various indications and 68 (9.2%) developed SCI (permanent: N = 38; 5.1%). Due to lack of adequate imaging for centerline analysis, 586 patients (any SCI, N = 43; 7.4%) were subsequently analyzed. Patients experiencing SCI after TEVAR were older (SCI 72±11 vs. No SCI, 65±15 years; P < .0001) and had significantly higher rates of multiple cardiovascular risk factors. The stepwise selection procedure identified five variables as the most important predictors of SCI: age (odds ratio, OR, multiplies by 1.3 per 10 years; 95% CI 0.9–1.8, P = .06), aortic coverage length (OR multiplies by 1.3 per 5cm; CI 1.1–1.6, P = .002), chronic obstructive pulmonary disease (OR, 1.9; CI .9–4.1, P = .1), chronic renal insufficiency(creatinine ≥ 1.6; OR, 1.9; CI .8–4.2, P = .1), and hypertension (defined as chart history and/or medication; OR, 6.4; CI 2.6–18, P < .0001). A logistic regression model with just these five covariates had excellent discrimination (AUC = .83) and calibration (χ2 = 9.8; P = .28). Conclusion This analysis generated a

  6. Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Propensity Score-Matched Cohort Study from a Canadian Multi-Center Spinal Cord Injury Registry

    PubMed Central

    Evaniew, Nathan; Noonan, Vanessa K.; Fallah, Nader; Kwon, Brian K.; Rivers, Carly S.; Ahn, Henry; Bailey, Christopher S.; Christie, Sean D.; Fourney, Daryl R.; Hurlbert, R. John; Linassi, A.G.; Fehlings, Michael G.

    2015-01-01

    Abstract In prior analyses of the effectiveness of methylprednisolone for the treatment of patients with acute traumatic spinal cord injuries (TSCIs), the prognostic importance of patients' neurological levels of injury and their baseline severity of impairment has not been considered. Our objective was to determine whether methylprednisolone improved motor recovery among participants in the Rick Hansen Spinal Cord Injury Registry (RHSCIR). We identified RHSCIR participants who received methylprednisolone according to the Second National Spinal Cord Injury Study (NASCIS-II) protocol and used propensity score matching to account for age, sex, time of neurological exam, varying neurological level of injury, and baseline severity of neurological impairment. We compared changes in total, upper extremity, and lower extremity motor scores using the Wilcoxon signed-rank test and performed sensitivity analyses using negative binomial regression. Forty-six patients received methylprednisolone and 1555 received no steroid treatment. There were no significant differences between matched participants for each of total (13.7 vs. 14.1, respectively; p=0.43), upper extremity (7.3 vs. 6.4; p=0.38), and lower extremity (6.5 vs. 7.7; p=0.40) motor recovery. This result was confirmed using a multivariate model and, as predicted, only cervical (C1–T1) rather than thoracolumbar (T2–L3) injury levels (p<0.01) and reduced baseline injury severity (American Spinal Injury Association [ASIA] Impairment Scale grades; p<0.01) were associated with greater motor score recovery. There was no in-hospital mortality in either group; however, the NASCIS-II methylprednisolone group had a significantly higher rate of total complications (61% vs. 36%; p=0.02) NASCIS-II methylprednisolone did not improve motor score recovery in RHSCIR patients with acute TSCIs in either the cervical or thoracic spine when the influence of anatomical level and severity of injury were included in the analysis. There

  7. Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Propensity Score-Matched Cohort Study from a Canadian Multi-Center Spinal Cord Injury Registry.

    PubMed

    Evaniew, Nathan; Noonan, Vanessa K; Fallah, Nader; Kwon, Brian K; Rivers, Carly S; Ahn, Henry; Bailey, Christopher S; Christie, Sean D; Fourney, Daryl R; Hurlbert, R John; Linassi, A G; Fehlings, Michael G; Dvorak, Marcel F

    2015-11-01

    In prior analyses of the effectiveness of methylprednisolone for the treatment of patients with acute traumatic spinal cord injuries (TSCIs), the prognostic importance of patients' neurological levels of injury and their baseline severity of impairment has not been considered. Our objective was to determine whether methylprednisolone improved motor recovery among participants in the Rick Hansen Spinal Cord Injury Registry (RHSCIR). We identified RHSCIR participants who received methylprednisolone according to the Second National Spinal Cord Injury Study (NASCIS-II) protocol and used propensity score matching to account for age, sex, time of neurological exam, varying neurological level of injury, and baseline severity of neurological impairment. We compared changes in total, upper extremity, and lower extremity motor scores using the Wilcoxon signed-rank test and performed sensitivity analyses using negative binomial regression. Forty-six patients received methylprednisolone and 1555 received no steroid treatment. There were no significant differences between matched participants for each of total (13.7 vs. 14.1, respectively; p=0.43), upper extremity (7.3 vs. 6.4; p=0.38), and lower extremity (6.5 vs. 7.7; p=0.40) motor recovery. This result was confirmed using a multivariate model and, as predicted, only cervical (C1-T1) rather than thoracolumbar (T2-L3) injury levels (p<0.01) and reduced baseline injury severity (American Spinal Injury Association [ASIA] Impairment Scale grades; p<0.01) were associated with greater motor score recovery. There was no in-hospital mortality in either group; however, the NASCIS-II methylprednisolone group had a significantly higher rate of total complications (61% vs. 36%; p=0.02) NASCIS-II methylprednisolone did not improve motor score recovery in RHSCIR patients with acute TSCIs in either the cervical or thoracic spine when the influence of anatomical level and severity of injury were included in the analysis. There was a

  8. Identification of risk factors for spinal cord ischemia by the use of monitoring of somatosensory evoked potentials during coarctation repair.

    PubMed

    Dasmahapatra, H K; Coles, J G; Taylor, M J; Cass, D; Couper, G; Adler, S; Burrows, F; Sherret, H; Trusler, G A; Williams, W G

    1987-09-01

    The infrequency of spinal cord infarction and paraplegia after occlusion of the descending thoracic aorta has effectively precluded statistical identification of risk factors. Reversible spinal cord ischemia (SCI), however, is more common, can be detected by intraoperative neurophysiologic monitoring, and can lead to irreversible spinal cord damage. Spinal somatosensory evoked potentials (SEPs) were monitored intraoperatively in 38 patients (18 days to 18 years) undergoing coarctation repair (1982-1986). Although no patients sustained perioperative neurologic dysfunction, 10 of 38 (26%) patients developed reversible SCI, as reflected by greater than 75% loss of SEP N1-P1 interpeak amplitude during aortic occlusion (mean clamp time, 29.1 +/- 1.1 min). During occlusion, seven of 38 (18%) sustained complete loss of the SEP; uniform and prompt (1 to 6 min after clamp release) recovery of the signal occurred in these patients with reperfusion following completion of the repair (n = 6), or temporary institution of partial occlusion (n = 1). By multiple regression analysis the degree of SCI was negatively related to the distal aortic pressure (mean 32.4 +/- 2.4 mm Hg, p = .03), and the occlusion PCO2 (mean 33.1 +/- 1.1 mm Hg; p = .013), and positively related to the change in proximal systolic pressure with aortic occlusion (mean 19.8 +/- 3 mm Hg, p = .003). We conclude that: (1) distal hypotension and SCI commonly occur during aortic occlusion for coarctation repair, and (2) intraoperative interventions that can potentially influence distal aortic perfusion and/or PCO2 should be used judiciously.

  9. Relationship Between Depressive State and Treatment Characteristics of Acute Cervical Spinal Cord Injury in Japan

    PubMed Central

    Matsuda, Yasufumi; Kubo, Tatsuhiko; Fujino, Yoshihisa; Matsuda, Shinya; Wada, Futoshi; Sugita, Atsuko

    2016-01-01

    Background Few studies have assessed whether treatment of acute cervical spinal cord injury (SCI) patients contributes to depression. Methods Using an administrative database, we assessed patients for whom the diagnosis was unspecified injuries of cervical spinal cord (International Classification of Diseases and Injuries-10th (ICD-10) code; S14.1). We categorized patients with codes for depressive episode (ICD-10 code; F32) or recurrent depressive disorder (F33), or those prescribed antidepressants (tricyclic, tetracyclic, Selective Serotonin Reuptake Inhibitors, Serotonin Noradrenaline Reuptake Inhibitors, Trazodone, Sulpiride, or Mirtazapine) as having a depressive state. We compared the rate of each acute treatment between the depressive state group and the non-depressive state group using chi-square tests, and a multiple logistic regression model was used to identify the association between the acute treatment and depressive state. Results There were 151 patients who were judged to be in a depressive state, and the other 2115 patients were categorized into the non-depressive state group. Intervention of intravenous anesthesia, tracheostomy, artificial respiration, and gastrostomy had a significant positive correlation with depressive state. Multiple logistic regression analysis showed that tracheostomy (odds ratio [OR] 2.18; 95% confidence interval [CI], 1.09–4.38) and artificial respiration (OR 2.28; 95% CI, 1.32–3.93) were significantly associated with depressive state, and men had a 36% reduction in the risk of depressive state compared with women (OR 0.64; 95% CI, 0.44–0.94), whereas age, wound-treatment, all of the orthopedic procedures, intravenous anesthesia, and gastrostomy were not associated with depressive state. Conclusions These findings suggest that tracheostomy, artificial respiration and female gender in the acute phase after cervical SCI might be associated with the development of depression. PMID:26567604

  10. A model for the future care of acute spinal cord injuries.

    PubMed

    Botterell, E H; Jousse, A T; Kraus, A S; Thompson, M G; WynneJones, M; Geisler, W O

    1975-11-01

    This is a review of the total care of those acute spinal cord injury patients in Ontario during the years 1969 and 1970, from extrication and transportation following the accident to death, or the completion of primary definitive rehabilitation. Information was extracted from the available ambulance records, the patients and many of the responsible physicians were interviewed personally. The study was detailed and intensive and included a review of each patient's hospital records in each hospital up to discharge from the rehabilitation programme into the community, or to a chronic care unit. The data was compiled in accordance with a detailed and lengthy questionnaire developed for this study. The incidence of acute cord injuries in Ontario in 1969 and 1970 amounted to 244; in 1969, 15.9 per million population and in 1970, 13.6 per million. As in other studies road accidents took first place, followed by falls from a height; sports injuries ranked third and 65.7% of these were caused by diving into shallow water. Age incidence, and incidence by month, day of week and time of day were identified. Fridays and Saturday afternoons in July and August are particularly hazardous. The study continued to the end of 1974 by which time 34 deaths had been recorded. Peak incidence of death occurred within fourteen days of injury. The most common cause of death was respiratory in origin. Geographical distribution was identified and the type of hospital treating the acutely injured patient. Fourteen percent of persons with spinal column injury suffered progressive or sequential spinal cord damage both prior to and following medical contact. The incidence of pressure sores and genitourinary sepsis and calculosis was high in all types of hospitals. The effect of operative treatment was noted in cases of complete quadriplegia and paraplegia. Of the 133 survivors who undertook a rehabilitation program, 84% returned to their homes and 59% achieved gainful employemnt or ongoing

  11. Management of Chronic Spinal Cord Dysfunction

    PubMed Central

    Abrams, Gary M.; Ganguly, Karunesh

    2015-01-01

    Purpose of Review: Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Recent Findings: Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. Summary: The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life. PMID:25651225

  12. Protection of rats spinal cord ischemia-reperfusion injury by inhibition of MiR-497 on inflammation and apoptosis: Possible role in pediatrics.

    PubMed

    Xu, Meng; Wang, Hai-Feng; Zhang, Ying-Ying; Zhuang, Hui-Wen

    2016-07-01

    MicroRNAs are extensively included in the pathogenesis and progression of many diseases by inhibiting target gene expression. Recently, studies have demonstrated that microRNA-497 (miR-497) may be implicated in human breast cancer that miR-497 predicts the prognosis of breast cancer patients from the posttranscriptional level. However, the specific function of miR-497 in spinal cord ischemia-reperfusion (IR) injury is far from clear nowadays. The present study was designed to determine the role of miR-497 in spinal cord IR injury and investigate the underlying spinal cord protective mechanism. The rat spinal cord IR injury model was performed by occluding the left anterior descending coronary artery for 30 min, which is then followed by 12h reperfusion. As predicted, miR-497 over-expression markedly decreased the expression of IL-1 receptor associated kinase (IRAK1) and Cyclic AMP response element binding protein (CREB). Moreover, Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and Caspase-3, as miR-497 potential targets were significantly suppressed after miR-497 transfection, then preventing inflammatory cytokines and factors regulating apoptosis. We also found that tumor necrosis factor-a (TNF-α) and interleukin-1beta (IL-1β) activity, pro-apoptotic related genes, such as extracellular regulated protein kinases (ERK), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL levels were all decreased associated with the down-regulation of IRAK1 and CREB. In conclusion, our data demonstrate that miR-497 could inhibit inflammation and apoptosis of spinal cord IR through its targets, IRAK1 of TLR4 and CREB signaling pathway. Thus, miR-497 may constitute a new therapeutic target for the prevention of spinal cord IR injury.

  13. Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review

    PubMed Central

    Savage, Katherine E.; Oleson, Christina V.; Schroeder, Gregory D.; Sidhu, Gursukhman S.; Vaccaro, Alexander R.

    2016-01-01

    Study Design  Systematic review. Objective  To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). Methods  A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. Results  The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. Conclusion  Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID:27556002

  14. Posterior spinal cord infarction due to fibrocartilaginous embolization in a 16-year-old athlete.

    PubMed

    Bansal, Seema; Brown, Wendy; Dayal, Anuradha; Carpenter, Jessica L

    2014-07-01

    Spinal cord infarction is extremely rare in children, and, similar to cerebrovascular infarcts, the pathogenesis is different from adults. Spinal cord infarcts are most commonly reported in adults in the context of aortic surgery; in children, the etiology is frequently unknown. Fibrocartilaginous embolization is a potential cause of spinal cord infarct in both populations. It is a process that occurs when spinal injury has resulted in disc disease, and subsequently disc fragments embolize to the cord, resulting in ischemia and/or infarction. In this report, we present a 16-year-old athlete who presented with symptoms of acute myelopathy after a period of intense exercise. Our original concern was for an inflammatory process of the spinal cord; however, given her history of competitive tumbling and degenerative disc changes on her initial spine magnetic resonance imaging scan, diffusion-weighted imaging was performed, which demonstrated acute spinal cord infarction. Unlike many cases of spinal cord infarction, our patient was fortunate to make a near-complete recovery. This case highlights the importance of recognizing rare causes of spinal cord pathology and considering infarction in the differential diagnosis of acute myelopathy because management and prognosis varies.

  15. Tethered Spinal Cord Syndrome

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Tethered Spinal Cord Syndrome Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What is Tethered Spinal Cord Syndrome? Tethered spinal cord syndrome is a neurological ...

  16. Spinal Cord Infarction

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Spinal Cord Infarction Information Page Table of Contents (click to ... Organizations Related NINDS Publications and Information What is Spinal Cord Infarction? Spinal cord infarction is a stroke either ...

  17. Biocompatibility of reduced graphene oxide nanoscaffolds following acute spinal cord injury in rats

    PubMed Central

    Palejwala, Ali H.; Fridley, Jared S.; Mata, Javier A.; Samuel, Errol L. G.; Luerssen, Thomas G.; Perlaky, Laszlo; Kent, Thomas A.; Tour, James M.; Jea, Andrew

    2016-01-01

    Background: Graphene has unique electrical, physical, and chemical properties that may have great potential as a bioscaffold for neuronal regeneration after spinal cord injury. These nanoscaffolds have previously been shown to be biocompatible in vitro; in the present study, we wished to evaluate its biocompatibility in an in vivo spinal cord injury model. Methods: Graphene nanoscaffolds were prepared by the mild chemical reduction of graphene oxide. Twenty Wistar rats (19 male and 1 female) underwent hemispinal cord transection at approximately the T2 level. To bridge the lesion, graphene nanoscaffolds with a hydrogel were implanted immediately after spinal cord transection. Control animals were treated with hydrogel matrix alone. Histologic evaluation was performed 3 months after the spinal cord transection to assess in vivo biocompatibility of graphene and to measure the ingrowth of tissue elements adjacent to the graphene nanoscaffold. Results: The graphene nanoscaffolds adhered well to the spinal cord tissue. There was no area of pseudocyst around the scaffolds suggestive of cytotoxicity. Instead, histological evaluation showed an ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells around the graphene nanoscaffolds. Conclusions: Graphene is a nanomaterial that is biocompatible with neurons and may have significant biomedical application. It may provide a scaffold for the ingrowth of regenerating axons after spinal cord injury. PMID:27625885

  18. Biocompatibility of reduced graphene oxide nanoscaffolds following acute spinal cord injury in rats

    PubMed Central

    Palejwala, Ali H.; Fridley, Jared S.; Mata, Javier A.; Samuel, Errol L. G.; Luerssen, Thomas G.; Perlaky, Laszlo; Kent, Thomas A.; Tour, James M.; Jea, Andrew

    2016-01-01

    Background: Graphene has unique electrical, physical, and chemical properties that may have great potential as a bioscaffold for neuronal regeneration after spinal cord injury. These nanoscaffolds have previously been shown to be biocompatible in vitro; in the present study, we wished to evaluate its biocompatibility in an in vivo spinal cord injury model. Methods: Graphene nanoscaffolds were prepared by the mild chemical reduction of graphene oxide. Twenty Wistar rats (19 male and 1 female) underwent hemispinal cord transection at approximately the T2 level. To bridge the lesion, graphene nanoscaffolds with a hydrogel were implanted immediately after spinal cord transection. Control animals were treated with hydrogel matrix alone. Histologic evaluation was performed 3 months after the spinal cord transection to assess in vivo biocompatibility of graphene and to measure the ingrowth of tissue elements adjacent to the graphene nanoscaffold. Results: The graphene nanoscaffolds adhered well to the spinal cord tissue. There was no area of pseudocyst around the scaffolds suggestive of cytotoxicity. Instead, histological evaluation showed an ingrowth of connective tissue elements, blood vessels, neurofilaments, and Schwann cells around the graphene nanoscaffolds. Conclusions: Graphene is a nanomaterial that is biocompatible with neurons and may have significant biomedical application. It may provide a scaffold for the ingrowth of regenerating axons after spinal cord injury.

  19. Spinal cord spectroscopy and diffusion-based tractography to assess acute disability in multiple sclerosis.

    PubMed

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

    2007-08-01

    There is a need to assess spinal cord involvement in multiple sclerosis with new imaging techniques in order to understand better the underlying pathology. We aimed to evaluate whether quantitative MRI measures, obtained using single-voxel (1)H-MR spectroscopy of the cervical cord and diffusion-based tractography of the major spinal cord pathways, in patients with a cervical cord relapse, differed from controls and correlated with acute disability. Fourteen patients at the onset of a cervical cord relapse with at least one lesion between C1 and C3 were imaged on a 1.5 T scanner and clinically assessed on the Expanded Disability Status Scale (EDSS), 9-hole peg test (HPT) and timed 25-foot walk test. Thirteen age- and gender-matched control subjects were also scanned. Metabolite concentrations, including total N-acetyl-aspartate (tNAA), choline-containing compounds (Cho), creatine plus phosphocreatine (Cr) and myo-Inositol (m-Ins), were quantified at C1-C3. Probabilistic tractography was performed at C1-C3 to track the lateral cortico-spinal tracts in the lateral columns, the anterior cortico-spinal tracts and the anterior spino-thalamic fasciculi in the anterior columns, and the bilateral fasciculus gracilis and cuneatus in the posterior columns. Diffusion- and tractography-derived measures of these tracts, including fractional anisotropy and voxel-based connectivity, which reflect fibre integrity, were obtained. These MRI measures were compared between patients and controls using the Mann-Whitney test. Univariate correlations between MRI measures and disability were assessed using the Spearman's rho correlation coefficient. Multiple regression analyses were performed to investigate which MRI measures independently correlated with the clinical scores, adjusting also for cross-sectional cord area, age and gender. Patients showed lower tNAA of the cervical cord, lower connectivity and lower fractional anisotropy of the lateral cortico-spinal tracts and posterior

  20. Incidence of deep vein thrombosis after spinal cord injury in Korean patients at acute rehabilitation unit.

    PubMed

    Do, Jong Geol; Kim, Du Hwan; Sung, Duk Hyun

    2013-09-01

    Deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE) remain significant causes of morbidity, mortality in patients with spinal cord injury (SCI). Since incidence of DVT after SCI in Korean population has not been much studied, we retrospectively analyzed the medical records of 185 SCI patients admitted for acute rehabilitation unit to investigate the incidence of DVT. Color Doppler ultrasonography was performed to screen for the occurrence of DVT at the time of initial presentation to acute rehabilitation unit. Primary study outcome was the incidence of DVT. Possible risk factors for DVT including the epidemiologic characteristics, completeness of motor paralysis, cause of injury, spasticity, surgery, and active cancer were analyzed. The incidence of DVT after SCI was 27.6%. In multiple logistic regression analysis, absence of spasticity was a significant independent risk factor (P<0.05) for occurrence of DVT. Symptomatic pulmonary embolism was evident in 7 patients without an episode of sudden death. Therefore, it is concluded that the incidence of DVT after SCI in Korean patients is comparable with that in Western populations. This result suggests that pharmacologic thromboprophylaxis should be considered in Korean patients with SCI.

  1. West Nile virus-induced acute flaccid paralysis is prevented by monoclonal antibody treatment when administered after infection of spinal cord neurons.

    PubMed

    Morrey, John D; Siddharthan, Venkatraman; Wang, Hong; Hall, Jeffery O; Skirpstunas, Ramona T; Olsen, Aaron L; Nordstrom, Jeffrey L; Koenig, Scott; Johnson, Syd; Diamond, Michael S

    2008-04-01

    Acute flaccid polio-like paralysis occurs during natural West Nile virus (WNV) infection in a subset of cases in animals and humans. To evaluate the pathology and the possibility for therapeutic intervention, the authors developed a model of acute flaccid paralysis by injecting WNV directly into the sciatic nerve or spinal cord of hamsters. By directly injecting selected sites of the nervous system with WNV, the authors mapped the lesions responsible for hind limb paralysis to the lumbar spinal cord. Immunohistochemical analysis of spinal cord sections from paralyzed hamsters revealed that WNV-infected neurons localized primarily to the ventral motor horn of the gray matter, consistent with the polio-like clinical presentation. Neuronal apoptosis and diminished cell function were identified by TUNEL (terminal deoxynucleotidyl transferase-mediated BrdUTP nick end labeling) and choline acetyltransferase staining, respectively. Administration of hE16, a potently neutralizing humanized anti-WNV monoclonal antibody, 2 to 3 days after direct WNV infection of the spinal cord, significantly reduced paralysis and mortality. Additionally, a single injection of hE16 as late as 5 days after WNV inoculation of the sciatic nerve also prevented paralysis. Overall, these experiments establish that WNV-induced acute flaccid paralysis in hamsters is due to neuronal infection and injury in the lumbar spinal cord and that treatment with a therapeutic antibody prevents paralysis when administered after WNV infection of spinal cord neurons. PMID:18444087

  2. Assessment of Disability in Patients with Acute Traumatic Spinal Cord Injury: A Systematic Review of the Literature

    PubMed Central

    Furlan, Julio C.; Noonan, Vanessa; Singh, Anoushka

    2011-01-01

    Abstract Given the importance of accurately and reliably assessing disability in future clinical trials, which will test therapeutic strategies in acute spinal cord injury (SCI), we sought to appraise comprehensively studies that focused on the psychometric properties (i.e., reliability, validity, and responsiveness) of all previously used outcome measures in the SCI population. The search strategy included Medline, CINAHL, EMBASE, and Cochrane databases. Two reviewers independently assessed each study regarding eligibility, level of evidence (using Sackett's criteria), and quality. Of 363 abstracts captured in our search, 36 full articles fulfilled the inclusion and exclusion criteria. Eight different outcome measures were used to assess disability in the SCI population, including Functional Independence Measure (FIM), Spinal cord Injury Measure (SCIM), Walking Index for Spinal Cord Injury (WISCI), Quadriplegia Index of Function (QIF), Modified Barthel Index (MBI), Timed Up & Go (TUG), 6-min walk test (6MWT), and 10-m walk test (10MWT). While 19 of 36 studies provided level-4 evidence, the remaining 17 articles were classified as level-2b evidence. Most of the instruments showed convergent construct validity in the SCI population, but criterion validity was not examined due to the lack a gold standard for assessment of disability. All instruments were tested in the rehabilitation and/or community setting, but only FIM was examined in the acute care setting. Based on our results of quality assessment, the SCIM has the most appropriate performance regarding the instrument's psychometric properties. Nonetheless, further investigations are required to confirm the adequate performance of the SCIM as a comprehensive measure of functional recovery in patients with SCI in rehabilitative care. The expert panel of the Spinal Cord Injury Solutions Network (SCISN) that participated in the modified Delphi process endorsed these conclusions. PMID:20367251

  3. A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

    PubMed Central

    Okon, Elena; Hillyer, Jessica; Mann, Cody; Baptiste, Darryl; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

    2011-01-01

    Abstract An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation. PMID:20146558

  4. A case of acute pancreatitis secondary to spinal cord injury. Case Report.

    PubMed

    Cao, Lijun; Sun, Yun; Lu, Zhonghua; Zhang, Pinjie; Yin, Lu; Li, Hui; Hua, Tianfeng; Zheng, Yao

    2015-01-01

    Acute pancreatitis (AP) is a frequent and potentially life-threatening disease with high morbidity and mortality. The overall mortality of AP is approximately 5%. Alcohol consumption and gallstones are the main etiology of AP. Hypertriglyceridemia, idiosyncratic reactions to drugs, anatomic alterations and ascaris lumbricoides can also give rise to AP. Although spinal cord injury (SCI) can cause AP, however, the case of induced by cervical spine surgery has not been reported. A 61-year-old man with quadriplegic and respiratory distress received cervical spine surgery for spinal cervical spondylosis and multi-stage longitudinal ligament. He was admitted to intensive care unit (ICU) after tracheotomy for progressive dyspnea, one day after the cervical spine surgery. The patient was diagnosed with AP, in the absence of any identifiable causes of pancreatitis. He was treated with intravenous fluids, no oral feeding, enteral and parenteral nutrition, antibiotic and mechanical ventilation. The patient's condition gradually improved after the treatment. This case describes a case of postoperative cervical spondylosis that led to AP. In this report, we highlight the importance of early diagnosis and subsequent appropriate treatment. We conclude that the outcome can be favorable, if the treatment is appropriate. PMID:26707037

  5. Hemorrhagic intramedullary hemangioblastoma of the cervical spinal cord presenting with acute-onset quadriparesis: Case report and review of the literature

    PubMed Central

    Gluf, Wayne M.; Dailey, Andrew T.

    2014-01-01

    Context Hemangioblastomas of the spinal cord are uncommon vascular tumors. Patients commonly present with subtle neurologic findings that are thought to represent growth of the lesion over time. Hemorrhage of an intramedullary hemangioblastoma presenting as acute neurologic deficit is an extremely rare occurrence. Although the cervical spine is the most common location for hemangioblastoma of the spinal cord, there have been no previously published cases in the literature of intramedullary hemorrhage from such a lesion. Findings A 22-year-old woman with a previously undiagnosed spinal cord hemangioblastoma presented with sudden-onset dense quadriparesis due to intramedullary hemorrhage in the cervical spinal cord. The patient did not have any clinical findings of von-Hippel Lindau disease. Laminoplasty from C5 to T2 and posterior midline myelotomy for resection of the intramedullary tumor with hematoma evacuation were completed without complication. Conclusion Intramedullary hemangioblastoma of the spinal cord is uncommon, and hemorrhage from a cervical spinal cord lesion has not previously been reported. Symptoms from these usually indolent lesions are commonly associated with tumor growth, edema, or associated syrinx, whereas devastating acute neurologic deficit from hemorrhage is exceedingly rare. Microsurgical resection should be done in cases of symptomatic lesions and considered in isolated symptomatic lesions without the known diagnosis of von Hippel-Lindau disease. PMID:25029412

  6. Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I.; Walker, Robert L.; Miranda, Jorge D.

    2012-01-01

    Abstract Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  7. Cardiac arrhythmias the first month after acute traumatic spinal cord injury

    PubMed Central

    Bartholdy, Kim; Biering-Sørensen, Tor; Malmqvist, Lasse; Ballegaard, Martin; Krassioukov, Andrei; Hansen, Birgitte; Svendsen, Jesper Hastrup; Kruse, Anders; Welling, Karen-Lise; Biering-Sørensen, Fin

    2014-01-01

    Objective Cardiovascular complications including cardiac arrest and arrhythmias remain a clinical challenge in the management of acute traumatic spinal cord injury (SCI). Still, there is a lack of knowledge regarding the characteristics of arrhythmias in patients with acute traumatic SCI. The aim of this prospective observational study was to investigate the occurrence of cardiac arrhythmias and cardiac arrests in patients with acute traumatic SCI. Methods As early as possible after SCI 24-hour Holter monitoring was performed. Additional Holter recordings were performed 1, 2, 3, and 4 weeks after SCI. Furthermore, 12-lead electrocardiograms (ECGs) were obtained shortly after SCI and at 4 weeks. Results Thirty patients were included. Bradycardia (heart rate (HR) <50 b.p.m.) was present in 17–35% of the patients with cervical (C1–C8) SCI (n = 24) within the first 14 days. In the following 14 days, the occurrence was 22–32%. Bradycardia in the thoracic (Th1–Th12) SCI group (n = 6) was present in 17–33% during the observation period. The differences between the two groups were not statistically significant. The mean minimum HR was significantly lower in the cervical group compared with the thoracic group both on 12-lead ECGs obtained shortly after SCI (P = 0.030) and at 4 weeks (P = 0.041). Conclusion Many patients with cervical SCI experience arrhythmias such as bradycardia, sinus node arrest, supraventricular tachycardia, and more rarely cardiac arrest the first month after SCI. Apart from sinus node arrests and limited bradycardia, no arrhythmias were seen in patients with thoracic SCI. Standard 12-lead ECGs will often miss the high prevalence these arrhythmias have. PMID:24559419

  8. Influence of intravascular low level He-Ne laser irradiation on iNOS, total-NOS, and ET-1 in acute spinal cord-injured rabbits

    NASA Astrophysics Data System (ADS)

    Yin, Zhenchun; Dong, Yinghai; Zhu, Jing

    2005-07-01

    Objective To research the influence of intravascular low level Laser irradiation (ILLLI) on total NOS, iNOS, and ET-1 in spinal cord following acute spinal cord injury (ASCI), and discuss the protective effects of ILLLI on neurons .Methods 72 rabbits were randomly divided into 3 groups: treatment group, injury group and control group. In treatment group and injury group, after laminectomy at the level of T-13, ASCI was performed by using Allen"s method with slight modification (6g×10cm) on rabbits. After injury, rabbits were treated immediately with He-Ne laser (power 5 mW, 1 hour per day for 10 days). At the day of 10th after treatment, total-NOS, iNOS, and ET-1 in spinal cord tissues were measured. Results The expression level of total-NOS, iNOS, and ET-1 in spinal cord in injury group were significantly higher than those in control group (P<0.05), while after ILLLI the level of these index in treatment group decreased statistically significantly compared with those in injury group (P<0.05). Conclusion ILLLI can significantly decrease the expression level of total-NOS, iNOS, and ET-1 in spinal cord. It indicates that ILLLI can relieve the overexpression of total-NOS, iNOS, and ET-1 ,and thus can perform protective effects on neurons in the course of secondary spinal cord injury (SSCI) following ASCI

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

    PubMed

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

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h. PMID:24071567

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

    PubMed

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

    2014-02-01

    Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h.

  11. Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

    PubMed Central

    Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

    2016-01-01

    Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients

  12. Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

    PubMed Central

    Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

    2016-01-01

    Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients

  13. Neurogenic motor evoked potential changes after acute experimental spinal cord i njury.

    PubMed

    Shen, Qiang; Jia, Lianshun; Zhou, Xuhui

    2000-08-15

    OBJECTIVE: To better understand the characte ristics of the neurogenic motor evoked potential (NMEP) before and after acute s pinal cord injury. METHODS: We recorded and characterized the spinal cord NMEP fro m 48 normal rats and from 38 rats with spinal cord hemisection lesion. Spinal co rd NMEPs were elicited by applying a range of current intensities with bipolar m icroelectrode stimuli to the C4 cord segment and recording the responses from sc iatic nerves with bipolar microelectrodes placed in the neurilemma. RESULTS: The evoked potentials consisted of three stable and re producible negative and three positive peaks. The meanplus minusSD latencies of N1 were 2.89plus minus0.22 ms on the right side and 2.89plus minus0.24 ms on th e left side. The mean conduction velocity was 47.9 m/s. The meanplus minusSD am plitudes of N1 were 3.61plus minus2.10 muV on the right side and 3.83plus minus2.3 2 muV on the left side. The amplitudes of N1 were signific antly different among the eight stimulus intensity groups (right side: F=2.22, df=7201, P=0.03; left side: F=2.11, df=7206, P=0.04). The amplitude was largest when the stimulus intensity was 1.1-2.5 mA. The latencies of N1 were not si gnificantly different among the eight stimulus intensity groups (right side: F=0.40, df=7201, P=0.9; left side: F=1.20, df=7206, P=0.3. The amplitudes and latencies of N2, N3 were not significantly different among the eight stimulus intensity groups. There were no significant changes in latency and amplitude between the left and the right side nerve responses. Thirty-eight rats underwent T9 cord right side hemisection. Among them, 20 (53%), 30 (79%), and 32 (84%) rats could not be reco rded in corresponding to N1, N2, and N3, respectively, in the right-side sciati c nerves; and 13 (79%), 18 (47%), and 21 (55%), in corresponding to N1, N2, and N3 in the left-side sciatic nerves. The latency was significantly delayed on th e both right and left sides. The amplitude N1 was significantly

  14. Therapeutic approaches for spinal cord injury

    PubMed Central

    Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Marcon, Raphael Martus; Letaif, Olavo Biraghi; da Rocha, Ivan Dias

    2012-01-01

    This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a “disease that should not be treated.” Over the last two decades, several studies have been performed to obtain more effective treatments for spinal cord injury. Most of these studies approach a patient with acute spinal cord injury in one of four manners: corrective surgery or a physical, biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life. PMID:23070351

  15. An expert consensus on the evaluation and treatment of acute thoracolumbar spine and spinal cord injury in China

    PubMed Central

    Zhang, Zhicheng; Li, Fang; Sun, Tiansheng

    2013-01-01

    This is an expert consensus on the evaluation and treatment of thoracolumbar spinal injury, established from February 2009 to July 2010. The expert consensus consists mainly of six parts with a total of 54 recommendations including the overview (one item); pre-hospital care (one item); evaluation and diagnosis (13 items); treatment (23 items); prevention and treatment of major complications (12 items); and rehabilitation (four items). This is the first time that Chinese experts have published a consensus on spine and spinal cord injury. The expert consensus was established based on Delphi methods, literature analysis, and clinical experiences. Each recommendation is supported by and was interpreted using multi-level evidences. The level of agreement with the recommendation among the panel members was assessed as either low, moderate, or strong. Each panel member was asked to indicate his or her level of agreement on a 5-point scale, with “1” corresponding to neutrality and “5” representing maximum agreement. Scores were aggregated across the panel members and an arithmetic mean was calculated. This mean score was then translated into low, moderate, or strong. After all of the votes were collected and calculated, the results showed no low-level recommendations, 10 moderate-level recommendations, and 44 strong-level recommendations. An expert consensus was reached and was recognized by Chinese spine surgeons. Wide-scale adoption of these recommendations is urgent in the management of acute thoracolumbar spine and spinal cord injury in a broader attempt to create a standard evaluation and treatment strategy for acute thoracolumbar spine and spinal cord injury in China. PMID:25206628

  16. Pretest of the clinical application of a management model for comprehensive treatments of acute spinal cord injury

    PubMed Central

    Zhang, Ruimin; Chen, Qiulan; Xiao, Yilei; Chong, Zonglei

    2015-01-01

    Objective: To explore the effects of a new management model of comprehensive treatments of acute spinal cord injury (SCI) on clinical application. Methods: From January 2010 to January 2011, there were 89 patients with acute SCI over the same admission period, including 32 cases divided into the management model group and the other 57 into the control group. Respectively, at the 1, 3 and 6 months after treatment, the score standardization, developed by the American Association of spinal cord injury (ASIA), was used to assess the motor and sensory function during the admission period. At the same time, a follow-up survey was made to investigate the satisfaction of patients and their families. Results: At 1 and 3 months after treatment, the motor and feeling function scores of patients in the experimental group both improved significantly compared with the control group, and the differences were statistically significant (P<0.05). In addition, six months after treatment, the motor and sensory function scores of patients in the control group were not significantly improved any longer; while those scores in the experimental group still significantly recovered, and the difference between experimental and control groups was also statistically significant (P<0.05). According to the follow-up, patients and their families in the experimental group were of greater satisfaction than the control group (P<0.05). Conclusions: The management model of acute SCI treatment performed perfect clinical effects, and was worth promoting. PMID:26464687

  17. Involvement of spinal cord opioid mechanisms in the acute antinociceptive effect of hyperbaric oxygen in mice1

    PubMed Central

    Heeman, Jacqueline H.; Zhang, Yangmiao; Shirachi, Donald Y.; Quock, Raymond M.

    2013-01-01

    Earlier research has demonstrated that treatment with hyperbaric oxygen (HBO2) can elicit an antinociceptive response in models of acute pain. We have demonstrated that this antinociceptive effect is centrally-mediated and is dependent on opioid receptors. The purpose of the present study was to examine the role of endogenous opioid peptides and opioid receptors specifically in the spinal cord in the acute antinociceptive effect of HBO2 in mice. Male NIH Swiss mice were exposed to HBO2 (100% oxygen @ 3.5 atmospheres absolute) for 11 min and their antinociceptive responsiveness was determined using the glacial acetic acid-induced abdominal constriction test. HBO2-induced antinociception was sensitive to antagonism by intrathecal (i.t.) pretreatment with the κ- and μ-selective opioid antagonists norbinaltorphimine and β-funalrexamine, respectively, but not the δ-selective antagonist naltrindole. The antinociceptive effect of HBO2 was also significantly attenuated by i.t. pretreatment with a rabbit antiserum against rat dynorphin1-13 but not antisera against β-endorphin or methionine-enkephalin. Based on these experimental findings, the acute antinociceptive effect of HBO2 appears to involve neuronal release of dynorphin and activation of κ and μ opioid receptors in the spinal cord. PMID:24113418

  18. Spinal Cord Injury Map

    MedlinePlus

    ... on the severity of the injury. Tap this spinal column to see how the level of injury affects loss of function and control. Learn more about spinal cord injuries. A spinal cord injury affects the ...

  19. A Rare Complication of Spinal Cord Ischemia Following Endovascular Aneurysm Repair of an Infrarenal Abdominal Aortic Aneurysm with Arteriosclerosis Obliterans: Report of a Case

    PubMed Central

    Matsumoto, Takuya; Matsubara, Yutaka; Inoue, Kentaro; Aoyagi, Yukihiko; Matsuda, Daisuke; Tanaka, Shinichi; Okadome, Jun; Maehara, Yoshihiko

    2016-01-01

    We herein report a case of a rare complication of spinal cord ischemia (SCI) following endovascular aneurysm repair (EVAR). Computed tomography showed stenosis and calcification of bilateral iliac arteries and a saccular aneurysm of the terminal aorta. Paraplegia occurred soon after balloon angioplasty of iliac arteries and EVAR. Cerebrospinal fluid drainage was not performed because the patient was on dual antiplatelet drugs. The patient was treated with intravenous methylpredonisolone and naloxone; however, this did not improve his paraplegia. SCI after EVAR is extremely rare and unpredictable complication, however, physicians should be aware of SCI after EVAR in patients with atherosclerosis. PMID:27738476

  20. Olprinone Attenuates the Acute Inflammatory Response and Apoptosis after Spinal Cord Trauma in Mice

    PubMed Central

    Esposito, Emanuela; Mazzon, Emanuela; Paterniti, Irene; Impellizzeri, Daniela; Bramanti, Placido; Cuzzocrea, Salvatore

    2010-01-01

    Background Olprinone hydrochloride is a newly developed compound that selectively inhibits PDE type III and is characterized by several properties, including positive inotropic effects, peripheral vasodilatory effects, and a bronchodilator effect. In clinical settings, olprinone is commonly used to treat congestive cardiac failure, due to its inotropic and vasodilating effects. The mechanism of these cardiac effects is attributed to increased cellular concentrations of cAMP. The aim of the present study was to evaluate the pharmacological action of olprinone on the secondary damage in experimental spinal cord injury (SCI) in mice. Methodology/Principal Findings Traumatic SCI is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should be preventable, no effective treatment options currently exist for patients with SCI. Spinal cord trauma was induced in mice by the application of vascular clips (force of 24 g) to the dura via a four-level T5–T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, apoptosis, and locomotor disturbance. Olprinone treatment (0.2 mg/kg, i.p.) 1 and 6 h after the SCI significantly reduced: (1) the degree of spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation, (4) pro-inflammatory cytokines, (5) NF-κB expression, (6) p-ERK1/2 and p38 expression and (7) apoptosis (TUNEL staining, FAS ligand, Bax and Bcl-2 expression). Moreover, olprinone significantly ameliorated the recovery of hind-limb function (evaluated by motor recovery score). Conclusions/Significance Taken together, our results clearly demonstrate that olprinone treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma. PMID

  1. Acute intraparenchymal spinal cord injury in a cat due to high-rise syndrome

    PubMed Central

    Cruz–Arámbulo, Robert; Nykamp, Stephanie

    2012-01-01

    A 9-year-old spayed female Bengal Red cat was evaluated for high-rise syndrome. The cat had paraplegia of the hind limbs, intact reflexes and pain perception, and hyperesthesia in the caudal thoracic area. Mentation, cranial nerve function, forelimb proprioceptive responses, and spinal reflexes were normal. There were no abnormalities on radiographs or computed tomography scan, but magnetic resonance imaging revealed a hyperintense intraparenchymal spinal cord lesion on T2-weighted and T2 fat saturation images. PMID:22942443

  2. Effect of technique and timing of tracheostomy in patients with acute traumatic spinal cord injury undergoing mechanical ventilation

    PubMed Central

    Ganuza, Javier Romero; Forcada, Angel Garcia; Gambarrutta, Claudia; De La Lastra Buigues, Elena Diez; Gonzalez, Victoria Eugenia Merlo; Fuentes, Fátima Paz; Luciani, Alejandro A.

    2011-01-01

    Objective To assess the effect of timing and techniques of tracheostomy on morbidity, mortality, and the burden of resources in patients with acute traumatic spinal cord injuries (SCIs) undergoing mechanical ventilation. Design Review of a prospectively collected database. Setting Intensive and intermediate care units of a monographic hospital for the treatment of SCI. Participants Consecutive patients admitted to the intensive care unit (ICU) during their first inpatient rehabilitation for cervical and thoracic traumatic SCI. A total of 323 patients were included: 297 required mechanical ventilation and 215 underwent tracheostomy. Outcome measures Demographic data, data relevant to the patients’ neurological injuries (level and grade of spinal cord damage), tracheostomy technique and timing, duration of mechanical ventilation, length of stay at ICU, incidence of pneumonia, incidence of perioperative and early postoperative complications, and mortality. Results Early tracheostomy (<7 days after orotracheal intubation) tracheostomy was performed in 101 patients (47%) and late (≥7 days) in 114 (53%). Surgical tracheostomy was employed in 119 cases (55%) and percutaneous tracheostomy in 96 (45%). There were 61 complications in 53 patients related to all tracheostomy procedures. Two were qualified as serious (tracheoesophageal fistula and mediastinal abscess). Other complications were mild. Bleeding was moderate in one case (late, percutaneous tracheostomy). Postoperative infection rate was low. Mortality of all causes was also low. Conclusion Early tracheostomy may have favorable effects in patients with acute traumatic SC. Both techniques, percutaneous and surgical tracheostomy, can be performed safely in the ICU. PMID:21528630

  3. Spinal Cord Injuries

    MedlinePlus

    ... your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... bone disks that make up your spine. Most injuries don't cut through your spinal cord. Instead, ...

  4. Decorin blocks scarring and cystic cavitation in acute and induces scar dissolution in chronic spinal cord wounds.

    PubMed

    Ahmed, Zubair; Bansal, Daljeet; Tizzard, Katie; Surey, Sarina; Esmaeili, Maryam; Gonzalez, Ana Maria; Berry, Martin; Logan, Ann

    2014-04-01

    In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarring and wound cavitation impede axon regeneration implying that a combination of both scar suppression and axogenic treatments is required to achieve functional recovery. After treating acute and chronic dorsal funicular spinal cord lesions (DFL) in adult rats with the pan-TGF-β1/2 antagonist Decorin, we report that in: (1), acute DFL, the development of all injury parameters was significantly retarded e.g., wound cavity area by 68%, encapsulation of the wound by a glia limitans accessoria (GLA) by 65%, GLA basal lamina thickness by 94%, fibronectin, NG2 and Sema-3A deposition by 87%, 48% and 48%, respectively, and both macrophage and reactive microglia accumulations by 60%; and (2), chronic DFL, all the above parameters were attenuated to a lesser extent e.g., wound cavity area by 11%, GLA encapsulation by 25%, GLA basal lamina thickness by 31%, extracellular fibronectin, NG2 and Sema-3A deposition by 58%, 22% and 29%, respectively, and macrophage and reactive microglia accumulations by 44%. Moreover, in acute and chronic DFL, levels of tissue plasminogen activator (tPA) were raised (by 236% and 482%, respectively), as were active-MMP-2 (by 64% and 91%, respectively) and active-MMP-9 (by 122% and 18%, respectively), while plasminogen activator inhibitor-1 (PAI-1) was suppressed (by 56% and 23%, respectively) and active-TIMP-1 and active TIMP-2 were both lower but only significantly suppressed in acute DFL (by 56 and 21%, respectively). These findings demonstrate that both scar tissue mass and cavitation are attenuated in acute and chronic spinal cord wounds by Decorin treatment and suggest that the dominant effect of Decorin during acute scarring is anti-fibrogenic through suppression of inflammatory fibrosis by neutralisation of TGF-β1/2 whereas, in chronic lesions, Decorin-induction of tPA and MMP (concomitant with reduced complimentary levels of TIMP and PAI-1

  5. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  6. 18F-FDG-PET imaging of rat spinal cord demonstrates altered glucose uptake acutely after contusion injury

    PubMed Central

    von Leden, Ramona E.; Selwyn, Reed G.; Jaiswal, Shalini; Wilson, Colin M.; Khayrullina, Guzal; Byrnes, Kimberly R.

    2016-01-01

    Spinal cord injury (SCI) results in an acute reduction in neuronal and glial cell viability, disruption in axonal tract integrity, and prolonged increases in glial activity and inflammation, all of which can influence regional metabolism and glucose utilization. To date, the understanding of glucose uptake and utilization in the injured spinal cord is limited. Positron emission tomography (PET)-based measurements of glucose uptake may therefore serve as a novel bio-marker for SCI. This study aimed to determine the acute and sub-acute glucose uptake pattern after SCI to determine its potential as a novel non-invasive tool for injury assessment and to begin to understand the glucose uptake pattern following acute SCI. Briefly, adult male Sprague-Dawley rats were subjected to moderate contusion SCI, confirmed by locomotor function and histology. PET imaging with [18F]Fluorodeoxyglucose (FDG) was performed prior to injury and at 6 and 24 hours and 15 days post-injury (dpi). FDG-PET imaging revealed significantly depressed glucose uptake at 6 hours post-injury at the lesion epicenter that returned to sham/naïve levels at 24 hours and 15 dpi after moderate injury. FDG uptake at 15 dpi was likely influenced by a combination of elevated glial presence and reduced neuronal viability. These results show that moderate SCI results in acute depression in glucose uptake followed by an increase in glucose uptake that may be related to neuroinflammation. This acute and sub-acute uptake, which is dependent on cellular responses, may represent a therapeutic target. PMID:27084688

  7. Spinal cord contusion models.

    PubMed

    Young, Wise

    2002-01-01

    Most human spinal cord injuries involve contusions of the spinal cord. Many investigators have long used weight-drop contusion animal models to study the pathophysiology and genetic responses of spinal cord injury. All spinal cord injury therapies tested to date in clinical trial were validated in such models. In recent years, the trend has been towards use of rats for spinal cord injury studies. The MASCIS Impactor is a well-standardized rat spinal cord contusion model that produces very consistent graded spinal cord damage that linearly predicts 24-h lesion volumes, 6-week white matter sparing, and locomotor recovery in rats. All aspects of the model, including anesthesia for male and female rats, age rather than body weight criteria, and arterial blood gases were empirically selected to enhance the consistency of injury. PMID:12440371

  8. Administration of low dose estrogen attenuates gliosis and protects neurons in acute spinal cord injury in rats.

    PubMed

    Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

    2016-03-01

    Spinal cord injury (SCI) is a debilitating condition with neurological deficits and loss of motor function that, depending on the severity, may lead to paralysis. The only treatment currently available is methylprednisolone, which is widely used and renders limited efficacy in SCI. Therefore, other therapeutic agents must be developed. The neuroprotective efficacy of estrogen in SCI was studied with a pre-clinical and pro-translational perspective. Acute SCI was induced in rats that were treated with low doses of estrogen (1, 5, 10, or 100 μg/kg) and compared with vehicle-treated injured rats or laminectomy control (sham) rats at 48 h post-SCI. Changes in gliosis and other pro-inflammatory responses, expression and activity of proteolytic enzymes (e.g., calpain, caspase-3), apoptosis of neurons in SCI, and cell death were monitored via Western blotting and immunohistochemistry. Negligible pro-inflammatory responses or proteolytic events and very low levels of neuronal death were found in sham rats. In contrast, vehicle-treated SCI rats showed profound pro-inflammatory responses with reactive gliosis, elevated expression and activity of calpain and caspase-3, elevated Bax:Bcl-2 ratio, and high levels of neuronal death in lesion and caudal regions of the injured spinal cord. Estrogen treatment at each dose reduced pro-inflammatory and proteolytic activities and protected neurons in the caudal penumbra in acute SCI. Estrogen treatment at 10 μg was found to be as effective as 100 μg in ameliorating the above parameters in injured animals. Results from this investigation indicated that estrogen at a low dose could be a promising therapeutic agent for treating acute SCI. Experimental studies with low dose estrogen therapy in acute spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes. Estrogen has been found to ameliorate several degenerative pathways following SCI. Thus, such early protective effects may even lead to functional

  9. Spinal cord infarction: a rare cause of paraplegia

    PubMed Central

    Patel, Sonali; Naidoo, Khimara; Thomas, Peter

    2014-01-01

    Spinal cord infarction is rare and represents a diagnostic challenge for many physicians. There are few reported cases worldwide with a prevalence of 1.2% of all strokes. Circulation to the spinal cord is supplied by a rich anastomosis. The anterior spinal artery supplies the anterior two thirds of the spinal cord and infarction to this area is marked by paralysis, spinothalamic sensory deficit and loss of sphincter control depending on where the lesion is. Treatment of spinal cord infarction focuses on rehabilitation with diverse outcomes. This report presents a case of acute spinal cord infarction with acquisition of MRI to aid diagnosis. PMID:24966260

  10. Spinal cord infarction: a rare cause of paraplegia.

    PubMed

    Patel, Sonali; Naidoo, Khimara; Thomas, Peter

    2014-06-25

    Spinal cord infarction is rare and represents a diagnostic challenge for many physicians. There are few reported cases worldwide with a prevalence of 1.2% of all strokes. Circulation to the spinal cord is supplied by a rich anastomosis. The anterior spinal artery supplies the anterior two thirds of the spinal cord and infarction to this area is marked by paralysis, spinothalamic sensory deficit and loss of sphincter control depending on where the lesion is. Treatment of spinal cord infarction focuses on rehabilitation with diverse outcomes. This report presents a case of acute spinal cord infarction with acquisition of MRI to aid diagnosis.

  11. Nanomedicine for Treating Spinal Cord Injury

    PubMed Central

    Tyler, Jacqueline Y.; Xu, Xiao-Ming; Cheng, Ji-Xin

    2015-01-01

    Spinal cord injury results in significant mortality and morbidity, lifestyle changes, and difficult rehabilitation. Treatment of spinal cord injury is challenging because the spinal cord is both complex to treat acutely and difficult to regenerate. Nanomaterials can be used to provide effective treatments; their unique properties can facilitate drug delivery to the injury site, enact as neuroprotective agents, or provide platforms to stimulate regrowth of damaged tissues. We review recent uses of nanomaterials including nanowires, micelles, nanoparticles, liposomes, and carbon-based nanomaterials for neuroprotection in the acute phase. We also review the design and neural regenerative application of electrospun scaffolds, conduits, and self-assembling peptide scaffolds. PMID:23945984

  12. Nanomedicine for treating spinal cord injury

    NASA Astrophysics Data System (ADS)

    Tyler, Jacqueline Y.; Xu, Xiao-Ming; Cheng, Ji-Xin

    2013-09-01

    Spinal cord injury results in significant mortality and morbidity, lifestyle changes, and difficult rehabilitation. Treatment of spinal cord injury is challenging because the spinal cord is both complex to treat acutely and difficult to regenerate. Nanomaterials can be used to provide effective treatments; their unique properties can facilitate drug delivery to the injury site, enact as neuroprotective agents, or provide platforms to stimulate regrowth of damaged tissues. We review recent uses of nanomaterials including nanowires, micelles, nanoparticles, liposomes, and carbon-based nanomaterials for neuroprotection in the acute phase. We also review the design and neural regenerative application of electrospun scaffolds, conduits, and self-assembling peptide scaffolds.

  13. Effects of deep barbiturate coma on acute spinal cord injury in the cat.

    PubMed

    Ducati, A; Schieppati, M; Giovanelli, M A

    1984-04-01

    The effects of barbiturate administration on experimental balloon-induced spinal cord injury were tested in cats. Somatosensory evoked potentials from sciatic nerve stimulation were obtained before trauma and every 60 minutes after it up to the sixth hour, when the animals were killed. Eight cats received no barbiturate treatment. On histologic examination the traumatic lesion was found to be extensive (mean, 72.8% of total cross section of the cord area), sparing dorsal columns only in six cats. Somatosensory evoked potentials were absent in two cats and profoundly modified (that is, the late waves were absent) in six cats at the sixth hour. Eight cats were given a continuous infusion for 1 hour of intravenous thiopental sodium (total dose, 65-90 mg/kg) starting 30 minutes after trauma. In these eight cats, the extent of the traumatic lesion was significantly reduced (8.8% of the cord area). Among them, three animals presented with unaltered somatosensory evoked potentials (that is, with the presence of both primary components and late waves) at the sixth hour. It was concluded that thiopental sodium improves the response of the spinal cord to trauma, both at an anatomic and at a functional level.

  14. Change in Neuroplasticity-Related Proteins in Response to Acute Activity-Based Therapy in Persons With Spinal Cord Injury

    PubMed Central

    Astorino, Todd A.; Knoblach, Susan M.; Feather, Jillenne

    2014-01-01

    Background: Activity-based therapy (ABT) focuses on regaining motor and sensory function below the level of the lesion in persons with a spinal cord injury (SCI). This is accomplished through repetitive training of specific motor tasks. Research has shown that ABT may increase neuroplasticity in the rat and human spinal cord. Objective: The primary aim of this study was to examine acute alterations in neuroplasticity-related proteins during ABT in persons with SCI. Methods: Volunteers were current participants in an ABT program and consisted of 12 men and 3 women (age, 31.8 ± 10.9 years) with chronic SCI (injury duration, 63.9 ± 54.4 months). A single 2-hour bout of ABT consisted of standing load bearing, body weight-supported treadmill training, whole body vibration, and functional electrical stimulation. Blood samples were obtained at baseline and immediately after completion of each modality to determine serum levels of brain-derived neurotrophic factor (BDNF), prolactin, and cortisol. Results: One-way analysis of variance (ANOVA) with repeated measures was used to examine differences in proteins over time. Results revealed baseline levels of BDNF (2.37 ± 1.41 ng/mL) that were lower than previous research has demonstrated in persons with SCI. No change in BDNF or cortisol was found, although prolactin was significantly reduced in response to ABT. Conclusion: Despite the length of the bout, acute changes in BDNF were not observed. Whether different intensities or modalities of ABT may promote acute increases in serum BDNF in individuals with SCI remains to be determined and further study is merited. PMID:25477737

  15. Neuroprotective effects and impact on caspase-12 expression of tauroursodeoxycholic acid after acute spinal cord injury in rats

    PubMed Central

    Dong, Yi; Miao, Lei; Hei, Long; Lin, Leilei; Ding, Huiqiang

    2015-01-01

    Objective: To observe the effects of tauroursodeoxycholic acid (TUDCA) on nerve function after acute spinal cord injury (SCI) in rats, observe its effect on neuronal apoptosis and caspase-12 expression levels, and investigate the underlying mechanism. Methods: We used a modified Allen’s weight-drop trauma method to establish a rat acute SCI model. The rats were randomly divided into three groups: group A (sham surgery group), group B (DMSO control group) and group C (TUDCA treatment group), with 36 rats in each group. At one minute and at 24 hours after successfully establishing the model, rats in group C received an intraperitoneal injection of TUDCA (200 mg/kg), while rats in group B received an equal amount of DMSO at the same time points. At 24 hours, three days, and five days after injury, a modified Tarlov scoring method and Rivlin’s oblique plate test were used to evaluate rat spinal cord nerve function recovery. Animals were sacrificed at 24 hours, three days, and five days after injury. Specimens were obtained from the center of the injury sites; the pathological changes in spinal cord tissue were observed after hematoxylin-eosin (HE) staining; apoptosis was detected using the TUNEL method, and the expression of caspase-12 was measured at the protein level using immunohistochemistry and Western blots. Results: Group C differed significantly from group B in Tarlov scores and the oblique table test as early as 24 hours after the injury (P < 0.05). The TUNEL assay test results showed that neurons underwent apoptosis after SCI, which peaked at 24 hours. The ratios of apoptotic cells in group C were significantly lower than those in group B at 24 hours, three days, and five days after injury (P < 0.01). The immunohistochemistry and Western blot results showed that the caspase-12 expression levels of group C were lower than those of group B at 24 hours, three days, and five days after injury (P < 0.05). Conclusion: TUDCA can inhibit the expression of caspase

  16. Acute spinal cord injury and infection with multidrug-resistant Acinetobacter calcoaceticus-baumannii complex among returning Operation Iraqi Freedom soldiers: Successful innovations in rehabilitation during isolation.

    PubMed

    Recio, Albert C; Bohart, Zachary W; Havens, Spencer R; Stiens, Steven A

    2010-04-01

    Concerns about drug-resistant infectious organisms are increasing in rehabilitation facilities. Resulting isolation protocols can potentially challenge the patients' access to medical care, psychological adaptation, mobility, and environmental interaction and therefore hinder the rehabilitation process. We report a systematic, retrospective case review of an active-duty Army sergeant who sustained a C5 American Spinal Cord Injury Association Impairment Scale A spinal cord injury while serving in Operation Iraqi Freedom. The patient's acute rehabilitation was complicated by an Acinetobacter calcoaceticus-baumannii complex infection, in the blood and urine, contracted while in Iraq. Isolation protocols were designed to enable regular hands-on contact for proprioceptive neuromuscular facilitation, transfers, wheelchair fitting, mobility training, and environmental control. After 1 mo of comprehensive acute interdisciplinary rehabilitation, delivered in a single room on the spinal cord injury unit, the patient acquired functional skills comparable with other complete C5 tetraplegics in our unit. If a patient with spinal cord injury must be placed in isolation, it is still feasible to conduct a comprehensive interdisciplinary rehabilitation program while strictly adhering to contact isolation protocols.

  17. Systematic analysis of axonal damage and inflammatory response in different white matter tracts of acutely injured rat spinal cord.

    PubMed

    Gomes-Leal, W; Corkill, D J; Picanço-Diniz, C W

    2005-12-20

    The mechanisms of white matter (WM) damage during secondary degeneration are a fundamental issue in the pathophysiology of central nervous system (CNS) diseases. Our main goal was to describe the pattern of an acute inflammatory response and secondary damage to axons in different WM tracts of acutely injured rat spinal cord. Adult rats were deeply anesthetized and injected with 20 nmol of NMDA into the spinal cord ventral horn on T7. Animals were perfused after survival times of 1 day, 3 days and 7 days. Ten micrometer sections were submitted to immunocytochemical analysis for activated macrophages/microglia, neutrophils and damaged axons. There were inflammatory response and progressive tissue destruction of ventral WM (VWM) with formation of microcysts in both VWM and lateral WM (LWM). In the VWM, the number of beta-amyloid precursor protein (beta-APP) end-bulbs increased from 1 day with a peak at 3 days, decreasing by 7 days following the injection. APP end-bulbs were present in the dorsal WM (DWM) at 3 days survival time but were not in the LWM. Electron microscopic analysis revealed different degrees of myelin disruption and axonal pathology in the vacuolated WM up to 14 mm along the rostrocaudal axis. Quantitative analysis revealed a significant loss of medium and large axons (P < 0.05), but not of small axons (P > 0.05). Our results suggest that bystander axonal damage and myelin vacuolation are important secondary component of the pathology of WM tracts following rat SCI. Further studies are needed to understand the mechanisms of these pathological events.

  18. A Pilot Feasibility Study of Massage to Reduce Pain in People with Spinal Cord Injury during Acute Rehabilitation

    PubMed Central

    Chase, Theresa; Jha, Amitabh; Brooks, C. A.; Allshouse, Amanda

    2013-01-01

    Objective To determine the feasibility of conducting a randomized controlled trial of massage therapy for patients with new spinal cord injury (SCI) during acute inpatient rehabilitation. Design A pilot single-center, randomized, single-blind, cross-over clinical trial. Setting Free-standing, not-for-profit, comprehensive rehabilitation center specializing in SCI rehabilitation Participants Forty adults ages 18 years and older undergoing acute rehabilitation following spinal cord injury reporting any type of pain. Intervention Rehabilitation nurses trained to give broad compression massage (BCM) and a control light contact touch (LCT) treatments. Participants were randomized to receive either BCM or LCT first, in six 20 minute treatment sessions over two weeks, with a one week wash-out between the two-week treatment periods. Main Outcome Measures Primary outcomes were changes in pain intensity and in fatigue, measured daily. Secondary outcomes included depressive symptoms measured by the Patient Health Questionnaire-9 (PHQ-9) and an assessment of pain medication usage. Results Pain intensity was higher at baseline and reduced more in the LCT-first group compared to the BCM-first group in period 1 (p=0.014); although this pattern was not found in period 2 (p=0.58). LCT and BCM groups did not significantly differ on any secondary measures except PHQ-9. Conclusions This study demonstrates the feasibility of using rehabilitation nurses to provide tactile therapy to patients with SCI and suggests a model for controlled clinical trials examining the efficacy of massage therapies. While efficacy was difficult to assess, broad compression massage was safe and well tolerated. PMID:24042991

  19. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

    PubMed Central

    Chen, Wenling; Marvizón, Juan Carlos G.

    2009-01-01

    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

  20. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) and DNA damage in the caudal region of acute and chronic spinal cord injured rats treated by embryonic neural stem cells.

    PubMed

    DAGCI, T; ARMAGAN, G; KONYALIOGLU, S; YALCIN, A

    2009-01-01

    The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA-damage levels in both study groups - acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured animals when compared to acute and chronic sham groups. Our data has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy.

  1. Development of topical BAPN delivery system for acute spinal cord injury in dogs.

    PubMed

    Chvapil, M; Weinstein, P R; Misiorowski, R L; Telles, D; Rankin, L; Stoy, V

    1984-09-01

    Topical sustained release of various medications by a subdurally implantable device at the site of spinal cord injury is considered advantageous in the treatment of early symptoms of tissue damage. A typical case is the interference with collagenous scar by beta-aminopropionitrile, inhibiting collagen polymerization. Four materials, silicone, polyethylene, polytetrafluoroethylene (PTFE), and polyacrylonitrile-based hydrogel were evaluated for biocompatibility in subcutaneous implantations. The hydrogel, the least reactive, was then compared with silicone sheets as subcural implants. The histology favored the hydrogel as the most inert material, which was then used for the construction of soft, pliable pouches, releasing the drug through the hydrated wall at a rate controlled by an osmotic pump. PMID:6544776

  2. FGF-1 Triggers Pannexin-1 Hemichannel Opening in Spinal Astrocytes of Rodents and Promotes Inflammatory Responses in Acute Spinal Cord Slices

    PubMed Central

    Yang, Guang; Bukauskas, Feliksas F.

    2016-01-01

    We show here that the growth factor FGF-1 is proinflammatory in the spinal cord and explore the inflammatory mechanisms. FGF-1 applied to rat spinal astrocytes in culture initiates calcium signaling and induces secretion of ATP that within minutes increases membrane permeability to ethidium (Etd+) and Ca2+ by activating P2X7 receptors (P2X7Rs) that open pannexin hemichannels (Px1 HCs) that release further ATP; by 7 h treatment, connexin 43 hemichannels (Cx43 HCs) are also opened. In acute mouse spinal cord slices ex vivo, we found that FGF-1 treatment for 1 h increases the percentage of GFAP-positive astrocytes that show enhanced Px1 HC-mediated Etd+ uptake. This response to FGF-1 was not observed in astrocytes in slices of cerebral cortex. FGF-1-induced dye uptake by astrocytes is prevented by BAPTA-AM or a phospholipase C (PLC) inhibitor. Furthermore, in spinal cord slices, P2X7R antagonists (BBG and A740003) and Px1 HC blockers (10Panx1 and carbenoxolone) prevent the increase in Etd+ uptake by astrocytes, whereas Gap19, a selective Cx43 HC blocker, has no effect on dye uptake at this time. Microglia are not required for the increase in Etd+ uptake by astrocytes induced by FGF-1, although they are activated by FGF-1 treatment. The morphological signs of microglia activation are inhibited by P2X7R antagonists and 10Panx1 and are associated with elevated levels of proinflammatory cytokines in cord slices treated with FGF-1. The FGF-1 initiated cascade may play an important role in spinal cord inflammation in vivo. SIGNIFICANCE STATEMENT We find that FGF-1 elevates [Ca2+]i in spinal astrocytes, which causes vesicular release of ATP and activation of P2X7Rs to trigger opening of Px1 HCs, which release further ATP. This regenerative response occurs in astrocyte cultures and in acute spinal cord slices. In the latter, FGF-1 application promotes the activation of microglia and increases the production of proinflammatory cytokines through mechanisms depending on P2X7

  3. Thromboembolism in the Sub-Acute Phase of Spinal Cord Injury: A Systematic Review of the Literature

    PubMed Central

    Belci, Maurizio; Van Middendorp, Joost J; Al Halabi, Ahmed; Meagher, Tom M

    2016-01-01

    To review the evidence of thromboembolism incidence and prophylaxis in the sub-acute phase of spinal cord injury (SCI) 3–6 months post injury. All observational and experimental studies with any length of follow-up and no limitations on language or publication status published up to March 2015 were included. Two review authors independently selected trials for inclusion and extracted data. Outcomes studied were incidence of pulmonary embolism (PE) and deep vein thrombosis (DVT) in the sub-acute phase of SCI. The secondary outcome was type of thromboprophylaxis. Our search identified 4305 references and seven articles that met the inclusion criteria. Five papers reported PE events and three papers reported DVT events in the sub-acute phase of SCI. Studies were heterogeneous in populations, design and outcome reporting, therefore a meta-analysis was not performed. The included studies report a PE incidence of 0.5%–6.0% and DVT incidence of 2.0%–8.0% in the sub-acute phase of SCI. Thromboprophylaxis was poorly reported. Spinal patients continue to have a significant risk of PE and DVT after the acute period of their injury. Clinicians are advised to have a low threshold for suspecting venous thromboembolism in the sub-acute phase of SCI and to continue prophylactic anticoagulation therapy for a longer period of time. PMID:27790330

  4. Significant clinical, neuropathological and behavioural recovery from acute spinal cord trauma by transplantation of a well-defined somatic stem cell from human umbilical cord blood.

    PubMed

    Schira, Jessica; Gasis, Marcia; Estrada, Veronica; Hendricks, Marion; Schmitz, Christine; Trapp, Thorsten; Kruse, Fabian; Kögler, Gesine; Wernet, Peter; Hartung, Hans-Peter; Müller, Hans Werner

    2012-02-01

    Stem cell therapy is a potential treatment for spinal cord injury and different stem cell types have been grafted into animal models and humans suffering from spinal trauma. Due to inconsistent results, it is still an important and clinically relevant question which stem cell type will prove to be therapeutically effective. Thus far, stem cells of human sources grafted into spinal cord mostly included barely defined heterogeneous mesenchymal stem cell populations derived from bone marrow or umbilical cord blood. Here, we have transplanted a well-defined unrestricted somatic stem cell isolated from human umbilical cord blood into an acute traumatic spinal cord injury of adult immune suppressed rat. Grafting of unrestricted somatic stem cells into the vicinity of a dorsal hemisection injury at thoracic level eight resulted in hepatocyte growth factor-directed migration and accumulation within the lesion area, reduction in lesion size and augmented tissue sparing, enhanced axon regrowth and significant functional locomotor improvement as revealed by three behavioural tasks (open field Basso-Beattie-Bresnahan locomotor score, horizontal ladder walking test and CatWalk gait analysis). To accomplish the beneficial effects, neither neural differentiation nor long-lasting persistence of the grafted human stem cells appears to be required. The secretion of neurite outgrowth-promoting factors in vitro further suggests a paracrine function of unrestricted somatic stem cells in spinal cord injury. Given the highly supportive functional characteristics in spinal cord injury, production in virtually unlimited quantities at GMP grade and lack of ethical concerns, unrestricted somatic stem cells appear to be a highly suitable human stem cell source for clinical application in central nervous system injuries. PMID:21903726

  5. Spinal Cord Diseases

    MedlinePlus

    ... damages the vertebrae or other parts of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such as meningitis and polio Inflammatory diseases Autoimmune diseases Degenerative diseases such as amyotrophic lateral sclerosis and spinal ...

  6. Swim Training Initiated Acutely after Spinal Cord Injury Is Ineffective and Induces Extravasation In and Around the Epicenter

    PubMed Central

    Smith, Rebecca R.; Brown, Edward H.; Shum-Siu, Alice; Whelan, Ashley; Burke, Darlene A.; Benton, Richard L.

    2009-01-01

    Abstract Activity-based rehabilitation is a promising strategy for improving functional recovery following spinal cord injury (SCI). While results from both clinical and animal studies have shown that a variety of approaches can be effective, debate still exists regarding the optimal post-injury period to apply rehabilitation. We recently demonstrated that rats with moderately severe thoracic contusive SCI can be re-trained to swim when training is initiated 2 weeks after injury and that swim training had no effect on the recovery of overground locomotion. We concluded that swim training is a task-specific model of post-SCI activity-based rehabilitation. In the present study, we ask if re-training initiated acutely is more or less effective than when initiated at 2 weeks post-injury. Using the Louisville Swim Scale, an 18-point swimming assessment, supplemented by kinematic assessment of hindlimb movement during swimming, we report that acute re-training is less effective than training initiated at 2 weeks. Using the bioluminescent protein luciferase as a blood-borne macromolecular marker, we also show a significant increase in extravasation in and around the site of SCI following only 8 min of swimming at 3 days post-injury. Taken together, these results suggest that acute re-training in a rat model of SCI may compromise rehabilitation efforts via mechanisms that may involve one or more secondary injury cascades, including acute spinal microvascular dysfunction. PMID:19331515

  7. [Case of cerebellar and spinal cord infarction presenting with acute brachial diplegia due to right vertebral artery occlusion].

    PubMed

    Fujii, Takayuki; Santa, Yo; Akutagawa, Noriko; Nagano, Sukehisa; Yoshimura, Takeo

    2012-01-01

    A 73-year-old man was admitted for evaluation of sudden onset of dizziness, bilateral shoulder pain, and brachial diplegia. Neurological examination revealed severe bilateral weakness of the triceps brachii, wrist flexor, and wrist extensor muscles. There was no paresis of the lower limbs. His gait was ataxic. Pinprick and temperature sensations were diminished at the bilateral C6-C8 dermatomes. Vibration and position senses were intact. An MRI of the head revealed a right cerebellar infarction and occlusion of the right vertebral artery. An MRI of the cervical spine on T₂ weighted imaging (T₂WI) showed cord compression at the C3/4-C5/6 level secondary to spondylotic degeneration without any intramedullary signal changes of the cord. On the following day, however, high-signal lesions on T₂WI appeared in the C5-C6 spinal cord, suggesting cord infarction. Unilateral vertebral artery occlusion does not usually result in cervical cord infarction because of anastomosis of arteries. Because of the long-term mechanical compression in our case, it was likely that cervical cord ischemia was present before the onset of symptoms. On the basis of chronic cord compression, our case suggests that occlusion of a unilateral vertebral artery could cause cervical cord infarction.

  8. Exogenous Neuritin Promotes Nerve Regeneration After Acute Spinal Cord Injury in Rats.

    PubMed

    Gao, Rui; Li, Xingyi; Xi, Shaosong; Wang, Haiyan; Zhang, Hong; Zhu, Jingling; Shan, Liya; Song, Xiaoming; Luo, Xing; Yang, Lei; Huang, Jin

    2016-07-01

    Insufficient local levels of neurotrophic factor after spinal cord injury (SCI) are the leading cause of secondary injury and limited axonal regeneration. Neuritin belongs to a family of neurotrophic factors that promote neurite outgrowth, maintain neuronal survival, and provide a favorable microenvironment for the regeneration and repair of nerve cells after injury. However, it is not known whether the exogenously applied neuritin protein has a positive effect on nerve repair after SCI. This was investigated in the present study using purified human recombinant neuritin expressed in and purified from Pichia pastoris, which was tested in a rat SCI model. A recombinant neuritin concentration of 60 μg/ml induced the recovery of hind limb motor function and stimulated nerve regeneration in rats with SCI. Continuous administration of neuritin at this dose at an early stage after SCI inhibited poly ADP ribose polymerase (PARP) protein degradation and decreased neuronal apoptosis. In addition, during the critical postinjury period of axonal regeneration, exogenous neuritin treatment increased the expression of neurofilament 200 and growth-associated protein 43 in the damaged tissue, which was associated with the restoration of hind limb movement. These results suggest that neuritin creates an environment that promotes nerve cell survival and neurite regeneration after SCI, which contribute to nerve regeneration and the recovery of motor function. PMID:27009445

  9. Deep venous thrombosis and pulmonary embolism in patients with acute spinal cord injury: a comparison with nonparalyzed patients immobilized due to spinal fractures

    SciTech Connect

    Myllynen, P.; Kammonen, M.; Rokkanen, P.; Boestman, O.L.; Lalla, M.; Laasonen, E.

    1985-06-01

    The occurrence of deep venous thrombosis (DVT) was studied in the series of 23 consecutive patients with acute spinal cord injury and 14 immobilized patients with spinal fractures without paralysis. The incidence of DVT in paralyzed patients was 100% as detected by the /sup 125/I-labeled fibrinogen test and confirmed by contrast venography, and 64% as detected by repeated clinical examinations and confirmed by contrast venography. The respective incidence of DVT in nonparalyzed patients with spinal fractures was 0%. The diagnosis of DVT was reached earlier with the radiofibrinogen test than with the clinical followup (5 days vs. 25 days). Two of the 23 paralyzed patients (9%) developed nonfatal clinical pulmonary embolism (PE). There were no differences in the values of routine coagulation tests. The result justifies prophylactic anticoagulant therapy in all cases of spinal cord injury during the acute post-traumatic phase.

  10. Spinal cord infarction complicating acute hydrocephalus secondary to a colloid cyst of the third ventricle. Case report.

    PubMed

    Siu, Timothy L T; Bannan, Paul; Stokes, Bryant A R

    2005-07-01

    Occipital lobe infarction secondary to tentorial herniation is a rare but well-recognized complication of posterior cerebral artery interruption during acute hydrocephalus; however, a similar event in which tonsillar herniation leads to symptomatic occlusion of the anterior spinal arteries (ASAs) has not been reported. The authors present the case of a third ventricular colloid cyst in a previously healthy 24-year-old man who presented with symptoms and signs of critically raised intracranial pressure. He subsequently survived the ictus of insults following emergency external cerebrospinal fluid drainage and definitive resection of the colloid cyst, but he sustained occipital lobe and spinal cord infarction despite the absence of systematic hypotension. The presence of watershed cervicothoracic cord infarction on magnetic resonance imaging suggested that the most likely causes were compromise of ASAs during the period of acute hydrocephalus and the accompanying downward brain herniation. To the authors' knowledge, this is the first report to provide evidence that acute hydrocephalus may lead to ASA syndrome.

  11. Heat shock proteins as biomarkers for the rapid detection of brain and spinal cord ischemia: a review and comparison to other methods of detection in thoracic aneurysm repair

    PubMed Central

    McGarvey, Michael

    2010-01-01

    The heat shock proteins (HSPs) are members of highly conserved families of molecular chaperones that have multiple roles in vivo. We discuss the HSPs in general, and Hsp70 and Hsp27 in particular, and their rapid induction by severe stress in the context of tissue and organ expression in physiology and disease. We describe the current state of knowledge of the relationship and interactions between extra- and intracellular HSPs and describe mechanisms and significance of extracellular expression of HSPs. We focus on the role of the heat shock proteins as biomarkers of central nervous system (CNS) ischemia and other severe stressors and discuss recent and novel technologies for rapid measurement of proteins in vivo and ex vivo. The HSPs are compared to other proposed small molecule biomarkers for detection of CNS injury and to other methods of detecting brain and spinal cord ischemia in real time. While other biomarkers may be of use in prognosis and in design of appropriate therapies, none appears to be as rapid as the HSPs; therefore, no other measurement appears to be of use in the immediate detection of ongoing severe ischemia with the intention to immediately intervene to reduce the severity or risk of permanent damage. PMID:20803353

  12. The burden of acute traumatic spinal cord injury among adults in the united states: an update.

    PubMed

    Selvarajah, Shalini; Hammond, Edward R; Haider, Adil H; Abularrage, Christopher J; Becker, Daniel; Dhiman, Nitasha; Hyder, Omar; Gupta, Deepak; Black, James H; Schneider, Eric B

    2014-02-01

    The current incidence estimate of 40 traumatic spinal cord injuries (TSCI) per million population/year in the United States (U.S.) is based on data from the 1990s. We sought to update the incidence and epidemiology of TSCI in U.S adults by using the Nationwide Emergency Department Sample (NEDS), the largest all-payer emergency department (ED) database in the United States. Adult ED visits between 2007 and 2009 with a principal diagnosis of TSCI were identified using International Classification of Diseases (ICD)-9 codes (806.0-806.9 and 952.0-952.9). We describe TSCI cumulative incidence, mortality, discharge disposition, and hospital charges weighted to the U.S. population. The estimated 3-year cumulative incidence of TSCI was 56.4 per million adults. Cumulative incidence of TSCI in older adults increased from 79.4 per million older adults in 2007 to 87.7 by the end of 2009, but remained steady among younger adults. Overall, falls were the leading cause of TSCI (41.5%). ED charges rose by 20% over the study period, and death occurred in 5.7% of patients. Compared with younger adults, older adults demonstrated higher adjusted odds of mortality in the ED (adjusted odds ratio [AOR]=4.4; 95% confidence interval [CI]: 1.1-16.6), mortality during hospitalization (AOR=5.9; 95% CI: 4.7-7.4), and being discharged to chronic care (AOR=3.7; 95% CI: 3.0-4.5). The incidence of TSCI is higher than previously reported with a progressive increase among older adults who also experience worse outcomes compared with younger adults. ED-related TSCI charges are also increasing. These updated national estimates support the development of customized prevention strategies based on age-specific risk factors.

  13. Acute exercise prevents the development of neuropathic pain and the sprouting of non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury.

    PubMed

    Detloff, Megan Ryan; Smith, Evan J; Quiros Molina, Daniel; Ganzer, Patrick D; Houlé, John D

    2014-05-01

    Spinal cord injury (SCI) impaired sensory fiber transmission leads to chronic, debilitating neuropathic pain. Sensory afferents are responsive to neurotrophic factors, molecules that are known to promote survival and maintenance of neurons, and regulate sensory neuron transduction of peripheral stimuli. A subset of primary afferent fibers responds only to the glial cell-line derived neurotrophic factor (GDNF) family of ligands (GFLs) and is non-peptidergic. In peripheral nerve injury models, restoration of GDNF or artemin (another GFL) to pre-injury levels within the spinal cord attenuates neuropathic pain. One non-invasive approach to increase the levels of GFLs in the spinal cord is through exercise (Ex), and to date exercise training is the only ameliorative, non-pharmacological treatment for SCI-induced neuropathic pain. The purpose of this study was 3-fold: 1) to determine whether exercise affects the onset of SCI-induced neuropathic pain; 2) to examine the temporal profile of GDNF and artemin in the dorsal root ganglia and spinal cord dorsal horn regions associated with forepaw dermatomes after SCI and Ex; and 3) to characterize GFL-responsive sensory fiber plasticity after SCI and Ex. Adult, female, Sprague-Dawley rats received a moderate, unilateral spinal cord contusion at C5. A subset of rats was exercised (SCI+Ex) on automated running wheels for 20min, 5days/week starting at 5days post-injury (dpi), continuing until 9 or 37dpi. Hargreaves' and von Frey testing was performed preoperatively and weekly post-SCI. Forty-two percent of rats in the unexercised group exhibited tactile allodynia of the forepaws while the other 58% retained normal sensation. The development of SCI-induced neuropathic pain correlated with a marked decrease in the levels of GDNF and artemin in the spinal cord and DRGs. Additionally, a dramatic increase in the density and the distribution throughout the dorsal horn of GFL-responsive afferents was observed in rats with SCI

  14. Sphingolipids in spinal cord injury

    PubMed Central

    Jones, Zachary B; Ren, Yi

    2016-01-01

    Spinal cord injury (SCI) is a debilitating condition that affects millions of individuals worldwide. Despite progress over the last few decades, the molecular mechanisms of secondary SCI that continue to occur days and weeks after the original trauma remain poorly understood. As a result, current therapies for SCI are only marginally effective. Sphingolipids, a diverse class of bioactive lipids, have been shown to regulate SCI repair and key secondary injury processes such as apoptosis, ischemia and inflammation. This review will discuss the numerous roles of sphingolipids and highlight the potential of sphingolipid-targeted therapies for SCI. PMID:27570580

  15. Sphingolipids in spinal cord injury.

    PubMed

    Jones, Zachary B; Ren, Yi

    2016-01-01

    Spinal cord injury (SCI) is a debilitating condition that affects millions of individuals worldwide. Despite progress over the last few decades, the molecular mechanisms of secondary SCI that continue to occur days and weeks after the original trauma remain poorly understood. As a result, current therapies for SCI are only marginally effective. Sphingolipids, a diverse class of bioactive lipids, have been shown to regulate SCI repair and key secondary injury processes such as apoptosis, ischemia and inflammation. This review will discuss the numerous roles of sphingolipids and highlight the potential of sphingolipid-targeted therapies for SCI. PMID:27570580

  16. Curcumin protects against ischemic spinal cord injury: The pathway effect

    PubMed Central

    Zhang, Jinhua; Wei, Hao; Lin, Meimei; Chen, Chunmei; Wang, Chunhua; Liu, Maobai

    2013-01-01

    Inducible nitric oxide synthase and N-methyl-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin. Reverse transcription-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyl-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tarlov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyl-D-aspartate receptor expression. PMID:25206661

  17. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

    PubMed Central

    Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  18. Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury.

    PubMed

    Shapiro, J; Smith, B; Beck, T; Ballard, P; Dapthary, M; BrintzenhofeSzoc, K; Caminis, J

    2007-05-01

    Acute spinal cord injury is associated with rapid bone loss and an increased risk of fracture. In this double-blind, randomized, placebo-controlled trial, 17 patients were followed for 1 year after administration of either 4 or 5 mg of zoledronic acid or placebo. Bone mineral density (BMD) and structural analyses of the proximal femur were performed using the hip structural analysis program at entry, 6 months, and 12 months. The 17 subjects completed 12 months of observation, nine receiving placebo and eight zoledronic acid. The placebo group showed a decrease in BMD, cross-sectional area, and section modulus and an increase in buckling ratio at each proximal femur site at 6 and 12 months. Six months after zoledronic acid, BMD, cross-sectional area, and section modulus increased at the femoral neck and intertrochanteric regions and buckling ratio decreased consistent with improved bone stability. However, at 12 months, the femoral narrow-neck values declined to baseline. In contrast to placebo, the intertrochanteric region and femur shaft were maintained at or near baseline through 12 months in the zoledronic acid-treated group. Urine N-telopeptide excretion was increased at baseline and declined in both the placebo and treatment groups during the 12 months of observation. We conclude that a single administration of zoledronic acid will ameliorate bone loss and maintain parameters of bone strength at the three proximal femur sites for 6 months and at the femur intertrochanteric and shaft sites for 12 months.

  19. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice.

    PubMed

    Borghi, Sergio M; Pinho-Ribeiro, Felipe A; Fattori, Victor; Bussmann, Allan J C; Vignoli, Josiane A; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  20. Spinal cord trauma

    MedlinePlus

    ... if the bones or disks have been weakened Fragments of bone (such as from broken vertebrae, which are the ... presses on the spinal cord (decompression laminectomy ) Remove bone fragments, disk fragments, or foreign objects Fuse broken spinal ...

  1. Spinal Cord Injury 101

    MedlinePlus

    ... is "Braingate" research? What is the status of stem-cell research? How would stem-cell therapies work in the treatment of spinal cord injuries? What does stem-cell research on animals tell us? When can we expect ...

  2. Spinal Cord Injury

    MedlinePlus

    ... Dramatically Improves Function After Spinal Cord Injury in Rats May 2004 press release on an experimental treatment ... NINDS). Signaling Molecule Improves Nerve Cell Regeneration in Rats August 2002 news summary on a signaling molecule ...

  3. Spinal cord abscess

    MedlinePlus

    ... irritation (inflammation) and the collection of infected material (pus) in or around the spinal cord. ... occurs as a complication of an epidural abscess . Pus forms as a collection of: Destroyed tissue cells ...

  4. Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury

    PubMed Central

    Jin, Mu; Yang, Yan-wei; Cheng, Wei-ping; Lu, Jia-kai; Hou, Si-yu; Dong, Xiu-hua; Liu, Shi-yao

    2015-01-01

    The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury. PMID:26807120

  5. Modeling spinal cord biomechanics

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  6. The penile erection efficacy of a new phosphodiesterase type 5 inhibitor, mirodenafil (SK3530), in rabbits with acute spinal cord injury.

    PubMed

    Jung, Ji-Youn; Kim, Sang-Ki; Kim, Byeong-Soo; Lee, Seung-Ho; Park, Young-Seok; Kim, So-Jung; Choi, Changsun; Yoon, Seong-Il; Kim, Jong-Suk; Cho, Sung-Dae; Im, Gwang-Jin; Lee, Soo-Min; Jung, Ji-Won; Lee, Yong-Soon

    2008-11-01

    Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury.

  7. Acute cervical spinal cord injury secondary to air bag deployment without proper use of lap or shoulder harnesses.

    PubMed

    Hart, R A; Mayberry, J C; Herzberg, A M

    2000-02-01

    The authors present a case report of a patient with cervical central spinal cord syndrome caused by a hyperextension injury after a motor vehicle collision in which the air bag deployed in the absence of shoulder or lap belt harnesses. The potential for cervical spine and spinal cord hyperextension injuries in passengers positioned in front of air bags without proper use of shoulder or lap belt harnesses is discussed. Cervical central spinal cord quadriplegia occurred with cervical spondylosis and kyphosis that was managed by early three-level cervical corpectomy in a 58-year-old patient. Early improvement in the patient's neurological status occurred but was incomplete at the time of this report. Cervical hyperextension injuries are possible in passengers positioned in the front seat of cars with air bags when shoulder or lap belt harnesses are not used properly. Previous biomechanical studies have documented the potential for these types of injuries.

  8. Acute Respiratory Tract Infection Visits of Veterans With Spinal Cord Injuries and Disorders: Rates, Trends, and Risk Factors

    PubMed Central

    Smith, Bridget M; Evans, Charlesnika T; Kurichi, Jibby E; Weaver, Frances M; Patel, Nayna; Burns, Stephen P

    2007-01-01

    Background/Objectives: Respiratory complications are a major cause of illness and death in persons with spinal cord injuries and dysfunction (SCI&Ds). The objectives of this study were to examine rates of outpatient visits over 5 years for acute respiratory tract infections (ARIs), including pneumonia and influenza (P&I), lower respiratory tract infections (LRIs), and upper respiratory tract infections (URIs), in veterans with SCI&Ds and to determine whether individual characteristics were associated with the number of annual visits for each type of ARI. Methods: This was a longitudinal (fiscal years 1998–2002) study of ARI visits at the Veterans Health Administration (VA) in 18,693 veterans with SCI&Ds. To examine the associations between time, patient characteristics, and annual number of ARI visits, we used random effect negative binomial models. Results: Veterans with SCI&Ds had a total of 11,113 ARI visits over the 5-year period. There was a slightly decreasing trend for LRI visits over time (P < 0.01) but no significant change for other ARIs over time. There were 30 to 35 pneumonia visits and 21 to 30 acute bronchitis visits per 1,000 SCI&D veterans per year. Older veterans were more likely than younger to have P&I visits and less likely to have URI visits (P < 0.01). Veterans with paraplegia had fewer P&I visits than subjects with tetraplegia (IRR = 0.58; CI = 0.51–0.67). Conclusions: Visit rates for ARIs are stable for veterans with SCI&Ds. Identifying risk factors associated with ARI visits is an important first step to improve prevention and treatment of ARIs and to improve the health of veterans with SCI&Ds. PMID:17853657

  9. Assessment of Impairment in Patients with Acute Traumatic Spinal Cord Injury: A Systematic Review of the Literature

    PubMed Central

    Furlan, Julio C.; Noonan, Vanessa; Singh, Anoushka

    2011-01-01

    Abstract The most common primary end-point of the trial on treatment of traumatic spinal cord injury (SCI) is the degree of impairment. The American Spinal Injury Association (ASIA) Standards have been widely used to assess motor function and pin-prick and light-touch sensory function. In addition, pain assessment is another clinically relevant aspect of the impairment in individuals with SCI. Given this, we sought to systematically review the studies that focused on the psychometric properties of ASIA Standards and all previously used outcome measures of pain in the SCI population in the acute care setting. For the primary literature search strategy, the MEDLINE, CINAHL, EMBASE, and Cochrane databases were sought out. Subsequently, a secondary search strategy was carried out using the articles listed in the references of meta-analysis, systematic, and non-systematic review articles. Two reviewers (JCF and VN) independently selected the articles that fulfill the inclusion and exclusion, assessed the level of evidence of each article, and appraised the psychometric properties of each instrument. Divergences during those steps were solved by consensus between both reviewers. Of 400 abstracts captured in our primary search strategy on the ASIA Standards, 16 full articles fulfilled the inclusion and exclusion criteria. An additional 40 references were obtained from two prior systematic reviews on ASIA Standards. While 45 of 56 of the studies on ASIA Standards provided level 4 evidence, there were 11 level 2b evidence studies. Convergent construct validity (n = 34), reliability (n = 12), and responsiveness (n = 10) were the most commonly studied psychometric properties of the ASIA Standards, but two prior studies examined their content validity. Of the 267 abstracts yielded in our primary search on pain assessment, 24 articles with level 4 evidence fulfilled the inclusion and exclusion criteria. There was no study that examined pain assessment in the acute

  10. Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury

    PubMed Central

    Hartigan, Clare; Kandilakis, Casey; Pharo, Elizabeth; Clesson, Ismari

    2015-01-01

    Background: Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. Objective: The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. Methods: Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (V̇O2peak), average oxygen consumption (V̇O2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. Results: Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, V̇O2avg, and METssci. Exoskeleton-assisted walking resulted in %V̇O2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. Conclusion: Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity. PMID:26364281

  11. Down-Regulation of CXCL12/CXCR4 Expression Alleviates Ischemia-Reperfusion-Induced Inflammatory Pain via Inhibiting Glial TLR4 Activation in the Spinal Cord

    PubMed Central

    Li, Xiao-Qian; Zhang, Zai-Li; Tan, Wen-Fei; Sun, Xi-Jia; Ma, Hong

    2016-01-01

    Toll-like receptor 4 (TLR4) is important for the pathogenesis of inflammatory reactions and the promotion of pain processing after ischemia/reperfusion (IR) in spinal cord. Recently, C-X-C chemokine ligand 12 (CXCL12) and its receptor, C-X-C chemokine receptor 4 (CXCR4), were demonstrated to be simultaneously critical for inflammatory reactions, thereby facilitating glial activation. However, whether CXCL12/CXCR4 expression can contribute to IR-induced inflammatory pain via spinal TLR4 remained unclear. A rat model was established by 8 min of aortic arch occlusion. The effects of CXCL12/CXCR4 expression and TLR4 activation on inflammatory hyperalgesia were investigated by pretreatments with CXCL12-neutralizing antibody, CXCR4 antagonist (AMD3100) and TLR4 antagonist (TAK-242) for 5 consecutive days before surgery. The results indicated that IR induced significant and sustained inflammatory pain, observed as decreases in paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), throughout the post-injury period. The increased levels of TLR4 and proinflammatory chemokine CXCL12, as well as its receptor, CXCR4, were closely correlated with the PWT and PWL trends. Double immunostaining further suggested that TLR4, which is mainly expressed on astrocytes and microglia, was closely co-localized with CXCL12 and CXCR4 in spinal dorsal horn. As expected, intrathecal pretreatment with the TLR4 antagonist, TAK-242 markedly ameliorated pain by inhibiting astrocytic and microglial activation, as shown by decreases in TLR4 immunoreactivity and the percentage of double-labeled cells. These protective effects were likely due in part to the reduced production of the downstream cytokines IL-1β and TNF-α, as well as for the recruitment of CXCL12 and CXCR4. Additionally, intrathecal pretreatment with CXCL12-neutralizing antibody and AMD3100 resulted in similar analgesic and anti-inflammatory effects as those receiving TAK-242 pretreatment. These results suggest that

  12. Lower limb conduit artery endothelial responses to acute upper limb exercise in spinal cord injured and able-bodied men.

    PubMed

    Totosy de Zepetnek, Julia O; Au, Jason S; Ditor, David S; MacDonald, Maureen J

    2015-04-01

    Vascular improvements in the nonactive regions during exercise are likely primarily mediated by increased shear rate (SR). Individuals with spinal cord injury (SCI) experience sublesional vascular deconditioning and could potentially benefit from upper body exercise-induced increases in lower body SR. The present study utilized a single bout of incremental arm-crank exercise to generate exercise-induced SR changes in the superficial femoral artery in an effort to evaluate the acute postexercise impact on superficial femoral artery endothelial function via flow-mediated dilation (FMD), and determine regulatory factors in the nonactive legs of individuals with and without SCI. Eight individuals with SCI and eight age, sex, and waist-circumference-matched able-bodied (AB) controls participated. Nine minutes of incremental arm-crank exercise increased superficial femoral artery anterograde SR (P = 0.02 and P < 0.01), retrograde SR (P < 0.01 and P < 0.01), and oscillatory shear index (OSI) (P < 0.001 and P < 0.001) in both SCI and AB, respectively. However, these SR alterations resulted in acute postexercise increases in FMD in the AB group only (SCI 6.0 ± 1.2% to 6.3 ± 2.7%, P = 0.74; AB 7.5 ± 1.4% to 11.2 ± 1.4%, P = 0.03). While arm exercise has many cardiovascular benefits and results in changes in SR patterns in the nonactive legs, these changes are not sufficient to induce acute changes in FMD among individuals with SCI, and therefore are less likely to stimulate exercise training-associated improvements in nonactive limb endothelial function. Understanding the role of SR patterns on FMD brings us closer to designing effective strategies to combat impaired vascular function in both healthy and clinical populations.

  13. Does surgical treatment within 4 hours after trauma have an influence on neurological remission in patients with acute spinal cord injury?

    PubMed Central

    Biglari, Bahram; Child, Christopher; Yildirim, Timur Mert; Swing, Tyler; Reitzel, Tim; Moghaddam, Arash

    2016-01-01

    Background The proper timing for surgery in patients with acute spinal cord injury is controversial. This study was conducted to detect if there is an advantage in early (within the first 4 hours after trauma) compared to late (between 4 and 24 hours after trauma) surgery on neurological outcome. Methods In this single institution prospective cohort study, data were analyzed from 51 spinal cord injured patients with an average age of 43.4 (±19.2) years. The influence of early (29 patients within the first 4 hours) as opposed to late (22 patients between 4 and 24 hours) decompression was evaluated by comparing data for neurological outcome. Patients of the study collectively suffered acute spinal fractures from C2 to L3 (cervical 39.2%, thoracic 29.4%, and lumbal 21.6%) or nonosseous lesions (9.8%). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades were assessed at time of admission and 6 months after trauma or longer depending on the time of release. Surgical treatment included early stabilization and decompression within 24 hours. Results No significant difference between improved neurological function, measured with the AIS, and an early or late surgery time can be seen (P=0.402). Furthermore, binary logistic regression shows no significant difference between sex or age, and AIS improvement as possible confounders. Conclusion In our study, all patients with spinal cord injury were treated with spine stabilization and decompression within the first 24 hours after trauma. Surgical decompression within the first 4 hours after trauma was not associated with improved neurological outcome compared to treatment between 4 and 24 hours. In a clinical context, this indicates that there is a time frame of at least 1 day in which optimal care is possible. PMID:27621643

  14. Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Systematic Review and Meta-Analysis.

    PubMed

    Evaniew, Nathan; Belley-Côté, Emilie P; Fallah, Nader; Noonan, Vanessa K; Rivers, Carly S; Dvorak, Marcel F

    2016-03-01

    Previous meta-analyses of methylprednisolone (MPS) for patients with acute traumatic spinal cord injuries (TSCIs) have not addressed confidence in the quality of evidence used for pooled effect estimates, and new primary studies have been recently published. We aimed to determine whether MPS improves motor recovery and is associated with increased risks for adverse events. We searched MEDLINE, EMBASE, and The Cochrane Library, and two reviewers independently screened articles, extracted data, and evaluated risk of bias. We pooled outcomes from randomized, controlled trials (RCTs) and controlled observational studies separately and used the Grades of Recommendation, Assessment, Development, and Evaluation approach to evaluate confidence. We included four RCTs and 17 observational studies. MPS was not associated with an increase in long-term motor score recovery (two RCTs: 335 participants; mean difference [MD], -1.11; 95% confidence interval [CI], -4.75 to 2.53; p = 0.55, low confidence; two observational studies: 528 participants; MD, 1.37; 95% CI, -3.08 to 5.83; p = 0.55, very low confidence) or improvement by at least one motor grade (three observational studies: 383 participants; risk ratio [RR], 0.84; 95% CI, 0.53-1.33; p = 0.46, very low confidence). Evidence from two RCTs demonstrated superior short-term motor score improvement if MPS was administered within 8 h of injury (two RCTs: 250 participants; MD, 4.46; 95% CI, 0.97-7.94; p = 0.01, low confidence), but risk of bias and imprecision limit confidence in these findings. Observational studies demonstrated a significantly increased risk for gastrointestinal bleeding (nine studies: 2857 participants; RR, 2.18; 95% CI, 1.13-4.19; p = 0.02, very low confidence), but RCTs did not. Pooled evidence does not demonstrate a significant long-term benefit for MPS in patients with acute TSCIs and suggests it may be associated with increased gastrointestinal bleeding. These findings support current guidelines against

  15. Spinal Cord Injury

    MedlinePlus

    ... How much do you know about taking good care of yourself? Links to more information girlshealth glossary girlshealth.gov home http://www.girlshealth.gov/ Home Illness & disability Types of ... Spinal cord injury Read advice from Dr. Jeffrey Rabin , a pediatric rehabilitation specialist at the Children’s National Medical Center. ...

  16. Transplantation of Mesenchymal Stem Cells for Acute Spinal Cord Injury in Rats: Comparative Study between Intralesional Injection and Scaffold Based Transplantation

    PubMed Central

    2016-01-01

    Experimental stem cell therapy for spinal cord injury (SCI) has been extensively investigated. The selection of effective cell transplantation route is also an important issue. Although various types of scaffold have been widely tried as a carrier of stem cells to the injured spinal cord, there was little comparative study to investigate the efficacy of transplantation comparing with conventional transplantation route. A total of 48 Sprague-Dawley rats were subjected to standardized SCI, followed by transplantation of allogeneic mesenchymal stem cells (MSCs), either via intralesional injection (IL group), or via the poly (lactic-co-glycolic acid) (PLGA) scaffold (IP group) or chitosan scaffold (IC group). Engraftment and differentiation of the transplanted cells, expression of neurotrophic factors in the injured spinal cord, and functional recovery were compared with those of the control group. The mean numbers of engrafted MSCs in the IL, IP, and IC groups were 20.6 ± 0.7, 25.6 ± 1.7 and 26.7 ± 1.8 cells/high power filed (HPF), respectively. Results showed higher success rate of MSCs engraftment in the scaffold groups compared to the IL group. Expression of neuroprotective growth factors in the SCI lesions showed no significant differences between the IL, IP, and IC groups. The mean Basso, Beattie and Bresnahan locomotor scales at 6 weeks post-transplantation in the IL, IP, IC, and control groups were 7.9 ± 1.1, 7.9 ± 2.1, 8.7 ± 2.1, and 2.9 ± 1.0, respectively. The functional improvement was most excellent in the IC group. The scaffold based MSC transplantation for acute SCI presented the better cell engraftment and neuroprotective effect compared to the intralesional injection transplantation. PMID:27510379

  17. Transplantation of Mesenchymal Stem Cells for Acute Spinal Cord Injury in Rats: Comparative Study between Intralesional Injection and Scaffold Based Transplantation.

    PubMed

    Kim, Yoon Chung; Kim, Young Hoon; Kim, Jang Woon; Ha, Kee Yong

    2016-09-01

    Experimental stem cell therapy for spinal cord injury (SCI) has been extensively investigated. The selection of effective cell transplantation route is also an important issue. Although various types of scaffold have been widely tried as a carrier of stem cells to the injured spinal cord, there was little comparative study to investigate the efficacy of transplantation comparing with conventional transplantation route. A total of 48 Sprague-Dawley rats were subjected to standardized SCI, followed by transplantation of allogeneic mesenchymal stem cells (MSCs), either via intralesional injection (IL group), or via the poly (lactic-co-glycolic acid) (PLGA) scaffold (IP group) or chitosan scaffold (IC group). Engraftment and differentiation of the transplanted cells, expression of neurotrophic factors in the injured spinal cord, and functional recovery were compared with those of the control group. The mean numbers of engrafted MSCs in the IL, IP, and IC groups were 20.6 ± 0.7, 25.6 ± 1.7 and 26.7 ± 1.8 cells/high power filed (HPF), respectively. Results showed higher success rate of MSCs engraftment in the scaffold groups compared to the IL group. Expression of neuroprotective growth factors in the SCI lesions showed no significant differences between the IL, IP, and IC groups. The mean Basso, Beattie and Bresnahan locomotor scales at 6 weeks post-transplantation in the IL, IP, IC, and control groups were 7.9 ± 1.1, 7.9 ± 2.1, 8.7 ± 2.1, and 2.9 ± 1.0, respectively. The functional improvement was most excellent in the IC group. The scaffold based MSC transplantation for acute SCI presented the better cell engraftment and neuroprotective effect compared to the intralesional injection transplantation. PMID:27510379

  18. Epidemiology of spinal cord injury.

    PubMed

    Kurtzke, J F

    1977-01-01

    Accidents are the cause of some 50 deaths per 100 000 population each year in the US; some 3% of these are from traumatic spinal cord injury alone. Traumatic spinal cord injury in socioeconomically advanced countries, has a probably annual incidence rate of 3 per 100 000 population. Males are affected five times as often as females, and in the US, Negroes have twice the rates of whites. Half the cases are due to motor vehicle accidents, 1/4 to falls, and 1/10 to sports injuries. Maximal ages at risk are 15 to 34; only for cord damage due to falls do this risk differ, and here elderly are the more prone. Associated injuries are common in traumatic cord injury, and head injury and pulmonary dysfunction are frequent causes of the acute deaths in traumatic SCI which is why complete quadriplegia has a high early case-fatality ratio. Late deaths in SCI are principally the direct or indirect result of the neurogenic bladder. With treatment in comprehensive spinal cord injury centers, more than 4 of 5 traumatic SCI patients will survive ten years with an average of almost 18 years. Median survival may be almost 14 years for complete quadriplegia, 17 for complete paraplegia, 19 for incomplete quadriplegia, 20 for incomplete paraplegia and 28 for cauda equina lesions. Prevalence is likely to be some 50 per 100 000 population with about 20 per 100 000 completely paralyzed (3 quadriplegic and 19 paraplegic). Some 4 out of 5 survivors of traumatic SCI should be able to live at home and perform gainful work after such treatment. PMID:616527

  19. Ischemic spinal cord infarction in children without vertebral fracture

    PubMed Central

    Nance, Jessica R.; Golomb, Meredith R.

    2007-01-01

    Spinal cord infarction in children is a rare condition which is becoming more widely recognized. There are few reports in the pediatric literature characterizing etiology, diagnosis, treament and prognosis. The risk factors for pediatric ischemic spinal cord infarction include obstruction of blood flow associated with cardiovascular compromise or malformation, iatrogenic or traumatic vascular inujury, cerebellar herniation, thrombotic or embolic disease, infection, and vasculitis. In many children the cause of spinal cord ischemia in the absence of vertebral fracture is unknown. Imaging diagnosis of spinal cord ischemia is often difficult due to the small transverse area of the cord, cerebrospinal fluid artifact and inadequate resolution of MRI. Physical therapy is the most important treatment option. The prognosis is dependent on the level of spinal cord damage, early identification and reversal of ischemia, and follow-up with intensive physical therapy and medical support. In addition to summarizing the literature regarding spinal cord infarction in children without vertebral fracture, this review article adds two cases to the literature which highlight the difficulties and controversies in the management of this condition. PMID:17437902

  20. Acute spinal cord compression: a rare complication of dual antiplatelet therapy.

    PubMed

    Iskandar, Muhammad Zaid; Chong, Victor; Hutcheon, Stuart

    2015-01-01

    A 73-year-old woman presented with acute shortness of breath and exacerbation of chronic back pain. She was diagnosed with pulmonary oedema and a non-ST-elevation myocardial infarction following chest X-ray, ECG and high sensitivity troponin levels. She subsequently underwent coronary angioplasty with deployment of drug-eluting stents to her circumflex and left anterior descending arteries and was started on aspirin and clopidogrel for her dual antiplatelet therapy. Unfortunately, following the procedure, she gradually lost power and sensation in both lower limbs. MRI of her spine confirmed an extradural haematoma causing thoracic cord compression. She was managed conservatively following discussions with neurosurgeons and developed further complications secondary to her immobility. PMID:26202314

  1. Acupuncture's Effects in Treating the Sequelae of Acute and Chronic Spinal Cord Injuries: A Review of Allopathic and Traditional Chinese Medicine Literature.

    PubMed

    Dorsher, Peter T; McIntosh, Peter M

    2011-01-01

    Each year, there are an estimated 12 000 individuals who sustain a spinal cord injury (SCI) in the United States. Improved understanding of the pathophysiology of SCI and its sequelae has over the past 50 years led to the development of medical treatments (especially urologic) that have enhanced short- and long-term survival from these injuries. The prevalence of individuals with SCI in this country is ~250 000 individuals; and beyond the incalculable personal consequences of these devastating neurologic injuries, substantial direct and indirect societal costs result from the sequelae of SCI including paralysis, sensory loss, chronic pain, decubiti and bladder and/or bowel incontinence. The purpose of this treatise is to review the allopathic and traditional Chinese medicine (TCM) literature available through MEDLINE, PubMed and eCAM search engines that discuss the potential uses of acupuncture to treat acute and chronic spinal cord injuries and their sequelae, and present the neurophysiologic mechanisms for acupuncture's beneficial effects. There is evidence that use of electroacupuncture in acute SCI may significantly improve long-term neurologic recovery from these injuries both in terms of motor, sensory and bowel/bladder function with essentially no risk. Acupuncture may even improve neurourologic function in individuals with chronic SCI, and help with management with chronic pain associated with these injuries.

  2. A Systematic Review of Experimental Strategies Aimed at Improving Motor Function after Acute and Chronic Spinal Cord Injury.

    PubMed

    Gomes-Osman, Joyce; Cortes, Mar; Guest, James; Pascual-Leone, Alvaro

    2016-03-01

    While various approaches have been proposed in clinical trials aimed at improving motor function after spinal cord injury in humans, there is still limited information regarding the scope, methodological quality, and evidence associated with single-intervention and multi-intervention approaches. A systematic review performed using the PubMed search engine and the key words "spinal cord injury motor recovery" identified 1973 records, of which 39 were selected (18 from the search records and 21 from reference list inspection). Study phase ( clinicaltrials.org criteria) and methodological quality (Cochrane criteria) were assessed. Studies included proposed a broad range of single-intervention (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) and multi-intervention approaches (that combined more than one strategy). The highest evidence level was for Phase III studies supporting the role of multi-intervention approaches that contained a rehabilitation component. Quality appraisal revealed that the percentage of selected studies classified with high risk of bias by Cochrane criteria was as follows: random sequence generation = 64%; allocation concealment = 77%; blinding of participants and personnel = 69%; blinding of outcome assessment = 64%; attrition = 44%; selective reporting = 44%. The current literature contains a high proportion of studies with a limited ability to measure efficacy in a valid manner because of low methodological strength in all items of the Cochrane risk of bias assessment. Recommendations to decrease bias are discussed and include increased methodological rigor in the study design and recruitment of study participants, and the use of electrophysiological and imaging measures that can assess functional integrity of the spinal cord (and may be sufficiently sensitive to detect changes that occur in response to therapeutic

  3. Assessment of axonal dysfunction in an in vitro model of acute compressive injury to adult rat spinal cord axons.

    PubMed

    Fehlings, M G; Nashmi, R

    1995-04-24

    An in vitro model of spinal cord injury was developed to study the pathophysiology of posttraumatic axonal dysfunction. A 25 mm length of thoracic spinal cord was removed from the adult male rat (n = 27). A dorsal column segment was isolated and pinned in a recording chamber and superfused with oxygenated (95% O2/5% CO2) Ringer. The cord was stimulated with a bipolar electrode, while two point responses were recorded extracellularly. Injury was accomplished by compression with a modified aneurysm clip which applied a 2 g force for 15 s. With injury the compound action potential (CAP) amplitude decreased to 53.7 +/- 5.4% (P < 0.001), while the latency increased to 115.6 +/- 3.1% (P < 0.0025) of control values. The absolute refractory period increased with injury from 1.7 +/- 0.1 ms to 2.1 +/- 0.1 ms (P < 0.05). The infusion of 5 mM 4-aminopyridine (4-AP), a blocker of voltage-sensitive 'fast' K channels confined to internodal regions, resulted in broadening of the CAP of injured axons to 114.9 +/- 3.1% of control (P < 0.05). Ultrastructural analysis of the injured dorsal column segments revealed marked axonal and myelin pathology, including considerable myelin disruption. In conclusion, we have developed and characterized an in vitro model of mammalian spinal cord injury which simulates many of the features of in vivo trauma. Injured axons display characteristic changes in physiological function including a shift in refractory period and high frequency conduction failure. The ultrastructural data and response of injured axons to 4-AP suggest that myelin disruption with exposure of 'fast' K+ channels contributes to posttraumatic axonal dysfunction.

  4. Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection

    PubMed Central

    Cheng, Chu-Hsun; Lin, Chi-Te; Lee, Meng-Jen; Tsai, May-Jywan; Huang, Wen-Hung; Huang, Ming-Chao; Lin, Yi-Lo; Chen, Ching-Jung

    2015-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are glial scar-associated molecules considered axonal regeneration inhibitors and can be digested by chondroitinase ABC (ChABC) to promote axonal regeneration after spinal cord injury (SCI). We previously demonstrated that intrathecal delivery of low-dose ChABC (1 U) in the acute stage of SCI promoted axonal regrowth and functional recovery. In this study, high-dose ChABC (50 U) introduced via intrathecal delivery induced subarachnoid hemorrhage and death within 48 h. However, most SCI patients are treated in the sub-acute or chronic stages, when the dense glial scar has formed and is minimally digested by intrathecal delivery of ChABC at the injury site. The present study investigated whether intraparenchymal delivery of ChABC in the sub-acute stage of complete spinal cord transection would promote axonal outgrowth and improve functional recovery. We observed no functional recovery following the low-dose ChABC (1 U or 5 U) treatments. Furthermore, animals treated with high-dose ChABC (50 U or 100 U) showed decreased CSPGs levels. The extent and area of the lesion were also dramatically decreased after ChABC treatment. The outgrowth of the regenerating axons was significantly increased, and some partially crossed the lesion site in the ChABC-treated groups. In addition, retrograde Fluoro-Gold (FG) labeling showed that the outgrowing axons could cross the lesion site and reach several brain stem nuclei involved in sensory and motor functions. The Basso, Beattie and Bresnahan (BBB) open field locomotor scores revealed that the ChABC treatment significantly improved functional recovery compared to the control group at eight weeks after treatment. Our study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Thus, our results will aid in

  5. FAQs about Spinal Cord Injury (SCI)

    MedlinePlus

    ... Website Managing Bowel Function After Spinal Cord Injury Resilience, Depression and Bouncing Back after SCI Getting to ... a “complete” and “incomplete” spinal cord injury? What recovery is expected following spinal cord injury? Where is ...

  6. In-vivo spinal cord deformation in flexion

    NASA Astrophysics Data System (ADS)

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

    1997-05-01

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

  7. Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury.

    PubMed

    Wang, Yang; Zhang, Shuquan; Luo, Min; Li, Yajun

    2014-12-15

    Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modification of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve fibers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats. Our findings indicate that hyperbaric oxygen therapy reduces apoptosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury.

  8. Acute mesenteric ischemia.

    PubMed

    Sise, Michael J

    2014-02-01

    Acute mesenteric ischemia is uncommon and always occurs in the setting of preexisting comorbidities. Mortality rates remain high. The 4 major types of acute mesenteric ischemia are acute superior mesenteric artery thromboembolic occlusion, mesenteric arterial thrombosis, mesenteric venous thrombosis, and nonocclusive mesenteric ischemia, including ischemic colitis. Delays in diagnosis are common and associated with high rates of morbidity and mortality. Prompt diagnosis requires attention to history and physical examination, a high index of suspicion, and early contract CT scanning. Selective use of nonoperative therapy has an important role in nonocclusive mesenteric ischemia of the small bowel and colon.

  9. The Influence of Time from Injury to Surgery on Motor Recovery and Length of Hospital Stay in Acute Traumatic Spinal Cord Injury: An Observational Canadian Cohort Study

    PubMed Central

    Noonan, Vanessa K.; Fallah, Nader; Fisher, Charles G.; Finkelstein, Joel; Kwon, Brian K.; Rivers, Carly S.; Ahn, Henry; Paquet, Jérôme; Tsai, Eve C.; Townson, Andrea; Attabib, Najmedden; Bailey, Christopher S.; Christie, Sean D.; Drew, Brian; Fourney, Daryl R.; Fox, Richard; Hurlbert, R. John; Johnson, Michael G.; Linassi, A.G.; Parent, Stefan; Fehlings, Michael G.

    2015-01-01

    Abstract To determine the influence of time from injury to surgery on neurological recovery and length of stay (LOS) in an observational cohort of individuals with traumatic spinal cord injury (tSCI), we analyzed the baseline and follow-up motor scores of participants in the Rick Hansen Spinal Cord Injury Registry to specifically assess the effect of an early (less than 24 h from injury) surgical procedure on motor recovery and on LOS. One thousand four hundred and ten patients who sustained acute tSCIs with baseline American Spinal Injury Association Impairment Scale (AIS) grades A, B, C, or D and were treated surgically were analyzed to determine the effect of the timing of surgery (24, 48, or 72 h from injury) on motor recovery and LOS. Depending on the distribution of data, we used different types of generalized linear models, including multiple linear regression, gamma regression, and negative binomial regression. Persons with incomplete AIS B, C, and D injuries from C2 to L2 demonstrated motor recovery improvement of an additional 6.3 motor points (SE=2.8 p<0.03) when they underwent surgical treatment within 24 h from the time of injury, compared with those who had surgery later than 24 h post-injury. This beneficial effect of early surgery on motor recovery was not seen in the patients with AIS A complete SCI. AIS A and B patients who received early surgery experienced shorter hospital LOS. While the issues of when to perform surgery and what specific operation to perform remain controversial, this work provides evidence that for an incomplete acute tSCI in the cervical, thoracic, or thoracolumbar spine, surgery performed within 24 h from injury improves motor neurological recovery. Early surgery also reduces LOS. PMID:25333195

  10. Modeling the Patient Journey from Injury to Community Reintegration for Persons with Acute Traumatic Spinal Cord Injury in a Canadian Centre

    PubMed Central

    Santos, Argelio; Gurling, James; Dvorak, Marcel F.; Noonan, Vanessa K.; Fehlings, Michael G.; Burns, Anthony S.; Lewis, Rachel; Soril, Lesley; Fallah, Nader; Street, John T.; Bélanger, Lise; Townson, Andrea; Liang, Liping; Atkins, Derek

    2013-01-01

    Background A patient’s journey through the health care system is influenced by clinical and system processes across the continuum of care. Methods To inform optimized access to care and patient flow for individuals with traumatic spinal cord injury (tSCI), we developed a simulation model that can examine the full impact of therapeutic or systems interventions across the care continuum for patients with traumatic spinal cord injuries. The objective of this paper is to describe the detailed development of this simulation model for a major trauma and a rehabilitation centre in British Columbia (BC), Canada, as part of the Access to Care and Timing (ACT) project and is referred to as the BC ACT Model V1.0. Findings To demonstrate the utility of the simulation model in clinical and administrative decision-making we present three typical scenarios that illustrate how an investigator can track the indirect impact(s) of medical and administrative interventions, both upstream and downstream along the continuum of care. For example, the model was used to estimate the theoretical impact of a practice that reduced the incidence of pressure ulcers by 70%. This led to a decrease in acute and rehabilitation length of stay of 4 and 2 days, respectively and a decrease in bed utilization of 9% and 3% in acute and rehabilitation. Conclusion The scenario analysis using the BC ACT Model V1.0 demonstrates the flexibility and value of the simulation model as a decision-making tool by providing estimates of the effects of different interventions and allowing them to be objectively compared. Future work will involve developing a generalizable national Canadian ACT Model to examine differences in care delivery and identify the ideal attributes of SCI care delivery. PMID:24023623

  11. Acute Molecular Perturbation of Inducible Nitric Oxide Synthase with an Antisense Approach Enhances Neuronal Preservation and Functional Recovery after Contusive Spinal Cord Injury

    PubMed Central

    Maggio, Dominic M.; Chatzipanteli, Katina; Masters, Neil; Patel, Samik P.; Dietrich, W. Dalton

    2012-01-01

    Abstract Inducible nitric oxide synthase (iNOS) is a key mediator of inflammation and oxidative stress produced during pathological conditions, including neurodegenerative diseases and central nervous system (CNS) injury. iNOS is responsible for the formation of high levels of nitric oxide (NO). The production of highly reactive and cytotoxic NO species, such as peroxynitrite, plays an important role in secondary tissue damage. We have previously demonstrated that acute administration of iNOS antisense oligonucleotides (ASOs) 3 h after moderate contusive spinal cord injury (SCI) potently inhibits iNOS-mediated increases in NO levels, leading to reduced blood–spinal cord barrier permeability, decreased neutrophil accumulation, and less neuronal cell death. In the current study we investigated if iNOS ASOs could also provide long-term (10-week) histological and behavioral improvements after moderate thoracic T8 contusive SCI. Adult rats were randomly assigned to three groups (n=10/group): SCI alone, SCI and mixed base control oligonucleotides (MBOs), or SCI and iNOS ASOs (200 nM). Oligonucleotides were administered by spinal superfusion 3 h after injury. Behavioral analysis (Basso-Beattie-Bresnahan [BBB] score and subscore) was employed weekly for 10 weeks post-SCI. Although animals treated with iNOS ASOs demonstrated no significant differences in BBB scores compared to controls, subscore analysis revealed a significant improvement in foot positioning, trunk stability, and tail clearance. Histologically, while no gross improvement in preserved white and gray matter was observed, greater numbers of surviving neurons were present adjacent to the lesion site in iNOS ASO-treated animals than controls. These results support the effectiveness of targeting iNOS acutely as a therapeutic approach after SCI. PMID:22708918

  12. Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

    PubMed

    Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

    2015-04-16

    Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to

  13. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

  14. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain. PMID:26490459

  15. Adjustment to Spinal Cord Injury

    MedlinePlus

    ... of injury are alive and easily get educational information on the Internet. Web happy. sites such as the National Spinal Cord Injury Association (www.spinalcord.org) and SPINAL CORD Injury ♦ “Because of my injury, it is now impossible for me Information Network (www.spinalcord.uab.edu) have to ever ...

  16. Evaluation of Early and Late Effects into the Acute Spinal Cord Injury of an Injectable Functionalized Self-Assembling Scaffold

    PubMed Central

    Cigognini, Daniela; Satta, Alessandro; Colleoni, Bianca; Silva, Diego; Donegà, Matteo; Antonini, Stefania; Gelain, Fabrizio

    2011-01-01

    The complex physiopathological events occurring after spinal cord injury (SCI) make this devastating trauma still incurable. Self-assembling peptides (SAPs) are nanomaterials displaying some appealing properties for application in regenerative medicine because they mimic the structure of the extra-cellular matrix (ECM), are reabsorbable, allow biofunctionalizations and can be injected directly into the lesion. In this study we evaluated the putative neurorigenerative properties of RADA16-4G-BMHP1 SAP, proved to enhance in vitro neural stem cells survival and differentiation. This SAP (RADA16-I) has been functionalized with a bone marrow homing motif (BMHP1) and optimized via the insertion of a 4-glycine-spacer that ameliorates scaffold stability and exposure of the biomotifs. We injected the scaffold immediately after contusion in the rat spinal cord, then we evaluated the early effects by semi-quantitative RT-PCR and the late effects by histological analysis. Locomotor recovery over 8 weeks was assessed using Basso, Beattie, Bresnahan (BBB) test. Gene expression analysis showed that at 7 days after lesion the functionalized SAP induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins, whereas 3 days after SCI no remarkable changes were observed. Hystological analysis revealed that 8 weeks after SCI our scaffold increased cellular infiltration, basement membrane deposition and axon regeneration/sprouting within the cyst. Moreover the functionalized SAP showed to be compatible with the surrounding nervous tissue and to at least partially fill the cavities. Finally SAP injection resulted in a statistically significant improvement of both hindlimbs' motor performance and forelimbs-hindlimbs coordination. Altogether, these results indicate that RADA16-4G-BMHP1 induced favourable reparative processes, such as matrix remodelling, and provided a physical and trophic support to nervous tissue ingrowth. Thus this biomaterial, eventually

  17. Retraining the injured spinal cord

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

  18. A clinical prediction model for long-term functional outcome after traumatic spinal cord injury based on acute clinical and imaging factors.

    PubMed

    Wilson, Jefferson R; Grossman, Robert G; Frankowski, Ralph F; Kiss, Alexander; Davis, Aileen M; Kulkarni, Abhaya V; Harrop, James S; Aarabi, Bizhan; Vaccaro, Alexander; Tator, Charles H; Dvorak, Marcel; Shaffrey, Christopher I; Harkema, Susan; Guest, James D; Fehlings, Michael G

    2012-09-01

    To improve clinicians' ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥ 6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. A logistic model was then created using the dichotomized secondary outcome and the same predictor variables. Model validation was performed using a bootstrap resampling procedure. Of 729 patients, 376 met the inclusion criteria. The mean FIM motor score at 1 year was 62.9 (±28.6). Better functional status was predicted by less severe initial American Spinal Injury Association (ASIA) Impairment Scale grade, and by an ASIA motor score >50 at admission. In contrast, older age and magnetic resonance imaging (MRI) signal characteristics consistent with spinal cord edema or hemorrhage predicted worse functional outcome. The linear model predicting FIM motor score demonstrated an R-square of 0.52 in the original dataset, and 0.52 (95% CI 0.52,0.53) across the 200 bootstraps. Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families.

  19. A Clinical Prediction Model for Long-Term Functional Outcome after Traumatic Spinal Cord Injury Based on Acute Clinical and Imaging Factors

    PubMed Central

    Wilson, Jefferson R.; Grossman, Robert G.; Frankowski, Ralph F.; Kiss, Alexander; Davis, Aileen M.; Kulkarni, Abhaya V.; Harrop, James S.; Aarabi, Bizhan; Vaccaro, Alexander; Tator, Charles H.; Dvorak, Marcel; Shaffrey, Christopher I.; Harkema, Susan; Guest, James D.

    2012-01-01

    Abstract To improve clinicians' ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. A logistic model was then created using the dichotomized secondary outcome and the same predictor variables. Model validation was performed using a bootstrap resampling procedure. Of 729 patients, 376 met the inclusion criteria. The mean FIM motor score at 1 year was 62.9 (±28.6). Better functional status was predicted by less severe initial American Spinal Injury Association (ASIA) Impairment Scale grade, and by an ASIA motor score >50 at admission. In contrast, older age and magnetic resonance imaging (MRI) signal characteristics consistent with spinal cord edema or hemorrhage predicted worse functional outcome. The linear model predicting FIM motor score demonstrated an R-square of 0.52 in the original dataset, and 0.52 (95% CI 0.52,0.53) across the 200 bootstraps. Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families. PMID:22709268

  20. Temporal and spatial patterns of Kv1.1 and Kv1.2 protein and gene expression in spinal cord white matter after acute and chronic spinal cord injury in rats: implications for axonal pathophysiology after neurotrauma.

    PubMed

    Karimi-Abdolrezaee, Soheila; Eftekharpour, Eftekhar; Fehlings, Michael G

    2004-02-01

    After spinal cord injury (SCI), surviving white matter axons display axonal dysfunction associated with demyelination and altered K+ channel activity. To clarify the molecular basis of posttraumatic axonal pathophysiology after SCI, we investigated the changes in expression and distribution of the axonal K+ channel subunits Kv1.1 and Kv1.2 in spinal cord white matter after in vivo SCI in the rat. Using Western blot analysis, we found an increased expression of Kv1.1 and Kv1.2 at 2 and 6 weeks after SCI. By real-time PCR we observed an increase in Kv1.1 and Kv1.2 mRNA levels 1 day after SCI, which persisted until 6 weeks. Confocal immunohistochemistry showed a markedly dispersed labelling of Kv1.1 and Kv1.2 along the injured axons, in contrast to the tight localization of these channels to the juxtaparanodes of noninjured axons. This redistribution of Kv1.1 and Kv1.2 occurred as early as 1 h postinjury along some injured axons, and persisted at 6 weeks postinjury. In parallel with the redistribution of Kv1.1 and 1.2, contactin-associated protein (Caspr), which is normally confined to a paranodal location, also displayed a more diffuse distribution along the injured spinal cord axons. Our results suggest that the increased expression of Kv1.1 and Kv1.2 proteins is transcriptionally regulated. In contrast, the redistribution of the axonal K+ channel subunits occurs very early postinjury and probably reflects a disruption of the juxtaparanodal axonal region due to physical trauma, as shown by altered localization of Caspr. PMID:14984408

  1. Attitudes Towards Individuals with Spinal Cord Injuries

    ERIC Educational Resources Information Center

    Conway, Cassandra Sligh D.; Gooden, Randy; Nowell, Jennifer; Wilson, Navodda

    2010-01-01

    This paper will shed light on the lives of persons with spinal cord injuries by revealing the literature on spinal cord injuries that focuses on research that can shed light on attitudes towards persons with spinal cord injuries. The background literature related to incidences, the definition of spinal cord injury, and vocational opportunities are…

  2. Overview of Spinal Cord Disorders

    MedlinePlus

    ... temperature from the body to the spinal cord. Did You Know... Doctors can often tell where the ... on symptoms and results of a physical examination. Did You Know... Nerves from the lowest parts of ...

  3. What Is Spinal Cord Injury?

    MedlinePlus

    ... lowest point on the spinal cord below which sensory feeling and motor movement diminish or disappear. The ... injury is so severe that almost all feeling (sensory function) and all ability to control movement (motor ...

  4. Mn porphyrin-based SOD mimic, MnTnHex-2-PyP5+, and non-SOD mimic, MnTBAP3−, suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways

    PubMed Central

    Celic, T.; Španjol, J.; Bobinac, M.; Tovmasyan, A.; Vukelic, I.; Reboucas, J. S.; Batinic-Haberle, I.; Bobinac, D.

    2015-01-01

    Herein we have demonstrated that both superoxide dismutase (SOD) mimic, cationic Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP5+), and non-SOD mimic, anionic Mn(III) meso-tetrakis(4-carboxylatophenyl)porphyrin (MnTBAP3−), protect against oxidative stress caused by spinal cord ischemia/reperfusion via suppression of nuclear factor kappa B (NF-κB) pro-inflammatory pathways. Earlier reports showed that Mn(III) N -alkylpyridylporphyrins were able to prevent the DNA binding of NF-κB in an aqueous system, whereas MnTBAP3− was not. Here, for the first time, in a complex in vivo system—animal model of spinal cord injury—a similar impact of MnTBAP3−, at a dose identical to that of MnTnHex-2-PyP5+, was demonstrated in NF-κB downregulation. Rats were treated subcutaneously at 1.5 mg/kg starting at 30 min before ischemia/reperfusion, and then every 12 h afterward for either 48 h or 7 days. The anti-inflammatory effects of both Mn porphyrins (MnPs) were demonstrated in the spinal cord tissue at both 48 h and 7 days. The down-regulation of NF-κ B, a major pro-inflammatory signaling protein regulating astrocyte activation, was detected and found to correlate well with the suppression of astrogliosis (as glial fibrillary acidic protein) by both MnPs. The markers of oxidative stress, lipid peroxidation and protein carbonyl formation, were significantly reduced by MnPs. The favorable impact of both MnPs on motor neurons (Tarlov score and inclined plane test) was assessed. No major changes in glutathione peroxidase- and SOD-like activities were demonstrated, which implies that none of the MnPs acted as SOD mimic. Increasing amount of data on the reactivity of MnTBAP3− with reactive nitrogen species (RNS) (·NO/HNO/ONOO−) suggests that RNS/MnTBAP3−-driven modification of NF-κB protein cysteines may be involved in its therapeutic effects. This differs from the therapeutic efficacy of MnTnHex-2-PyP5+ which presumably occurs via reactive

  5. Expansion duroplasty improves intraspinal pressure, spinal cord perfusion pressure, and vascular pressure reactivity index in patients with traumatic spinal cord injury: injured spinal cord pressure evaluation study.

    PubMed

    Phang, Isaac; Werndle, Melissa C; Saadoun, Samira; Varsos, Georgios; Czosnyka, Marek; Zoumprouli, Argyro; Papadopoulos, Marios C

    2015-06-15

    We recently showed that, after traumatic spinal cord injury (TSCI), laminectomy does not improve intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), or the vascular pressure reactivity index (sPRx) at the injury site sufficiently because of dural compression. This is an open label, prospective trial comparing combined bony and dural decompression versus laminectomy. Twenty-one patients with acute severe TSCI had re-alignment of the fracture and surgical fixation; 11 had laminectomy alone (laminectomy group) and 10 had laminectomy and duroplasty (laminectomy+duroplasty group). Primary outcomes were magnetic resonance imaging evidence of spinal cord decompression (increase in intradural space, cerebrospinal fluid around the injured cord) and spinal cord physiology (ISP, SCPP, sPRx). The laminectomy and laminectomy+duroplasty groups were well matched. Compared with the laminectomy group, the laminectomy+duroplasty group had greater increase in intradural space at the injury site and more effective decompression of the injured cord. In the laminectomy+duroplasty group, ISP was lower, SCPP higher, and sPRx lower, (i.e., improved vascular pressure reactivity), compared with the laminectomy group. Laminectomy+duroplasty caused cerebrospinal fluid leak that settled with lumbar drain in one patient and pseudomeningocele that resolved completely in five patients. We conclude that, after TSCI, laminectomy+duroplasty improves spinal cord radiological and physiological parameters more effectively than laminectomy alone.

  6. Baseline Prevalence of Heart Diseases, Hypertension, Diabetes, and Obesity in Persons with Acute Traumatic Spinal Cord Injury: Potential Threats in the Recovery Trajectory

    PubMed Central

    2013-01-01

    Background: Chronic diseases impede the recovery trajectory of acutely injured persons with traumatic spinal cord injury (TSCI). This study compares the odds of prevalent heart disease, hypertension, diabetes mellitus, and obesity between persons with TSCI and persons with lower extremity fractures (LEF) who were discharged from acute care facilities. Methods: 1,776 patients with acute TSCI (cases) and 1,780 randomly selected patients with LEF (controls) discharged from January 1, 1998, through December 31, 2009, from all nonfederal hospitals were identified. Data extracted from uniform billing files were compared between cases and controls in a multivariable logistic regression model controlling for sociodemographic and clinical covariables. Results: Thirty percent of patients with acute TSCI had at least 1 of 4 conditions compared with 18% of patients with LEF (P < .0001). Persons with acute TSCI were 4 times more likely (odds ratio [OR], 4.05; 95% CI, 1.65–9.97) to have obesity, 2.7 times more likely to have heart disease (P < .001), 2 times more likely to have hypertension (P < .001), and 1.7 times more likely to have diabetes (P = .044) at the onset of TSCI. Disproportionately more Blacks than Whites have TSCI and chronic diseases. Conclusion: This study suggests that there is an increased burden of cardiovascular and cardiometabolic diseases among persons with acute TSCI compared with LEF trauma controls. Unattended comorbid conditions will affect quality of life and the recovery process. This warrants continuous monitoring and management of chronic diseases during the rehabilitation process. PMID:23960701

  7. Survival, Differentiation, and Migration of High-Purity Mouse Embryonic Stem Cell-derived Progenitor Motor Neurons in Fibrin Scaffolds after Sub-Acute Spinal Cord Injury.

    PubMed

    McCreedy, D A; Wilems, T S; Xu, H; Butts, J C; Brown, C R; Smith, A W; Sakiyama-Elbert, S E

    2014-11-01

    Embryonic stem (ES) cells can be differentiated into many neural cell types that hold great potential as cell replacement therapies following spinal cord injury (SCI). Coupling stem cell transplantation with biomaterial scaffolds can produce a unified combination therapy with several potential advantages including enhanced cell survival, greater transplant retention, reduced scarring, and improved integration at the transplant/host interface. Undesired cell types, however, are commonly present in ES-cell derived cultures due to the limited efficiency of most ES cell induction protocols. Heterogeneous cell populations can confound the interaction between the biomaterial and specific neural populations leading to undesired outcomes. In particular, biomaterials scaffolds may enhance tumor formation by promoting survival and proliferation of undifferentiated ES cells that can persist after induction. Methods for purification of specific ES cell-derived neural populations are necessary to recognize the full potential of combination therapies involving biomaterials and ES cell-derived neural populations. We previously developed a method for enriching ES cell-derived progenitor motor neurons (pMNs) induced from mouse ES cells via antibiotic selection and showed that the enriched cell populations are depleted of pluripotent stem cells. In this study, we demonstrate the survival and differentiation of enriched pMNs within three dimensional (3D) fibrin scaffolds in vitro and when transplanted into a sub-acute dorsal hemisection model of SCI into neurons, oligodendrocytes and astrocytes. PMID:25346848

  8. Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury.

    PubMed

    Cho, Youngnam; Shi, Riyi; Borgens, Richard B

    2010-05-01

    Chitosan, a non-toxic biodegradable polycationic polymer with low immunogenicity, has been extensively investigated in various biomedical applications. In this work, chitosan has been demonstrated to seal compromised nerve cell membranes thus serving as a potent neuroprotector following acute spinal cord trauma. Topical application of chitosan after complete transection or compression of the guinea pig spinal cord facilitated sealing of neuronal membranes in ex vivo tests, and restored the conduction of nerve impulses through the length of spinal cords in vivo, using somatosensory evoked potential recordings. Moreover, chitosan preferentially targeted damaged tissues, served as a suppressor of reactive oxygen species (free radical) generation, and the resultant lipid peroxidation of membranes, as shown in ex vivo spinal cord samples. These findings suggest a novel medical approach to reduce the catastrophic loss of behavior after acute spinal cord and brain injury.

  9. Evaluation of spinal cord injury animal models

    PubMed Central

    Zhang, Ning; Fang, Marong; Chen, Haohao; Gou, Fangming; Ding, Mingxing

    2014-01-01

    Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. PMID:25598784

  10. Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous Congestive Myelopathy.

    PubMed

    Vuong, Shawn M; Jeong, William J; Morales, Humberto; Abruzzo, Todd A

    2016-10-01

    Vascular pathologies of the spinal cord are rare and often overlooked. This article presents clinical and imaging approaches to the diagnosis and management of spinal vascular conditions most commonly encountered in clinical practice. Ischemia, infarction, hemorrhage, aneurysms, and vascular malformations of the spine and spinal cord are discussed. Pathophysiologic mechanisms, clinical classification schemes, clinical presentations, imaging findings, and treatment modalities are considered. Recent advances in genetic and syndromic vascular pathologies of the spinal cord are also discussed. Clinically relevant spinal vascular anatomy is reviewed in detail. PMID:27616317

  11. A Grading System To Evaluate Objectively the Strength of Pre-Clinical Data of Acute Neuroprotective Therapies for Clinical Translation in Spinal Cord Injury

    PubMed Central

    Okon, Elena B.; Tsai, Eve; Beattie, Michael S.; Bresnahan, Jacqueline C.; Magnuson, David K.; Reier, Paul J.; McTigue, Dana M.; Popovich, Phillip G.; Blight, Andrew R.; Oudega, Martin; Guest, James D.; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

    2011-01-01

    Abstract The past three decades have seen an explosion of research interest in spinal cord injury (SCI) and the development of hundreds of potential therapies that have demonstrated some promise in pre-clinical experimental animal models. A growing number of these treatments are seeking to be translated into human clinical trials. Conducting such a clinical trial, however, is extremely costly, not only for the time and money required to execute it, but also for the limited resources that will then no longer be available to evaluate other promising therapies. The decision about what therapies have sufficient pre-clinical evidence of efficacy to justify testing in humans is therefore of utmost importance. Here, we have developed a scoring system for objectively grading the body of pre-clinical literature on neuroprotective treatments for acute SCI. The components of the system include an evaluation of a number of factors that are thought to be important in considering the “robustness” of a therapy's efficacy, including the animal species and injury models that have been used to test it, the time window of efficacy, the types of functional improvements effected by it, and whether efficacy has been independently replicated. The selection of these factors was based on the results of a questionnaire that was performed within the SCI research community. A modified Delphi consensus-building exercise was then conducted with experts in pre-clinical SCI research to refine the criteria and decide upon how to score them. Finally, the grading system was applied to a series of potential neuroprotective treatments for acute SCI. This represents a systematic approach to developing an objective method of evaluating the extent to which the pre-clinical literature supports the translation of a particular experimental treatment into human trials. PMID:20507235

  12. Toll-like receptor 2-mediated alternative activation of microglia is protective after spinal cord injury.

    PubMed

    Stirling, David P; Cummins, Karen; Mishra, Manoj; Teo, Wulin; Yong, V Wee; Stys, Peter

    2014-03-01

    Improving neurological outcome after spinal cord injury is a major clinical challenge because axons, once severed, do not regenerate but 'dieback' from the lesion site. Although microglia, the immunocompetent cells of the brain and spinal cord respond rapidly to spinal cord injury, their role in subsequent injury or repair remains unclear. To assess the role of microglia in spinal cord white matter injury we used time-lapse two-photon and spectral confocal imaging of green fluorescent protein-labelled microglia, yellow fluorescent protein-labelled axons, and Nile Red-labelled myelin of living murine spinal cord and revealed dynamic changes in white matter elements after laser-induced spinal cord injury in real time. Importantly, our model of acute axonal injury closely mimics the axonopathy described in well-characterized clinically relevant models of spinal cord injury including contusive-, compressive- and transection-based models. Time-lapse recordings revealed that microglia were associated with some acute pathophysiological changes in axons and myelin acutely after laser-induced spinal cord injury. These pathophysiological changes included myelin and axonal spheroid formation, spectral shifts in Nile Red emission spectra in axonal endbulbs detected with spectral microscopy, and 'bystander' degeneration of axons that survived the initial injury, but then succumbed to secondary degeneration. Surprisingly, modulation of microglial-mediated release of neurotoxic molecules failed to protect axons and myelin. In contrast, sterile stimulation of microglia with the specific toll-like receptor 2 agonist Pam2CSK4 robustly increased the microglial response to ablation, reduced secondary degeneration of central myelinated fibres, and induced an alternative (mixed M1:M2) microglial activation profile. Conversely, Tlr2 knock out: Thy1 yellow fluorescent protein double transgenic mice experienced greater axonal dieback than littermate controls. Thus, promoting an alternative

  13. Clinically relevant concentration of pregabalin has no acute inhibitory effect on excitation of dorsal horn neurons under normal or neuropathic pain conditions: An intracellular calcium-imaging study in spinal cord slices from adult rats.

    PubMed

    Baba, Hiroshi; Petrenko, Andrey B; Fujiwara, Naoshi

    2016-10-01

    Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to α2δ-1 subunits of voltage-gated calcium (Ca(2+)) channels. However, the exact analgesic mechanism after its binding to α2δ-1 subunits remains largely unknown. Whether a clinical concentration of pregabalin (≈10μM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca(2+)-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca(2+) signals predominantly in the superficial dorsal horn. Clinically relevant (10μM) and a very high concentration of pregabalin (100μM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca(2+) signals, whereas an extremely high dose of pregabalin (300μM) slightly but significantly attenuated Ca(2+) signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. PMID:27543338

  14. Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

    PubMed Central

    Solovyev, Alexey; Mi, Qi; Tzen, Yi-Ting; Brienza, David; Vodovotz, Yoram

    2013-01-01

    Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. PMID:23696726

  15. Non-painful sensory phenomena after spinal cord injury

    PubMed Central

    Siddall, P.; McClelland, J.

    1999-01-01

    OBJECTIVES—Non-painful sensory phenomena or "phantom" sensations are common after spinal cord injury. However, the physiological mechanisms responsible for these sensations are poorly understood. The aim of this study, therefore, was to document in a prospective fashion the time course, prevalence, and features of non-painful sensory phenomena after spinal cord injury, and to determine whether there was a relation between the presence of these sensations and completeness, level of injury, and type of spinal cord injury.
METHODS—Patients admitted to an acute spinal injuries unit were interviewed after admission and at several time points over a 2 year period to determine the presence and characteristics of non-painful sensations. Sensations were divided into simple and complex, with complex referring to sensations that incorporated a sensation of volume, length, posture, or movement.
RESULTS—The present study showed that the large majority (90%) of patients experience either type of sensation and most complex sensations (60%) are first experienced within 24 hours after the injury. Complex sensations were more common in those patients who had complete spinal cord injuries. The presence of either type of sensation did not seem to be related to the level of injury or the type of injury (cord syndrome). A relatively small proportion (22%) of patients reported that the postural sensations were related to their position at the time of injury and sensations were more commonly related to a familiar, comfortable, or often used position before the spinal cord injury.
CONCLUSION—Complex sensations such as postural illusions seem to be due to functional changes in the CNS that may occur almost immediately after spinal cord injury. These sensations may be related to a strong sensory memory "imprint" that has been established before injury.

 PMID:10209173

  16. Spinal cord compression in two related Ursus arctos horribilis.

    PubMed

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

    2012-09-01

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

  17. Spinal cord compression in two related Ursus arctos horribilis.

    PubMed

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

    2012-09-01

    Two 15-yr-old grizzly bear littermates were evaluated within 9 mo of each other with the symptom of acute onset of progressive paraparesis and proprioceptive ataxia. The most significant clinical examination finding was pelvic limb paresis in both bears. Magnetic resonance examinations of both bears showed cranial thoracic spinal cord compression. The first bear had left-sided extradural, dorsolateral spinal cord compression at T3-T4. Vertebral canal stenosis was also observed at T2-T3. Images of the second bear showed lateral spinal cord compression from T2-T3 to T4-T5. Intervertebral disk disease and associated spinal cord compression was also observed at T2-T3 and T3-T4. One grizzly bear continued to deteriorate despite reduced exercise, steroid, and antibiotic therapy. The bear was euthanized, and a necropsy was performed. The postmortem showed a spinal ganglion cyst that caused spinal cord compression at the level of T3-T4. Wallerian-like degeneration was observed from C3-T6. The second bear was prescribed treatment that consisted of a combination of reduced exercise and steroid therapy. He continued to deteriorate with these medical therapies and was euthanized 4 mo after diagnosis. A necropsy showed hypertrophy and protrusion of the dorsal longitudinal ligament at T2-T3 and T3-T4, with resulting spinal cord compression in this region. Wallerian-like degeneration was observed from C2-L1. This is one of few case reports that describes paresis in bears. It is the only case report, to the authors' knowledge, that describes spinal magnetic resonance imaging findings in a grizzly bear and also the only report that describes a cranial thoracic myelopathy in two related grizzly bears with neurologic signs. PMID:23082524

  18. Aquaporin 1 – a novel player in spinal cord injury

    PubMed Central

    Nesic, O.; Lee, J.; Unabia, G. C.; Johnson, K.; Ye, Z.; Vergara, L.; Hulsebosch, C. E.; Perez-Polo, J. R.

    2008-01-01

    The role of water channel aquaporin 1 (AQP-1) in uninjured or injured spinal cords is unknown. AQP-1 is weakly expressed in neurons and gray matter astrocytes, and more so in white matter astrocytes in uninjured spinal cords, a novel finding. As reported before, AQP-1 is also present in ependymal cells, but most abundantly in small diameter sensory fibers of the dorsal horn. Rat contusion spinal cord injury (SCI) induced persistent and significant four- to eightfold increases in AQP-1 levels at the site of injury (T10) persisting up to 11 months post-contusion, a novel finding. Delayed AQP-1 increases were also found in cervical and lumbar segments, suggesting the spreading of AQP-1 changes over time after SCI. Given that the antioxidant melatonin significantly decreased SCI-induced AQP-1 increases and that hypoxia inducible factor-1α was increased in acutely and chronically injured spinal cords, we propose that chronic hypoxia contributes to persistent AQP-1 increases after SCI. Interestingly; AQP-1 levels were not affected by long-lasting hypertonicity that significantly increased astrocytic AQP-4, suggesting that the primary role of AQP-1 is not regulating isotonicity in spinal cords. Based on our results we propose possible novel roles for AQP-1 in the injured spinal cords: (i) in neuronal and astrocytic swelling, as AQP-1 was increased in all surviving neurons and reactive astrocytes after SCI and (ii) in the development of the neuropathic pain after SCI. We have shown that decreased AQP-1 in melatonin-treated SCI rats correlated with decreased AQP-1 immunolabeling in the dorsal horns sensory afferents, and with significantly decreased mechanical allodynia, suggesting a possible link between AQP-1 and chronic neuropathic pain after SCI. PMID:18248364

  19. Mineral metabolism in spinal cord injury.

    PubMed

    Naftchi, N E; Viau, A T; Sell, G H; Lowman, E W

    1980-03-01

    In 10 paraplegic and 10 quadroplegic subjects, bone resorption was investigated by determining urinary excretion of hydroxyproline, calcium, and phosphorus. Measurements were performed weekly from the onset to 4 months after injury. During the first 7 weeks following injury, urinary excretion of calcium in paraplegic and quadriplegic subjects reached the highest level (380 +/- 180 mg/24hr). From 7 to 16 weeks after injury average urinary excretion of calcium (245 +/- 72 mg/24hr) remained significantly greater than that in controls (100 +/- 25 mg/24hr; p less than 0.05). Urinary hydroxyproline was elevated in paraplegic subjects (80 +/- 18 mg/24hr) for 8 weeks and in quadriplegic subjects (102 +/- 37 mg/24hr) for the entire 16 weeks following injury compared with that in controls (48 +/- 12 mg/24hr; p less than 0.05). Both paraplegic and quadriplegic subjects excreted more phosphorus (1.6 +/- 0.4 gm/24hr) than controls (0.85 +/- 0.2 gm/24hr; p less than 0.05) only during the first 2 weeks following spinal cord injury. During the acute phase of the injury (0-3 months), urinary excretion of calcium and magnesium was significantly higher (p less than 0.05) in subjects with complete compared with incomplete spinal cord lesions. PMID:7369852

  20. [Central necrosis of the lumbo-sacral segment of the spinal cord associated with multiple cholesterin emboli, clinically presenting as acute paraplegia].

    PubMed

    Yoshimura, M; Uchigata, M; Shimizu, S; Sakamoto, T; Murayama, S

    2000-10-01

    A seventy-six-year-old man suddenly suffered from paraplegia and pain in both legs. He had been maintained on hemodialysis and committed a suicide attempt by cutting the shunt at the paraplegic attack. He was brought to the emergency ward for the treatment of hemorrhagic preshock. Neurological examination demonstrated flaccid paraplegia, loss of tendon reflex in the lower extremities, dissociated sensory loss below the fourth lumbar level; and incontinence in defecation. MRI showed T2 shortening in the ventral spinal cord caudal below the level of the eleventh thoracic cord. Postmortem examination confirmed ischemic infarct in the central area of the spinal cord, associated with disseminated cholesterin emboli in the small arteries. This case was the first MRI demonstration of central necrosis caused by cholesterin emboli, and may emphasize the significance of cholesterin emboli in the spinal arterial disorders in the aged.

  1. Ganglioglioma of the Spinal Cord

    PubMed Central

    Oppenheimer, Daniel C; Johnson, Mahlon D; Judkins, Alexander R

    2015-01-01

    Ganglioglioma is a rare tumor consisting of neoplastic glial and neuronal elements. It accounts for only 0.5% of all primary central nervous system (CNS) neoplasms. We report an unusual case of extensive intramedullary thoracic spinal cord ganglioglioma in a 14-month-old girl who underwent subtotal resection followed by adjuvant chemotherapy. The epidemiology, histopathologic features, imaging findings, treatment, and prognosis are subsequently reviewed. PMID:26605127

  2. Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.

    PubMed

    Emgård, Mia; Piao, Jinghua; Aineskog, Helena; Liu, Jia; Calzarossa, Cinzia; Odeberg, Jenny; Holmberg, Lena; Samuelsson, Eva-Britt; Bezubik, Bartosz; Vincent, Per Henrik; Falci, Scott P; Seiger, Åke; Åkesson, Elisabet; Sundström, Erik

    2014-03-01

    To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.

  3. How Are Brain and Spinal Cord Tumors in Children Diagnosed?

    MedlinePlus

    ... spinal cord tumors in children staged? How are brain and spinal cord tumors diagnosed in children? Brain ... resonance angiography (MRA) or computerized tomographic angiography (CTA). Brain or spinal cord tumor biopsy Imaging tests such ...

  4. Testosterone Plus Finasteride Treatment After Spinal Cord Injury

    ClinicalTrials.gov

    2016-07-07

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

  5. Contusive spinal cord injury up regulates mu-opioid receptor (mor) gene expression in the brain and down regulates its expression in the spinal cord: possible implications in spinal cord injury research.

    PubMed

    Michael, Felicia Mary; Mohapatra, Alok Nath; Venkitasamy, Lavanya; Chandrasekar, Kirubhanand; Seldon, Tenzin; Venkatachalam, Sankar

    2015-09-01

    Traumatic spinal cord injury (SCI) is one of the dreaded neurological conditions and finding a cure for it has been a hot area of research. Naloxone - a mu-opiate receptor (mor) antagonist was considered for SCI treatment based on its positive effects under shock conditions. In contrary to animal studies based reports about the potential benefits of naloxone in treating SCI, a large scale clinical trial [National Acute Spinal Cord Injury Study II (NASCIS II)] conducted in USA failed to witness any effectiveness. The inconsistency noticed was intriguing. Therefore, the objective of the present study was to re-examine the role of naloxone in treating SCI using a highly standardised Multicenter Animal Spinal Cord Injury Study (MASCIS) animal model of contusive SCI. Results indicated that naloxone produced negligible and insignificant neuroprotection. In an attempt to understand the cause for the failure, it was found that mu-opioid receptor (mor) gene expression was upregulated in the brain but was down regulated in the spinal cord after contusive SCI. Given that the beneficial effects of naloxone are through its action on the mor, the results indicate that unlike the brain, spinal cord might not be bracing to utilise the opiate system in the repair process. This could possibly explain the failure of naloxone treatment in NASCIS II. To conclude, opiate antagonists like naloxone may be neuroprotective for treating traumatic brain injuries, but not for traumatic/contusive spinal cord injuries. PMID:26039701

  6. Spinal cord compression due to ethmoid adenocarcinoma.

    PubMed

    Johns, D R; Sweriduk, S T

    1987-10-15

    Adenocarcinoma of the ethmoid sinus is a rare tumor which has been epidemiologically linked to woodworking in the furniture industry. It has a low propensity to metastasize and has not been previously reported to cause spinal cord compression. A symptomatic epidural spinal cord compression was confirmed on magnetic resonance imaging (MRI) scan in a former furniture worker with widely disseminated metastases. The clinical features of ethmoid sinus adenocarcinoma and neoplastic spinal cord compression, and the comparative value of MRI scanning in the neuroradiologic diagnosis of spinal cord compression are reviewed.

  7. Rat models of spinal cord injury: from pathology to potential therapies

    PubMed Central

    2016-01-01

    ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748

  8. G-CSF promotes autophagy and reduces neural tissue damage after spinal cord injury in mice.

    PubMed

    Guo, Yuji; Liu, Shangming; Zhang, Xianghong; Wang, Liyan; Gao, Jiangang; Han, Aiqing; Hao, Aijun

    2015-12-01

    Granulocyte colony-stimulating factor (G-CSF) was investigated for its capacity to induce autophagy and related neuroprotective mechanisms in an acute spinal cord injury model. To accomplish this goal, we established a mouse spinal cord hemisection model to test the effects of recombinant human G-CSF. The results showed that autophagy was activated after spinal cord injury and G-CSF appears to induce a more rapid activation of autophagy within injured spinal cords as compared with that of non-treated animals. Apoptosis as induced in mechanically injured neurons with G-CSF treatment was enhanced after inhibiting autophagy by 3-methyladenine (3-MA), which partially blocked the neuroprotective effect of autophagy as induced by G-CSF. In addition, G-CSF inhibited the activity of the NF-κB signal pathway in neurons after mechanical injury. We conclude that G-CSF promotes autophagy by inhibiting the NF-κB signal pathway and protects neuronal structure after spinal cord injury. We therefore suggest that G-CSF, which rapidly induces autophagy after spinal cord injury to inhibit neuronal apoptosis, may thus provide an effective auxiliary therapeutic intervention for spinal cord injury.

  9. Recent advances in managing a spinal cord injury secondary to trauma

    PubMed Central

    Ahuja, Christopher S.; Martin, Allan R.; Fehlings, Michael

    2016-01-01

    Traumatic spinal cord injuries (SCIs) affect 1.3 million North Americans, producing devastating physical, social, and vocational impairment. Pathophysiologically, the initial mechanical trauma is followed by a significant secondary injury which includes local ischemia, pro-apoptotic signaling, release of cytotoxic factors, and inflammatory cell infiltration. Expedient delivery of medical and surgical care during this critical period can improve long-term functional outcomes, engendering the concept of “Time is Spine”. We emphasize the importance of expeditious care while outlining the initial clinical and radiographic assessment of patients. Key evidence-based early interventions (surgical decompression, blood pressure augmentation, and methylprednisolone) are also reviewed, including findings of the landmark Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). We then describe other neuroprotective approaches on the edge of translation such as the sodium-channel blocker riluzole, the anti-inflammatory minocycline, and therapeutic hypothermia. We also review promising neuroregenerative therapies that are likely to influence management practices over the next decade including chondroitinase, Rho-ROCK pathway inhibition, and bioengineered strategies. The importance of emerging neural stem cell therapies to remyelinate denuded axons and regenerate neural circuits is also discussed. Finally, we outline future directions for research and patient care. PMID:27303644

  10. Recent advances in managing a spinal cord injury secondary to trauma.

    PubMed

    Ahuja, Christopher S; Martin, Allan R; Fehlings, Michael

    2016-01-01

    Traumatic spinal cord injuries (SCIs) affect 1.3 million North Americans, producing devastating physical, social, and vocational impairment. Pathophysiologically, the initial mechanical trauma is followed by a significant secondary injury which includes local ischemia, pro-apoptotic signaling, release of cytotoxic factors, and inflammatory cell infiltration. Expedient delivery of medical and surgical care during this critical period can improve long-term functional outcomes, engendering the concept of "Time is Spine". We emphasize the importance of expeditious care while outlining the initial clinical and radiographic assessment of patients. Key evidence-based early interventions (surgical decompression, blood pressure augmentation, and methylprednisolone) are also reviewed, including findings of the landmark Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). We then describe other neuroprotective approaches on the edge of translation such as the sodium-channel blocker riluzole, the anti-inflammatory minocycline, and therapeutic hypothermia. We also review promising neuroregenerative therapies that are likely to influence management practices over the next decade including chondroitinase, Rho-ROCK pathway inhibition, and bioengineered strategies. The importance of emerging neural stem cell therapies to remyelinate denuded axons and regenerate neural circuits is also discussed. Finally, we outline future directions for research and patient care. PMID:27303644

  11. Infertility in spinal-cord injured male.

    PubMed

    Ver Voort, S M

    1987-02-01

    Sterility in spinal-cord injured (SCI) men is believed to be caused by ejaculatory dysfunction, genital ductal blockage secondary to infection, and/or impaired spermatogenesis. Semen from SCI men demonstrates diminished numbers of motile, morphologically normal sperm. Testicular biopsies demonstrate impaired spermatogenesis. Leydig and Sertoli cells appear to be normal. Endocrine evaluations reveal normal testosterone levels with an adequate Leydig cell reserve. Luteinizing hormone (LD) and follicle-stimulating hormone (FSH) levels are normal or high with normal or exaggerated stimulation responses. Acute depressions in testosterone, FSH, and LH levels can be seen following SCI, most markedly in quadriplegics. A normal hypothalamic-pituitary-testicular axis is implied by these findings, indicating a primary hypogonadism. Causes of impaired spermatogenesis may include local testicular temperature elevations, nondrainage of the reproductive tract, antisperm antibodies, and recurrent genitourinary infections. Treatment of infertility involves removal of these offending factors, and research is needed to correlate the impaired spermatogenesis with these factors.

  12. A Neonatal Mouse Spinal Cord Compression Injury Model.

    PubMed

    Züchner, Mark; Glover, Joel C; Boulland, Jean-Luc

    2016-01-01

    Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life(1), this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques(1). Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections(1). PMID:27078037

  13. A Neonatal Mouse Spinal Cord Compression Injury Model

    PubMed Central

    Züchner, Mark; Glover, Joel C.; Boulland, Jean-Luc

    2016-01-01

    Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1. PMID:27078037

  14. Nutrition of People with Spinal Cord Injuries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This conference proceeding summarizes current knowledge about the nutritional status and needs of the spinal cord injured patient. Topics covered include the aspects of spinal cord injury that influence nutrient intakes and status, and the nutrients most likely to be problematic in this diverse gro...

  15. Psychological Aspects of Spinal Cord Injury

    ERIC Educational Resources Information Center

    Cook, Daniel W.

    1976-01-01

    Reviewing literature on the psychological impact of spinal cord injury suggests: (a) depression may not be a precondition for injury adjustment; (b) many persons sustaining cord injury may have experienced psychological disruption prior to injury; and (c) indexes of rehabilitation success need to be developed for the spinal cord injured. (Author)

  16. Ambulation and spinal cord injury.

    PubMed

    Hardin, Elizabeth C; Kobetic, Rudi; Triolo, Ronald J

    2013-05-01

    Walking is possible for many patients with a spinal cord injury. Avenues enabling walking include braces, robotics and FES. Among the benefits are improved musculoskeletal and mental health, however unrealistic expectations may lead to negative changes in quality of life. Use rigorous assessment standards to gauge the improvement of walking during the rehabilitation process, but also yearly. Continued walking after discharge may be limited by challenges, such as lack of accessibility in and outside the home, and complications, such as shoulder pain or injuries from falls. It is critical to determine the risks and benefits of walking for each patient.

  17. Efficacy of a metalloproteinase inhibitor in spinal cord injured dogs.

    PubMed

    Levine, Jonathan M; Cohen, Noah D; Heller, Michael; Fajt, Virginia R; Levine, Gwendolyn J; Kerwin, Sharon C; Trivedi, Alpa A; Fandel, Thomas M; Werb, Zena; Modestino, Augusta; Noble-Haeusslein, Linda J

    2014-01-01

    Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic

  18. Efficacy of a Metalloproteinase Inhibitor in Spinal Cord Injured Dogs

    PubMed Central

    Levine, Jonathan M.; Cohen, Noah D.; Heller, Michael; Fajt, Virginia R.; Levine, Gwendolyn J.; Kerwin, Sharon C.; Trivedi, Alpa A.; Fandel, Thomas M.; Werb, Zena; Modestino, Augusta; Noble-Haeusslein, Linda J.

    2014-01-01

    Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0–4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0–8.0) or GM6001 (mean, 5; 95% CI 2.0–8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse

  19. Efficacy of a metalloproteinase inhibitor in spinal cord injured dogs.

    PubMed

    Levine, Jonathan M; Cohen, Noah D; Heller, Michael; Fajt, Virginia R; Levine, Gwendolyn J; Kerwin, Sharon C; Trivedi, Alpa A; Fandel, Thomas M; Werb, Zena; Modestino, Augusta; Noble-Haeusslein, Linda J

    2014-01-01

    Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic

  20. Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats.

    PubMed

    Iorgulescu, J Bryan; Patel, Samik P; Louro, Jack; Andrade, Christian M; Sanchez, Andre R; Pearse, Damien D

    2015-01-01

    Schwann cell (SC) transplantation exhibits significant potential for spinal cord injury (SCI) repair and its use as a therapeutic modality has now progressed to clinical trials for subacute and chronic human SCI. Although SC implants provide a receptive environment for axonal regrowth and support functional recovery in a number of experimental SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without additional combinatory approaches. In the current study we investigated whether the concurrent delivery of the polyamine putrescine, started either 30 min or 1 week after SCI, could enhance the efficacy of SCs when implanted subacutely (1 week after injury) into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in the regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. We show that the combination of putrescine with SCs provides a significant increase in implant size, an enhancement in axonal (sensory and serotonergic) sparing and/or growth, and improved open field locomotion after SCI, as compared to SC implantation alone. These findings demonstrate that polyamine supplementation can augment the effectiveness of SCs when used as a therapeutic approach for subacute SCI repair. PMID:26550496

  1. Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.

    PubMed

    Fehlings, Michael G; Wilson, Jefferson R; Frankowski, Ralph F; Toups, Elizabeth G; Aarabi, Bizhan; Harrop, James S; Shaffrey, Christopher I; Harkema, Susan J; Guest, James D; Tator, Charles H; Burau, Keith D; Johnson, Michele W; Grossman, Robert G

    2012-09-01

    In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889.

  2. Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats

    PubMed Central

    Iorgulescu, J. Bryan; Patel, Samik P.; Louro, Jack; Andrade, Christian M.; Sanchez, Andre R.; Pearse, Damien D.

    2015-01-01

    Schwann cell (SC) transplantation exhibits significant potential for spinal cord injury (SCI) repair and its use as a therapeutic modality has now progressed to clinical trials for subacute and chronic human SCI. Although SC implants provide a receptive environment for axonal regrowth and support functional recovery in a number of experimental SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without additional combinatory approaches. In the current study we investigated whether the concurrent delivery of the polyamine putrescine, started either 30 min or 1 week after SCI, could enhance the efficacy of SCs when implanted subacutely (1 week after injury) into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in the regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. We show that the combination of putrescine with SCs provides a significant increase in implant size, an enhancement in axonal (sensory and serotonergic) sparing and/or growth, and improved open field locomotion after SCI, as compared to SC implantation alone. These findings demonstrate that polyamine supplementation can augment the effectiveness of SCs when used as a therapeutic approach for subacute SCI repair. PMID:26550496

  3. Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.

    PubMed

    Fehlings, Michael G; Wilson, Jefferson R; Frankowski, Ralph F; Toups, Elizabeth G; Aarabi, Bizhan; Harrop, James S; Shaffrey, Christopher I; Harkema, Susan J; Guest, James D; Tator, Charles H; Burau, Keith D; Johnson, Michele W; Grossman, Robert G

    2012-09-01

    In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889. PMID:22985381

  4. Rehabilitation of spinal cord injuries

    PubMed Central

    Nas, Kemal; Yazmalar, Levent; Şah, Volkan; Aydın, Abdulkadir; Öneş, Kadriye

    2015-01-01

    Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion. The most common causes of SCI in the world are traffic accidents, gunshot injuries, knife injuries, falls and sports injuries. There is a strong relationship between functional status and whether the injury is complete or not complete, as well as the level of the injury. The results of SCI bring not only damage to independence and physical function, but also include many complications from the injury. Neurogenic bladder and bowel, urinary tract infections, pressure ulcers, orthostatic hypotension, fractures, deep vein thrombosis, spasticity, autonomic dysreflexia, pulmonary and cardiovascular problems, and depressive disorders are frequent complications after SCI. SCI leads to serious disability in the patient resulting in the loss of work, which brings psychosocial and economic problems. The treatment and rehabilitation period is long, expensive and exhausting in SCI. Whether complete or incomplete, SCI rehabilitation is a long process that requires patience and motivation of the patient and relatives. Early rehabilitation is important to prevent joint contractures and the loss of muscle strength, conservation of bone density, and to ensure normal functioning of the respiratory and digestive system. An interdisciplinary approach is essential in rehabilitation in SCI, as in the other types of rehabilitation. The team is led by a physiatrist and consists of the patients’ family, physiotherapist, occupational therapist, dietician, psychologist, speech therapist, social worker and other consultant specialists as necessary. PMID:25621206

  5. Therapeutic approaches for spinal cord injury.

    PubMed

    Cristante, Alexandre Fogaça; Barros Filho, Tarcísio Eloy Pessoa de; Marcon, Raphael Martus; Letaif, Olavo Biraghi; Rocha, Ivan Dias da

    2012-10-01

    This study reviews the literature concerning possible therapeutic approaches for spinal cord injury. Spinal cord injury is a disabling and irreversible condition that has high economic and social costs. There are both primary and secondary mechanisms of damage to the spinal cord. The primary lesion is the mechanical injury itself. The secondary lesion results from one or more biochemical and cellular processes that are triggered by the primary lesion. The frustration of health professionals in treating a severe spinal cord injury was described in 1700 BC in an Egyptian surgical papyrus that was translated by Edwin Smith; the papyrus reported spinal fractures as a "disease that should not be treated." Over the last biological or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at minimum, allow for partial functional recoveries for these patients, which could improve their quality of life. PMID:23070351

  6. Regenerative treatment in spinal cord injury.

    PubMed

    Ozdemir, Mevci; Attar, Ayhan; Kuzu, Isinsu

    2012-09-01

    Spinal cord injury is a devastating, traumatic event, and experienced mainly among young people. Until the modern era, spinal cord injury was so rapidly fatal that no seriously injured persons would survive long enough for regeneration to occur. Treatment of spinal cord injury can be summarized as follows: prevent further cord injury, maintain blood flow, relieve spinal cord compression, and provide secure vertebral stabilization so as to allow mobilization and rehabilitation, none of which achieves functional recovery. Previous studies have focused on analyzing the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as the tissue damage and neural cell death associated with secondary injury. Now, there are hundreds of current experimental and clinical regenerative treatment studies. One of the most popular treatment method is cell transplantation in injured spinal cord. For this purpose bone marrow stromal cells, mononuclear stem cells, mesenchymal stem cells, embryonic stem cells, neural stem cells, and olfactory ensheathing cells can be used. As a result, cell transplantation has become a promising therapeutic option for spinal cord injury patients. In this paper we discuss the effectiveness of stem cell therapy in spinal cord injury.

  7. Microsurgical resection of intramedullary spinal cord hemangioblastoma.

    PubMed

    McCormick, Paul C

    2014-09-01

    Spinal cord hemangioblastomas account for about 10% of spinal cord tumors. They usually arise from the dorsolateral pia mater and are characterized by their significant vascularity. The principles and techniques of safe resection are different than those employed for the more commonly occurring intramedullary glial tumors (e.g. ependymoma, astrocytoma) and consist of circumferential detachment of the tumor margin from the surrounding normal pia. This video demonstrates the microsurgical techniques of resection of a thoracic spinal cord hemangioblastoma. The video can be found here: http://youtu.be/yT5KLi4VyAo. PMID:25175571

  8. Contribution of bone marrow-derived endothelial progenitor cells to neovascularization and astrogliosis following spinal cord injury.

    PubMed

    Kamei, Naosuke; Kwon, Sang-Mo; Kawamoto, Atsuhiko; Ii, Masaaki; Ishikawa, Masakazu; Ochi, Mitsuo; Asahara, Takayuki

    2012-12-01

    Spinal cord injury causes initial mechanical damage, followed by ischemia-induced, secondary degeneration, worsening the tissue damage. Although endothelial progenitor cells (EPCs) have been reported to play an important role for pathophysiological neovascularization in various ischemic tissues, the EPC kinetics following spinal cord injury have never been elucidated. In this study, we therefore assessed the in vivo kinetics of bone marrow-derived EPCs by EPC colony-forming assay and bone marrow transplantation from Tie2/lacZ transgenic mice into wild-type mice with spinal cord injury. The number of circulating mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day 3 postspinal cord injury. Bone marrow transplantation study revealed that bone marrow-derived EPCs recruited into the injured spinal cord markedly increased at day 7, when neovascularization and astrogliosis drastically occurred in parallel with axon growth in the damaged tissue. To elucidate further the contribution of EPCs to recovery after spinal cord injury, exogenous EPCs were systemically infused immediately after the injury. The administered EPCs were incorporated into the injured spinal cord and accelerated neovascularization and astrogliosis. These findings suggest that bone marrow-derived EPCs may contribute to the tissue repair by augmenting neovascularization and astrogliosis following spinal cord injury.

  9. A telerehabilitation intervention for persons with spinal cord dysfunction.

    PubMed

    Houlihan, Bethlyn Vergo; Jette, Alan; Paasche-Orlow, Michael; Wierbicky, Jane; Ducharme, Stan; Zazula, Judi; Cuevas, Penelope; Friedman, Robert H; Williams, Steve

    2011-09-01

    Pressure ulcers and depression are common preventable conditions secondary to a spinal cord dysfunction. However, few successful, low-cost preventive approaches have been identified. We have developed a dynamic automated telephone calling system, termed Care Call, to empower and motivate people with spinal cord dysfunction to improve their skin care, seek treatment for depression, and appropriately use the healthcare system. Herein, we describe the design and development of Care Call, its novel features, and promising preliminary results of our pilot testing. Voice quality testing showed that Care Call was able to understand all voice characteristics except very soft-spoken speech. Importantly, pilot study subjects felt Care Call could be particularly useful for people who are depressed, those with acute injury, and those without access to quality care. The results of a randomized controlled trial currently underway to evaluate Care Call will be available in 2011. PMID:21389846

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

    PubMed

    Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

    2016-03-01

    Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner.

  11. Plasticity of interneuronal networks of the functionally isolated human spinal cord

    PubMed Central

    Harkema, Susan J.

    2009-01-01

    The loss of walking after human spinal cord injury has been attributed to the dominance of supraspinal over spinal mechanisms. The evidence for central pattern generation in humans is limited due to the inability to conclusively isolate the circuitry from descending and afferent input. However, studying individuals following spinal cord injury with no detectable influence on spinal networks from supraspinal centers can provide insight to their interaction with afferent input. The focus of this article is on the interaction of sensory input with human spinal networks in the generation of locomotor patterns. The functionally isolated human spinal cord has the capacity to generate locomotor patterns with appropriate afferent input. Locomotor Training is a rehabilitative strategy that has evolved from animal and humans studies focused on the neural plasticity of the spinal cord and has been successful for many people with acute and chronic incomplete spinal cord injury. However, even those individuals with clinically complete spinal cord injury that generate appropriate locomotor patterns during stepping with assistance on a treadmill with body weight support cannot sustain overground walking. This suggests that although a significant control of locomotion can occur at the level of spinal interneuronal networks the level of sustainable excitability of these circuits is still compromised. Future studies should focus on approaches to increase the central state of excitability and may include neural repair strategies, pharmacological interventions or epidural stimulation in combination with Locomotor Training. PMID:18042493

  12. Malignancies of the spinal cord.

    PubMed

    Waters, J Dawn; Peran, Encarnacion Maria Navarro; Ciacci, Joseph

    2012-01-01

    The management of intramedullary spinal cord tumors (IMSCT) is primarily concerned with the preservation of existing neurologic function. To this end, clinical scientists are continually seeking tools and techniques to improve the safety and efficacy of tumor resection and control. Further advances in safety and efficacy can be proposed at each phase of management, from pre-operative screening to post-treatment monitoring. Innovations within the areas of molecular biology and genetics, intraoperative imaging and stereotactic radiosurgery offer exciting new options to explore in the management of IMSCT. This section will review the pathophysiology and epidemiology of IMSCT and the state-of-the-art management before delving into the promising new tools and techniques for each phase of management. PMID:23281516

  13. Spinal cord injury in youth.

    PubMed

    Apple, D F; Anson, C A; Hunter, J D; Bell, R B

    1995-02-01

    To identify special characteristics of the pediatric spinal cord-injured (SCI) population, we analyzed a database of 1,770 traumatic SCI patients; 88 (5%) fell into the two pediatric subgroups: 0-12 years (n = 26) and 13-15 years (n = 62) at time of injury. Differences between age groups were identified with regard to demographics, neurologic characteristics, associated injuries and complications, and management. Mode level of bony injury was C2 in preteens, C4 in teens, and C4-C5 in adults. Scoliosis developed far more frequently in children, particularly preteens (23%), than in adults (5%). Violent etiologies, predominantly gunshots, accounted for a disproportionate share of injuries to preteens (19%) and African-Americans (28%), as compared with adults (12%) and Caucasians (7%). This last finding underscores the urgent need to mount a response to the nationwide proliferation of gunshot-related SCI in children and minorities.

  14. Spinal cord injury in youth.

    PubMed

    Apple, D F; Anson, C A; Hunter, J D; Bell, R B

    1995-02-01

    To identify special characteristics of the pediatric spinal cord-injured (SCI) population, we analyzed a database of 1,770 traumatic SCI patients; 88 (5%) fell into the two pediatric subgroups: 0-12 years (n = 26) and 13-15 years (n = 62) at time of injury. Differences between age groups were identified with regard to demographics, neurologic characteristics, associated injuries and complications, and management. Mode level of bony injury was C2 in preteens, C4 in teens, and C4-C5 in adults. Scoliosis developed far more frequently in children, particularly preteens (23%), than in adults (5%). Violent etiologies, predominantly gunshots, accounted for a disproportionate share of injuries to preteens (19%) and African-Americans (28%), as compared with adults (12%) and Caucasians (7%). This last finding underscores the urgent need to mount a response to the nationwide proliferation of gunshot-related SCI in children and minorities. PMID:7729113

  15. Measurement of Intraspinal Pressure After Spinal Cord Injury: Technical Note from the Injured Spinal Cord Pressure Evaluation Study.

    PubMed

    Werndle, Melissa C; Saadoun, Samira; Phang, Isaac; Czosnyka, Marek; Varsos, Georgios; Czosnyka, Zofia; Smielewski, Peter; Jamous, Ali; Bell, B Anthony; Zoumprouli, Argyro; Papadopoulos, Marios C

    2016-01-01

    Intracranial pressure (ICP) is routinely measured in patients with severe traumatic brain injury (TBI). We describe a novel technique that allowed us to monitor intraspinal pressure (ISP) at the injury site in 14 patients who had severe acute traumatic spinal cord injury (TSCI), analogous to monitoring ICP after brain injury. A Codman probe was inserted subdurally to measure the pressure of the injured spinal cord compressed against the surrounding dura. Our key finding is that it is feasible and safe to monitor ISP for up to a week in patients after TSCI, starting within 72 h of the injury. With practice, probe insertion and calibration take less than 10 min. The ISP signal characteristics after TSCI were similar to the ICP signal characteristics recorded after TBI. Importantly, there were no associated complications. Future studies are required to determine whether reducing ISP improves neurological outcome after severe TSCI. PMID:27165930

  16. Spinal cord protection in aortic endovascular surgery.

    PubMed

    Scott, D A; Denton, M J

    2016-09-01

    A persistent neurological deficit, such as paraplegia or paraparesis, secondary to spinal cord injury remains one of the most feared complications of surgery on the descending thoracic or abdominal aorta. This is despite sophisticated advances in imaging and the use of less invasive endovascular procedures. Extensive fenestrated endovascular aortic graft prostheses still carry a risk of spinal cord injury of up to 10%; thus, this risk should be identified and strategies implemented to protect the spinal cord and maintain perfusion. The patients at highest risk are those undergoing extensive thoracic aortic stenting including thoracic, abdominal, and pelvic vessels. Although many techniques are available, lumbar cerebrospinal fluid drainage remains the most frequent intervention, along with maintenance of perfusion pressure and possibly staged procedures to allow collateral vessel stabilization. Many questions remain regarding other technical aspects, spinal cord monitoring and cooling, pharmacological protection, and the optimal duration of interventions into the postoperative period. PMID:27566805

  17. Spinal Cord Injury: Hope through Research

    MedlinePlus

    ... chronic pain in people with spinal cord injury. Robotic-assisted therapy Most recovery following SCI takes place ... the safety and efficacy of a type of robotic therapy device known as the AMES device. The ...

  18. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

  19. Spinal Cord Injury Model System Information Network

    MedlinePlus

    ... the UAB-SCIMS More The UAB-SCIMS Information Network The University of Alabama at Birmingham Spinal Cord Injury Model System (UAB-SCIMS) maintains this Information Network as a resource to promote knowledge in the ...

  20. Unusual aetiology of malignant spinal cord compression.

    PubMed

    Boland, Jason; Rennick, Adrienne

    2013-06-01

    Malignant spinal cord compression (MSCC) is an oncological emergency requiring rapid diagnosis and treatment to prevent irreversible spinal cord injury and disability. A case is described in a 45-year-old male with renal cell carcinoma in which the presentation of the MSCC was atypical with principally proximal left leg weakness with no evidence of bone metastasis. This was due to an unusual aetiology of the MSCC as the renal carcinoma had metastasised to his left psoas muscle causing a lumbosacral plexopathy and infiltrated through the intervertebral disc spaces, initially causing left lateral cauda equina and upper lumbar cord compression, before complete spinal cord compression. This case illustrates the varied aetiology of MSCC and reinforces the importance of maintaining a high index of suspicion of the possibility of spinal cord compression. PMID:24644568

  1. Staging Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  2. Segmentation of the human spinal cord.

    PubMed

    De Leener, Benjamin; Taso, Manuel; Cohen-Adad, Julien; Callot, Virginie

    2016-04-01

    Segmenting the spinal cord contour is a necessary step for quantifying spinal cord atrophy in various diseases. Delineating gray matter (GM) and white matter (WM) is also useful for quantifying GM atrophy or for extracting multiparametric MRI metrics into specific WM tracts. Spinal cord segmentation in clinical research is not as developed as brain segmentation, however with the substantial improvement of MR sequences adapted to spinal cord MR investigations, the field of spinal cord MR segmentation has advanced greatly within the last decade. Segmentation techniques with variable accuracy and degree of complexity have been developed and reported in the literature. In this paper, we review some of the existing methods for cord and WM/GM segmentation, including intensity-based, surface-based, and image-based methods. We also provide recommendations for validating spinal cord segmentation techniques, as it is important to understand the intrinsic characteristics of the methods and to evaluate their performance and limitations. Lastly, we illustrate some applications in the healthy and pathological spinal cord. One conclusion of this review is that robust and automatic segmentation is clinically relevant, as it would allow for longitudinal and group studies free from user bias as well as reproducible multicentric studies in large populations, thereby helping to further our understanding of the spinal cord pathophysiology and to develop new criteria for early detection of subclinical evolution for prognosis prediction and for patient management. Another conclusion is that at the present time, no single method adequately segments the cord and its substructure in all the cases encountered (abnormal intensities, loss of contrast, deformation of the cord, etc.). A combination of different approaches is thus advised for future developments, along with the introduction of probabilistic shape models. Maturation of standardized frameworks, multiplatform availability, inclusion

  3. Mediastinal paraganglioma causing spinal cord compression.

    PubMed Central

    Reyes, M G; Fresco, R; Bruetman, M E

    1977-01-01

    An invasive paraganglioma of the posterior mediastinum caused spinal cord compression in a 31 year old women. Electron microscopic examination of the paraganglioma invading the epidural space revealed numerous dense-cored granules in the cytoplasm of the tumour cells. We are reporting this case to present the ultrastructure of mediastinal paraganglioma, and to call attention to an unusual cause of spinal cord compression. Images PMID:886352

  4. Inflammogenesis of Secondary Spinal Cord Injury

    PubMed Central

    Anwar, M. Akhtar; Al Shehabi, Tuqa S.; Eid, Ali H.

    2016-01-01

    Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine. PMID:27147970

  5. Spinal cord lesions - The rehabilitation perspective.

    PubMed

    Faria, Filipa

    2006-02-01

    The present study provides an overview of the spinal cord injury focusing mainly on aspects related to rehabilitation. Spinal cord injury affects young people in an active phase of life, determining severe handicaps. Most of the lesions are traumatic, caused by car accidents. Until fifty years ago, the survival of individuals with spinal cord injury was very reduced and the leading cause of death was renal failure. Due to developments in medical knowledge and technical advances, the survival rates have significantly improved. The causes of death have also changed being respiratory complications, particularly pneumonia, the leading causes. Immediately after a spinal cord lesion there is a phase of spinal shock which is characterized by flaccid paralysis and bladder and bowel retention. Progressively there is a return of the spinal cord automatism with the beginning of some reflex activities. Based on neurological evaluation it is pos-sible to predict motor and functional recovery and establish the rehabilitation program. We can consider three phases on the rehabilitation program: the first while the patient is still in bed, directed to prevent or treat complications due to immobility and begin sphincters reeducation; the second phase is intended to achieve wheelchair autonomy; the last phase is training in ortostatism. The rehabilitation program also comprises sports and recreational activities, psychological and social support in order to achieve an integral of the individual with a spinal cord injury.

  6. Perturbed cholesterol homeostasis in aging spinal cord.

    PubMed

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2016-09-01

    The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging.

  7. Perturbed cholesterol homeostasis in aging spinal cord.

    PubMed

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2016-09-01

    The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging. PMID:27459933

  8. Neuroprotective role of neurophysiological monitoring during endovascular procedures in the spinal cord.

    PubMed

    Sala, F; Niimi, Y; Berenstein, A; Deletis, V

    2001-06-01

    The endovascular treatment of spinal vascular malformations places the spinal cord at risk for ischemia. When these procedures are performed using general anesthesia, the neurophysiological monitoring methods currently available provide the only means by which to assess the functional integrity of sensory and motor pathways. Neurophysiological monitoring allows a warning for the neuroradiologist of impending irreversible neurological damage so that action may be taken for the prompt restoration of adequate spinal cord perfusion. Muscle motor evoked potentials (mMEPs) better reflect spinal cord perfusion in the anterior spinal artery territory than do somatosensory evoked potentials (SEPs), although their use during spinal endovascular procedures remains anecdotal in the literature. In the study reported here we assessed: (1) the feasibility of intraoperative neurophysiological monitoring, (2) the role of provocative tests with Amytal and Xylocaine, and (3) the specific but complementary role played by SEPs and mMEPs, during endovascular embolization of spinal vascular malformations and tumors. The results suggest that: (1) neurophysiological monitoring is feasible during most endovascular procedures in the spine and spinal cord under general anesthesia, (2) provocative tests enhance the safety of the procedure, (3) mMEPs are more feasible than SEPs and more sensitive than SEPs to provocative tests. We strongly suggest the use of multimodal neurophysiological monitoring and provocative tests during the endovascular treatment of spinal and spinal cord vascular lesions.

  9. Osteoporosis in individuals with spinal cord injury.

    PubMed

    Bauman, William A; Cardozo, Christopher P

    2015-02-01

    The pathophysiology, clinical considerations, and relevant experimental findings with regard to osteoporosis in individuals with spinal cord injury (SCI) will be discussed. The bone loss that occurs acutely after more neurologically motor complete SCI is unique for its sublesional skeletal distribution and rate, at certain skeletal sites approaching 1% of bone mineral density per week, and its resistance to currently available treatments. The areas of high bone loss include the distal femur, proximal tibia, and more distal boney sites. Evidence from a study performed in monozygotic twins discordant for SCI indicates that sublesional bone loss in the twin with SCI increases for several decades, strongly suggesting that the heightened net bone loss after SCI may persist for an extended period of time. The increased frequency of fragility fracture after paralysis will be discussed, and a few risk factors for such fractures after SCI will be examined. Because vitamin D deficiency, regardless of disability, is a relevant consideration for bone health, as well as an easily reversible condition, the increased prevalence of and treatment target values for vitamin D in this deficiency state in the SCI population will be reviewed. Pharmacological and mechanical approaches to preserving bone integrity in persons with acute and chronic SCI will be reviewed, with emphasis placed on efficacy and practicality. Emerging osteoanabolic agents that improve functioning of WNT/β-catenin signaling after paralysis will be introduced as therapeutic interventions that may hold promise.

  10. HDAC6 Regulates the Chaperone-Mediated Autophagy to Prevent Oxidative Damage in Injured Neurons after Experimental Spinal Cord Injury

    PubMed Central

    Su, Min; Guan, Huaqing; Zhang, Fan; Gao, Yarong; Teng, Xiaomei; Yang, Weixin

    2016-01-01

    Hypoxia-ischemia- (HI-) induced oxidative stress plays a role in secondary pathocellular processes of acute spinal cord injury (SCI) due to HI from many kinds of mechanical trauma. Increasing evidence suggests that the histone deacetylase-6 (HDAC6) plays an important role in cell homeostasis in both physiological and abnormal, stressful, pathological conditions. This paper found that inhibition of HDAC6 accelerated reactive oxygen species (ROS) generation and cell apoptosis in response to the HI. Deficiency of HDAC6 hindered the chaperone-mediated autophagy (CMA) activity to resistance of HI-induced oxidative stress. Furthermore, this study provided the experimental evidence for the potential role of HDAC6 in the regulation of CMA by affecting HSP90 acetylation. Therefore, HDAC6 plays an important role in the function of CMA pathway under the HI stress induced by SCI and it may be a potential therapeutic target in acute SCI model. PMID:26649145

  11. Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair.

    PubMed

    Devaux, Stephanie; Cizkova, Dasa; Quanico, Jusal; Franck, Julien; Nataf, Serge; Pays, Laurent; Hauberg-Lotte, Lena; Maass, Peter; Kobarg, Jan H; Kobeissy, Firas; Mériaux, Céline; Wisztorski, Maxence; Slovinska, Lucia; Blasko, Juraj; Cigankova, Viera; Fournier, Isabelle; Salzet, Michel

    2016-08-01

    Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D matrix-assisted laser desorption ionization (MALDI) imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after SCI are altered between the lesion proximity, i.e. rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e. R2-C2 and R3-C3 levels coexpressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover, the presence of immunoglobulins (IgGs) in neurons at the lesion site at 3 days, validated by mass spectrometry, may present additional factor that contributes to limited regeneration. Treatment in vivo with anti-CD20 one hour after SCI did not improve locomotor function and decrease IgG expression. These results open the door of a novel view of the SCI treatment by considering the C1 as the therapeutic target. PMID:27250205

  12. Adiposity and spinal cord injury

    PubMed Central

    Gorgey, Ashraf S; Wells, Kathryn M; Austin, Timothy L

    2015-01-01

    The drastic changes in body composition following spinal cord injury (SCI) have been shown to play a significant role in cardiovascular and metabolic health. The pattern of storage and distribution of different types of adipose tissue may impact metabolic health variables similar to carbohydrate, lipid and bone metabolism. The use of magnetic resonance imaging provides insights on the interplay among different regional adipose tissue compartments and their role in developing chronic diseases. Regional adipose tissue can be either distributed centrally or peripherally into subcutaneous and ectopic sites. The primary ectopic adipose tissue sites are visceral, intramuscular and bone marrow. Dysfunction in the central nervous system following SCI impacts the pattern of distribution of adiposity especially between tetraplegia and paraplegia. The current editorial is focused primarily on introducing different types of adipose tissue and establishing scientific basis to develop appropriate dietary, rehabilitation or pharmaceutical interventions to manage the negative consequences of increasing adiposity after SCI. We have also summarized the clinical implications and future recommendations relevant to study adiposity after SCI. PMID:26396933

  13. Chronic complications of spinal cord injury

    PubMed Central

    Sezer, Nebahat; Akkuş, Selami; Uğurlu, Fatma Gülçin

    2015-01-01

    Spinal cord injury (SCI) is a serious medical condition that causes functional, psychological and socioeconomic disorder. Therefore, patients with SCI experience significant impairments in various aspects of their life. The goals of rehabilitation and other treatment approaches in SCI are to improve functional level, decrease secondary morbidity and enhance health-related quality of life. Acute and long-term secondary medical complications are common in patients with SCI. However, chronic complications especially further negatively impact on patients’ functional independence and quality of life. Therefore, prevention, early diagnosis and treatment of chronic secondary complications in patients with SCI is critical for limiting these complications, improving survival, community participation and health-related quality of life. The management of secondary chronic complications of SCI is also important for SCI specialists, families and caregivers as well as patients. In this paper, we review data about common secondary long-term complications after SCI, including respiratory complications, cardiovascular complications, urinary and bowel complications, spasticity, pain syndromes, pressure ulcers, osteoporosis and bone fractures. The purpose of this review is to provide an overview of risk factors, signs, symptoms, prevention and treatment approaches for secondary long-term complications in patients with SCI. PMID:25621208

  14. Radiation tolerance of the cervical spinal cord

    SciTech Connect

    McCunniff, A.J.; Liang, M.J.

    1989-03-01

    The incidence of permanent injury to the spinal cord as a complication of radiation therapy generally correlates positively with total radiation dosage. However, several reports in the literature have indicated that fraction size is also an important factor in the development or nondevelopment of late injuries in normal tissue. To determine the effect of fraction size on the incidence of radiation-induced spinal cord injuries, we reviewed 144 cases of head and neck cancer treated at our institution between 1971 and 1980 with radiation greater than 5600 cGy to a portion of the cervical spinal cord. Most of these patients received greater than or equal to 6000 cGy, with fraction sizes ranging from 133 cGy to 200 cGy. Fifty-three of the 144 patients have been followed up for 2 years or more. Nearly half of these (26 patients) received greater than 6000 cGy with fraction sizes of 133 cGy to 180 cGy. Only 1 of the 53 (1.9%) has sustained permanent spinal cord injury; 20 months after completion of radiation treatments he developed Brown-Sequard syndrome. Our experience suggests that radiation injuries to the spinal cord correlate not only with total radiation dosage, but also with fraction size; low fraction sizes appear to decrease the incidence of such injuries.

  15. General Information about Childhood Brain and Spinal Cord Tumors

    MedlinePlus

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

  16. What Are the Treatments for Spinal Cord Injury (SCI)?

    MedlinePlus

    ... Resources and Publications What are the treatments for spinal cord injury (SCI)? Skip sharing on social media links ... no known ways to reverse damage to the spinal cord. However, researchers are continually working on new treatments, ...

  17. Vocational Rehabilitation of Persons with Spinal Cord Injuries

    ERIC Educational Resources Information Center

    Poor, Charles R.

    1975-01-01

    Reviews historical development of organized vocational rehabilitation programming for the spinal cord injured in the United States. Significant factors that affect vocational rehabilitation outcomes with spinal cord injured persons are listed and discussed. (Author)

  18. Causes of Spinal Cord Injury

    PubMed Central

    2013-01-01

    Background: Knowledge of the causes of spinal cord injury (SCI) and associated factors is critical in the development of successful prevention programs. Objective: This study analyzed data from the National SCI Database (NSCID) and National Shriners SCI Database (NSSCID) in the United States to examine specific etiologies of SCI by age, sex, race, ethnicity, day and month of injury, and neurologic outcomes. Methods: NSCID and NSSCID participants who had a traumatic SCI from 2005 to 2011 with known etiology were included in the analyses (N=7,834). Thirty-seven causes of injury documented in the databases were stratified by personal characteristics using descriptive analysis. Results: The most common causes of SCI were automobile crashes (31.5%) and falls (25.3%), followed by gunshot wounds (10.4%), motorcycle crashes (6.8%), diving incidents (4.7%), and medical/surgical complications (4.3%), which collectively accounted for 83.1% of total SCIs since 2005. Automobile crashes were the leading cause of SCI until age 45 years, whereas falls were the leading cause after age 45 years. Gunshot wounds, motorcycle crashes, and diving caused more SCIs in males than females. The major difference among race/ethnicity was in the proportion of gunshot wounds. More SCIs occurred during the weekends and warmer months, which seemed to parallel the increase of motorcycle- and diving-related SCIs. Level and completeness of injury are also associated with etiology of injury. Conclusions: The present findings suggest that prevention strategies should be tailored to the targeted population and major causes to have a meaningful impact on reducing the incidence of SCI. PMID:23678280

  19. Primary Multifocal Gliosarcoma of the Spinal Cord

    PubMed Central

    Kumar, Ramesh M.; Finn, Michael

    2016-01-01

    Gliosarcoma (GS) is a rare and exceedingly malignant neoplasm of the central nervous system. It displays clinical features similar to glioblastoma, yet is histologically unique as it harbors both gliomatous and sarcomatous cellular components. Involvement of the neuro-axis is predominantly limited to the cerebral parenchyma and meninges. Primary GS of the spinal cord is rarely encountered. We report a case of a 54 year old male who presented with 2 months of progressive, bilateral lower extremity sensory deficits. Magnetic resonance imaging of the neuro-axis revealed multiple intradural lesions involving the cervical and thoracic spinal cord without evidence of intracranial involvement. Surgical resection of a dural based, extramedullary cervical lesion and two exophytic, intramedullary thoracic lesions revealed gliosarcoma, WHO grade IV. The patient died approximately 11 months after presentation. This report confirms that GS is not limited to supratentorial involvement and can primarily affect the spinal cord. PMID:27134708

  20. Intractable Pruritus After Traumatic Spinal Cord Injury

    PubMed Central

    Crane, Deborah A; Jaffee, Kenneth M; Kundu, Anjana

    2009-01-01

    Background: This report describes a young woman with incomplete traumatic cervical spinal cord injury and intractable pruritus involving her dorsal forearm. Method: Case report. Findings: Anatomic distribution of the pruritus corresponded to the dermatomal distribution of her level of spinal cord injury and vertebral fusion. Symptoms were attributed to the spinal cord injury and possible cervical root injury. Pruritus was refractory to all treatments, including topical lidocaine, gabapentin, transcutaneous electrical nerve stimulation, intravenous Bier block, stellate ganglion block, and acupuncture. Conclusions: Further understanding of neuropathic pruritus is needed. Diagnostic workup of intractable pruritus should include advanced imaging to detect ongoing nerve root compression. If diagnostic studies suggest radiculopathy, epidural steroid injection should be considered. Because the autonomic nervous system may be involved in complex chronic pain or pruritic syndromes, sympatholysis via such techniques as stellate ganglion block might be effective. PMID:19777867

  1. Applier tool for intradural spinal cord implants.

    PubMed

    Oya, H; Reddy, C G; Dahdaleh, N S; Wilson, S; Howard, M A; Jeffery, N D; Utz, M; Gillies, G T

    2012-04-01

    We have designed, built and tested a novel device for placing intradural neurmodulator implants directly on the pial surface of the spinal cord. This applier tool is designed for ergonomic handling of delicate electro-mechanical devices such as the Iowa-Patch™ spinal cord stimulator implant, which is aimed at overcoming certain shortcomings in the performance of standard epidural stimulator devices. The applier is approximately 14 cm long, 6 mm in diameter, made of stainless steel components, and has simple and reliable mechanisms for the attachment and release of the implant from it. We describe the design of the device, details of its construction, and its performance during in vivo testing of somatosensory evoked potentials in an ovine model of intradural spinal cord stimulation. PMID:22339111

  2. Turkish Adaptation of Spinal Cord Independence Measure--Version III

    ERIC Educational Resources Information Center

    Kesiktas, Nur; Paker, Nurdan; Bugdayci, Derya; Sencan, Sureyya; Karan, Ayse; Muslumanoglu, Lutfiye

    2012-01-01

    Various rating scales have been used to assess ability in individuals with spinal cord injury. There is no specific functional assessment scale for Turkish patients with spinal cord injury. The Spinal Cord Independence Measure (SCIM) is a specific test, which has become popular in the last decade. A study was conducted to validate and evaluate the…

  3. Sexuality Counseling with Clients Who Have Spinal Cord Injuries.

    ERIC Educational Resources Information Center

    Farrow, Jeff

    1990-01-01

    Examines effects of spinal cord injury on sexuality. Discusses areas of sexual concern. Provides suggestions for treating clients with spinal cord injuries experiencing sexual difficulties. Concludes that major goal in working with clients with spinal cord injuries who have sexual difficulties should be the facilitation of a creative and…

  4. Characteristics and rehabilitation for patients with spinal cord stab injury.

    PubMed

    Wang, Fangyong; Zhang, Junwei; Tang, Hehu; Li, Xiang; Jiang, Shudong; Lv, Zhen; Liu, Shujia; Chen, Shizheng; Liu, Jiesheng; Hong, Yi

    2015-12-01

    [Purpose] The objective of the study was to compare the incidence, diagnosis, treatment, and prognosis of patients with spinal cord stab injury to those with the more common spinal cord contusion injury. [Subjects] Of patients hospitalized in China Rehabilitation Research Center from 1994 to 2014, 40 of those having a spinal cord stab injury and 50 with spinal cord contusion were selected. [Methods] The data of all patients were analyzed retrospectively. The cases were evaluated by collecting admission and discharge ASIA (American Spinal Injury Association) and ADL (activity of daily living) scores. [Results] After a comprehensive rehabilitation program, ASIA and ADL scores of patients having both spinal cord stab injury and spinal cord contusion significantly increase. However, the increases were noted to be higher in patients having a spinal cord stab injury than those having spinal cord contusion. [Conclusion] Comprehensive rehabilitation is effective both for patients having spinal cord stab injury and those with spinal cord contusion injury. However, the prognosis of patients having spinal cord stab injury is better than that of patients with spinal cord contusion.

  5. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation

    PubMed Central

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4’,6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons. PMID:26309595

  6. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

    PubMed

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

  7. Microsurgical resection of intramedullary spinal cord ependymoma.

    PubMed

    McCormick, Paul C

    2014-09-01

    Ependymomas are the most commonly occurring intramedullary spinal cord tumor in adults. With few exceptions these tumors are histologically benign, although they exhibit some biologic variability with respect to growth rate. While unencapsulated, spinal ependymomas are non-infiltrative and present a clear margin of demarcation from the surrounding spinal cord that serves as an effective dissection plane. This video demonstrates the technique of microsurgical resection of an intramedullary ependymoma through a posterior midline myelotomy. The video can be found here: http://youtu.be/lcHhymSvSqU. PMID:25175587

  8. [Non-invasive transcutaneous spinal cord stimulation facilitates locomotor activity in decerebrated and spinal cats].

    PubMed

    Musienko, P E; Bogacheva, I N; Savochin, A A; Kilimnik, V A; Gorskiĭ, O V; Nikitin, O A; Gerasimenko, Ia P

    2013-08-01

    It is known that spinal neuronal networks activated by epidural electrical stimulation (EES) can produce the stepping EMG pattern and control the locomotor behavior. At present study we showed that non-invasive transcutaneous electrical spinal cord stimulation (tESCS) applied to the lumbar-sacral enlargement can facilitate the locomotor activity in decerebrated and spinal animals. The comparison of the motor responses evoked by EES vs tESCS showed that both methods produce the locomotor patterns with close properties and similar reflex mechanisms. The data obtained suggest that tESCS is an efficient approach for investigation of the locomotor control in acute and chronic experiments as well as facilitates of the locomotor abilities after spinal cord injury. Taking to account the non-invasivity and easement of tESCS, this approach could be further implemented in clinical practice for rehabilitation of the patient with spinal cord injury.

  9. Non-surgical management of superior mesenteric artery thrombosis using spinal cord stimulation.

    PubMed

    Tod, Laura; Ghosh, Jonathan; Lieberman, Ilan; Baguneid, Mohamed

    2013-08-05

    We report the use of a spinal cord stimulator (SCS) for non-surgical management of superior mesenteric artery thrombosis. A 59-year-old woman with polycythaemia rubra vera presented with extensive superior mesenteric artery thrombosis not amenable to surgical or endovascular revascularisation. A SCS was implanted for analgesia thereby allowing enteral feeding to be tolerated during the acute period. Four months later the patient developed a focal ischaemic jejunal stricture and underwent resection of a short segment of small bowel with primary anastomosis that healed without complication. Spinal cord stimulation can facilitate non-surgical management of mesenteric ischaemia.

  10. Surgical resection of subependymoma of the cervical spinal cord.

    PubMed

    Tan, Lee A; Kasliwal, Manish K; Mhanna, Nakhle; Fontes, Ricardo B V; Traynelis, Vincent C

    2014-09-01

    Subependymomas can rarely occur in the spinal cord, and account for about 2% of symptomatic spinal cord tumors. It most often occurs in the cervical spinal cord, followed by cervicothoracic junction, thoracic cord and conus medullaris. It often has an eccentric location in the spinal cord and lacks gadolinium enhancement on magnetic resonance imaging. We present a rare case of symptomatic subependymoma of the cervical spinal cord, which underwent successful gross total resection. Surgical pearls and nuances are discussed to help surgeons to avoid potential complications. The video can be found here: http://youtu.be/Rsm9KxZX7Yo. PMID:25175581

  11. Spinal cord injury--scientific challenges for the unknown future.

    PubMed

    Anderberg, Leif; Aldskogius, Håkan; Holtz, Anders

    2007-01-01

    the research field of spinal cord injury. We will focus our discussion on methods either preventing the consequences of secondary injury in the acute period (neuroprotection) and/or various techniques of neural regeneration in the sub-acute and chronic phase and finally expose some thoughts about future avenues within this scientific field.

  12. Spinal cord injury--scientific challenges for the unknown future.

    PubMed

    Anderberg, Leif; Aldskogius, Håkan; Holtz, Anders

    2007-01-01

    the research field of spinal cord injury. We will focus our discussion on methods either preventing the consequences of secondary injury in the acute period (neuroprotection) and/or various techniques of neural regeneration in the sub-acute and chronic phase and finally expose some thoughts about future avenues within this scientific field. PMID:18484069

  13. Proprioceptive pathways of the spinal cord.

    PubMed Central

    Schneider, R J; Kulics, A T; Ducker, T B

    1977-01-01

    In the Macaque, surgical lesions were made in the dorsal funiculus, in the dorsolateral funiculus, and through half of the spinal cord. The somatosensory and motor capacity of the animal were examined neurologically and electrophysiologically. The exact lesion was then confirmed pathologically in detail. The results of these experiments indicate that limb position information from the distal limb and proximal limb are relayed to the brain in two different fashions. Distal limb position information, especially the cortical representation of the limbs' volar surface as it moves in space, is drastically impaired by dorsal funiculus or posterior white column lesions. Proximal limb position may or may not be impaired by similar lesions, for this information while initially in the dorsal or posterior white columns is sorted out (as it ascends in the spinal cord) to the dorsolateral funiculus or white columns. For example, in the lower thoracic spinal cord, both distal and proximal hind limb sensation are impaired by posterior white column damage; in the cervical cord, only distal sensation is impaired by the same lesion, and proximal information is spared. We refer to this neuroanatomic rearranging as "fibre sorting", and we believe that it is clinically significant in spinal cord disease. Images PMID:408463

  14. Accommodating Workers with Spinal Cord Injury.

    ERIC Educational Resources Information Center

    Dowler, Denetta; Batiste, Linda; Whidden, Eddie

    1998-01-01

    Examination of over 1,000 calls to the Job Accommodation Network involving workers with spinal cord injury identified the nature of the industry, job, career progression, and accessibility solutions. The number of calls increased dramatically after passage of the Americans with Disabilities Act. (SK)

  15. Employment Outcomes Following Spinal Cord Injury.

    ERIC Educational Resources Information Center

    Engel, S.; Murphy, G. S.; Athanasou, J. A.; Hickey, L.

    1998-01-01

    A study of 83 Australian adults with spinal cord injuries found that at least 56% had worked at some time post-injury and those who were working when surveyed had done so for an average of close to 10 years. Clerical, office, and administrative occupations proved to be the most suitable. (Author/CR)

  16. Simplified spinal cord phantom for evaluation of SQUID magnetospinography

    NASA Astrophysics Data System (ADS)

    Adachi, Y.; Oyama, D.; Somchai, N.; Kawabata, S.; Uehara, G.

    2014-05-01

    Spinal cord functional imaging by magnetospinography (MSG) is a noninvasive diagnostic method for spinal cord diseases. However, the accuracy and spatial resolution of lesion localization by MSG have barely been evaluated in detail so far. We developed a simplified spinal cord phantom for MSG evaluation. The spinal cord phantom is composed of a cylindrical vessel filled with saline water, which acts as a model of a neck. A set of modeled vertebrae is arranged in the cylindrical vessel, which has a neural current model made from catheter electrodes. The neural current model emulates the current distribution around the activated site along the axon of the spinal cord nerve. Our MSG system was used to observe the magnetic field from the phantom; a quadrupole-like pattern of the magnetic field distribution, which is a typical distribution pattern for spinal cord magnetic fields, was successfully reproduced by the phantom. Hence, the developed spinal cord phantom can be used to evaluate MSG source analysis methods.

  17. Cortical reorganization after spinal cord injury: always for good?

    PubMed Central

    Moxon, Karen A.; Oliviero, Antonio; Aguilar, Juan; Foffani, Guglielmo

    2015-01-01

    Plasticity constitutes the basis of behavioral changes as a result of experience. It refers to neural network shaping and re-shaping at the global level and to synaptic contacts remodeling at the local level, either during learning or memory encoding, or as a result of acute or chronic pathological conditions. ‘Plastic’ brain reorganization after central nervous system lesions has a pivotal role in the recovery and rehabilitation of sensory and motor dysfunction, but can also be “maladaptive”. Moreover, it is clear that brain reorganization it is not a “static” phenomenon but rather a very dynamic process. Spinal cord injury immediately initiates a change in brain state and starts cortical reorganization. In the long term, the impact of injury – with or without accompanying therapy – on the brain is a complex balance between supraspinal reorganization and spinal recovery. The degree of cortical reorganization after spinal cord injury is highly variable, and can range from no reorganization (i.e. “silencing”) to massive cortical remapping. This variability critically depends on the species, the age of the animal when the injury occurs, the time after the injury has occurred, and the behavioral activity and possible therapy regimes after the injury. We will briefly discuss these dependencies, trying to highlight their translational value. Overall, it is not only necessary to better understand how the brain can reorganize after injury with or without therapy, it is also necessary to clarify when and why brain reorganization can be either “good” or “bad” in terms of its clinical consequences. This information is critical in order to develop and optimize cost-effective therapies to maximize functional recovery while minimizing maladaptive states after spinal cord injury. PMID:24997269

  18. Exercise modulates chloride homeostasis after spinal cord injury.

    PubMed

    Côté, Marie-Pascale; Gandhi, Sapan; Zambrotta, Marina; Houlé, John D

    2014-07-01

    Activity-based therapies are routinely integrated in spinal cord injury (SCI) rehabilitation programs because they result in a reduction of hyperreflexia and spasticity. However, the mechanisms by which exercise regulates activity in spinal pathways to reduce spasticity and improve functional recovery are poorly understood. Persisting alterations in the action of GABA on postsynaptic targets is a signature of CNS injuries, including SCI. The action of GABA depends on the intracellular chloride concentration, which is determined largely by the expression of two cation-chloride cotransporters (CCCs), KCC2 and NKCC1, which serve as chloride exporters and importers, respectively. We hypothesized that the reduction in hyperreflexia with exercise after SCI relies on a return to chloride homeostasis. Sprague Dawley rats received a spinal cord transection at T12 and were assigned to SCI-7d, SCI-14d, SCI-14d+exercise, SCI-28d, SCI-28d+exercise, or SCI-56d groups. During a terminal experiment, H-reflexes were recorded from interosseus muscles after stimulation of the tibial nerve and the low-frequency-dependent depression (FDD) was assessed. We provide evidence that exercise returns spinal excitability and levels of KCC2 and NKCC1 toward normal levels in the lumbar spinal cord. Acutely altering chloride extrusion using the KCC2 blocker DIOA masked the effect of exercise on FDD, whereas blocking NKCC1 with bumetanide returned FDD toward intact levels after SCI. Our results indicate that exercise contributes to reflex recovery and restoration of endogenous inhibition through a return to chloride homeostasis after SCI. This lends support for CCCs as part of a pathway that could be manipulated to improve functional recovery when combined with rehabilitation programs.

  19. Cortical reorganization after spinal cord injury: always for good?

    PubMed

    Moxon, K A; Oliviero, A; Aguilar, J; Foffani, G

    2014-12-26

    Plasticity constitutes the basis of behavioral changes as a result of experience. It refers to neural network shaping and re-shaping at the global level and to synaptic contacts remodeling at the local level, either during learning or memory encoding, or as a result of acute or chronic pathological conditions. 'Plastic' brain reorganization after central nervous system lesions has a pivotal role in the recovery and rehabilitation of sensory and motor dysfunction, but can also be "maladaptive". Moreover, it is clear that brain reorganization is not a "static" phenomenon but rather a very dynamic process. Spinal cord injury immediately initiates a change in brain state and starts cortical reorganization. In the long term, the impact of injury - with or without accompanying therapy - on the brain is a complex balance between supraspinal reorganization and spinal recovery. The degree of cortical reorganization after spinal cord injury is highly variable, and can range from no reorganization (i.e. "silencing") to massive cortical remapping. This variability critically depends on the species, the age of the animal when the injury occurs, the time after the injury has occurred, and the behavioral activity and possible therapy regimes after the injury. We will briefly discuss these dependencies, trying to highlight their translational value. Overall, it is not only necessary to better understand how the brain can reorganize after injury with or without therapy, it is also necessary to clarify when and why brain reorganization can be either "good" or "bad" in terms of its clinical consequences. This information is critical in order to develop and optimize cost-effective therapies to maximize functional recovery while minimizing maladaptive states after spinal cord injury.

  20. Differential Neuroproteomic and Systems Biology Analysis of Spinal Cord Injury.

    PubMed

    Moghieb, Ahmed; Bramlett, Helen M; Das, Jyotirmoy H; Yang, Zhihui; Selig, Tyler; Yost, Richard A; Wang, Michael S; Dietrich, W Dalton; Wang, Kevin K W

    2016-07-01

    Acute spinal cord injury (SCI) is a devastating condition with many consequences and no known effective treatment. Although it is quite easy to diagnose traumatic SCI, the assessment of injury severity and projection of disease progression or recovery are often challenging, as no consensus biomarkers have been clearly identified. Here rats were subjected to experimental moderate or severe thoracic SCI. At 24h and 7d postinjury, spinal cord segment caudal to injury center versus sham samples was harvested and subjected to differential proteomic analysis. Cationic/anionic-exchange chromatography, followed by 1D polyacrylamide gel electrophoresis, was used to reduce protein complexity. A reverse phase liquid chromatography-tandem mass spectrometry proteomic platform was then utilized to identify proteome changes associated with SCI. Twenty-two and 22 proteins were up-regulated at 24 h and 7 day after SCI, respectively; whereas 19 and 16 proteins are down-regulated at 24 h and 7 day after SCI, respectively, when compared with sham control. A subset of 12 proteins were identified as candidate SCI biomarkers - TF (Transferrin), FASN (Fatty acid synthase), NME1 (Nucleoside diphosphate kinase 1), STMN1 (Stathmin 1), EEF2 (Eukaryotic translation elongation factor 2), CTSD (Cathepsin D), ANXA1 (Annexin A1), ANXA2 (Annexin A2), PGM1 (Phosphoglucomutase 1), PEA15 (Phosphoprotein enriched in astrocytes 15), GOT2 (Glutamic-oxaloacetic transaminase 2), and TPI-1 (Triosephosphate isomerase 1), data are available via ProteomeXchange with identifier PXD003473. In addition, Transferrin, Cathepsin D, and TPI-1 and PEA15 were further verified in rat spinal cord tissue and/or CSF samples after SCI and in human CSF samples from moderate/severe SCI patients. Lastly, a systems biology approach was utilized to determine the critical biochemical pathways and interactome in the pathogenesis of SCI. Thus, SCI candidate biomarkers identified can be used to correlate with disease progression or

  1. Novel combination strategies to repair the injured mammalian spinal cord.

    PubMed

    Bunge, Mary Bartlett

    2008-01-01

    Due to the varied and numerous changes in spinal cord tissue following injury, successful treatment for repair may involve strategies combining neuroprotection (pharmacological prevention of some of the damaging intracellular cascades that lead to secondary tissue loss), axonal regeneration promotion (cell transplantation, genetic engineering to increase growth factors, neutralization of inhibitory factors, reduction in scar formation), and rehabilitation. Our goal has been to find effective combination strategies to improve outcome after injury to the adult rat thoracic spinal cord. Combination interventions tested have been implantation of Schwann cells (SCs) plus neuroprotective agents and growth factors administered in various ways, olfactory ensheathing cell (OEC) implantation, chondroitinase addition, or elevation of cyclic AMP. The most efficacious strategy in our hands for the acute complete transection/SC bridge model, including improvement in locomotion [Basso, Beattie, Bresnahan Scale (BBB)], is the combination of SCs, OECs, and chondroitinase administration (BBB 2.1 vs 6.6, 3 times more myelinated axons in the SC bridge, increased serotonergic axons in the bridge and beyond, and significant correlation between the number of bridge myelinated axons and functional improvement). We found the most successful combination strategy for a subacute spinal cord contusion injury (12.5-mm, 10-g weight, MASCIS impactor) to be SCs and elevation of cyclic AMP (BBB 10.4 vs 15, significant increases in white matter sparing, in myelinated axons in the implant, and in responding reticular formation and red and raphe nuclei, and a significant correlation between the number of serotonergic fibers and improvement in locomotion). Thus, in two injury paradigms, these combination strategies as well as others studied in our laboratory have been found to be more effective than SCs alone and suggest ways in which clinical application may be developed. PMID:18795474

  2. The Sir Ludwig Guttmann lecture 2012: the contribution of Stoke Mandeville Hospital to spinal cord injuries.

    PubMed

    Frankel, H L

    2012-11-01

    This Ludwig Guttmann Lecture was presented at the 2012 meeting of the International Spinal Cord Society in London. It describes the contribution of Stoke Mandeville Hospital to the field of spinal cord injuries. Dr Ludwig Guttmann started the Spinal Unit at Stoke Mandeville Hospital in 1944 and introduced a novel, comprehensive method of care, which included early admission, prevention and treatment of spinal cord injury related complications, active rehabilitation and social reintegration. Soon a dedicated specialist team was assembled and training of visitors was encouraged, some of whom went on to start their own spinal units. Research went hand in hand with clinical work, and over the years more than 500 scientific contributions from Stoke Mandeville have been published in peer reviewed journals and books. Guttmann introduced sport as a means of physical therapy, which soon lead to organised Stoke Mandeville Games, first national in 1948, then international in 1952 and finally the Paralympic Games in 1960. Stoke Mandeville is regarded as the birthplace of the Paralympic movement, and Guttmann was knighted in 1966. Stoke Mandeville is also the birthplace of the International Medical Society of Paraplegia, later International Spinal Cord Society, which was formed during the International Stoke Mandeville Games in 1961, and of the Society's medical journal Paraplegia, later Spinal Cord, first published in 1963. Guttmann's followers have continued his philosophy and, with some new developments and advances, the present day National Spinal Injuries Centre at Stoke Mandeville Hospital provides comprehensive, multidisciplinary acute care, rehabilitation and life-long follow-up for patient with spinal cord injuries of all ages. PMID:23045299

  3. Acute limb ischemia: contemporary approach.

    PubMed

    Fukuda, Ikuo; Chiyoya, Mari; Taniguchi, Satoshi; Fukuda, Wakako

    2015-10-01

    Acute limb ischemia is a critical condition with high mortality and morbidity even after surgical or endovascular intervention. Early recognition is important, but a delayed presentation is not uncommon. Viability of the limb is assessed by motor and sensory function and with interrogating Doppler flow signals in pedal arteries and popliteal veins as categorized by Rutherford. Category IIa indicates mild-to-moderate threat to limb salvage over a time frame without revascularization. Limb ischemia is critical without prompt revascularization in category IIb. Because the risk of reperfusion injury is high in this group of patients, perioperative management is important. In category III, reperfusion is not indicated except for embolism within several hours of onset. Intimal injury should be avoided by careful tactile control of a balloon with a smaller size catheter and under radiographic monitoring. Adjunctive treatment with catheter-directed thrombolysis or bypass surgery is sometimes necessary. Endovascular treatment is a promising option for thrombotic occlusion of an atherosclerotic artery. Ischemia-reperfusion injury is a serious problem. Controlled reperfusion with low-pressure perfusion at a reduced temperature and use of a leukocyte filter should be considered. The initial reperfusate is hyperosmolar, hypocalcemic, slightly alkaline, and contains free radical scavengers such as allopurinol. Immediate hemodialysis is necessary for acute renal injury caused by myoglobinemia. Compartment syndrome should be managed with assessment of intra-compartment pressure and fasciotomy.

  4. Successful Spinal Cord Stimulator Trial and Permanent Implant in Patient with Diabetic Peripheral Neuropathy on Chronic Dual Antiplatelet Therapy.

    PubMed

    Covert, Brian P; Nobles, Ryan H

    2015-01-01

    The safety of neuraxial anesthetic techniques in the setting of oral and parenteral anticoagulation is an area of growing interest and clinical inquiry as the multitude of anticoagulant medications rapidly increases. Additionally, the indications for spinal cord stimulation therapy are evolving as both technique and technology in the field continue to advance. The estimated incidence of spinal hematoma following epidural injection has been estimated to be 1 in 150,000-200,000. However, there is very little data on the risk of indwelling spinal cord simulation leads and chronic use of anticoagulant medications. We would like to report a recent case for consideration in which a spinal cord stimulator trial was successful and led to permanent spinal cord stimulator implantation in a patient with diabetic peripheral neuropathy taking life-long aspirin and clopidogrel therapy secondary to extensive coronary and carotid atherosclerosis. The report serves as a novel case to encourage exploration into the topic of anticoagulation therapy with indwelling spinal cord stimulator leads. The case brings up a number of critical questions that cannot clearly be answered with the current literature and some interesting topics for discussion including the need for acute systemic anticoagulation in the future for vascular interventions and risk stratification for those patients selected for spinal cord stimulation. PMID:26431144

  5. Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

    SciTech Connect

    Guss, Zachary D.; Moningi, Shalini; Jallo, George I.; Cohen, Kenneth J.; Wharam, Moody D.; Terezakis, Stephanie A.

    2013-04-01

    Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy

  6. Multiple sclerosis of the spinal cord: Magnetic resonance appearance

    SciTech Connect

    Thielen, K.R.; Miller, G.M.

    1996-05-01

    To determine the MR appearance of spinal cord multiple sclerosis (MS) plaques in patients presenting with myclopathy by using a high-field (1.5 T) imager. We studied 119 patients who underwent high-field (1.5 T) MR studies of the spinal cord for evaluation of myelopathy. All 119 patients were thought to have possible findings of spinal cord MS at the time of the MRI interpretation. Sixty-four plaques were studied in 47 patients with clinically definite MS and adequate quality MRI. Of these patients 68% had a single spinal cord plaque, 19% had two plaques, and 13% had three or more plaques. Sixty-two percent of the plaques occurred in the cervical spinal cord and most frequently involved the posterior (41%) and lateral (25%) aspects of the spinal cord. None of the 64 lesions involved the entire thickness of the spinal cord. The lesion length varied from 2 to 60 mm, with 84% of the lesions <15 mm in length. The spinal cord diameter was unchanged in 84% of plaques, enlarged at the level of the lesion in 14%, and atrophic in 2%. Just over half (55%) of the plaques enhanced with intravenously administered gadolinium. Of the patients who received synchronous head and spinal cord examinations on the same day, 24% had normal findings on the MR study of the head. Follow-up spinal cord studies were available in nine patients. New lesions developed in two patients, while previously described lesions resolved. In three patients only new lesions developed. In four patients no change occurred in the existing number of cord plaques. Spinal cord demyelinating plaques present as well-circumscribed foci of increased T2 signal that asymmetrically involve the spinal cord parenchyma. Knowledge of their usual appearance may prevent unnecessary biopsy. An MR examination of the head may confirm the imaging suggestion of spinal cord demyelinating disease, because up to 76% of patients have abnormal intracranial findings. 15 refs., 7 figs.

  7. Gene therapy approaches for spinal cord injury

    NASA Astrophysics Data System (ADS)

    Bright, Corinne

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

  8. Training a Spinal Cord Injury Rehabilitation Team in Motivational Interviewing

    PubMed Central

    Lusilla-Palacios, Pilar; Castellano-Tejedor, Carmina

    2015-01-01

    Background. An acute spinal cord injury (ASCI) is a severe condition that requires extensive and very specialized management of both physical and psychological dimensions of injured patients. Objective. The aim of the part of the study reported here was twofold: (1) to describe burnout, empathy, and satisfaction at work of these professionals and (2) to explore whether a tailored program based on motivational interviewing (MI) techniques modifies and improves such features. Methods. This paper presents findings from an intervention study into a tailored training for professionals (N = 45) working in a spinal cord injury (SCI) unit from a general hospital. Rehabilitation professionals' empathy skills were measured with the Jefferson Scale of Physician Empathy (JSPE), burnout was measured with the Maslach Burnout Inventory (MBI), and additional numeric scales were used to assess the perceived job-related stress and perceived satisfaction with job. Results. Findings suggest that professionals are performing quite well and they refer to satisfactory empathy, satisfaction at work, and no signs of burnout or significant stress both before and after the training. Conclusions. No training effect was observed in the variables considered in the study. Some possible explanations for these results and future research directions are discussed in depth in this paper. The full protocol of this study is registered in ClinicalTrials.gov (identifier: NCT01889940). PMID:26770827

  9. An Intermediate Animal Model of Spinal Cord Stimulation

    PubMed Central

    Guiho, Thomas; Coste, Christine Azevedo; Delleci, Claire; Chenu, Jean-Patrick; Vignes, Jean-Rodolphe; Bauchet, Luc; Guiraud, David

    2016-01-01

    Spinal cord injuries (SCI) result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self-) catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session. PMID:27478570

  10. The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury.

    PubMed

    Schwab, Jan M; Zhang, Yi; Kopp, Marcel A; Brommer, Benedikt; Popovich, Phillip G

    2014-08-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the "immune privileged/specialized" milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of "SCI disease" and are important therapeutic targets to improve neural repair and neurological outcome. Generic immune suppressive therapies have been largely unsuccessful, mostly because inflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, "compartimentalized" investigations, limited to only intraspinal inflammation and associated cellular or molecular changes in the spinal cord, neglect the reality that the structure and function of the CNS are influenced by systemic immune challenges and that the immune system is 'hardwired' into the nervous system. Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the context of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and "neurogenic" spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired "host-defense" and trauma-induced autoimmunity. PMID:25017893

  11. Basic Advances and New Avenues in Therapy of Spinal Cord Injury

    PubMed Central

    Dobkin, Bruce H.; Havton, Leif A.

    2014-01-01

    The prospects for successful clinical trials of neuroprotective and neurorestorative interventions for patients with acute and chronic myelopathies depend on preclinical animal models of injury and repair that reflect the human condition. Remarkable progress continues in the attempt to promote connections between the brain and the sensory and motor neurons below a spinal cord lesion. Recent experiments demonstrate the potential for biological therapies to regenerate or remyelinate axons and to incorporate new neural cells into the milieu of a traumatic spinal cord injury. The computational flexibility and plasticity of the sensorimotor systems of the brain, spinal cord, and motor unit make functional use of new circuitry feasible in patients. To incorporate residual and new pathways, neural repair strategies must be coupled to rehabilitation therapies that drive activity-dependent plasticity for walking, for reaching and grasping, and for bowel and bladder control. Prevention of pain and dysautonomia are also clinical targets. Research aims to define the temporal windows of opportunity for interventions, test the safety and efficacy of delivery systems of agents and cells, and provide a better understanding of the cascades of gene expression and cell interactions both acutely and chronically after injury. These bench-to-bedside studies are defining the neurobiology of spinal cord injury rehabilitation. PMID:14746521

  12. In vivo imaging of spinal cord in contusion injury model mice by multi-photon microscopy

    NASA Astrophysics Data System (ADS)

    Oshima, Y.; Horiuchi, H.; Ogata, T.; Hikita, A.; Miura, H.; Imamura, T.

    2014-03-01

    Fluorescent imaging technique is a promising method and has been developed for in vivo applications in cellular biology. In particular, nonlinear optical imaging technique, multi-photon microscopy has make it possible to analyze deep portion of tissues in living animals such as axons of spinal code. Traumatic spinal cord injuries (SCIs) are usually caused by contusion damages. Therefore, observation of spinal cord tissue after the contusion injury is necessary for understanding cellular dynamics in response to traumatic SCI and development of the treatment for traumatic SCI. Our goal is elucidation of mechanism for degeneration of axons after contusion injuries by establishing SCI model and chronic observation of injured axons in the living animals. Firstly we generated and observed acute SCI model by contusion injury. By using a multi-photon microscope, axons in dorsal cord were visualized approximately 140 micron in depth from the surface. Immediately after injury, minimal morphological change of spinal cord was observed. At 3 days after injury, spinal cord was swelling and the axons seem to be fragmented. At 7 days after injury, increased degradation of axons could be observed, although the image was blurred due to accumulation of the connective tissue. In the present study, we successfully observed axon degeneration after the contusion SCI in a living animal in vivo. Our final goal is to understand molecular mechanisms and cellular dynamics in response to traumatic SCIs in acute and chronic stage.

  13. Evaluation of spinal cord function by means of lower limb somatosensory evoked potentials in reparative aortic surgery.

    PubMed

    Fava, E; Bortolani, E M; Ducati, A; Ruberti, U

    1988-01-01

    A group of patients undergoing aortic replacement of thoracic and abdominal aneurysms were studied by intraoperative recording of Somatosensory Evoked Potentials (SEPs). Lower limb nerves were stimulated and SEPs recorded at spinal and cortical level. Progressive changes of cortical SEPs until their disappearance were observed. In operations on the thoracic aorta, the spinal response was essentially unmodified, so that the observed alterations reflected true dysfunction of the spinal cord. The only patient who developed an intraoperative anterior spinal infarct had the longest period of absent SEPs and a striking latency prolongation when they returned. Postoperative recordings were absolutely normal. When the abdominal aorta was occluded, SEP alterations involved both cortical and spinal responses, so that it is difficult to distinguish between the relative roles of peripheral nerve and spinal cord ischemia. These findings indicate that SEPs can be reliably applied to spinal cord monitoring in the course of aortic surgery, even though they are mainly conducted in the posterior cord tracts.

  14. Thoracic spinal cord compression by a tophus.

    PubMed

    Ntsiba, Honoré; Makosso, Edouard; Moyikoua, Armand

    2010-03-01

    We report a case of thoracic (T10) spinal cord compression by a tophus in a patient with known chronic gout. Spastic paraplegia developed gradually over 6 months in this 43-year-old man with hypertension, alcohol abuse, and chronic gouty arthritis with tophi. Magnetic resonance imaging and computed tomography visualized an intradural nodule measuring 1.5cm in diameter at the level of T10, as well as geodes in the left T10 lamina and left T9-T10 articular processes. The nodule was removed surgically and shown by histological examination to be a tophus. The neurological impairments resolved rapidly and completely. We found about 60 similar cases in the literature. Spinal cord compression in a patient with chronic gout can be caused by a tophus.

  15. Growing up with a spinal cord injury.

    PubMed

    Johnson, K M; Berry, E T; Goldeen, R A; Wicker, E

    1991-04-01

    Much of what we need to know to be independent adults is learned in the first five years of life. In the toddler, instead of reteaching learned skills, as we do with older spinal cord injury persons, we are teaching skills for the first time. It is therefore imperative to have a creative therapeutic team who can teach skills which were never acquired and encourage the child's cognitive growth as well as growth towards independence. This paper will include a case report of a 2 year-old C3-4 quadriplegic child rehabilitated through an interdisciplinary family-centered model of care. We will share some of the issues our team has encountered when "rehabilitating" very young children with spinal cord injuries based on the observations of the team members as well as the scant literature available. This will also include a parent's reflections of modification needed in family structure and roles. PMID:2011723

  16. Reducing cardiometabolic disease in spinal cord injury.

    PubMed

    Kressler, Jochen; Cowan, Rachel E; Bigford, Gregory E; Nash, Mark S

    2014-08-01

    Accelerated cardiometabolic disease is a serious health hazard after spinal cord injuries (SCI). Lifestyle intervention with diet and exercise remains the cornerstone of effective cardiometabolic syndrome treatment. Behavioral approaches enhance compliance and benefits derived from both diet and exercise interventions and are necessary to assure that persons with SCI profit from intervention. Multitherapy strategies will likely be needed to control challenging component risks, such as gain in body mass, which has far reaching implications for maintenance of daily function as well as health.

  17. Anorgasmia in anterior spinal cord syndrome.

    PubMed Central

    Berić, A; Light, J K

    1993-01-01

    Three male and two female patients with anorgasmia and dissociated sensory loss due to an anterior spinal cord syndrome are described. Clinical, neurophysiological and quantitative sensory evaluation revealed preservation of the large fibre dorsal column functions from the lumbosacral segments with concomitant severe dysfunction or absence of the small fibre neospinothalamic mediated functions. These findings indicate a role for the spinothalamic system in orgasm. PMID:8505649

  18. An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

    PubMed

    Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

    2014-11-25

    Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular

  19. An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

    PubMed

    Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

    2014-01-01

    Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular

  20. Therapeutic activities of engrafted neural stem/precursor cells are not dormant in the chronically injured spinal cord.

    PubMed

    Kumamaru, Hiromi; Saiwai, Hirokazu; Kubota, Kensuke; Kobayakawa, Kazu; Yokota, Kazuya; Ohkawa, Yasuyuki; Shiba, Keiichiro; Iwamoto, Yukihide; Okada, Seiji

    2013-08-01

    The transplantation of neural stem/precursor cells (NSPCs) is a promising therapeutic strategy for many neurodegenerative disorders including spinal cord injury (SCI) because it provides for neural replacement or trophic support. This strategy is now being extended to the treatment of chronic SCI patients. However, understanding of biological properties of chronically transplanted NSPCs and their surrounding environments is limited. Here, we performed temporal analysis of injured spinal cords and demonstrated their multiphasic cellular and molecular responses. In particular, chronically injured spinal cords were growth factor-enriched environments, whereas acutely injured spinal cords were enriched by neurotrophic and inflammatory factors. To determine how these environmental differences affect engrafted cells, NSPCs transplanted into acutely, subacutely, and chronically injured spinal cords were selectively isolated by flow cytometry, and their whole transcriptomes were compared by RNA sequencing. This analysis revealed that NSPCs produced many regenerative/neurotrophic molecules irrespective of transplantation timing, and these activities were prominent in chronically transplanted NSPCs. Furthermore, chronically injured spinal cords permitted engrafted NSPCs to differentiate into neurons/oligodendrocytes and provided more neurogenic environment for NSPCs than other environments. Despite these results demonstrate that transplanted NSPCs have adequate capacity in generating neurons/oligodendrocytes and producing therapeutic molecules in chronic SCI microenvironments, they did not improve locomotor function. Our results indicate that failure in chronic transplantation is not due to the lack of therapeutic activities of engrafted NSPCs but the refractory state of chronically injured spinal cords. Environmental modulation, rather modification of transplanting cells, will be significant for successful translation of stem cell-based therapies into chronic SCI patients.

  1. Nitrous oxide myelopathy posing as spinal cord injury.

    PubMed

    Ghobrial, George M; Dalyai, Richard; Flanders, Adam E; Harrop, James

    2012-05-01

    The authors describe a patient who presented with acute tetraparesis and a proposed acute traumatic spinal cord injury that was the result of nitrous oxide myelopathy. This 19-year-old man sustained a traumatic fall off a 6-ft high wall. His examination was consistent with a central cord syndrome with the addition of dorsal column impairment. Cervical MRI demonstrated an isolated dorsal column signal that was suggestive of a nontraumatic etiology. The patient's symptoms resolved entirely over the course of 48 hours. Nitrous oxide abuse is increasing in prevalence. Its toxic side effects can mask vitamin B12 and folate deficiency and central cord syndrome. The patient's history and radiographic presentation are key to establishing a diagnosis.

  2. New products tissue-engineering in the treatment of spinal cord injury

    NASA Astrophysics Data System (ADS)

    Bolshakov, I. N.; Sergienko, V. I.; Kiselev, S. L.; Lagarkova, M. A.; Remigaylo, A. A.; Mihaylov, A. A.; Prokopenko, S. V.

    2015-11-01

    In the treatment of patients with complicated spinal cord injury the Russian Health spends about one million rubles for each patient in the acute and the interim period after the injury. The number of complicated spinal cord injury is different in geographical areas Russian Federation from 30 to 50 people per 1 million that is affected by the year 5600. Applied to the present surgical and pharmacological techniques provide unsatisfactory results or minimally effective treatment. Transplantation of 100 thousand neuronal mouse predecessors (24 rats) or human neuronal predecessors (18 rats) in the anatomical gap rat spinal cord, followed by analysis of neurological deficit. The neuro-matrix implantation in the rat spinal cord containing 100 thousand neuronal precursors hESC, repeatable control neuro-matrix transplantation, non-cell mass, eliminating neurological deficit for 14 weeks after transplantation about 5-9 points on the scale of the BBB. The cultivation under conditions in vitro human induced pluripotent stem cells on collagen-chitosan matrix (hIPSC) showed that neurons differentiated from induced pluripotent stem cells grown on scaffolds as compact groups and has no neurites. Cells do not penetrate into the matrix during long-term cultivation and formed near the surface of the spherical structures resembling neurospheres. At least 90% of the cells were positive for the neuronal marker tubulin b3. Further studies should be performed to examine the compatibility of neuronal cultures and matrices.

  3. Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

    1988-01-01

    Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

  4. THE EFFECT OF MONOSIALOGANGLYOSIDE (GM-1) ADMINISTRATION IN SPINAL CORD INJURY

    PubMed Central

    BARROS, TARCÍSIO ELOY PESSOA; ARAUJO, FERNANDO FLORES DE; HIGINO, LUCAS DA PAZ; MARCON, RAPHAEL MARTUS; CRISTANTE, ALEXANDRE FOGAÇA

    2016-01-01

    ABSTRACT Objective: To evaluate the effect of monosialoganglioside (GM-1) in spinal cord trauma patients seen in our service who have not been treated with methylprednisolone. Methods: Thirty patients with acute spinal cord trauma were randomly divided into two groups. In Group 1, patients received 200 mg GM-1 in the initial assessment and thereafter received 100 mg intravenous per day for 30 days and Group 2 (control) received saline. Patients were evaluated periodically (at 6 weeks, 6 months, one year and two years), using a standardized neurological assessment of the American Spinal Injury Association / International Spinal Cord Society. Results: The comparative statistical analysis of motor indices, sensitive indices for pain and touch according to the standardization of ASIA / ISCOS showed that the assessments at 6 weeks, 6 months and 2 years, GM-Group 1 patients had higher rates than the control group regarding sensitivity to pain and touch, with no statistically significant difference from the motor index. Conclusion: The functional assessment showed improvement in the sensitive indices of patients treated with GM1 after post-traumatic spinal cord injury compared to patients who received placebo. Level of Evidence IV, Prospective Case Studies Series. PMID:27217811

  5. Repetitive magnetic stimulation affects the microenvironment of nerve regeneration and evoked potentials after spinal cord injury

    PubMed Central

    Jiang, Jin-lan; Guo, Xu-dong; Zhang, Shu-quan; Wang, Xin-gang; Wu, Shi-feng

    2016-01-01

    Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen's method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord. PMID:27335567

  6. Opioid administration following spinal cord injury: implications for pain and locomotor recovery.

    PubMed

    Woller, Sarah A; Hook, Michelle A

    2013-09-01

    Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries.

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

    PubMed

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

    2014-10-01

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

  8. Neurocontrol of Movement in Humans With Spinal Cord Injury.

    PubMed

    Dimitrijevic, Milan R; Danner, Simon M; Mayr, Winfried

    2015-10-01

    In this review of neurocontrol of movement after spinal cord injury, we discuss neurophysiological evidences of conducting and processing mechanisms of the spinal cord. We illustrate that external afferent inputs to the spinal cord below the level of the lesion can modify, initiate, and maintain execution of movement in absence or partial presence of brain motor control after chronic spinal cord injury. We review significant differences between spinal reflex activity elicited by single and repetitive stimulation. The spinal cord can respond with sensitization, habituation, and dis-habituation to regular repetitive stimulation. Therefore, repetitive spinal cord reflex activity can contribute to the functional configuration of the spinal network. Moreover, testing spinal reflex activity in individuals with motor complete spinal cord injury provided evidences for subclinical residual brain influence, suggesting the existence of axons traversing the injury site and influencing the activities below the level of lesion. Thus, there are two motor control models of chronic spinal cord injury in humans: "discomplete" and "reduced and altered volitional motor control." We outline accomplishments in modification and initiation of altered neurocontrol in chronic spinal cord injury people with epidural and functional electrical stimulation. By nonpatterned electrical stimulation of lumbar posterior roots, it is possible to evoke bilateral extension as well as rhythmic motor outputs. Epidural stimulation during treadmill stepping shows increased and/or modified motor activity. Finally, volitional efforts can alter epidurally induced rhythmic activities in incomplete spinal cord injury. Overall, we highlight that upper motor neuron paralysis does not entail complete absence of connectivity between cortex, brain stem, and spinal motor cells, but there can be altered anatomy and corresponding neurophysiological characteristics. With specific input to the spinal cord below the level

  9. The impact of spinal cord injury on breathing during sleep

    PubMed Central

    Fuller, David D.; Lee, Kun-Ze; Tester, Nicole J.

    2014-01-01

    The prevalence of sleep disordered breathing (SDB) following spinal cord injury (SCI) is considerably greater than in the general population. While the literature on this topic is still relatively small, and in some cases contradictory, a few general conclusions can be drawn. First, while both central and obstructive sleep apnea (OSA) has been reported after SCI, OSA appears to be more common. Second, SDB after SCI likely reflects a complex interplay between multiple factors including body mass, lung volume, autonomic function, sleep position, and respiratory neuroplasticity. It is not yet possible to pinpoint a “primary factor” which will predispose an individual with SCI to SDB, and the underlying mechanisms may change during progression from acute to chronic injury. Given the prevalence and potential health implications of SDB in the SCI population, we suggest that additional studies aimed at defining the underlying mechanisms are warranted. PMID:23791824

  10. Neuroprotective effects of electroacupuncture on early- and late-stage spinal cord injury.

    PubMed

    Wu, Min-Fei; Zhang, Shu-Quan; Liu, Jia-Bei; Li, Ye; Zhu, Qing-San; Gu, Rui

    2015-10-01

    Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating RhoA. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting RhoA expression. We established a rat model of acute spinal cord injury using a modification of Allen's method. The rats were given electroacupuncture treatment at Dazhui (Du14), Mingmen (Du4), Sanyinjiao (SP6), Huantiao (GB30), Zusanli (ST36) and Kunlun (BL60) acupoints with a sparse-dense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan (BBB) locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and RhoA and Nogo-A mRNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases RhoA and Nogo-A mRNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery. PMID:26692861

  11. Neuroprotective effects of electroacupuncture on early- and late-stage spinal cord injury

    PubMed Central

    Wu, Min-fei; Zhang, Shu-quan; Liu, Jia-bei; Li, Ye; Zhu, Qing-san; Gu, Rui

    2015-01-01

    Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating RhoA. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting RhoA expression. We established a rat model of acute spinal cord injury using a modification of Allen's method. The rats were given electroacupuncture treatment at Dazhui (Du14), Mingmen (Du4), Sanyinjiao (SP6), Huantiao (GB30), Zusanli (ST36) and Kunlun (BL60) acupoints with a sparse-dense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan (BBB) locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and RhoA and Nogo-A mRNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases RhoA and Nogo-A mRNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery. PMID:26692861

  12. An innovative spinal cord injury model for the study of locomotor networks.

    PubMed

    Nistri, A

    2012-03-01

    An acute lesion to the spinal cord triggers complex mechanisms responsible for amplification of the initial damage and its chronicity. In vitro preparations of the rodent spinal cord retain the intrinsic ability to produce locomotor-like discharges from lumbar ventral roots and, thus, offer the opportunity to study the still unclear process of lesion progression in relation to cell number and topography. In addition, these models enable a detailed approach to the molecular mechanisms of damage and to pharmacological tools to counteract them. Using the rat spinal cord in vitro, our laboratory has shown how to reliably produce discrete lesions by applying the glutamate agonist kainate that evokes delayed neuronal loss via a non-apoptotic cell death mechanism termed parthanatos. Parthanatos is believed to be due to mitochondrial damage and exhaustion of cell energy stores caused by hyperactivation of enzymatic systems initially set to repair DNA damage. Locomotor network activity is irreversibly destroyed by kainate in a virtually all-or-none manner, suggesting destruction of a highly-vulnerable cell population crucial for the expression of locomotion. Hypoxic challenge to the spinal cord together with toxic radicals primarily damages white matter cells with deficit (without full suppression) of locomotor network function, while neurons are less vulnerable. Pharmacological agents to inhibit different targets involved in the early pathophysiology of spinal injury provided limited success, indicating that novel approaches based on newly identified steps in the biochemical cascade leading to cell death should be investigated for their potential to improve the outcome of spinal cord injury.

  13. An innovative spinal cord injury model for the study of locomotor networks.

    PubMed

    Nistri, A

    2012-03-01

    An acute lesion to the spinal cord triggers complex mechanisms responsible for amplification of the initial damage and its chronicity. In vitro preparations of the rodent spinal cord retain the intrinsic ability to produce locomotor-like discharges from lumbar ventral roots and, thus, offer the opportunity to study the still unclear process of lesion progression in relation to cell number and topography. In addition, these models enable a detailed approach to the molecular mechanisms of damage and to pharmacological tools to counteract them. Using the rat spinal cord in vitro, our laboratory has shown how to reliably produce discrete lesions by applying the glutamate agonist kainate that evokes delayed neuronal loss via a non-apoptotic cell death mechanism termed parthanatos. Parthanatos is believed to be due to mitochondrial damage and exhaustion of cell energy stores caused by hyperactivation of enzymatic systems initially set to repair DNA damage. Locomotor network activity is irreversibly destroyed by kainate in a virtually all-or-none manner, suggesting destruction of a highly-vulnerable cell population crucial for the expression of locomotion. Hypoxic challenge to the spinal cord together with toxic radicals primarily damages white matter cells with deficit (without full suppression) of locomotor network function, while neurons are less vulnerable. Pharmacological agents to inhibit different targets involved in the early pathophysiology of spinal injury provided limited success, indicating that novel approaches based on newly identified steps in the biochemical cascade leading to cell death should be investigated for their potential to improve the outcome of spinal cord injury. PMID:22407008

  14. Volume effects in Rhesus monkey spinal cord

    SciTech Connect

    Schultheiss, T.E. ); Stephens, L.C.; Price, R.E.; Ang, K.K.; Peters, L.J. )

    1994-04-30

    An experiment was conducted to test for the existence of a volume effect in radiation myelopathy using Rhesus monkeys treated with clinically relevant field sizes and fractionation schedules. Five groups of Rhesus monkeys were irradiated using 2.2 Gy per fraction to their spinal cords. Three groups were irradiated with 8 cm fields to total doses of 70.4, 77, and 83.6 Gy. Two additional groups were irradiated to 70.4 Gy using 4 and 16 cm fields. The incidence of paresis expressed within 2 years following the completion of treatment was determined for each group. Maximum likelihood estimation was used to determine parameters of a logistic dose response function. The volume effect was modeled using the probability model in which the probability of producing a lesion in an irradiated volume is governed by the probability of the occurrence of independent events. This is a two parameter model requiring only the estimates of the parameters of the dose-response function for the reference volume, but not needing any additional parameters for describing the volume effect. The probability model using a logistic dose-response function fits the data well with the D[sub 50] = 75.8 Gy for the 8-cm field. No evidence was seen for a difference in sensitivities for different anatomical levels of the spinal cord. Most lesions were type 3, combined white matter parenchymal and vascular lesions. Latent periods did not differ significantly from those of type 3 lesions in humans. The spinal cord exhibits a volume effect that is well described by the probability model. Because the dose response function for radiation myelopathy is steep, the volume effect is modest. The Rhesus monkey remains the animal model most similar to humans in dose response, histopathology, and latency for radiation myelopathy. 22 refs., 3 figs., 1 tab.

  15. Pediatric spinal cord injury: a review by organ system.

    PubMed

    Powell, Aaron; Davidson, Loren

    2015-02-01

    In this article, an overview is provided of pediatric spinal cord injury, organized by effects of this injury on various organ systems. Specific management differences between children and adults with spinal cord injury are highlighted. A detailed management approach is offered for particularly complex topics, such as spasticity and upper extremity reconstruction. PMID:25479784

  16. Spinal cord injury following an attempted thoracic epidural.

    PubMed

    Mayall, M F; Calder, I

    1999-10-01

    Unsuccessful attempts were made to insert a thoracic epidural in an anaesthetised patient. Signs of spinal cord damage were observed the following day. Magnetic resonance imaging demonstrated a haematoma anterior to the spinal cord. Surgical exploration revealed an intradural haematoma and a needle puncture of the cord. The patient suffered a permanent paraparesis.

  17. Cardiovascular health and fitness in persons with spinal cord injury.

    PubMed

    Lavis, Timothy D; Scelza, William M; Bockenek, William L

    2007-05-01

    There are many issues after spinal cord injury that have an impact on cardiovascular health and fitness. This article discusses many of the secondary conditions and changes that occur and how they are affected by maintenance of an active lifestyle. It also discusses many of the benefits and difficulties individuals face in maintaining a regular exercise program after spinal cord injury.

  18. Personal Adjustment Training for the Spinal Cord Injured

    ERIC Educational Resources Information Center

    Roessler, Richard; And Others

    1976-01-01

    This article describes experiences with Personal Achievement Skills (PAS), a group counseling process in a spinal cord injury project, emphasizing training in communication and goal setting in the context of group process. Issues in conducting such training and providing comprehensive service to the spinal cord injured are discussed in detail.…

  19. Shriners Hospital Spinal Cord Injury Self Care Manual.

    ERIC Educational Resources Information Center

    Fox, Carol

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

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

    PubMed

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

    2016-09-01

    The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans. PMID:27357536

  1. Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury

    PubMed Central

    Sun, Tiansheng; Ye, Chaoqun; Wu, Jun; Zhang, Zhicheng; Cai, Yanhua; Yue, Feng

    2013-01-01

    A large body of evidence shows that spinal circuits are significantly affected by training, and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection. However, after incomplete lesions, the effect of treadmill training has been debated, which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects. In this study, rats with moderate spinal cord contusion were jected to either step training on a treadmill or used in the model (control) group. The treadmill training began at day 7 post-injury and lasted 20 ± 10 minutes per day, 5 days per week for 10 weeks. The speed of the treadmill was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat. After 3 weeks of step training, the step training group exhibited a sig-nificantly greater improvement in the Basso, Beattie and Bresnahan score than the model group. The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury, while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups. These results suggest that treadmill training significantly improves functional re-covery and neural plasticity after incomplete spinal cord injury. PMID:25206564

  2. Natural Polyphenols and Spinal Cord Injury

    PubMed Central

    Khalatbary, Ali Reza

    2014-01-01

    Polyphenols have been shown to have some of the neuroprotective effects against neurodegenerative diseases. These effects are attributed to a variety of biological activities, including free radical scavenging/antioxidant and anti-inflammatory and anti-apoptotic activities. In this regard, many efforts have been made to study the effects of various well-known dietary polyphenols on spinal cord injury (SCI) and to explore the mechanisms behind the neuroprotective effects. The aim of this paper is to present the mechanisms of neuroprotection of natural polyphenols used in animal models of SCI. PMID:24842137

  3. Functional electrical stimulation and spinal cord injury.

    PubMed

    Ho, Chester H; Triolo, Ronald J; Elias, Anastasia L; Kilgore, Kevin L; DiMarco, Anthony F; Bogie, Kath; Vette, Albert H; Audu, Musa L; Kobetic, Rudi; Chang, Sarah R; Chan, K Ming; Dukelow, Sean; Bourbeau, Dennis J; Brose, Steven W; Gustafson, Kenneth J; Kiss, Zelma H T; Mushahwar, Vivian K

    2014-08-01

    Spinal cord injuries (SCI) can disrupt communications between the brain and the body, resulting in loss of control over otherwise intact neuromuscular systems. Functional electrical stimulation (FES) of the central and peripheral nervous system can use these intact neuromuscular systems to provide therapeutic exercise options to allow functional restoration and to manage medical complications following SCI. The use of FES for the restoration of muscular and organ functions may significantly decrease the morbidity and mortality following SCI. Many FES devices are commercially available and should be considered as part of the lifelong rehabilitation care plan for all eligible persons with SCI.

  4. Immunotherapy strategies for spinal cord injury.

    PubMed

    Wang, Yong-Tang; Lu, Xiu-Min; Chen, Kai-Ting; Shu, Ya-Hai; Qiu, Chun-Hong

    2015-01-01

    Regeneration in the central nervous system (CNS) of adult mammalian after traumatic injury is limited, which often causes permanent functional motor and sensory loss. After spinal cord injury (SCI), the lack of regeneration is mainly attributed to the presence of a hostile microenvironment, glial scarring, and cavitation. Besides, inflammation has also been proved to play a crucial role in secondary degeneration following SCI. The more prominent treatment strategies in experimental models focus mainly on drugs and cell therapies, however, only a few strategies applied in clinical studies and therapies still have only limited effects on the repair of SCI. Recently, the interests in immunotherapy strategies for CNS are increasing in number and breadth. Immunotherapy strategies have made good progresses in treating many CNS degenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS). However, the strategies begin to be considered to the treatment of SCI and other neurological disorders in recent years. Besides anti-inflamatory therapy, immunization with protein vaccines and DNA vaccines has emerged as a novel therapy strategy because of the simplicity of preparation and application. An inflammatory response followed by spinal cord injury, and is controled by specific signaling molecules, such as some cytokines playing a crucial role. As a result, appropriate immunoregulation, the expression of pro-inflammatory cytokines and anti-inflammatory cytokines may be an effective therapy strategy for earlier injury of spinal cord. In addition, myelinassociated inhibitors (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte- myelin glycoprotein (OMgp) are known to prevent axonal regeneration through their co-receptors, and to trigger demyelinating autoimmunity through T cell-mediated harmful autoimmune response. The antagonism of the MAIs through vaccinating with

  5. Functional electrical stimulation and spinal cord injury.

    PubMed

    Ho, Chester H; Triolo, Ronald J; Elias, Anastasia L; Kilgore, Kevin L; DiMarco, Anthony F; Bogie, Kath; Vette, Albert H; Audu, Musa L; Kobetic, Rudi; Chang, Sarah R; Chan, K Ming; Dukelow, Sean; Bourbeau, Dennis J; Brose, Steven W; Gustafson, Kenneth J; Kiss, Zelma H T; Mushahwar, Vivian K

    2014-08-01

    Spinal cord injuries (SCI) can disrupt communications between the brain and the body, resulting in loss of control over otherwise intact neuromuscular systems. Functional electrical stimulation (FES) of the central and peripheral nervous system can use these intact neuromuscular systems to provide therapeutic exercise options to allow functional restoration and to manage medical complications following SCI. The use of FES for the restoration of muscular and organ functions may significantly decrease the morbidity and mortality following SCI. Many FES devices are commercially available and should be considered as part of the lifelong rehabilitation care plan for all eligible persons with SCI. PMID:25064792

  6. Chronic prostatitis in spinal cord injury patients.

    PubMed

    Wyndaele, J J

    1985-06-01

    Six spinal cord injury patients with chronic prostatitis were reviewed, all of whom had been treated with an indwelling Foley catheter during the phase of spinal shock. The 3 glass urine specimen test, the bladder wash-out test, a study of antibody coated bacteria and urethrography had limited diagnostic value. A specific diagnostic 5 glass specimen test proved to be useful and reliable. Longterm antibiotic treatment was successful in only one patient. Injection of antibiotics into the prostate gland was ineffective in the five patients in whom it was carried out. During a follow up from 1 to 5 years urological complications were rare in all five patients who remained infected.

  7. Electroacupuncture promotes the recovery of motor neuron function in the anterior horn of the injured spinal cord

    PubMed Central

    Yang, Jian-hui; Lv, Jian-guo; Wang, Hui; Nie, Hui-yong

    2015-01-01

    Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury. However, the mechanism of action remains unclear. In this study, a rat model of spinal cord injury was established by compressing the T8–9 segments using a modified Nystrom method. Twenty-four hours after injury, Zusanli (ST36), Xuanzhong (GB39), Futu (ST32) and Sanyinjiao (SP6) were stimulated with electroacupuncture. Rats with spinal cord injury alone were used as controls. At 2, 4 and 6 weeks after injury, acetylcholinesterase (AChE) activity at the site of injury, the number of medium and large neurons in the spinal cord anterior horn, glial cell line-derived neurotrophic factor (GDNF) mRNA expression, and Basso, Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group. These results demonstrate that electroacupuncture increases AChE activity, up-regulates GDNF mRNA expression, and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury. PMID:26889195

  8. Electroacupuncture promotes the recovery of motor neuron function in the anterior horn of the injured spinal cord.

    PubMed

    Yang, Jian-Hui; Lv, Jian-Guo; Wang, Hui; Nie, Hui-Yong

    2015-12-01

    Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury. However, the mechanism of action remains unclear. In this study, a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method. Twenty-four hours after injury, Zusanli (ST36), Xuanzhong (GB39), Futu (ST32) and Sanyinjiao (SP6) were stimulated with electroacupuncture. Rats with spinal cord injury alone were used as controls. At 2, 4 and 6 weeks after injury, acetylcholinesterase (AChE) activity at the site of injury, the number of medium and large neurons in the spinal cord anterior horn, glial cell line-derived neurotrophic factor (GDNF) mRNA expression, and Basso, Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group. These results demonstrate that electroacupuncture increases AChE activity, up-regulates GDNF mRNA expression, and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury. PMID:26889195

  9. Regeneration of adult rat spinal cord is promoted by the soluble KDI domain of gamma1 laminin.

    PubMed

    Wiksten, Markus; Väänänen, Antti J; Liebkind, Ron; Liesi, Päivi

    2004-11-01

    Regeneration in the central nervous system (CNS) of adult mammals is hampered by formation of a glial scar and by proteins released from the myelin sheaths of injured neuronal pathways. Our recent data indicate that the KDI (Lys-Asp-Ile) domain of gamma1 laminin neutralizes both glial- and myelin-derived inhibitory signals and promotes survival and neurite outgrowth of cultured human spinal cord neurons. We show that after complete transection of the adult rat spinal cord, animals receiving onsite infusion of the KDI domain via osmotic mini-pumps recover and are able to sustain their body weights and walk with their hindlimbs. Animals treated with placebo suffer from irreversible hindlimb paralysis. Microscopic and molecular analyses of the spinal cords indicate that the KDI domain reduces tissue damage at the lesion site and enables neurite outgrowth through the injured area to effect functional recovery of the initially paralyzed animals. That the KDI domain enhances regeneration of acute spinal cord injuries in the adult rat suggests that it may be used to promote regeneration of spinal cord injuries in humans.

  10. RhoA/Rho kinase in spinal cord injury

    PubMed Central

    Wu, Xiangbing; Xu, Xiao-ming

    2016-01-01

    A spinal cord injury refers to an injury to the spinal cord that is caused by a trauma instead of diseases. Spinal cord injury includes a primary mechanical injury and a much more complex secondary injury process involving inflammation, oxidation, excitotoxicity, and cell death. During the secondary injury, many signal pathways are activated and play important roles in mediating the pathogenesis of spinal cord injury. Among them, the RhoA/Rho kinase pathway plays a particular role in mediating spinal degeneration and regeneration. In this review, we will discuss the role and mechanism of RhoA/Rho kinase-mediated spinal cord pathogenesis, as well as the potential of targeting RhoA/Rho kinase as a strategy for promoting both neuroprotection and axonal regeneration. PMID:26981071

  11. RhoA/Rho kinase in spinal cord injury.

    PubMed

    Wu, Xiangbing; Xu, Xiao-Ming

    2016-01-01

    A spinal cord injury refers to an injury to the spinal cord that is caused by a trauma instead of diseases. Spinal cord injury includes a primary mechanical injury and a much more complex secondary injury process involving inflammation, oxidation, excitotoxicity, and cell death. During the secondary injury, many signal pathways are activated and play important roles in mediating the pathogenesis of spinal cord injury. Among them, the RhoA/Rho kinase pathway plays a particular role in mediating spinal degeneration and regeneration. In this review, we will discuss the role and mechanism of RhoA/Rho kinase-mediated spinal cord pathogenesis, as well as the potential of targeting RhoA/Rho kinase as a strategy for promoting both neuroprotection and axonal regeneration.

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

    PubMed Central

    Cleveland, Christine; Walker, Heather

    2015-01-01

    Context Cervical myelopathy is a spinal cord dysfunction that results from extrinsic compression of the spinal cord, its blood supply, or both. It is the most common cause of spinal cord dysfunction in patients greater than 55 years of age. Findings: A 57-year-old male with right shoulder septic arthritis underwent surgical debridement of his right shoulder and sustained a spinal cord injury intraoperatively. The most likely etiology is damage to the cervical spinal cord during difficult intubation requiring multiple attempts in this patient with underlying asymptomatic severe cervical stenosis. Conclusion Although it is not feasible to perform imaging studies on all patients undergoing intubation for surgery, this patient's outcome would suggest consideration of inclusion of additional pre-surgical screening examination techniques, such as testing for a positive Hoffman's reflex, is appropriate to detect asymptomatic patients who may have underlying cervical stenosis. PMID:24679185

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

    PubMed

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

    2016-09-01

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

  14. Combined Transplantation of Human Neuronal and Mesenchymal Stem Cells following Spinal Cord Injury.

    PubMed

    Park, D Y; Mayle, R E; Smith, R L; Corcoran-Schwartz, I; Kharazi, A I; Cheng, I

    2013-03-01

    Transplantation of human fetal neural stem cells (hNSCs) previously demonstrated significant functional recovery after spinal cord contusion in rats. Other studies indicated that human mesenchymal stem cells (hMSCs) can home to areas of damage and cross the blood-brain barrier. The purpose of this article is to determine if combined administration of mesenchymal stem cells and neuronal stem cells improves functional outcomes in rats. The study design was a randomized controlled animal trial. Female adult Long-Evans hooded rats underwent laminectomy at T10 level. Moderate spinal cord contusion at T10 level was induced by the MASCIS Impactor. Four groups were identified. The MSC + NSC group received hMSCs intravenously (IV) immediately after spinal cord injury (acute) and returned 1 week later (subacute) for injection of hNSC directly at site of injury. The MSC-only group received hMSC IV acutely and cell media subacutely. The NSC-only group received cell media IV acutely and hNSC subacutely. The control group received cell media IV acutely and subacutely. Subjects were assessed for 6 weeks using Basso, Beattie, Bresnahan Locomotor Rating Score. Twenty-four subjects were utilized, six subjects in each group. Statistically significant functional improvement was seen in the MSC + NSC group and the NSC-only group versus controls (p = 0.027, 0.042, respectively). The MSC-only group did not demonstrate a significant improvement over control (p = 0.145). Comparing the MSC + NSC group and the NSC-only group, there was no significant difference (p = 0.357). Subacute transplantation of hNSCs into contused spinal cord of rats led to significant functional recovery when injected either with or without acute IV administration of hMSCs. Neither hMSCs nor addition of hMSC to hNSC resulted in significant improvement.

  15. Combined Transplantation of Human Neuronal and Mesenchymal Stem Cells following Spinal Cord Injury.

    PubMed

    Park, D Y; Mayle, R E; Smith, R L; Corcoran-Schwartz, I; Kharazi, A I; Cheng, I

    2013-03-01

    Transplantation of human fetal neural stem cells (hNSCs) previously demonstrated significant functional recovery after spinal cord contusion in rats. Other studies indicated that human mesenchymal stem cells (hMSCs) can home to areas of damage and cross the blood-brain barrier. The purpose of this article is to determine if combined administration of mesenchymal stem cells and neuronal stem cells improves functional outcomes in rats. The study design was a randomized controlled animal trial. Female adult Long-Evans hooded rats underwent laminectomy at T10 level. Moderate spinal cord contusion at T10 level was induced by the MASCIS Impactor. Four groups were identified. The MSC + NSC group received hMSCs intravenously (IV) immediately after spinal cord injury (acute) and returned 1 week later (subacute) for injection of hNSC directly at site of injury. The MSC-only group received hMSC IV acutely and cell media subacutely. The NSC-only group received cell media IV acutely and hNSC subacutely. The control group received cell media IV acutely and subacutely. Subjects were assessed for 6 weeks using Basso, Beattie, Bresnahan Locomotor Rating Score. Twenty-four subjects were utilized, six subjects in each group. Statistically significant functional improvement was seen in the MSC + NSC group and the NSC-only group versus controls (p = 0.027, 0.042, respectively). The MSC-only group did not demonstrate a significant improvement over control (p = 0.145). Comparing the MSC + NSC group and the NSC-only group, there was no significant difference (p = 0.357). Subacute transplantation of hNSCs into contused spinal cord of rats led to significant functional recovery when injected either with or without acute IV administration of hMSCs. Neither hMSCs nor addition of hMSC to hNSC resulted in significant improvement. PMID:24436845

  16. Combined Transplantation of Human Neuronal and Mesenchymal Stem Cells following Spinal Cord Injury

    PubMed Central

    Park, D. Y.; Mayle, R. E.; Smith, R. L.; Corcoran-Schwartz, I.; Kharazi, A. I.; Cheng, I.

    2013-01-01

    Transplantation of human fetal neural stem cells (hNSCs) previously demonstrated significant functional recovery after spinal cord contusion in rats. Other studies indicated that human mesenchymal stem cells (hMSCs) can home to areas of damage and cross the blood–brain barrier. The purpose of this article is to determine if combined administration of mesenchymal stem cells and neuronal stem cells improves functional outcomes in rats. The study design was a randomized controlled animal trial. Female adult Long-Evans hooded rats underwent laminectomy at T10 level. Moderate spinal cord contusion at T10 level was induced by the MASCIS Impactor. Four groups were identified. The MSC + NSC group received hMSCs intravenously (IV) immediately after spinal cord injury (acute) and returned 1 week later (subacute) for injection of hNSC directly at site of injury. The MSC-only group received hMSC IV acutely and cell media subacutely. The NSC-only group received cell media IV acutely and hNSC subacutely. The control group received cell media IV acutely and subacutely. Subjects were assessed for 6 weeks using Basso, Beattie, Bresnahan Locomotor Rating Score. Twenty-four subjects were utilized, six subjects in each group. Statistically significant functional improvement was seen in the MSC + NSC group and the NSC-only group versus controls (p = 0.027, 0.042, respectively). The MSC-only group did not demonstrate a significant improvement over control (p = 0.145). Comparing the MSC + NSC group and the NSC-only group, there was no significant difference (p = 0.357). Subacute transplantation of hNSCs into contused spinal cord of rats led to significant functional recovery when injected either with or without acute IV administration of hMSCs. Neither hMSCs nor addition of hMSC to hNSC resulted in significant improvement. PMID:24436845

  17. Time-frequency patterns of somatosensory evoked potentials in predicting the location of spinal cord injury.

    PubMed

    Wang, Yazhou; Cui, Hongyan; Pu, Jiangbo; Luk, K D K; Hu, Yong

    2015-08-31

    Somatosensory evoked potentials (SEPs) were found to exhibit different time-frequency patterns after acute spinal cord injury (SCI) at different levels, which implies that changes of these patterns may be associated with the location of SCI. Based on this finding, we propose the hypothesis that there are information regarding the location of SCI contained in the time-frequency patterns of SEPs. Purpose of the present study is to verify this hypothesis by comparing the time-frequency patterns of SEPs after acute and chronic SCI at the same level. The study examined the distribution patterns of the time-frequency components (TFCs) of SEPs before and after acute and chronic injury at C5 level in the spinal cord. Experimental results of SEP recordings from 24 adult rats show that there are common areas in the time-frequency distributions of SEPs. The TFCs from both the acute injury group and the chronic injury group are located in these areas with no TFCs from the normal group. Findings suggest that these areas are likely to possess information concerning the site of neurological deficits in spinal cord while independent of the modality of injury. This study provides basis for identification of stable time-frequency patterns of SEPs after different types and locations of SCI, which will guide the development of SEP-based SCI location detection. PMID:26170248

  18. Neurogenic bladder in spinal cord injury patients

    PubMed Central

    Taweel, Waleed Al; Seyam, Raouf

    2015-01-01

    Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

  19. Spinal cord effects of antipyretic analgesics.

    PubMed

    Brune, K

    1994-01-01

    Tissue damage results in the release of inflammatory mediators, including prostaglandins, which sensitive fine nerve endings in the periphery to mechanical and thermal changes. Sensitisation of these nerve endings, or nociceptors, contributes to the phenomenon of hyperalgesia, which routinely accompanies tissue damage. It has been shown that the acidic antipyretic analgesics reduce or down-regulate the enhanced nociceptor sensitivity in damaged tissue, an effect probably attributable to inhibition of prostaglandin synthesis. Recent studies suggest that these drugs may have an additional mechanism of action in the spinal cord or higher centres. When enantiomers of flurbiprofen were used in the rat, it was shown that S- and R-flurbiprofen exert differential antinociceptive effects. The R-enantiomer, which is practically devoid of peripheral cyclo-oxygenase inhibitory activity in vitro, showed comparable analgesic potency to the S-enantiomer, which does inhibit cyclo-oxygenase activity, in experimental models of nociception. It is possible that the antinociceptive action of the R-enantiomer is related to a reduction in prostaglandin synthesis in the CNS rather than at the site of tissue damage, although other mechanisms may also contribute to its antinociceptive action. In contrast to earlier indications, it would appear that a significant part of the antinociceptive action of the antipyretic analgesics is exerted in the spinal cord. The observed accumulation of acidic antipyretic analgesics in inflamed tissue may account for the superior anti-inflammatory activity of these latter compounds.

  20. Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis.

    PubMed

    Szarek, Dariusz; Marycz, Krzysztof; Lis, Anna; Zawada, Zbigniew; Tabakow, Paweł; Laska, Jadwiga; Jarmundowicz, Włodzimierz

    2016-04-01

    Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, differentin vivomodels are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability ofin vivostudy with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of

  1. Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis.

    PubMed

    Szarek, Dariusz; Marycz, Krzysztof; Lis, Anna; Zawada, Zbigniew; Tabakow, Paweł; Laska, Jadwiga; Jarmundowicz, Włodzimierz

    2016-04-01

    Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, differentin vivomodels are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability ofin vivostudy with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of

  2. 21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted spinal cord stimulator for pain relief... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to...

  3. 21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted spinal cord stimulator for pain relief... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to...

  4. 21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for pain relief... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to...

  5. 21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted spinal cord stimulator for pain relief... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to...

  6. 21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted spinal cord stimulator for pain relief... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to...

  7. Timing of Decompressive Surgery of Spinal Cord after Traumatic Spinal Cord Injury: An Evidence-Based Examination of Pre-Clinical and Clinical Studies

    PubMed Central

    Furlan, Julio C.; Noonan, Vanessa; Cadotte, David W.

    2011-01-01

    Abstract While the recommendations for spine surgery in specific cases of acute traumatic spinal cord injury (SCI) are well recognized, there is considerable uncertainty regarding the role of the timing of surgical decompression of the spinal cord in the management of patients with SCI. Given this, we sought to critically review the literature regarding the pre-clinical and clinical evidence on the potential impact of timing of surgical decompression of the spinal cord on outcomes after traumatic SCI. The primary literature search was performed using MEDLINE, CINAHL, EMBASE, and Cochrane databases. A secondary search strategy incorporated articles referenced in prior meta-analyses and systematic and nonsystematic review articles. Two reviewers independently assessed every study with regard to eligibility, level of evidence, and study quality. Of 198 abstracts of pre-clinical studies, 19 experimental studies using animal SCI models fulfilled our inclusion and exclusion criteria. Despite some discrepancies in the results of those pre-clinical studies, there is evidence for a biological rationale to support early decompression of the spinal cord. Of 153 abstracts of clinical studies, 22 fulfilled the inclusion and exclusion criteria. While the vast majority of the clinical studies were level-4 evidence, there were two studies of level-2b evidence. The quality assessment scores varied from 7 to 25 with a mean value of 12.41. While 2 of 22 clinical studies assessed feasibility and safety, 20 clinical studies examined efficacy of early surgical intervention to stabilize and align the spine and to decompress the spinal cord; the most common definitions of early operation used 24 and 72 h after SCI as timelines. A number of studies indicated that patients who undergo early surgical decompression can have similar outcomes to patients who received a delayed decompressive operation. However, there is evidence to suggest that early surgical intervention is safe and feasible

  8. Fluoxetine and vitamin C synergistically inhibits blood-spinal cord barrier disruption and improves functional recovery after spinal cord injury.

    PubMed

    Lee, Jee Y; Choi, Hae Y; Yune, Tae Y

    2016-10-01

    Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI.

  9. Fluoxetine and vitamin C synergistically inhibits blood-spinal cord barrier disruption and improves functional recovery after spinal cord injury.

    PubMed

    Lee, Jee Y; Choi, Hae Y; Yune, Tae Y

    2016-10-01

    Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI. PMID:27256500

  10. What are the people's attitudes toward spinal cord injury victims (from common to elite)

    PubMed Central

    Hosseinigolafshani, Zahra; Abedi, Heidarali; Ahmadi, Fazlolah

    2014-01-01

    Background: One of the acutely fatal and prevalent crises in all societies is acute spinal cord injury. Individuals with a spinal cord injury are prone to numerous challenges, perturbation, and acute mental distresses. One of their concerns, often expressed generally and in the form of a complaint, is how people deal with them. The present study aims to analyze the experiences and interactions of the disabled with the society and to achieve a deep clarification of their internal attitudes and realistic approaches in various social classes (from common people to elite). Materials and Methods: The present study is a part of a greater research with a classical grounded theory approach conducted on 12 successful and nationally and internationally popular disabled people. Sampling was firstly purposive and then continued with snowball sampling. The data were collected by open deep interviews which were recorded and transcribed verbatim. The obtained data were analyzed by Graneheim content analysis method. Results: The findings obtained through analysis of the interviews yielded the theme of a socially suppressing attitude which contained four subthemes of compassionate attitude, disability attitude, inhuman attitude, and atonement attitude. Conclusions: The results showed that both groups of common, and educated and elite classes of Iranian society have identically suppressing attitudes and interactions toward spinal cord injury victims. It seems that traditional attitudes yet preponderate academic and scientific knowledge in Iranian society. This gap needs notable attention of all the Iranians, especially policy makers and social personalities. PMID:24949065

  11. Optimizing Speech Production in the Ventilator-Assisted Individual Following Cervical Spinal Cord Injury: A Preliminary Investigation

    ERIC Educational Resources Information Center

    MacBean, Naomi; Ward, Elizabeth; Murdoch, Bruce; Cahill, Louise; Solley, Maura; Geraghty, Timothy; Hukins, Craig

    2009-01-01

    Background: Mechanical ventilation is commonly used during the acute management of cervical spinal cord injury, and is required on an ongoing basis in the majority of patients with injuries at or above C3. However, to date there have been limited systematic investigations of the options available to improve speech while ventilator-assisted…

  12. Neuroprotective effects of adipose-derived stem cells against ischemic neuronal damage in the rabbit spinal cord.

    PubMed

    Chung, Jin Young; Kim, Woosuk; Im, Wooseok; Yoo, Dae Young; Choi, Jung Hoon; Hwang, In Koo; Won, Moo-Ho; Chang, In Bok; Cho, Byung Moon; Hwang, Hyung Sik; Moon, Seung Myung

    2012-06-15

    Transplantation of adipose-derived stem cells (ASCs) is one of the possible therapeutic tools for ischemic damage. In this study, we observed the effects of ASCs against ischemic damage in the ventral horn of L(5-6) levels in the rabbit spinal cord. ASCs were isolated from rabbits, and cell type was confirmed by flow cytometry analysis, labeling with CM-DiI dye and differentiation into adipocytes in adipogenesis differentiation medium. ASCs were administered intrathecally into recipient rabbits (2 × 10⁵) immediately after reperfusion following a 15-min aortic artery occlusion in the subrenal region. Transplantation of ASCs significantly improved functions of the hindlimb and morphology of the ventral horn of spinal cord although CM-DiI-labeled ASCs were not observed in the spinal cord parenchyma. In addition, transplantation of ASCs significantly increased brain-derived neurotrophic factor (BDNF) levels at 72h after ischemia/reperfusion. These results suggest that transplantation of ASCs prevents motor neurons from spinal ischemic damage and reactive gliosis by increasing neurotrophic factors such as BDNF in the spinal cord.

  13. Stromal cell-derived factor-1 alpha (SDF-1α) improves neural recovery after spinal cord contusion in rats.

    PubMed

    Zendedel, Adib; Nobakht, Maliheh; Bakhtiyari, Mehrdad; Beyer, Cordian; Kipp, Markus; Baazm, Maryam; Joghataie, Mohammad Taghi

    2012-09-14

    Stromal cell-derived factor-1 alpha (SDF-1α) is an important cytokine, implicated in the control of stem cell trafficking and bone marrow-derived stem cell mobilization. Generally, SDF-1α regulates multiple physiological processes such as embryonic development and organ homeostasis. There is also good evidence that SDF-1α and its receptor CXCR4(1) are key regulators of neurorepair processes after brain ischemia and spinal cord injury. In this study, we investigated the influence of chronic intrathecal delivery of SDF-1α after spinal cord contusion. After contusion T9, male Wistar rats at the age of 12 weeks were intrathecally treated with SDF-1α in different doses (100, 500 and 1000 ng/ml) via an osmotic pump for 28 days. Thereafter, animals were subjected to an open field locomotor test. Behavioral scores were significantly higher in SDF-1α treated animals compared to placebo-treated groups. In addition, we evaluated histopathological changes in the spinal cord in the presence or absence of SDF-1α. Chronic delivery of SDF-1α decreased numbers of apoptotic cells, boosted astroglia and microglia response, induced angiogenesis, and potentiated the number of proliferating cells in a dose-dependent manner. These results clearly indicate an improved functional CNS long-term recovery after spinal cord injury. This behavioral restoration was paralleled by a reduction of apoptosis and changes in neuroinflammatory cells.

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

    PubMed Central

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

    2016-01-01

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

  15. Evaluation of optimal electrode configurations for epidural spinal cord stimulation in cervical spinal cord injured rats

    PubMed Central

    Alam, Monzurul; Garcia-Alias, Guillermo; Shah, Prithvi K.; Gerasimenko, Yury; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

    2015-01-01

    Background Epidural spinal cord stimulation is a promising technique for modulating the level of excitability and reactivation of dormant spinal neuronal circuits after spinal cord injury (SCI). We examined the ability of chronically implanted epidural stimulation electrodes within the cervical spinal cord to (1) directly elicit spinal motor evoked potentials (sMEPs) in forelimb muscles and (2) determine whether these sMEPs can serve as a biomarker of forelimb motor function after SCI. New method We implanted EMG electrodes in forelimb muscles and epidural stimulation electrodes at C6 and C8 in adult rats. After recovering from a dorsal funiculi crush (C4), rats were tested with different stimulation configurations and current intensities to elicit sMEPs and determined forelimb grip strength. Results: sMEPs were evoked in all muscles tested and their characteristics were dependent on electrode configurations and current intensities. C6(−) stimulation elicited more robust sMEPs than stimulation at C8(−). Stimulating C6 and C8 simultaneously produced better muscle recruitment and higher grip strengths than stimulation at one site. Comparison with existing method(s) Classical method to select the most optimal stimulation configuration is to empirically test each combination individually for every subject and relate to functional improvements. This approach is impractical, requiring extensively long experimental time to determine the more effective stimulation parameters. Our proposed method is fast and physiologically sound. Conclusions Results suggest that sMEPs from forelimb muscles can be useful biomarkers for identifying optimal parameters for epidural stimulation of the cervical spinal cord after SCI. PMID:25791014

  16. Biological Basis of Exercise-based Treatments: Spinal Cord Injury

    PubMed Central

    Basso, D. Michele; Hansen, Christopher N.

    2016-01-01

    Despite intensive neurorehabilitation, extensive functional recovery after spinal cord injury is unattainable for most individuals. Optimal recovery will likely depend on activity-based, task-specific training that personalizes the timing of intervention with the severity of injury. Exercise paradigms elicit both beneficial and deleterious biophysical effects after spinal cord injury. Modulating the type, intensity, complexity, and timing of training may minimize risk and induce greater recovery. This review discusses the following: (a) the biological underpinning of training paradigms that promote motor relearning and recovery, and (b) how exercise interacts with cellular cascades after spinal cord injury. Clinical implications are discussed throughout. PMID:21703584

  17. Impact of spinal cord injury on sexuality: Broad-based clinical practice intervention and practical application

    PubMed Central

    Hess, Marika J.; Hough, Sigmund

    2012-01-01

    This study focuses on the impact a spinal cord injury may have on achieving physical and emotional intimacy, and potential to maximize sexual ability and quality of life. Spinal cord injury is a traumatic, life-altering event that is usually associated with loss of motor and sensory function, as well as sexual impairment. At the time of injury, the individual is faced with devastating loss and an abundance of new information in a setting of extreme stress and challenge. In the acute rehabilitation setting, there is often a considerable void in providing education and resources regarding sexual concerns and needs. There is a positive relationship between sexual education and sexual activity. The impact of inadequate sexual counseling and education as a part of rehabilitation can be deleterious. PMID:22925747

  18. Management of sexual disorders in spinal cord injured patients.

    PubMed

    Rahimi-Movaghar, Vafa; Vaccaro, Alexander R

    2012-01-01

    Spinal cord injured (SCI) patients have sexual disorders including erectile dysfunction (ED), impotence, priapism, ejaculatory dysfunction and infertility. Treatments for erectile dysfunction include four steps. Step 1 involves smoking cessation, weight loss, and increasing physical activity. Step 2 is phosphodiesterase type 5 inhibitors (PDE5I) such as Sildenafil (Viagra), intracavernous injections of Papaverine or prostaglandins, and vacuum constriction devices. Step 3 is a penile prosthesis, and Step 4 is sacral neuromodulation (SNM). Priapism can be resolved spontaneously if there is no ischemia found on blood gas measurement or by Phenylephrine. For anejaculatory dysfunction, massage, vibrator, electrical stimulation and direct surgical biopsy can be used to obtain sperm which can then be used for intra-uterine or in-vitro fertilization. Infertility treatment in male SCI patients involves a combination of the above treatments for erectile and anejaculatory dysfunctions. The basic approach to and management of sexual dysfunction in female SCI patients are similar as for men but do not require treatment for erectile or ejaculatory problems. PMID:22837080

  19. The Prevalence, Etiologic Agents and Risk Factors for Urinary Tract Infection Among Spinal Cord Injury Patients

    PubMed Central

    Togan, Turhan; Azap, Ozlem Kurt; Durukan, Elif; Arslan, Hande

    2014-01-01

    Background: Urinary tract infections (UTIs) are important causes of morbidity and mortality in patients with spinal cord injury and 22% of patients with acute spinal cord injury develop UTI during the first 50 days. Objectives: The aim of this study was to determine the prevalence, etiologic agents and risk factors for asymptomatic bacteriuria and symptomatic urinary tract infections in patients with spinal cord injury. Patients and Methods: This was a prospective investigation of spinal cord injury patients with asymptomatic bacteriuria and symptomatic urinary tract infections in Baskent University Medical Faculty Ayas Rehabilitation Center and Ankara Physical Therapy and Rehabilitation Center between January 2008 and December 2010. The demographic status, clinical and laboratory findings of 93 patients with spinal cord injury were analyzed in order to determine the risk factors for asymptomatic or symptomatic bacteriuria Results: Sixty three (67.7%) of 93 patients had asymptomatic bacteriuria and 21 (22.6%) had symptomatic urinary tract infection. Assessment of the frequency of urinary bladder emptying methods revealed that 57 (61.3%) of 93 patients employed permanent catheters and 24 (25.8%) employed clean intermittent catheterization. One hundred and thirty-five (48.0%) of 281 strains isolated form asymptomatic bacteriuria attacks and 16 (66.6%) of 24 strains isolated from symptomatic urinary tract infection attacks, totaling 151 strains, had multidrug resistance (P > 0.05). One hundred (70.4%) of 142 Escherichia coli strains and 19 (34.5%) of 55 Klebsiella spp strains proliferated in patients with asymptomatic bacteriuria; 8 (80%) of 10 E. coli strains and 4 (80%) of 5 Klebsiella spp. strains were multidrug resistant. Conclusions: The most common infectious episode among spinal cord injury patients was found to be urinary tract ınfection. E. coli was the most common microorganism isolated from urine samples. Antibiotic use in the previous 2 weeks or 3 months

  20. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury

    PubMed Central

    Aloe, Luigi; Bianchi, Patrizia; De Bellis, Alberto; Soligo, Marzia; Rocco, Maria Luisa

    2014-01-01

    The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells. PMID:25206755

  1. The importance of EHD1 in neurite outgrowth contributing to the functional recovery after spinal cord injury.

    PubMed

    Wu, Chunshuai; Cui, Zhiming; Liu, Yonghua; Zhang, Jinlong; Ding, Wensen; Wang, Song; Bao, Guofeng; Xu, Guanhua; Sun, Yuyu; Chen, Jiajia

    2016-08-01

    Traumatic spinal cord injury is one of the most common and severe problems for using NGF to promote the neurite outgrowth of survival neurons. EHD1 regulates and controls the endocytosis and transportation of neurotrophins and transmembrane cargo via recycling endosome for neurite outgrowth. TrkA is particularly considered to be a functional specific recepter in the cell membrane for NGF and is activated upon NGF binding. The transcytosis of TrkA is dependent on Rab11 recycling endosomes and is promoted by NGF signaling itself at the axon terminal. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of EHD1 during the pathological process of SCI. Western blot analysis suggested that EHD1 expression was low in the sham-operated adult rat spinal cords and was significantly up-regulated 1d after injury. Immunohistochemical staining detected the general distribution of EHD1 protein in both the gray and white matter of adult rat spinal cords. Double immunofluorescent staining indicated that EHD1 was expressed in neurons, astrocytes and microglias in the adult rat spinal cord, and obvious changes of EHD1 expression occurred in neurons during SCI pathological process. Significant up-regulation of EHD1 expression was observed in MAP2 positive neurons at 1 day after SCI, in comparison with the sham-operated control, which indicated that EHD1 might play a vital role in neurite outgrowth. Our data indicated that EHD1 could interact with TrkA, and is in the upstream of TrkA. EHD1 up-regulated the expression of TrkA in the glutamate stimulated primary neurons. Based on our experimental data, we boldly conclude that EHD1 regulates the recycling of TrkA back to cell membrane, improving the utilization efficiency of the NGF, which is vital for neurite outgrowth and functional recovery after spinal cord injury. PMID:27211346

  2. Hindlimb Stretching Alters Locomotor Function Post-Spinal Cord Injury in the Adult Rat

    PubMed Central

    Caudle, Krista L.; Atkinson, Darryn A.; Brown, Edward H.; Donaldson, Katie; Seibt, Erik; Chea, Tim; Smith, Erin; Chung, Karianne; Shum-Siu, Alice; Cron, Courtney C.; Magnuson, David S. K.

    2014-01-01

    Background Stretching is a widely accepted standard-of-care therapy following spinal cord injury that has not been systematically studied in animal models. Objective To investigate the influence of a daily stretch-based physical therapy program on locomotor recovery in adult rats with moderate T9 contusive SCI. Methods A randomized treatment and control study of stretching in an animal model of acute spinal cord injury (SCI). Moderate spinal cord injuries were delivered with the NYU Impactor. Daily stretching (30 min./day, 5 days/wk for 8 wks) was provided by a team of animal handlers. Hindlimb function was assessed using the BBB Open Field Locomotor Scale and kinematically. Passive range-of-motion for each joint was determined weekly using a goniometer. Results Declines in hindlimb function during overground stepping were observed for the first 4 weeks. BBB scores improved weeks 5–10 but remained below the control group. Stretched animals had significant deficits in knee passive ROM starting at week 4 and for the duration of the study. Kinematic assessment showed decreased joint excursion during stepping that partially recovered beginning at week 5. Conclusion Stretch-based therapy significantly impaired functional recovery in adult rats with a moderate contusive SCI at T10. The negative impact on function was greatest acutely, but persisted even after the stretching ceased at 8 weeks post-injury. PMID:25106555

  3. Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

    PubMed

    Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

    2015-12-10

    Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI. PMID:26343846

  4. Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

    PubMed

    Kabu, Shushi; Gao, Yue; Kwon, Brian K; Labhasetwar, Vinod

    2015-12-10

    Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI.

  5. Spinal cord injury and outdoor experiences.

    PubMed

    Beringer, Almut

    2004-03-01

    Anecdotal evidence from spinal cord injury (SCI) rehabilitation clients suggests that nature experiences and outdoor pursuits are valued ingredients in a SCI rehabilitation program, in particular for those individuals who were outdoor enthusiasts pre-injury and/or who sustained their injury during outdoor pursuits. Model SCI centres in North America offer outdoor activities as components of SCI rehabilitation. A literature review on the effects and dynamics of nature experiences and outdoor pursuits in SCI rehabilitation and adjustment reveals a lacuna of empirical research in this area. Studies on leisure and recreation following SCI offer insights into how non-vocational rehabilitation activities assist functional independence, quality of life, and community re-integration. Systematic research is needed to ascertain the value and contribution of outdoor experiences in SCI rehabilitation; further, research is needed to document how contact with 'blue-green nature' may assist in the identity reconstruction process and in adjustment to life with a physical disability.

  6. Early elective colostomy following spinal cord injury.

    PubMed

    Boucher, Michelle

    Elective colostomy is an accepted method of bowel management for patients who have had a spinal cord injury (SCI). Approximately 2.4% of patients with SCI have a colostomy, and traditionally it is performed as a last resort several years after injury, and only if bowel complications persist when all other methods have failed. This is despite evidence that patients find a colostomy easier to manage and frequently report wishing it had been performed earlier. It was noticed in the author's spinal unit that increasing numbers of patients were requesting colostomy formation during inpatient rehabilitation following SCI. No supporting literature was found for this; it appears to be an emerging and untested practice. This article explores colostomy formation as a method of bowel management in patients with SCI, considers the optimal time for colostomy formation after injury and examines issues for health professionals. PMID:26973012

  7. Functional Electrical Stimulation and Spinal Cord Injury

    PubMed Central

    Ho, Chester H.; Triolo, Ronald J.; Elias, Anastasia L.; Kilgore, Kevin L.; DiMarco, Anthony F.; Bogie, Kath; Vette, Albert H.; Audu, Musa; Kobetic, Rudi; Chang, Sarah R.; Chan, K. Ming; Dukelow, Sean; Bourbeau, Dennis J.; Brose, Steven W.; Gustafson, Kenneth J.; Kiss, Zelma; Mushahwar, Vivian K.

    2015-01-01

    Synopsis Spinal cord injuries (SCI) can disrupt communications between the brain and the body, leading to a loss of control over otherwise intact neuromuscular systems. The use of electrical stimulation (ES) of the central and peripheral nervous system can take advantage of these intact neuromuscular systems to provide therapeutic exercise options, to allow functional restoration, and even to manage or prevent many medical complications following SCI. The use of ES for the restoration of upper extremity, lower extremity and truncal functions can make many activities of daily living a potential reality for individuals with SCI. Restoring bladder and respiratory functions and preventing pressure ulcers may significantly decrease the morbidity and mortality following SCI. Many of the ES devices are already commercially available and should be considered by all SCI clinicians routinely as part of the lifelong rehabilitation care plan for all eligible individuals with SCI. PMID:25064792

  8. Pain in patients with spinal cord injury.

    PubMed

    Finnerup, Nanna Brix

    2013-12-01

    Individuals with spinal cord injury (SCI) often have chronic pain, which may have a major impact on their quality of life. The purpose of this article is to present an update on the classification of SCI pain, recent advances in the understanding of underlying mechanisms, and current evidence-based treatment of SCI pain. The paper also discusses difficulties in assessing pain after SCI, both in the clinic and in preclinical research. While we continue to increase our understanding of underlying mechanisms, treatment is still unsatisfactory, and there is an unmet need to improve pain relief. We need to improve preclinical assessment of pain-like behavior in central pain models, and improve the clinical assessment of pain and our understanding of the interaction with cognitive, emotional, and social factors. In future studies on mechanisms and treatment, we need to acknowledge the different phenotypes of chronic SCI pain.

  9. Spinal cord injury, immunodepression, and antigenic challenge

    PubMed Central

    Held, Katherine S.; Lane, Thomas E.

    2016-01-01

    The inability to effectively control microbial infection is a leading cause of morbidity and mortality in individuals affected by spinal cord injury (SCI). Available evidence from clinical studies as well as animal models of SCI demonstrate that increased susceptibility to infection is derived from disruption of central nervous system (CNS) communication with the host immune system that ultimately leads to immunodepression. Understanding the molecular and cellular mechanisms governing muted cellular and humoral responses that occur post-injury resulting in impaired host defense following infection is critical for improving the overall quality of life of individuals with SCI. This review focuses on studies performed using preclinical animal models of SCI to evaluate how injury impacts T and B lymphocyte responses following either viral infection or antigenic challenge. PMID:24747011

  10. Spinal Cord Schistosomiasis: Two Different Outcomes

    PubMed Central

    Alsomaili, Mohammed; Abulaban, Ahmad A.

    2016-01-01

    Spinal cord schistosomiasis is difficult to diagnose in nonendemic areas. We report the clinical profile of 2 young Saudi males who presented with myelopathy. The first patient arrived at our hospital relatively late, i.e. 3 months following the presentation of initial symptoms, and had received both pulse steroid therapy and a plasma exchange. Praziquantel was administered late and the patient did not recover. The second case presented early, i.e. within around 8 weeks of initial symptoms. This patient received praziquantel without any kind of steroid and had a complete recovery. We concluded that prompt recognition and early treatment with praziquantel is crucial for a better outcome. The role of steroids in these cases still needs to be proven. PMID:27293404

  11. Spinal Cord Anatomy and Clinical Syndromes.

    PubMed

    Diaz, Eric; Morales, Humberto

    2016-10-01

    We review the anatomy of the spinal cord, providing correlation with key functional and clinically relevant neural pathways, as well as magnetic resonance imaging. Peripherally, the main descending (corticospinal tract) and ascending (gracilis or cuneatus fasciculi and spinothalamic tracts) pathways compose the white matter. Centrally, the gray matter can be divided into multiple laminae. Laminae 1-5 carry sensitive neuron information in the posterior horn, and lamina 9 carries most lower motor neuron information in the anterior horn. Damage to the unilateral corticospinal tract (upper motor neuron information) or gracillis-cuneatus fasciculi (touch and vibration) correlates with ipsilateral clinical findings, whereas damage to unilateral spinothalamic tract (pain-temperature) correlates with contralateral clinical findings. Damage to commissural fibers correlates with a suspended bilateral "girdle" sensory level. Autonomic dysfunction is expected when there is bilateral cord involvement. PMID:27616310

  12. Prolonged Local Hypothermia Has No Long-Term Adverse Effect on the Spinal Cord

    PubMed Central

    Vipin, Ashwati; Kortelainen, Jukka; Al-Nashash, Hasan; Chua, Soo Min; Thow, Xinyuan; Manivannan, Janani; Astrid; Thakor, Nitish V.; Kerr, Candace L.

    2015-01-01

    Hypothermia is known to be neuroprotective and is one of the most effective and promising first-line treatments for central nervous system (CNS) trauma. At present, induction of local hypothermia, as opposed to general hypothermia, is more desired because of its ease of application and safety; fewer side effects and an absence of severe complications have been noted. Local hypothermia involves temperature reduction of a small and specific segment of the spinal cord. Our group has previously shown the neuroprotective effect of short-term, acute moderate general hypothermia through improvements in electrophysiological and motor behavioral assessments, as well as histological examination following contusive spinal cord injury (SCI) in rats. We have also shown the benefit of using short-term local hypothermia versus short-term general hypothermia post-acute SCI. The overall neuroprotective benefit of hypothermia can be categorized into three main components: (1) induction modality, general versus local, (2) invasive, semi-invasive or noninvasive, and (3) duration of hypothermia induction. In this study, a series of experiments were designed to investigate the feasibility, long-term safety, as well as eventual complications and side effects of prolonged, semi-invasive, moderate local hypothermia (30°C±0.5°C for 5 and 8 hours) in rats with uninjured spinal cord while maintaining their core temperature at 37°C±0.5°C. The weekly somatosensory evoked potential and motor behavioral (Basso, Beattie and Bresnahan) assessments of rats that underwent 5 and 8 hours of semi-invasive local hypothermia, which revealed no statistically significant changes in electrical conductivity and behavioral outcomes. In addition, 4 weeks after local hypothermia induction, histological examination showed no anatomical damages or morphological changes in their spinal cord structure and parenchyma. We concluded that this method of prolonged local hypothermia is feasible, safe, and has the

  13. The older adult with a spinal cord injury.

    PubMed

    Roth, E J; Lovell, L; Heinemann, A W; Lee, M Y; Yarkony, G M

    1992-07-01

    Sixty-two consecutive acute spinal cord injury (SCI) patients who were aged 55 years or older were studied and compared to 296 SCI patients of age less than 55 years. Compared to younger patients, the older group had significantly more females (29%), preexisting medical conditions (87%), associated injuries (55%), incomplete quadriplegic patients (63%), and persons whose injuries resulted from falls (53%). There were no differences between groups in frequency of ventilator use, occurrence of medical complications, or acute length of stay, but older patients tended to have fewer surgical spinal fusions (40%), shorter rehabilitation stays (66.5 days), more indwelling urethral cathteters (31%), and more nursing home discharges (19%). With other factors being controlled, advancing age was predictive only of nursing home discharge, and not of acute or rehabilitation lengths of stay. Among older SCI patients, those with complete injuries were nearly 3 times as likely to have been discharged to nursing homes in our series compared to older patients with incomplete lesions. Although many aspects of the presentation, course, and care of older SCI individuals are similar to those of younger patients, there are several unique features of older adults with a SCI. PMID:1508569

  14. Assessment of Glial Scar, Tissue Sparing, Behavioral Recovery and Axonal Regeneration following Acute Transplantation of Genetically Modified Human Umbilical Cord Blood Cells in a Rat Model of Spinal Cord Contusion

    PubMed Central

    Mukhamedshina, Yana O.; Garanina, Ekaterina E.; Masgutova, Galina A.; Galieva, Luisa R.; Sanatova, Elvira R.; Chelyshev, Yurii A.; Rizvanov, Albert A.

    2016-01-01

    Objective and Methods This study investigated the potential for protective effects of human umbilical cord blood mononuclear cells (UCB-MCs) genetically modified with the VEGF and GNDF genes on contusion spinal cord injury (SCI) in rats. An adenoviral vector was constructed for targeted delivery of VEGF and GDNF to UCB-MCs. Using a rat contusion SCI model we examined the efficacy of the construct on tissue sparing, glial scar severity, the extent of axonal regeneration, recovery of motor function, and analyzed the expression of the recombinant genes VEGF and GNDF in vitro and in vivo. Results Transplantation of UCB-MCs transduced with adenoviral vectors expressing VEGF and GDNF at the site of SCI induced tissue sparing, behavioral recovery and axonal regeneration comparing to the other constructs tested. The adenovirus encoding VEGF and GDNF for transduction of UCB-MCs was shown to be an effective and stable vehicle for these cells in vivo following the transplantation into the contused spinal cord. Conclusion Our results show that a gene delivery using UCB-MCs-expressing VEGF and GNDF genes improved both structural and functional parameters after SCI. Further histological and behavioral studies, especially at later time points, in animals with SCI after transplantation of genetically modified UCB-MCs (overexpressing VEGF and GDNF genes) will provide additional insight into therapeutic potential of such cells. PMID:27003408

  15. Transforming care for patients with spinal cord injury in Haiti.

    PubMed

    Stephenson, Fiona

    Patients with spinal cord injury in Haiti previously had a poor prognosis. This article features a case study showing how care was transformed after the earthquake in 2010 by providing simple bladder care.

  16. Toxoplasmosis of the spinal cord in an immunocompromised patient

    PubMed Central

    Martínez, Ernesto; Bolívar, Guillermo; Sánchez, Sandra; Carrascal, Edwin

    2013-01-01

    We, herein, describe an HIV-positive patient with toxoplasmosis of the spinal cord. We also carried out a comprehensive literature review of this topic, with emphasis on the diagnostic tools and therapeutic approach. PMID:24892240

  17. Mechanisms underlying spinal cord damage in decompression sickness.

    PubMed

    Hallenbeck, J M; Bove, A A; Elliott, D H

    1975-04-01

    Decompression sickness, which damaged the spinal cord, was produced in anesthetized dogs using a compression chamber. Cerebrospinal fluid pressure and several intravascular and intracardiac pressures were monitored during the course of the simulated dives. Manometric responses to forcible lung inflation and abdominal compression were measured both predive and postdive after signs of spinal cord damage were evident. Cinevenography of the epidural vertebral venous system was performed both predive and postdive. Histopathologic studies of the brains and cords of both predive and postdive. Histopathologic studies of the brains and cords of paretic animals were carried out. The results indicate that the epidural vertebral venous system becomes obstructed during spinal cord damaging decompression sickness and strongly suggests that spinal cord infarction in decompression sickness is caused by obstruction of cord venous drainage at the level of the epidural vertebral venous system. PMID:1168317

  18. Dynamic loading characteristics of an intradural spinal cord stimulator

    NASA Astrophysics Data System (ADS)

    Oliynyk, M. S.; Gillies, G. T.; Oya, H.; Wilson, S.; Reddy, C. G.; Howard, M. A.

    2013-01-01

    We have measured the forces that act on the electrode-bearing surface of an intradural neuromodulator designed to be in direct contact with the pial surface of the spinal cord, as part of our effort to develop a new method for treating intractable pain. The goal was to investigate the pressures produced by this device on the spinal cord and compare them with normal intrathecal pressure. For this purpose, we employed a dual-sensor arrangement that allowed us to measure the response of a custom-designed silicone spinal cord surrogate to the forces applied by the device. We found that the device had a mean compliance of ≈63 μN μm-1, and that over a 3 mm range of compression, the mid-span pressure it exerted on the spinal cord was ≈1.88 × 103 Pa = 14.1 mm Hg, which lies within the range of normal intrathecal pressure in humans.

  19. Senegenin inhibits neuronal apoptosis after spinal cord contusion injury

    PubMed Central

    Zhang, Shu-quan; Wu, Min-fei; Gu, Rui; Liu, Jia-bei; Li, Ye; Zhu, Qing-san; Jiang, Jin-lan

    2016-01-01

    Senegenin has been shown to inhibit neuronal apoptosis, thereby exerting a neuroprotective effect. In the present study, we established a rat model of spinal cord contusion injury using the modified Allen's method. Three hours after injury, senegenin (30 mg/g) was injected into the tail vein for 3 consecutive days. Senegenin reduced the size of syringomyelic cavities, and it substantially reduced the number of apoptotic cells in the spinal cord. At the site of injury, Bax and Caspase-3 mRNA and protein levels were decreased by senegenin, while Bcl-2 mRNA and protein levels were increased. Nerve fiber density was increased in the spinal cord proximal to the brain, and hindlimb motor function and electrophysiological properties of rat hindlimb were improved. Taken together, our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury. PMID:27212931

  20. Molecular and cellular development of spinal cord locomotor circuitry

    PubMed Central

    Lu, Daniel C.; Niu, Tianyi; Alaynick, William A.

    2015-01-01

    The spinal cord of vertebrate animals is comprised of intrinsic circuits that are capable of sensing the environment and generating complex motor behaviors. There are two major perspectives for understanding the biology of this complicated structure. The first approaches the spinal cord from the point of view of function and is based on classic and ongoing research in electrophysiology, adult behavior, and spinal cord injury. The second view considers the spinal cord from a developmental perspective and is founded mostly on gene expression and gain-of-function and loss-of-function genetic experiments. Together these studies have uncovered functional classes of neurons and their lineage relationships. In this review, we summarize our knowledge of developmental classes, with an eye toward understanding the functional roles of each group. PMID:26136656

  1. Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries

    PubMed Central

    Straley, Karin S.; Po Foo, Cheryl Wong

    2010-01-01

    Abstract The highly debilitating nature of spinal cord injuries has provided much inspiration for the design of novel biomaterials that can stimulate cellular regeneration and functional recovery. Many experts agree that the greatest hope for treatment of spinal cord injuries will involve a combinatorial approach that integrates biomaterial scaffolds, cell transplantation, and molecule delivery. This manuscript presents a comprehensive review of biomaterial-scaffold design strategies currently being applied to the development of nerve guidance channels and hydrogels that more effectively stimulate spinal cord tissue regeneration. To enhance the regenerative capacity of these two scaffold types, researchers are focusing on optimizing the mechanical properties, cell-adhesivity, biodegradability, electrical activity, and topography of synthetic and natural materials, and are developing mechanisms to use these scaffolds to deliver cells and biomolecules. Developing scaffolds that address several of these key design parameters will lead to more successful therapies for the regeneration of spinal cord tissue. PMID:19698073

  2. Childhood Brain and Spinal Cord Tumors Treatment Overview

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  3. Care of spinal cord injury in non-specialist settings.

    PubMed

    Rodger, Sian

    Patient with spinal cord injuries have individualised care routines to help prevent complications. Disruption to these routines following admission to non-specialist settings can have long-term consequences. This article focuses on the key long-term problems of pressure ulcers, bladder and bowel dysfunction, and autonomic dysreflexia. Nurses working on general wards need to consider how to manage these problems when caring for patients with spinal cord injury. PMID:27544957

  4. Myelin water fraction in human cervical spinal cord in vivo.

    PubMed

    Wu, Yijing; Alexander, Andrew L; Fleming, John O; Duncan, Ian D; Field, Aaron S

    2006-01-01

    The noninvasive discrimination of myelin disease from axonal loss and other pathologic confounds remains an unsolved problem in multiple sclerosis but may be possible through magnetic resonance quantitation of the intramyelinic water compartment. Technical challenges have limited the study of this approach in the spinal cord, a common site of involvement in multiple sclerosis. This technical note reports the test-retest reproducibility of a short T2-based estimate of myelin content in human spinal cord in vivo.

  5. Injury alters intrinsic functional connectivity within the primate spinal cord.

    PubMed

    Chen, Li Min; Mishra, Arabinda; Yang, Pai-Feng; Wang, Feng; Gore, John C

    2015-05-12

    Recent demonstrations of correlated low-frequency MRI signal variations between subregions of the spinal cord at rest in humans, similar to those found in the brain, suggest that such resting-state functional connectivity constitutes a common feature of the intrinsic organization of the entire central nervous system. We report our detection of functional connectivity within the spinal cords of anesthetized squirrel monkeys at rest and show that the strength of connectivity within these networks is altered by the effects of injuries. By quantifying the low-frequency MRI signal correlations between different horns within spinal cord gray matter, we found distinct functional connectivity relationships between the different sensory and motor horns, a pattern that was similar to activation patterns evoked by nociceptive heat or tactile stimulation of digits. All horns within a single spinal segment were functionally connected, with the strongest connectivity occurring between ipsilateral dorsal and ventral horns. Each horn was strongly connected to the same horn on neighboring segments, but this connectivity reduced drastically along the spinal cord. Unilateral injury to the spinal cord significantly weakened the strength of the intrasegment horn-to-horn connectivity only on the injury side and in slices below the lesion. These findings suggest resting-state functional connectivity may be a useful biomarker of functional integrity in injured and recovering spinal cords. PMID:25902510

  6. Spontaneous resolution of idiopathic thoracic spinal cord herniation: case report.

    PubMed

    Samuel, Nardin; Goldstein, Christina L; Santaguida, Carlo; Fehlings, Michael G

    2015-09-01

    Spinal cord herniation is a relatively rare but increasingly recognized clinical entity, with fewer than 200 cases reported in the literature to date. The etiology of this condition remains unknown, and surgery is used as the primary treatment to correct the herniation and consequent spinal cord compromise. Some patients without clinical progression have been treated with nonoperative measures, including careful follow-up and symptomatic physical therapy. To date, however, there has been no published report on the resolution of spinal cord herniation without surgical intervention. The patient in the featured case is a 58-year-old man who presented with mild thoracic myelopathy and imaging findings consistent with idiopathic spinal cord herniation. Surprisingly, updated MRI studies, obtained to better delineate the pathology, showed spontaneous resolution of the herniation. Subsequent MRI 6 months later revealed continued resolution of the previous spinal cord herniation. This is the first report of spontaneous resolution of a spinal cord herniation in the literature. At present, the treatment of this disorder is individualized, with microsurgical correction used in patients with progressive neurological impairment. The featured case highlights the potential variability in the natural history of this condition and supports considering an initial trial of nonoperative management for patients with mild, nonprogressive neurological deficits. PMID:26023901

  7. Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury

    PubMed Central

    Yoo, Myungsik; Khaled, Muntasir; Gibbs, Kurt M.; Kim, Jonghun; Kowalewski, Björn; Dierks, Thomas; Schachner, Melitta

    2013-01-01

    Bacterial chondroitinase ABC (ChaseABC) has been used to remove the inhibitory chondroitin sulfate chains from chondroitin sulfate proteoglycans to improve regeneration after rodent spinal cord injury. We hypothesized that the mammalian enzyme arylsulfatase B (ARSB) would also enhance recovery after mouse spinal cord injury. Application of the mammalian enzyme would be an attractive alternative to ChaseABC because of its more robust chemical stability and reduced immunogenicity. A one-time injection of human ARSB into injured mouse spinal cord eliminated immunoreactivity for chondroitin sulfates within five days, and up to 9 weeks after injury. After a moderate spinal cord injury, we observed improvements of locomotor recovery assessed by the Basso Mouse Scale (BMS) in ARSB treated mice, compared to the buffer-treated control group, at 6 weeks after injection. After a severe spinal cord injury, mice injected with equivalent units of ARSB or ChaseABC improved similarly and both groups achieved significantly more locomotor recovery than the buffer-treated control mice. Serotonin and tyrosine hydroxylase immunoreactive axons were more extensively present in mouse spinal cords treated with ARSB and ChaseABC, and the immunoreactive axons penetrated further beyond the injury site in ARSB or ChaseABC treated mice than in control mice. These results indicate that mammalian ARSB improves functional recovery after CNS injury. The structural/molecular mechanisms underlying the observed functional improvement remain to be elucidated. PMID:23520469

  8. Spontaneous resolution of idiopathic thoracic spinal cord herniation: case report.

    PubMed

    Samuel, Nardin; Goldstein, Christina L; Santaguida, Carlo; Fehlings, Michael G

    2015-09-01

    Spinal cord herniation is a relatively rare but increasingly recognized clinical entity, with fewer than 200 cases reported in the literature to date. The etiology of this condition remains unknown, and surgery is used as the primary treatment to correct the herniation and consequent spinal cord compromise. Some patients without clinical progression have been treated with nonoperative measures, including careful follow-up and symptomatic physical therapy. To date, however, there has been no published report on the resolution of spinal cord herniation without surgical intervention. The patient in the featured case is a 58-year-old man who presented with mild thoracic myelopathy and imaging findings consistent with idiopathic spinal cord herniation. Surprisingly, updated MRI studies, obtained to better delineate the pathology, showed spontaneous resolution of the herniation. Subsequent MRI 6 months later revealed continued resolution of the previous spinal cord herniation. This is the first report of spontaneous resolution of a spinal cord herniation in the literature. At present, the treatment of this disorder is individualized, with microsurgical correction used in patients with progressive neurological impairment. The featured case highlights the potential variability in the natural history of this condition and supports considering an initial trial of nonoperative management for patients with mild, nonprogressive neurological deficits.

  9. Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

    PubMed Central

    DePaul, Marc A.; Palmer, Marc; Lang, Bradley T.; Cutrone, Rochelle; Tran, Amanda P.; Madalena, Kathryn M.; Bogaerts, Annelies; Hamilton, Jason A.; Deans, Robert J.; Mays, Robert W.; Busch, Sarah A.; Silver, Jerry

    2015-01-01

    Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammation and promote recovery following SCI. In vitro, we show that human multipotent adult progenitor cells (MAPCs) have the ability to modulate macrophage activation, and prior exposure to MAPC secreted factors can reduce macrophage-mediated axonal dieback of dystrophic axons. Using a contusion model of SCI, we found that intravenous delivery of MAPCs one day, but not immediately, after SCI significantly improves urinary and locomotor recovery, which was associated with marked spinal cord tissue sparing. Intravenous MAPCs altered the immune response in the spinal cord and periphery, however biodistribution studies revealed that no MAPCs were found in the cord and instead preferentially homed to the spleen. Our results demonstrate that MAPCs exert their primary effects in the periphery and provide strong support for the use of these cells in acute human contusive SCI. PMID:26582249

  10. Pushing the science forward: chitosan nanoparticles and functional repair of CNS tissue after spinal cord injury

    PubMed Central

    2013-01-01

    Background We continue our exploration of the large polysaccharide polymer Chitosan as an acute therapy for severe damage to the nervous system. We tested the action of subcutaneously injected nanoparticles (~ 100 – 200 nanometers in diameter; 1 mg per ml) against control injections (silica particle of the same size and concentration) in a standardized in vivo spinal cord injury model. These functional tests used standardized physiological measurements of evoked potentials arriving at the sensorimotor cortex subsequent to stimulation of the tibial nerve of the contralateral hindlimb. We further explored the degree of acetylation and molecular weight of chitosan on the success of sealing cell damage using specific probes of membrane integrity. Results Not one of the control group showed restored conduction of evoked potentials stimulated from the tibial nerve of the hindleg – through the lesion – and recorded at the sensorimotor cortex of the brain. Investigation if the degree of acetylation and molecular weight impacted “membrane sealing” properties of Chitosan were unsuccessful. Dye - exchange membrane probes failed to show a difference between the comparators in the function of Chitosan in ex vivo injured spinal cord tests. Conclusions We found that Chitosan nanoparticles effectively restore nerve impulse transmission through the crushed adult guinea pig spinal cord in vivo after severe crush/compression injury. The tests of the molecular weight (MW) and degree of acetylation did not produce any improvement in Chitosan’s membrane sealing properties. PMID:23731718

  11. Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury.

    PubMed

    Wang, Difei; Ichiyama, Ronaldo M; Zhao, Rongrong; Andrews, Melissa R; Fawcett, James W

    2011-06-22

    Chondroitinase ABC (ChABC) in combination with rehabilitation has been shown to promote functional recovery in acute spinal cord injury. For clinical use, the optimal treatment window is concurrent with the beginning of rehabilitation, usually 2-4 weeks after injury. We show that ChABC is effective when given 4 weeks after injury combined with rehabilitation. After C4 dorsal spinal cord injury, rats received no treatment for 4 weeks. They then received either ChABC or penicillinase control treatment followed by hour-long daily rehabilitation specific for skilled paw reaching. Animals that received both ChABC and task-specific rehabilitation showed the greatest recovery in skilled paw reaching, approaching similar levels to animals that were treated at the time of injury. There was also a modest increase in skilled paw reaching ability in animals receiving task-specific rehabilitation alone. Animals treated with ChABC and task-specific rehabilitation also showed improvement in ladder and beam walking. ChABC increased sprouting of the corticospinal tract, and these sprouts had more vGlut1(+ve) presynaptic boutons than controls. Animals that received rehabilitation showed an increase in perineuronal net number and staining intensity. Our results indicate that ChABC treatment opens a window of opportunity in chronic spinal cord lesions, allowing rehabilitation to improve functional recovery. PMID:21697383

  12. Transplantation of human telomerase reverse transcriptase gene-transfected Schwann cells for repairing spinal cord injury

    PubMed Central

    Zhang, Shu-quan; Wu, Min-fei; Liu, Jia-bei; Li, Ye; Zhu, Qing-san; Gu, Rui

    2015-01-01

    Transfection of the human telomerase reverse transcriptase (hTERT) gene has been shown to increase cell proliferation and enhance tissue repair. In the present study, hTERT was transfected into rat Schwann cells. A rat model of acute spinal cord injury was established by the modified free-falling method. Retrovirus PLXSN was injected at the site of spinal cord injury as a vector to mediate hTERT gene-transfected Schwann cells (1 × 1010/L; 10 μL) or Schwann cells (1 × 1010/L; 10 μL) without hTERT gene transfection. Between 1 and 4 weeks after model establishment, motor function of the lower limb improved in the hTERT-transfected group compared with the group with non-transfected Schwann cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and reverse transcription-polymerase chain reaction results revealed that the number of apoptotic cells, and gene expression of aquaporin 4/9 and matrix metalloproteinase 9/2 decreased at the site of injury in both groups; however, the effect improved in the hTERT-transfected group compared with the Schwann cells without hTERT transfection group. Hematoxylin and eosin staining, PKH26 fluorescent labeling, and electrophysiological testing demonstrated that compared with the non-transfected group, spinal cord cavity and motor and sensory evoked potential latencies were reduced, while the number of PKH26-positive cells and the motor and sensory evoked potential amplitude increased at the site of injury in the hTERT-transfected group. These findings suggest that transplantation of hTERT gene-transfected Schwann cells repairs the structure and function of the injured spinal cord. PMID:26889196

  13. A combination of keratan sulfate digestion and rehabilitation promotes anatomical plasticity after rat spinal cord injury.

    PubMed

    Ishikawa, Yoshimoto; Imagama, Shiro; Ohgomori, Tomohiro; Ishiguro, Naoki; Kadomatsu, Kenji

    2015-04-23

    Functional recovery after neuronal injuries relies on neuronal network reconstruction which involves many repair processes, such as sealing of injured axon ends, axon regeneration/sprouting, and construction and refinement of synaptic connections. Chondroitin sulfate (CS) is a major inhibitor of axon regeneration/sprouting. It has been reported that the combination of task-specific rehabilitation and CS-digestion is much more effective than either treatment alone with regard to the promotion of functional and anatomical plasticity for dexterity in acute and chronic spinal cord injury models. We previously reported that keratan sulfate (KS) is another inhibitor and has a potency equal to CS. Here, we compared the effects of KS- or CS-digestion plus rehabilitation on recovery from spinal cord injury. Keratanase II or chondroitinase ABC was locally administered at the lesion after spinal cord injury at C3/4. Task-specific rehabilitation training, i.e., a single pellet reaching task using a Whishaw apparatus, was done for 3 weeks before injury, and then again at 1-6 weeks after injury. The combination of KS-digestion and rehabilitation yielded a better rate of pellet removal than either KS-digestion alone or rehabilitation alone, although these differences were not statistically significant. The combination of CS-digestion and rehabilitation showed similar results. Strikingly, both KS-digestion/rehabilitation and CS-digestion/rehabilitation showed significant increases in neurite growth in vivo as estimated by 5-hydroxytryptamine and GAP43 staining. Thus, KS-digestion and rehabilitation exerted a synergistic effect on anatomical plasticity, and this effect was comparable with that of CS-digestion/rehabilitation. KS-digestion might widen the therapeutic window of spinal cord injury if combined with rehabilitation.

  14. The effect of whole-body resonance vibration in a porcine model of spinal cord injury.

    PubMed

    Streijger, Femke; Lee, Jae H T; Chak, Jason; Dressler, Dan; Manouchehri, Neda; Okon, Elena B; Anderson, Lisa M; Melnyk, Angela D; Cripton, Peter A; Kwon, Brian K

    2015-06-15

    Whole-body vibration has been identified as a potential stressor to spinal cord injury (SCI) patients during pre-hospital transportation. However, the effect that such vibration has on the acutely injured spinal cord is largely unknown, particularly in the frequency domain of 5 Hz in which resonance of the spine occurs. The objective of the study was to investigate the consequences of resonance vibration on the injured spinal cord. Using our previously characterized porcine model of SCI, we subjected animals to resonance vibration (5.7±0.46 Hz) or no vibration for a period of 1.5 or 3.0 h. Locomotor function was assessed weekly and cerebrospinal fluid (CSF) samples were collected to assess different inflammatory and injury severity markers. Spinal cords were evaluated histologically to quantify preserved white and gray matter. No significant differences were found between groups for CSF levels of monocyte chemotactic protein-1, interleukin 6 (IL-6) and lL-8. Glial fibrillary acidic protein levels were lower in the resonance vibration group, compared with the non-vibrated control group. Spared white matter tissue was increased within the vibrated group at 7 d post-injury but this difference was not apparent at the 12-week time-point. No significant difference was observed in locomotor recovery following resonance vibration of the spine. Here, we demonstrate that exposure to resonance vibration for 1.5 or 3 h following SCI in our porcine model is not detrimental to the functional or histological outcomes. Our observation that a 3.0-h period of vibration at resonance frequency induces modest histological improvement at one week post-injury warrants further study.

  15. Robotic Radiosurgery for the Treatment of Intramedullary Spinal Cord Metastases: A Case Report and Literature Review

    PubMed Central

    Garcia, Rafael; Sallabanda, Kita; Santa-Olalla, Iciar; Avilés, Lijia; Sallabanda, Morena; Rivin, Eleonor; Samblás, José

    2016-01-01

    Modern technologies allow the delivery of high radiation doses to intramedullary spinal cord metastases while lowering the dose to the neighboring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known. This study evaluates the acute and late toxicity outcomes in a patient treated with robotic radiosurgery for an intramedullary spinal cord metastasis. A 50-year-old woman diagnosed in May 2006 with invasive ductal carcinoma of the right breast T2N3M1 (two liver metastases) received chemotherapy with a complete response. Subsequently, she underwent adjuvant whole-breast radiotherapy, along with tamoxifen. After several distant relapses, treated mainly with systemic therapy, the patient developed an intramedullary lesion at the C3-C4 level and was referred to our CyberKnife unit for assessment. A total dose of 14 Gy prescribed to the 74% isodose line was administered to the intramedullary lesion in one fraction. One hundred and two treatment beams were used covering 95.63% of the target volume. The mean dose was 15.93 Gy and the maximum dose, 18.92 Gy. Maximum dose to the spinal cord was 13.96 Gy, V12 ~ 0.13 cc and V8 ~ 0.43 cc. Three months after treatment, magnetic resonance imaging showed a reduction in size and enhancement of the intramedullary lesion with no associated toxicity. During this period, the patient showed a good performance status without neurological deficits. Currently, with a follow-up of 37 months, the patient has the ability to perform activities of daily life. Intramedullary spinal cord metastases is a rare and aggressive disease, often treatment-refractory. Our case demonstrates that radiation therapy delivery with robotic radiosurgery allows the achievement of a high local control without adding toxicity. PMID:27330877

  16. Evaluation of the Combination of Methylprednisolone and Tranilast after Spinal Cord Injury in Rat Models

    PubMed Central

    Chuan, Xie Yun; Feng, Qiao Xiao; Alizada, Mujahid; Zhan, Jing

    2016-01-01

    Objective The aim of our study was to evaluate the neuroprotective functions of the combination therapy using methylprednisolone (MP) and tranilast (TR) after spinal cord injury (SCI) in adult rats. Methods Spinal cord compression injury model was achieved using Yasargil aneurysm clip. Rats were divided into control group, MP group, TR group, and combination therapy group using TR and MP. Rat models were assessed for locomotor functional recovery using Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content and myeloperoxidase (MPO) activity 24 hours post SCI, haematoxylin and eosin staining and glial fibrillary acid protein (GFAP) staining at 7 and 14 days post SCI. Results The spinal cord water content and MPO activity in the combination therapy group was significantly lower than the control group and the individual therapy groups p<0.05. The combination therapy group had significantly higher BBB scores than control group and individual therapy groups (p<0.05). At one week after SCI, GFAP expression in the combination group was significantly lower than the control group (p<0.05) but there was no significant difference compared to the individual therapy groups (p>0.05). At 2 weeks after SCI there was a slight decrease in GFAP expression compared to the first week but the difference was not statistically significant (p>0.05), GFAP expression between the groups was not statistically significant p>0.05. Conclusion Combining MP and TR is therapeutically more effective in improving functional recovery, inhibiting inflammation and glial scar formation after acute SCI. PMID:27446512

  17. An efficient device to experimentally model compression injury of mammalian spinal cord.

    PubMed

    Ropper, Alexander E; Zeng, Xiang; Anderson, Jamie E; Yu, Dou; Han, InBo; Haragopal, Hariprakash; Teng, Yang D

    2015-09-01

    We report an efficient and effective device to reproducibly model clinically relevant spinal cord injury (SCI) via controlled mechanical compression. In the present study, following skin incision, dorsal laminectomy was performed to expose T10 spinal cord of adult female Sprague-Dawley rats (230-250 g). The vertebral column was suspended and stabilized by Allis clamps at T8 and 12 spinous processes. A metal impounder was then gently loaded onto T10 dura (20, 35 or 50 g × 5 min; n=7/group), resulting in acute mild, moderate, or severe standing weight compression, respectively. Neurobehavioral outcomes were evaluated using the BBB locomotor scale and inclined plane test for coordinated hindlimb function, and a battery of spinal reflex tests for sensorimotor functions, at 1 day following SCI and weekly thereafter for 7 weeks. Quantitative histopathology was used to assess injury-triggered loss of white matter, gray matter and ventral horn motor neurons. Immunocytochemical levels of glial fibrillary acidic protein (GFAP) and β-amyloid precursor protein (APP) at the cervical and lumbar regions were measured to determine the distal segment impact of T10 compression. The data demonstrates that the standardized protocol generates weight-dependent hindlimb motosensory deficits and neurodegeneration primarily at and near the lesion epicenter. Importantly, there are significantly increased GFAP and APP expressions in spinal cord segments involved in eliciting post-SCI allodynia. Therefore, the described system reliably produces compression trauma in manners partially emulating clinical quasi-static insults to the spinal cord, providing a pragmatic model to investigate pathophysiological events and potential therapeutics for compression SCI. PMID:26210871

  18. Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord

    PubMed Central

    Kaufmann, Nathalie; Zeka, Bleranda; Schanda, Kathrin; Fujihara, Kazuo; Illes, Zsolt; Dahle, Charlotte; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID:26990978

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

    PubMed

    Rodriguez-Jimenez, Francisco Javier; Alastrue-Agudo, Ana; Stojkovic, Miodrag; Erceg, Slaven; Moreno-Manzano, Victoria

    2015-01-01

    Ion channels included in the family of Connexins (Cx) help to control cell proliferation and differentiation of neuronal progenitors. Here we explored the role of Connexin 50 (Cx50) in cell fate modulation of adult spinal cord derived neural precursors located in the ependymal canal (epSPC). epSPC from non-injured animals showed high expression levels of Cx50 compared to epSPC from animals with spinal cord injury (SCI) (epSPCi). When epSPC or epSPCi were induced to spontaneously differentiate in vitro we found that Cx50 favors glial cell fate, since higher expression levels, endogenous or by over-expression of Cx50, augmented the expression of the astrocyte marker GFAP and impaired the neuronal marker Tuj1. Cx50 was found in both the cytoplasm and nucleus of glial cells, astrocytes and oligodendrocyte-derived cells. Similar expression patterns were found in primary cultures of mature astrocytes. In addition, opposite expression profile for nuclear Cx50 was observed when epSPC and activated epSPCi were conducted to differentiate into mature oligodendrocytes, suggesting a different role for this ion channel in spinal cord beyond cell-to-cell communication. In vivo detection of Cx50 by immunohistochemistry showed a defined location in gray matter in non-injured tissues and at the epicenter of the injury after SCI. epSPCi transplantation, which accelerates locomotion regeneration by a neuroprotective effect after acute SCI is associated with a lower signal of Cx50 within the injured area, suggesting a minor or detrimental contribution of this ion channel in spinal cord regeneration by activated epSPCi. PMID:26561800

  20. Neuregulin-1 controls an endogenous repair mechanism after spinal cord injury.

    PubMed

    Bartus, Katalin; Galino, Jorge; James, Nicholas D; Hernandez-Miranda, Luis R; Dawes, John M; Fricker, Florence R; Garratt, Alistair N; McMahon, Stephen B; Ramer, Matt S; Birchmeier, Carmen; Bennett, David L H; Bradbury, Elizabeth J

    2016-05-01

    Following traumatic spinal cord injury, acute demyelination of spinal axons is followed by a period of spontaneous remyelination. However, this endogenous repair response is suboptimal and may account for the persistently compromised function of surviving axons. Spontaneous remyelination is largely mediated by Schwann cells, where demyelinated central axons, particularly in the dorsal columns, become associated with peripheral myelin. The molecular control, functional role and origin of these central remyelinating Schwann cells is currently unknown. The growth factor neuregulin-1 (Nrg1, encoded by NRG1) is a key signalling factor controlling myelination in the peripheral nervous system, via signalling through ErbB tyrosine kinase receptors. Here we examined whether Nrg1 is required for Schwann cell-mediated remyelination of central dorsal column axons and whether Nrg1 ablation influences the degree of spontaneous remyelination and functional recovery following spinal cord injury. In contused adult mice with conditional ablation of Nrg1, we found an absence of Schwann cells within the spinal cord and profound demyelination of dorsal column axons. There was no compensatory increase in oligodendrocyte remyelination. Removal of peripheral input to the spinal cord and proliferation studies demonstrated that the majority of remyelinating Schwann cells originated within the injured spinal cord. We also examined the role of specific Nrg1 isoforms, using mutant mice in which only the immunoglobulin-containing isoforms of Nrg1 (types I and II) were conditionally ablated, leaving the type III Nrg1 intact. We found that the immunoglobulin Nrg1 isoforms were dispensable for Schwann cell-mediated remyelination of central axons after spinal cord injury. When functional effects were examined, both global Nrg1 and immunoglobulin-specific Nrg1 mutants demonstrated reduced spontaneous locomotor recovery compared to injured controls, although global Nrg1 mutants were more impaired in

  1. Neuregulin-1 controls an endogenous repair mechanism after spinal cord injury.

    PubMed

    Bartus, Katalin; Galino, Jorge; James, Nicholas D; Hernandez-Miranda, Luis R; Dawes, John M; Fricker, Florence R; Garratt, Alistair N; McMahon, Stephen B; Ramer, Matt S; Birchmeier, Carmen; Bennett, David L H; Bradbury, Elizabeth J

    2016-05-01

    Following traumatic spinal cord injury, acute demyelination of spinal axons is followed by a period of spontaneous remyelination. However, this endogenous repair response is suboptimal and may account for the persistently compromised function of surviving axons. Spontaneous remyelination is largely mediated by Schwann cells, where demyelinated central axons, particularly in the dorsal columns, become associated with peripheral myelin. The molecular control, functional role and origin of these central remyelinating Schwann cells is currently unknown. The growth factor neuregulin-1 (Nrg1, encoded by NRG1) is a key signalling factor controlling myelination in the peripheral nervous system, via signalling through ErbB tyrosine kinase receptors. Here we examined whether Nrg1 is required for Schwann cell-mediated remyelination of central dorsal column axons and whether Nrg1 ablation influences the degree of spontaneous remyelination and functional recovery following spinal cord injury. In contused adult mice with conditional ablation of Nrg1, we found an absence of Schwann cells within the spinal cord and profound demyelination of dorsal column axons. There was no compensatory increase in oligodendrocyte remyelination. Removal of peripheral input to the spinal cord and proliferation studies demonstrated that the majority of remyelinating Schwann cells originated within the injured spinal cord. We also examined the role of specific Nrg1 isoforms, using mutant mice in which only the immunoglobulin-containing isoforms of Nrg1 (types I and II) were conditionally ablated, leaving the type III Nrg1 intact. We found that the immunoglobulin Nrg1 isoforms were dispensable for Schwann cell-mediated remyelination of central axons after spinal cord injury. When functional effects were examined, both global Nrg1 and immunoglobulin-specific Nrg1 mutants demonstrated reduced spontaneous locomotor recovery compared to injured controls, although global Nrg1 mutants were more impaired in

  2. In Vivo Measurement of Cervical Spinal Cord Deformation During Traumatic Spinal Cord Injury in a Rodent Model.

    PubMed

    Bhatnagar, Tim; Liu, Jie; Yung, Andrew; Cripton, Peter A; Kozlowski, Piotr; Oxland, Thomas

    2016-04-01

    The spinal cord undergoes physical deformation during traumatic spinal cord injury (TSCI), which results in biological damage. This study demonstrates a novel approach, using magnetic resonance imaging and image registration techniques, to quantify the three-dimensional deformation of the cervical spinal cord in an in vivo rat model. Twenty-four male rats were subjected to one of two clinically relevant mechanisms of TSCI (i.e. contusion and dislocation) inside of a MR scanner using a novel apparatus, enabling imaging of the deformed spinal cords. The displacement fields demonstrated qualitative differences between injury mechanisms. Three-dimensional Lagrangian strain fields were calculated, and the results from the contusion injury mechanism were deemed most reliable. Strain field error was assessed using a Monte Carlo approach, which showed that simulated normal strain error experienced a bias, whereas shear strain error did not. In contusion injury, a large region of dorso-ventral compressive strain was observed under the impactor which extended into the ventral region of the spinal cord. High tensile lateral strains under the impactor and compressive lateral strains in the lateral white matter were also observed in contusion. The ability to directly observe and quantify in vivo spinal cord deformation informs our knowledge of the mechanics of TSCI.

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  4. Influence of Spinal Cord Integrity on Gait Control in Human Spinal Cord Injury.

    PubMed

    Awai, Lea; Bolliger, Marc; Ferguson, Adam R; Courtine, Grégoire; Curt, Armin

    2016-07-01

    Background Clinical trials in spinal cord injury (SCI) primarily rely on simplified outcome metrics (ie, speed, distance) to obtain a global surrogate for the complex alterations of gait control. However, these assessments lack sufficient sensitivity to identify specific patterns of underlying impairment and to target more specific treatment interventions. Objective To disentangle the differential control of gait patterns following SCI beyond measures of time and distance. Methods The gait of 22 individuals with motor-incomplete SCI and 21 healthy controls was assessed using a high-resolution 3-dimensional motion tracking system and complemented by clinical and electrophysiological evaluations applying unbiased multivariate analysis. Results Motor-incomplete SCI patients showed varying degrees of spinal cord integrity (spinal conductivity) with severe limitations in walking speed and altered gait patterns. Principal component (PC) analysis applied on all the collected data uncovered robust coherence between parameters related to walking speed, distortion of intralimb coordination, and spinal cord integrity, explaining 45% of outcome variance (PC 1). Distinct from the first PC, the modulation of gait-cycle variables (step length, gait-cycle phases, cadence; PC 2) remained normal with respect to regained walking speed, whereas hip and knee ranges of motion were distinctly altered with respect to walking speed (PC 3). Conclusions In motor-incomplete SCI, distinct clusters of discretely controlled gait parameters can be discerned that refine the evaluation of gait impairment beyond outcomes of walking speed and distance. These findings are specifically different from that in other neurological disorders (stroke, Parkinson) and are more discrete at targeting and disentangling the complex effects of interventions to improve walking outcome following motor-incomplete SCI.

  5. [SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

    PubMed

    Shepehtko, E N; Garmash, D A; Kurbanov, A K; Marchenko, V O; Kozak, Yu S

    2016-04-01

    Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection. PMID:27434952

  6. Exercise recommendations for individuals with spinal cord injury.

    PubMed

    Jacobs, Patrick L; Nash, Mark S

    2004-01-01

    Persons with spinal cord injury (SCI) exhibit deficits in volitional motor control and sensation that limit not only the performance of daily tasks but also the overall activity level of these persons. This population has been characterised as extremely sedentary with an increased incidence of secondary complications including diabetes mellitus, hypertension and atherogenic lipid profiles. As the daily lifestyle of the average person with SCI is without adequate stress for conditioning purposes, structured exercise activities must be added to the regular schedule if the individual is to reduce the likelihood of secondary complications and/or to enhance their physical capacity. The acute exercise responses and the capacity for exercise conditioning are directly related to the level and completeness of the spinal lesion. Appropriate exercise testing and training of persons with SCI should be based on the individual's exercise capacity as determined by accurate assessment of the spinal lesion. The standard means of classification of SCI is by application of the International Standards for Classification of Spinal Cord Injury, written by the Neurological Standards Committee of the American Spinal Injury Association. Individuals with complete spinal injuries at or above the fourth thoracic level generally exhibit dramatically diminished cardiac acceleration with maximal heart rates less than 130 beats/min. The work capacity of these persons will be limited by reductions in cardiac output and circulation to the exercising musculature. Persons with complete spinal lesions below the T(10) level will generally display injuries to the lower motor neurons within the lower extremities and, therefore, will not retain the capacity for neuromuscular activation by means of electrical stimulation. Persons with paraplegia also exhibit reduced exercise capacity and increased heart rate responses (compared with the non-disabled), which have been associated with circulatory limitations

  7. Patients with Spinal Cord Injuries Favor Administration of Methylprednisolone

    PubMed Central

    Bowers, Christian A.; Kundu, Bornali; Rosenbluth, Jeffrey; Hawryluk, Gregory W. J.

    2016-01-01

    Methylprednisolone sodium succinate (MPSS) for treatment of acute spinal cord injury (SCI) has been associated with both benefits and adverse events. MPSS administration was the standard of care for acute SCI until recently when its use has become controversial. Patients with SCI have had little input in the debate, thus we sought to learn their opinions regarding administration of MPSS. A summary of the published literature to date on MPSS use for acute SCI was created and adjudicated by 28 SCI experts. This summary was then emailed to 384 chronic SCI patients along with a survey that interrogated the patients’ neurological deficits, communication with physicians and their views on MPSS administration. 77 out of 384 patients completed the survey. 28 respondents indicated being able to speak early after injury and of these 24 reported arriving at the hospital within 8 hours of injury. One recalled a physician speaking to them about MPSS and one patient reported choosing whether or not to receive MPSS. 59.4% felt that the small neurological benefits associated with MPSS were ‘very important’ to them (p<0.0001). Patients had ‘little concern’ for potential side-effects of MPSS (p = 0.001). Only 1.4% felt that MPSS should not be given to SCI patients regardless of degree of injury (p<0.0001). This is the first study to report SCI patients’ preferences regarding MPSS treatment for acute SCI. Patients favor the administration of MPSS for acute SCI, however few had input into whether or not it was administered. Conscious patients should be given greater opportunity to decide their treatment. These results also provide some guidance regarding MPSS administration in patients unable to communicate. PMID:26789007

  8. Transplanted Oligodendrocytes and Motoneuron Progenitors Generated from Human Embryonic Stem Cells Promote Locomotor Recovery After Spinal Cord Transection

    PubMed Central

    Erceg, Slaven; Ronaghi, Mohammad; Oria, Marc; García Roselló, Mireia; Aragó, Maria Amparo Pérez; Lopez, Maria Gomez; Radojevic, Ivana; Moreno-Manzano, Victoria; Rodríguez-Jiménez, Francisco-Javier; Shanker Bhattacharya, Shom; Cordoba, Juan; Stojkovic, Miodrag

    2010-01-01

    Human embryonic stem cells (hESC) hold great promise for the treatment of patients with many neurodegenerative diseases particularly those arising from cell loss or neural dysfunction including spinal cord injury. This study evaluates the therapeutic effects of transplanted hESC-derived oligodendrocyte progenitors (OPC) and/or motoneuron progenitors (MP) on axonal remyelination and functional recovery of adult rats after complete spinal cord transection. OPC and/or MP were grafted into the site of injury in the acute phase. Based on Basso-Beattie-Bresnahan scores recovery of locomotor function was significantly enhanced in rats treated with OPC and/or MP when compared with control animals. When transplanted into the spinal cord immediately after complete transection, OPC and MP survived, migrated, and differentiated into mature oligodendrocytes and neurons showing in vivo electrophysiological activity. Taken together, these results indicate that OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord. Stem Cells 2010; 28:1541–1549. PMID:20665739

  9. Regulation of choline acetyltransferase expression by 17 β-oestradiol in NSC-34 cells and in the spinal cord.

    PubMed

    Johann, S; Dahm, M; Kipp, M; Zahn, U; Beyer, C

    2011-09-01

    Motoneurones located in the ventral horn of the spinal cord conciliate cholinergic innervation of skeletal muscles. These neurones appear to be exceedingly affected in neurodegenerative diseases such as amyotrophic lateral sclerosis. The dysfunction of motoneurones is typically accompanied by alterations of cholinergic metabolism and signalling, as demonstrated by a decrease in choline acetyltransferase (ChAT) expression. 17 β-Oestradiol (E(2)) is generally accepted as neuroprotective factor in the brain under acute toxic and neurodegenerative conditions and also appears to exert a protective role for motoneurones. In the present study, we attempted to analyse the role of E(2) signalling on ChAT expression in the motoneurone-like cell line NSC-34 and in vivo. In a first step, we demonstrated the presence of oestrogen receptor α and β in NSC-34 cells, as well as in the cervical and lumbar parts, of the male mouse spinal cord. Subsequently, we investigated the effect of E(2) treatment on ChAT expression. The application of E(2) significantly increased the transcription of ChAT in NSC-34 cells and in the cervical but not lumbar part of the spinal cord. Our results indicate that E(2) can influence the cholinergic system by increasing ChAT expression in the mouse spinal cord. This mechanism might support motoneurones, in addition to survival-promoting mechanisms, in the temporal balance toxic or neurodegenerative challenges. PMID:21790808

  10. EphB3 receptors function as dependence receptors to mediate oligodendrocyte cell death following contusive spinal cord injury

    PubMed Central

    Tsenkina, Y; Ricard, J; Runko, E; Quiala- Acosta, M M; Mier, J; Liebl, D J

    2015-01-01

    We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and disturbances in EphB3-ephrinB3 protein balance acutely (days) after the initial impact creating an environment for a dependence receptor-mediated cell death to occur. Genetic ablation of EphB3 promotes OL survival associated with increased expression of myelin basic protein and improved locomotor function in mice after SCI. Moreover, administration of its ephrinB3 ligand to the spinal cord after injury also promotes OL survival. Our in vivo findings are supported by in vitro studies showing that ephrinB3 administration promotes the survival of both oligodendroglial progenitor cells and mature OLs cultured under pro-apoptotic conditions. In conclusion, the present study demonstrates a novel dependence receptor role of EphB3 in OL cell death after SCI, and supports further development of ephrinB3-based therapies to promote recovery. PMID:26469970

  11. Effect of nimodipine on rat spinal cord injury.

    PubMed

    Jia, Y-F; Gao, H-L; Ma, L-J; Li, J

    2015-02-13

    We evaluated the potentially protective effect of nimodipine on rat spinal cord injury. Sprague-Dawley rats received spinal cord injury, and were separated into nimodipine (N = 12) and saline groups (N = 12). Within 1 h of the injury, rats were treated intraperitoneally with nimodipine (1.0 mg/kg) or an equal amount of saline. Treatment was performed 3 times a day for 1 week. Operation BBB score and track experiment were used to measure the physical function of the hind legs 1 and 2 weeks after injury. Two weeks after the injury, malondialdehyde (MDA) content and spinal cord myeloperoxidase (MPO) activity of the injured part were determined, and the glial scar and dead room were studied using the immune tissue chemical test. ED1 was used to observe active gitter cell and macrophages. The physical function of the nimodipine group improved significantly (P < 0.01). Two weeks after injury, spinal cord MDA content in the spinal cord in the nimodipine group (nmol/g, 25.6 ± 9.7 vs 68.5 ± 16.7) and MPO activity (U/g, 252.2 ± 63.9 vs 382.8 ± 108.2) decreased significantly (P < 0.01); nimodipine whole dead space (mm2, 4.45 ± 1.28 vs 6.16 ± 2.65) and ED1 antibody immunity colored positive room (mm2, 1.87 ± 0.42 vs 2.86 ± 1.01) reduced significantly (P < 0.01). Nimodipine treatment could reduce oxidative injury after spinal cord injury, reduce the whole dead space and inflammation, and repair spinal cord injury.

  12. Cardiovascular dysfunction following spinal cord injury

    PubMed Central

    Partida, Elizabeth; Mironets, Eugene; Hou, Shaoping; Tom, Veronica J.

    2016-01-01

    Both sensorimotor and autonomic dysfunctions often occur after spinal cord injury (SCI). Particularly, a high thoracic or cervical SCI interrupts supraspinal vasomotor pathways and results in disordered hemodynamics due to deregulated sympathetic outflow. As a result of the reduced sympathetic activity, patients with SCI may experience hypotension, cardiac dysrhythmias, and hypothermia post-injury. In the chronic phase, changes within the CNS and blood vessels lead to orthostatic hypotension and life-threatening autonomic dysreflexia (AD). AD is characterized by an episodic, massive sympathetic discharge that causes severe hypertension associated with bradycardia. The syndrome is often triggered by unpleasant visceral or sensory stimuli below the injury level. Currently the only treatments are palliative – once a stimulus elicits AD, pharmacological vasodilators are administered to help reduce the spike in arterial blood pressure. However, a more effective means would be to mitigate AD development by attenuating contributing mechanisms, such as the reorganization of intraspinal circuits below the level of injury. A better understanding of the neuropathophysiology underlying cardiovascular dysfunction after SCI is essential to better develop novel therapeutic approaches to restore hemodynamic performance. PMID:27073353

  13. An update on spinal cord injury research.

    PubMed

    Cao, He-Qi; Dong, Er-Dan

    2013-02-01

    Spinal cord injury (SCI) can have a range of debilitating effects and permanently alter the capabilities and quality of life of survivors. The first specialized centers of care for SCI were established in 1944 and since then an increasing amount of research has been carried out in this area. Despite this, the present treatment and care levels for SCI are not comparable to those in other areas of medicine. In the clinic, the aim of SCI treatment is primarily to limit secondary damage by reducing compression in trauma spots and stabilizing the spinal column. Currently, no effective strategy for functional recovery is offered. In this review, we focus on research progress on the molecular mechanisms underlying SCI, and assess the treatment outcomes of SCI in animal models, i.e., neurotrophins and stem cells are discussed as pre-clinical therapies in animal models. We also assess the resources available and national research projects carried out on SCI in China in recent years, as well as making recommendations for the future allocation of funds in this area.

  14. Symptomatic spinal cord metastasis from cerebral oligodendroglioma.

    PubMed

    Elefante, A; Peca, C; Del Basso De Caro, M L; Russo, C; Formicola, F; Mariniello, G; Brunetti, A; Maiuri, F

    2012-06-01

    Spinal subarachnoid spread is not uncommon in brain oligodendrogliomas; on the other hand, symptomatic involvement of the spinal cord and cauda is very rare, with only 16 reported cases. We report the case of a 41-year-old man who underwent resection of a low-grade frontal oligodendroglioma 4 years previously. He was again observed because of bilateral sciatic pain followed by left leg paresis. A spine MRI showed an intramedullary T12-L1 tumor with root enhancement. At operation, an intramedullary anaplastic oligodendroglioma with left exophytic component was found and partially resected. Two weeks later, a large left frontoparietal anaplastic oligodendroglioma was diagnosed and completely resected. The patient was neurologically stable for 8 months and died 1 year after the spinal surgery because of diffuse brain and spinal leptomeningeal spread. The review of the reported cases shows that spinal symptomatic metastases can occur in both low-grade and anaplastic oligodendrogliomas, even many years after surgery of the primary tumor; however, they exceptionally occur as first clinical manifestation or as anaplastic progression. The spinal seeding represents a negative event leading to a short survival.

  15. The thoracic anterior spinal cord adhesion syndrome

    PubMed Central

    Taylor, T R; Dineen, R; White, B; Jaspan, T

    2012-01-01

    Objectives This study included a series of middle-aged male and female patients who presented with chronic anterior hemicord dysfunction progressing to paraplegia. Imaging of anterior thoracic cord displacement by either a dural adhesion or a dural defect with associated cord herniation is presented. Methods This is a retrospective review of cases referred to a tertiary neuroscience centre over a 19-year period. Imaging series were classified by two experienced neuroradiologists against several criteria and correlated with clinical examination and/or findings at surgery. Results 16 cases were available for full review. Nine were considered to represent adhesions (four confirmed surgically) and four to represent true herniation (three confirmed surgically). In the three remaining cases the diagnosis was radiologically uncertain. Conclusion The authors propose “thoracic anterior spinal cord adhesion syndrome” as a novel term to describe this patient cohort and suggest appropriate clinicoradiological features for diagnosis. Several possible aetiologies are also suggested, with disc rupture and inflammation followed by disc resorption and dural pocket formation being a possible mechanism predisposing to herniation at the extreme end of a clinicopathological spectrum. PMID:22665931

  16. General surgery problems in patients with spinal cord injuries.

    PubMed

    Charney, K J; Juler, G L; Comarr, A E

    1975-09-01

    Twenty-four patients with spinal cord injuries were studied to correlate their responses to intra-abdominal disease with the level and completeness of the cord lesion. Patients with complete cervical lesions and lesions of the upper part of the thoracic region (C-4 to T-6) usually responded by early noniocalized abdominal pain associated with signs of autonomic dysreflexia. As the disease progressed to involve the parietal peritoneum, these patients were more capable of localizing pain to the corresponding dermatome, whereas patients with incomplete lesions were able to localize their pain earlier. Patients with lumbar lesions and lesions of the lower part of the thoracic region (T-7 to L-3) were able to localize their pain earlier than those with lesions located higher in the thoracic region. All patients had delayed diagnoses except those with hemorrhage of the upper part of the gastrointestinal tract. Irrespective of level of cord lesion, increased pulse rate was themost prominent objective acute intra-abdominal pathologic finding. Shoulder pain in the quadriplegic is a most helpful sign. PMID:1080412

  17. Animal assisted therapy and the individual with spinal cord injury.

    PubMed

    Counsell, C M; Abram, J; Gilbert, M

    1997-06-01

    Spinal cord injury (SCI) is a devastating event that results in significant adjustments during the acute and rehabilitation phase. During this period, it is imperative to maintain the patient's self-esteem, reduce stress levels, encourage the expression of feelings, and provide sensory stimulation. Animal Assisted Therapy (AAT) involves the use of animals as a complement to more traditional forms of therapy. The program is based on the knowledge that animals have a positive influence on people who are ill in the healthcare setting. The Animals Heal Hearts Program (TM) has two components, pet visitation and pet therapy. Pet visitation consists of allowing a patient to have his/her own personal dog for a visit, provided there are no medical contraindications. Pet therapy is a structured program using a dog that has completed behavioral and health screening. Dogs are used in the hospital to reduce patients' stress, increase their self-esteem, and help them express feelings. The dogs provide sensory stimulation as patients view and handle the animals and learn about animals and pets. A carefully planned and evaluated program ensures that it is safe and effective. PMID:9295752

  18. Skeletal muscle mitochondrial health and spinal cord injury

    PubMed Central

    O’Brien, Laura C; Gorgey, Ashraf S

    2016-01-01

    Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury (SCI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type II diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic SCI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with SCI to type II diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following SCI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic SCI. PMID:27795944

  19. The Use of Cell Transplantation in Spinal Cord Injuries.

    PubMed

    Schroeder, Gregory D; Kepler, Christopher K; Vaccaro, Alexander R

    2016-04-01

    Acute spinal cord injuries are life-changing events that lead to substantial morbidity and mortality, but the role of cell-based treatment for these injuries is unclear. Cell therapy is a rapidly evolving treatment methodology, with basic science and early phase I/II human trials showing promise. Multiple cell lines can be used in cell therapy, including adult or embryonic stem cells, Schwann cells, olfactory ensheathing cells, and induced pluripotent stem cells. Adult stem cells, Schwann cells, and olfactory ensheathing cells are readily available but lack the ability to differentiate into cells of the central nervous system. Mesenchymal stem cells can decrease cell death by modifying the local environment into which they are introduced. Peripheral nerve cells, such as Schwann cells and olfactory ensheathing cells, can myelinate existing axons and foster axonal growth in the central nervous system, and embryonic stem cells can differentiate into neural progenitor stem cells of the central nervous system. Induced pluripotent stem cells are the basis of an emerging technology that has yet to be implemented in human trials but may offer a means of cell therapy without the ethical dilemmas associated with embryonic cells. PMID:26945167

  20. Early Decompression (< 8 h) after Traumatic Cervical Spinal Cord Injury Improves Functional Outcome as Assessed by Spinal Cord Independence Measure after One Year.

    PubMed

    Grassner, Lukas; Wutte, Christof; Klein, Barbara; Mach, Orpheus; Riesner, Silvie; Panzer, Stephanie; Vogel, Matthias; Bühren, Volker; Strowitzki, Martin; Vastmans, Jan; Maier, Doris

    2016-09-15

    There is an ongoing controversy about the optimal timing for surgical decompression after acute traumatic cervical spinal cord injury (SCI). For this reason, we performed a retrospective study of patients who were operated on after traumatic cervical SCI at the Trauma Center Murnau, Germany, and who met inclusion as well as exclusion criteria (n = 70 patients). Follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury (EMSCI) protocol over a period of 1 year. Early decompression was defined as within the first 8 h after the insult (n = 35 patients). Primary outcome was the difference in the SCIM (Spinal Cord Independence Measure) 1 year after the trauma. After the follow-up period, patients who were decompressed earlier had a significantly higher SCIM difference (45.8 vs. 27.1, p < 0.005). A regression analysis showed that timing of decompression, age, as well as basal AIS (American Spinal Injury Association Impairment Scale) and basal SCIM scores were independent predictors for a better functional outcome (SCIM). Further, patients from the early decompression group had better AIS grades (p < 0.006) and a higher AIS conversion rate (p < 0.029). Additionally, this cohort also had a better total motor performance as well as upper extremity motor function after 1 year (p < 0.025 and p < 0.002). The motor and neurological levels of patients who were operated on within 8 h were significantly more caudal (p < 0.003 and p < 0.014) after 1 year. The present study suggests that early decompression after traumatic cervical SCI might have a positive impact on the functional and neurological outcome of affected individuals.

  1. Cervical disc herniation as a trigger for temporary cervical cord ischemia

    PubMed Central

    Acker, Güliz; Schneider, Ulf C.; Grozdanovic, Zarko; Vajkoczy, Peter

    2016-01-01

    Background Disc herniations are only reported in few case reports as a rare cause of acute spinal ischemia. A surgical treatment has not been described so far in these reports with analysis of diffusion weighted magnetic resonance imaging (DWI/MRI) before and after surgery. The aim of our study is to report a case of cervical spinal cord ischemia caused by cervical disc herniation and discuss the literature concerning diagnostic and treatment options. Methods A 72-year-old female patient developed an acute progressive tetraparesis with emphasis on the upper extremities. MRI showed a disc herniation at the cervical segment 5/6 (C5/6) with consecutive spinal canal stenosis and additional signs of spinal cord ischemia in T2-weighted imaging (T2WI) and DWI reaching from C3 to C5 level. With the MRI being highly suggestive for anterior spinal cord ischemia, we hypothesized that this might be caused by compression of the anterior spinal artery through the significant disc herniation. Therefore, we decided to perform an anterior discectomy and fusion at C5/6 level. Results Following surgery, the patient’s symptoms showed immediate regression with complete recovery after two months in correspondence with the normalization in the control MRI scan of cervical cord. Conclusions Assumedly our patient suffered from a partial anterior spinal artery syndrome, possibly caused by a disc herniation-related compression that was reversible following surgery. This was accompanied by a complete resolution of spinal cord signal abnormalities in T2WI and DWI.

  2. Improved rat spinal cord injury model using spinal cord compression by percutaneous method

    PubMed Central

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

    2013-01-01

    Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 µL (n = 18), 50 µL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 µL was used, but not after 50 µL was applied. In the 50 µL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo. PMID:23820159

  3. Characterization of vascular disruption and blood-spinal cord barrier permeability following traumatic spinal cord injury.

    PubMed

    Figley, Sarah A; Khosravi, Ramak; Legasto, Jean M; Tseng, Yun-Fan; Fehlings, Michael G

    2014-03-15

    Significant vascular changes occur subsequent to spinal cord injury (SCI), which contribute to progressive pathophysiology. In the present study, we used female Wistar rats (300-350 g) and a 35-g clip-compression injury at T6 to T7 to characterize the spatial and temporal vascular changes that ensue post-SCI. Before sacrifice, animals were injected with vascular tracing dyes (2% Evans Blue (EB) or fluorescein isothiocyanate/Lycopersicon esculentum agglutinin [FITC-LEA]) to assess blood-spinal cord barrier (BSCB) integrity or vascular architecture, respectively. Spectrophotometry of EB tissue showed maximal BSCB disruption at 24 h postinjury, with significant disruption observed until 5 days postinjury (p<0.01). FITC-LEA-identified functional vasculature was dramatically reduced by 24 h. Similarly, RECA-1 immunohistochemistry showed a significant decrease in the number of vessels at 24 h postinjury, compared to uninjured animals (p<0.01), with slight increases in endogenous revascularization by 10 days postinjury. White versus gray matter (GM) quantification showed that GM vessels are more susceptible to SCI. Finally, we observed an endogenous angiogenic response between 3 and 7 days postinjury: maximal endothelial cell proliferation was observed at day 5. These data indicate that BSCB disruption and endogenous revascularization occur at specific time points after injury, which may be important for developing effective therapeutic interventions for SCI. PMID:24237182

  4. Management of angina pectoris: the role of spinal cord stimulation.

    PubMed

    Eckert, Siegfried; Horstkotte, Dieter

    2009-01-01

    Progress in prevention as well as drug and interventional therapy has improved the prognosis of patients with cardiovascular disorders. Many patients at risk have advanced coronary artery disease (CAD), have had multiple coronary interventions, and present with significant co-morbidity. Despite adequate risk factor modulation and often several revascularization procedures, some of these patients still have refractory angina pectoris. Apart from advanced CAD and insufficient collateralization, the cause is often endothelial dysfunction. For this situation, one treatment option is neuromodulation. Controlled studies suggest that, in patients with chronic refractory angina pectoris, spinal cord stimulation (SCS) provides a relief from symptoms equivalent to that provided by surgical therapy, but with fewer complications and lower rehospitalization rates. SCS may result in significant long-term pain relief with improved quality of life. In patients with refractory angina undergoing SCS, some studies have shown not only a symptomatic improvement, but also a decrease in myocardial ischemia and an increase in coronary blood flow. Discussion is ongoing as to whether this is a direct effect on parasympathetic vascodilation or merely a secondary phenomenon resulting from increased physical activity following an improvement in clinical symptoms. Results from nuclear medical studies have sparked discussion about improved endothelial function and increased collateralization. SCS is a safe treatment option for patients with refractory angina pectoris, and its long-term effects are evident. It is a procedure without significant complications that is easy to tolerate. SCS does not interact with pacemakers, provided that strict bipolar right-ventricular sensing is used. Use in patients with implanted cardioverter defibrillators is under discussion. Individual testing is mandatory in order to assess optimal safety in each patient. PMID:19178129

  5. Methylprednisolone fails to improve functional and histological outcome following spinal cord injury in rats.

    PubMed

    Pereira, José E; Costa, Luís M; Cabrita, António M; Couto, Pedro A; Filipe, Vítor M; Magalhães, Luís G; Fornaro, Michele; Di Scipio, Federica; Geuna, Stefano; Maurício, Ana C; Varejão, Artur S P

    2009-11-01

    Currently, methylprednisolone sodium succinate (MPSS) is the standard treatment following acute spinal cord injury (SCI) as a consequence of the results obtained from the National Acute Spinal Cord Injury Studies. However, many have questioned the efficacy of MPSS because of its marginal effects. Additionally there has been criticism of both study design and statistical interpretation. The functional consequences of experimental SCI have been assessed in many ways. The purpose of this investigation was to determine the effects of MPSS vs. saline solution (SS) following moderate T10 contusion injury in rat. Functional recovery was evaluated using the 21-point Basso, Beattie and Bresnahan (BBB) locomotor recovery scale, the inclined plane, the beam walk, footprint analysis and the horizontal ladder. To optimize the precision and accuracy of functional results we examined the locomotion on a treadmill using three-dimensional (3D) analysis. Stereology was used to estimate the amount of damaged tissue. The results of the traditional functional methods showed that administration of the NASCIS dosage of MPSS following acute spinal cord contusion did not lead to any significant differences in the functional recovery of MPSS- vs. SS-treated animals. More importantly, the results of the 3D kinematic showed that the MPSS administration did not affect the flexion/extension of the hip, knee and ankle joints during the step cycle. Finally, stereological results revealed no statistically significant differences between the two experimental groups. Altogether, our results support data previously reported by several authors, suggesting that MPSS does not lead to improved functional outcome following experimental acute SCI. PMID:19665461

  6. Frequency Mapping of Rat Spinal Cord at 7T

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  7. Use of intraoperative ultrasonography in canine spinal cord lesions.

    PubMed

    Nanai, Beatrix; Lyman, Ronald; Bichsel, Pierre S

    2007-01-01

    The purpose of this retrospective study was to describe the intraoperative appearance of various spinal cord conditions, and to investigate how intraoperative ultrasonography assisted in modification of surgical and postoperative treatment plans. Intraoperative ultrasonography (B-mode, and power Doppler mode) was used in 25 dogs undergoing spinal surgery. The neurologic conditions included cervical spondylomyelopathy, intervertebral disc (IVD) protrusion, IVD extrusion, spinal tumors, nerve sheath mass, granulomatous myelitis, and discospondylitis. All of these diagnoses were supported by histopathologic and/or cytologic evaluation. It was possible to visualize the spinal cord and the abnormal spinal tissue in all of the patients. Power Doppler imaging allowed assessment of the spinal cord microcirculation, and assisted in judgment of the degree of decompression. Ultrasound imaging directly impacted the surgical and the medical treatment plans in four patients. Owing to the intraoperative imaging, two hemilaminectomies were extended cranially and caudally, and additional disc spaces were fenestrated, one hemilaminectomy site was extended dorsally to retrieve the disc material from the opposite side, and one intramedullary cervical spinal cord lesion was discovered, aspirated, and consequently diagnosed as granulomatous inflammation, which altered the long-term medication protocol in that dog. This study suggests that intraoperative sonographic spinal cord imaging is a useful and viable technique.

  8. Stem cell therapy in spinal cord injuries: current concepts.

    PubMed

    Chhabra, H S

    2012-05-01

    The list of experimental therapies that have been developed in animal models to improve functional outcomes after spinal cord injury is extensive. Though preclinical trials have shown a good potential for cellular therapies in spinal cord injury, there is no documentary proof as of now that any form of cellular therapy definitely improves outcome in management of human spinal cord injury. The adverse effects of many such therapies are well-documented. There is a need to conduct proper clinical trials. Some early-stage spinal cord injury clinical trials have recently been done and some have been started. However, some experimental therapies have been introduced into clinical practice without a clinical trial being completed. Undue hype by the media and claims by professionals have a profound psychological effect on the spinal cord injured and interferes in their rehabilitation. While we know that the future holds a good promise, this should not prevent patients from aggressively pursuing rehabilitation since we are not sure when a clinical breakthrough will be achieved. PMID:23155794

  9. Coping and adaptation in adults living with spinal cord injury.

    PubMed

    Barone, Stacey Hoffman; Waters, Katherine

    2012-10-01

    Biopsychosocial adaptation remains a multifaceted challenge for individuals with spinal cord injury, their families, and healthcare providers alike. The development of frequent medical complications necessitating healthcare interventions is an ongoing, debilitating, and costly problem for those living with spinal cord injuries. Although several demographic variables have been correlated with positive adaptation in individuals with spinal cord injury, the research outcome data present limitations in understanding and facilitating which coping techniques work best to augment biopsychosocial adaptation in this population. Coping facilitates adaptation and adjustment to stress and can help to increase quality of life in people living with spinal cord injury and reduce common complications. The purpose of this study was to determine the extent to which sociodemographic characteristics and hardiness explain coping in 243 adults living with a spinal cord injury. In addition, this study examined which predictors of coping explain biopsychosocial adaptation. A descriptive explanatory design was utilized. Standardized instruments were administered nationally to assess hardiness, coping, and physiological and psychosocial adaptation. Canonical correlation and multiple regression analyses indicated that less educated, less hardy, and recently injured participants were more likely to use escape-avoidance coping and less likely to use social support, problem solving, and positive reappraisal coping behaviors (p < .05). Individuals with paraplegia had a higher level of functional ability, spent less time in rehabilitation, had a greater sense of control, and experienced less frequent complications. The control dimension of hardiness was the only dimension that significantly related to biopsychosocial adaptation within this sample.

  10. Fully automated grey and white matter spinal cord segmentation

    PubMed Central

    Prados, Ferran; Cardoso, M. Jorge; Yiannakas, Marios C.; Hoy, Luke R.; Tebaldi, Elisa; Kearney, Hugh; Liechti, Martina D.; Miller, David H.; Ciccarelli, Olga; Wheeler-Kingshott, Claudia A. M. Gandini; Ourselin, Sebastien

    2016-01-01

    Axonal loss in the spinal cord is one of the main contributing factors to irreversible clinical disability in multiple sclerosis (MS). In vivo axonal loss can be assessed indirectly by estimating a reduction in the cervical cross-sectional area (CSA) of the spinal cord over time, which is indicative of spinal cord atrophy, and such a measure may be obtained by means of image segmentation using magnetic resonance imaging (MRI). In this work, we propose a new fully automated spinal cord segmentation technique that incorporates two different multi-atlas segmentation propagation and fusion techniques: The Optimized PatchMatch Label fusion (OPAL) algorithm for localising and approximately segmenting the spinal cord, and the Similarity and Truth Estimation for Propagated Segmentations (STEPS) algorithm for segmenting white and grey matter simultaneously. In a retrospective analysis of MRI data, the proposed method facilitated CSA measurements with accuracy equivalent to the inter-rater variability, with a Dice score (DSC) of 0.967 at C2/C3 level. The segmentation performance for grey matter at C2/C3 level was close to inter-rater variability, reaching an accuracy (DSC) of 0.826 for healthy subjects and 0.835 people with clinically isolated syndrome MS. PMID:27786306

  11. 76 FR 56504 - Proposed Information Collection (Spinal Cord Injury Patient Care Survey) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-13

    ... AFFAIRS Proposed Information Collection (Spinal Cord Injury Patient Care Survey) Activity: Comment Request... spinal cord patients' satisfaction with VA rehabilitation and health care system. Affected Public... of automated collection techniques or the use of other forms of information technology. Title:...

  12. Elevated Serum Insulin-Like Growth Factor 1 Levels in Patients with Neurological Remission after Traumatic Spinal Cord Injury

    PubMed Central

    Moghaddam, Arash; Sperl, André; Heller, Raban; Kunzmann, Kevin; Graeser, Viola; Akbar, Michael; Gerner, Hans Jürgen; Biglari, Bahram

    2016-01-01

    After traumatic spinal cord injury, an acute phase triggered by trauma is followed by a subacute phase involving inflammatory processes. We previously demonstrated that peripheral serum cytokine expression changes depend on neurological outcome after spinal cord injury. In a subsequent intermediate phase, repair and remodeling takes place under the mediation of growth factors such as Insulin-like Growth Factor 1 (IGF-1). IGF-1 is a promising growth factor which is thought to act as a neuroprotective agent. Since previous findings were taken from animal studies, our aim was to investigate this hypothesis in humans based on peripheral blood serum. Forty-five patients after traumatic spinal cord injury were investigated over a period of three months after trauma. Blood samples were taken according to a fixed schema and IGF-1 levels were determined. Clinical data including AIS scores at admission to the hospital and at discharge were collected and compared with IGF-1 levels. In our study, we could observe distinct patterns in the expression of IGF-1 in peripheral blood serum after traumatic spinal cord injury regardless of the degree of plegia. All patients showed a marked increase of levels seven days after injury. IGF-1 serum levels were significantly different from initial measurements at four and nine hours and seven and 14 days after injury, as well as one, two and three months after injury. We did not detect a significant correlation between fracture and the IGF-1 serum level nor between the quantity of operations performed after trauma and the IGF-1 serum level. Patients with clinically documented neurological remission showed consistently higher IGF-1 levels than patients without neurological remission. This data could be the base for the establishment of animal models for further and much needed research in the field of spinal cord injury. PMID:27447486

  13. Elevated Serum Insulin-Like Growth Factor 1 Levels in Patients with Neurological Remission after Traumatic Spinal Cord Injury.

    PubMed

    Moghaddam, Arash; Sperl, André; Heller, Raban; Kunzmann, Kevin; Graeser, Viola; Akbar, Michael; Gerner, Hans Jürgen; Biglari, Bahram

    2016-01-01

    After traumatic spinal cord injury, an acute phase triggered by trauma is followed by a subacute phase involving inflammatory processes. We previously demonstrated that peripheral serum cytokine expression changes depend on neurological outcome after spinal cord injury. In a subsequent intermediate phase, repair and remodeling takes place under the mediation of growth factors such as Insulin-like Growth Factor 1 (IGF-1). IGF-1 is a promising growth factor which is thought to act as a neuroprotective agent. Since previous findings were taken from animal studies, our aim was to investigate this hypothesis in humans based on peripheral blood serum. Forty-five patients after traumatic spinal cord injury were investigated over a period of three months after trauma. Blood samples were taken according to a fixed schema and IGF-1 levels were determined. Clinical data including AIS scores at admission to the hospital and at discharge were collected and compared with IGF-1 levels. In our study, we could observe distinct patterns in the expression of IGF-1 in peripheral blood serum after traumatic spinal cord injury regardless of the degree of plegia. All patients showed a marked increase of levels seven days after injury. IGF-1 serum levels were significantly different from initial measurements at four and nine hours and seven and 14 days after injury, as well as one, two and three months after injury. We did not detect a significant correlation between fracture and the IGF-1 serum level nor between the quantity of operations performed after trauma and the IGF-1 serum level. Patients with clinically documented neurological remission showed consistently higher IGF-1 levels than patients without neurological remission. This data could be the base for the establishment of animal models for further and much needed research in the field of spinal cord injury. PMID:27447486

  14. Racial disparities in outcomes after spinal cord injury.

    PubMed

    Lad, Shivanand P; Umeano, Odera A; Karikari, Isaac O; Somasundaram, Aravind; Bagley, Carlos A; Gottfried, Oren N; Isaacs, Robert E; Ugiliweneza, Beatrice; Patil, Chirag G; Huang, Kevin; Boakye, Maxwell

    2013-03-15

    Spinal Cord Injury (SCI) is an acute trauma to the neural elements resulting in temporary or permanent sensory and motor deficit. Studies have indicated that although 66% of SCI occur in Caucasians, there are a growing number of other racial groups affected by SCI. Furthermore, there has been a lack of research concerning racial disparities in outcomes following SCI. As such, a retrospective analysis using the National Trauma Data Bank (NTDB) from 2000 to 2009 was performed. African Americans, Caucasians, Hispanics, Asians, and Native Americans were included in the study. We calculated adjusted odds ratios (OR) to examine the relationship between racial backgrounds and mortality, length of intensive care unit (ICU) stay, length of hospital stay, in-hospital complications, and patient disposition. Our results showed that significant differences were found in length of hospital stay, with African American and Hispanic populations having longer hospital stays than Caucasian and Asians. For all type complications, African Americans (OR 1.228, confidence interval [CI] 1.11-1.356) and Native Americans (OR 1.618, CI 1.083-2.419) were more likely than Caucasian and Hispanic patients to have in-hospital complications. For disposition status, African Americans (OR 0.844, CI 0.730-0.976) and Asians (OR 0.475, CI 0.297-0.760) were much less likely than Caucasians or Hispanic populations to be discharged to an acute rehabilitation program. The results from this large-scale study (n=18,671) demonstrate a number of racial disparities following SCI at the national level, including rate of complications, length of stay, and disposition to acute rehabilitation centers. This should raise awareness to cultural differences but also serve as an opportunity to reduce gaps in care across ethnicities for this universally life-altering condition.

  15. Cervical spinal cord injury exacerbates ventilator-induced diaphragm dysfunction.

    PubMed

    Smuder, Ashley J; Gonzalez-Rothi, Elisa J; Kwon, Oh Sung; Morton, Aaron B; Sollanek, Kurt J; Powers, Scott K; Fuller, David D

    2016-01-15

    Cervical spinal cord injury (SCI) can dramatically impair diaphragm muscle function and often necessitates mechanical ventilation (MV) to maintain adequate pulmonary gas exchange. MV is a life-saving intervention. However, prolonged MV results in atrophy and impaired function of the diaphragm. Since cervical SCI can also trigger diaphragm atrophy, it may create preconditions that exacerbate ventilator-induced diaphragm dysfunction (VIDD). Currently, no drug therapy or clinical standard of care exists to prevent or minimize diaphragm dysfunction following SCI. Therefore, we first tested the hypothesis that initiating MV acutely after cervical SCI will exacerbate VIDD and enhance proteolytic activation in the diaphragm to a greater extent than either condition alone. Rats underwent controlled MV for 12 h following acute (∼24 h) cervical spinal hemisection injury at C2 (SCI). Diaphragm tissue was then harvested for comprehensive functional and molecular analyses. Second, we determined if antioxidant therapy could mitigate MV-induced diaphragm dysfunction after cervical SCI. In these experiments, SCI rats received antioxidant (Trolox, a vitamin E analog) or saline treatment prior to initiating MV. Our results demonstrate that compared with either condition alone, the combination of SCI and MV resulted in increased diaphragm atrophy, contractile dysfunction, and expression of atrophy-related genes, including MuRF1. Importantly, administration of the antioxidant Trolox attenuated proteolytic activation, fiber atrophy, and contractile dysfunction in the diaphragms of SCI + MV animals. These findings provide evidence that cervical SCI greatly exacerbates VIDD, but antioxidant therapy with Trolox can preserve diaphragm contractile function following acute SCI. PMID:26472866

  16. Hypocretinergic control of spinal cord motoneurons.

    PubMed

    Yamuy, Jack; Fung, Simon J; Xi, Mingchu; Chase, Michael H

    2004-06-01

    Hypocretinergic (orexinergic) neurons in the lateral hypothalamus project to motor columns in the lumbar spinal cord. Consequently, we sought to determine whether the hypocretinergic system modulates the electrical activity of motoneurons. Using in vivo intracellular recording techniques, we examined the response of spinal motoneurons in the cat to electrical stimulation of the lateral hypothalamus. In addition, we examined the membrane potential response to orthodromic stimulation and intracellular current injection before and after both hypothalamic stimulation and the juxtacellular application of hypocretin-1. It was found that (1) hypothalamic stimulation produced a complex sequence of depolarizing- hyperpolarizing potentials in spinal motoneurons; (2) the depolarizing potentials decreased in amplitude after the application of SB-334867, a hypocretin type 1 receptor antagonist; (3) the EPSP induced by dorsal root stimulation was not affected by the application of SB-334867; (4) subthreshold stimulation of dorsal roots and intracellular depolarizing current steps produced spike potentials when applied in concert to stimulation of the hypothalamus or after the local application of hypocretin-1; (5) the juxtacellular application of hypocretin-1 induced motoneuron depolarization and, frequently, high-frequency discharge; (6) hypocretin-1 produced a significant decrease in rheobase (36%), membrane time constant (16.4%), and the equalizing time constant (23.3%); (7) in a small number of motoneurons, hypocretin-1 produced an increase in the synaptic noise; and (8) the input resistance was not affected after hypocretin-1. The juxtacellular application of vehicle (saline) and denatured hypocretin-1 did not produce changes in the preceding electrophysiological properties. We conclude that hypothalamic hypocretinergic neurons are capable of modulating the activity of lumbar motoneurons through presynaptic and postsynaptic mechanisms. The lack of hypocretin

  17. Spinal cord evolution in early Homo.

    PubMed

    Meyer, Marc R; Haeusler, Martin

    2015-11-01

    The discovery at Nariokotome of the Homo erectus skeleton KNM-WT 15000, with a narrow spinal canal, seemed to show that this relatively large-brained hominin retained the primitive spinal cord size of African apes and that brain size expansion preceded postcranial neurological evolution. Here we compare the size and shape of the KNM-WT 15000 spinal canal with modern and fossil taxa including H. erectus from Dmanisi, Homo antecessor, the European middle Pleistocene hominins from Sima de los Huesos, and Pan troglodytes. In terms of shape and absolute and relative size of the spinal canal, we find all of the Dmanisi and most of the vertebrae of KNM-WT 15000 are within the human range of variation except for the C7, T2, and T3 of KNM-WT 15000, which are constricted, suggesting spinal stenosis. While additional fossils might definitively indicate whether H. erectus had evolved a human-like enlarged spinal canal, the evidence from the Dmanisi spinal canal and the unaffected levels of KNM-WT 15000 show that unlike Australopithecus, H. erectus had a spinal canal size and shape equivalent to that of modern humans. Subadult status is unlikely to affect our results, as spinal canal growth is complete in both individuals. We contest the notion that vertebrae yield information about respiratory control or language evolution, but suggest that, like H. antecessor and European middle Pleistocene hominins from Sima de los Huesos, early Homo possessed a postcranial neurological endowment roughly commensurate to modern humans, with implications for neurological, structural, and vascular improvements over Pan and Australopithecus. PMID:26553817

  18. Spinal Cord Tolerance for Stereotactic Body Radiotherapy

    SciTech Connect

    Sahgal, Arjun; Ma Lijun; Gibbs, Iris; Gerszten, Peter C.; Ryu, Sam; Soltys, Scott; Weinberg, Vivian; Wong Shun; Chang, Eric; Fowler, Jack; Larson, David A.

    2010-06-01

    Purpose: Dosimetric data are reported for five cases of radiation-induced myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis per the biologically effective dose (BED) model was performed. Methods and Materials: Five patients with radiation myelopathy were compared to a subset of 19 patients with no radiation myelopathy post-SBRT. In all patients, the thecal sac was contoured to represent the spinal cord, and doses to the maximum point, 0.1-, 1-, 2-, and 5-cc volumes, were analyzed. The mean normalized 2-Gy-equivalent BEDs (nBEDs), calculated using an alpha/beta value of 2 for late toxicity with units Gy 2/2, were compared using the t test and analysis of variance test. Results: Radiation myelopathy was observed at the maximum point with doses of 25.6 Gy in two fractions, 30.9 Gy in three fractions, and 14.8, 13.1, and 10.6 Gy in one fraction. Overall, there was a significant interaction between patient subsets and volume based on the nBED (p = 0.0003). Given individual volumes, a significant difference was observed for the mean maximum point nBED (p = 0.01). Conclusions: The maximum point dose should be respected for spine SBRT. For single-fraction SBRT 10 Gy to a maximum point is safe, and up to five fractions an nBED of 30 to 35 Gy 2/2 to the thecal sac also poses a low risk of radiation myelopathy.

  19. Somatotopic arrangement of thermal sensory regions in the healthy human spinal cord determined by means of spinal cord functional MRI.

    PubMed

    Stroman, Patrick W; Bosma, Rachael L; Tsyben, Anastasia

    2012-09-01

    Previous functional MRI studies of normal sensory function in the human spinal cord, including right-to-left symmetry of activity, have been influenced by order effects between repeated studies. In this study, we apply thermal sensory stimulation to four dermatomes within each functional MRI time-series acquisition. Each of the four dermatomes receives a unique stimulation paradigm, such that the four paradigms form a linearly independent set, enabling detection of each individual stimulus response. Functional MRI data are shown spanning the cervical spinal cord and brainstem in 10 healthy volunteers. Results of general linear model analysis demonstrate consistent patterns of activity within the spinal cord segments corresponding to each dermatome, and a high degree of symmetry between right-side and left-side stimulation. Connectivity analyses also demonstrate consistent areas of activity and connectivity between spinal cord and brainstem regions corresponding to known anatomy. However, right-side and left-side responses are not at precisely the same rostral-caudal positions, but are offset by several millimeters, with left-side responses consistently more caudal than right-side responses. The results confirm that distinct responses to multiple interleaved sensory stimuli can be distinguished, enabling studies of sensory responses within the spinal cord without the confounding effects of comparing sequential studies.

  20. Respiration following Spinal Cord Injury: Evidence for Human Neuroplasticity

    PubMed Central

    Hoh, Daniel J.; Mercier, Lynne M.; Hussey, Shaunn P.; Lane, Michael A.

    2013-01-01

    Respiratory dysfunction is one of the most devastating consequences of cervical spinal cord injury (SCI) with impaired breathing being a leading cause of morbidity and mortality in this population. However, there is mounting experimental and clinical evidence for moderate spontaneous respiratory recovery, or “plasticity”, after some spinal cord injuries. Pre-clinical models of respiratory dysfunction following SCI have demonstrated plasticity at neural and behavioral levels that result in progressive recovery of function. Temporal changes in respiration after human SCI have revealed some functional improvements suggesting plasticity paralleling that seen in experimental models – a concept that has been previously under-appreciated. While the extent of spontaneous recovery remains limited, it is possible that enhancing or facilitating neuroplastic mechanisms may have significant therapeutic potential. The next generation of treatment strategies for SCI and related respiratory dysfunction should aim to optimize these recovery processes of the injured spinal cord for lasting functional restoration. PMID:23891679

  1. Stem cell-based therapies for spinal cord injury.

    PubMed

    Nandoe Tewarie, Rishi S; Hurtado, Andres; Bartels, Ronald H; Grotenhuis, Andre; Oudega, Martin

    2009-01-01

    Spinal cord injury (SCI) results in loss of nervous tissue and consequently loss of motor and sensory function. There is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. Transplantation of stem cells or progenitors may support spinal cord repair. Stem cells are characterized by self-renewal and their ability to become any cell in an organism. Promising results have been obtained in experimental models of SCI. Stem cells can be directed to differentiate into neurons or glia in vitro, which can be used for replacement of neural cells lost after SCI. Neuroprotective and axon regeneration-promoting effects have also been credited to transplanted stem cells. There are still issues related to stem cell transplantation that need to be resolved, including ethical concerns. This paper reviews the current status of stem cell application for spinal cord repair.

  2. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  3. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  4. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  5. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  6. 76 FR 71623 - Agency Information Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-18

    ... AFFAIRS Agency Information Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review AGENCY.... 2900-New (VA Form 10-0515).'' SUPPLEMENTARY INFORMATION: Title: Spinal Cord Injury Patient Care Survey... Collection. Abstract: Information collected on VA Form 10-0515 will be used to determine spinal cord...

  7. 21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted spinal cord stimulator for bladder....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal... paraplegic patient who has a complete transection of the spinal cord and who is unable to empty his or...

  8. Potential associations between chronic whiplash and incomplete spinal cord injury

    PubMed Central

    Smith, Andrew C.; Parrish, Todd B.; Hoggarth, Mark A.; McPherson, Jacob G.; Tysseling, Vicki M.; Wasielewski, Marie; Kim, Hyosub E.; Hornby, T. George; Elliott, James M.

    2016-01-01

    Study Design This research utilized a cross-sectional design with control group inclusion. Objectives Preliminary evidence suggests that a portion of the patient population with chronic whiplash may have sustained spinal cord damage. Our hypothesis is that in some cases of chronic whiplash-associated disorders (WAD), observed muscle weakness in the legs will be associated with local signs of a partial spinal cord injury of the cervical spine. Setting University based laboratory in Chicago, IL, USA. Methods Five participants with chronic WAD were compared with five gender/age/height/weight/body mass index (BMI) control participants. For a secondary investigation, the chronic WAD group was compared with five unmatched participants with motor incomplete spinal cord injury (iSCI). Spinal cord motor tract integrity was assessed using magnetization transfer imaging. Muscle fat infiltration (MFI) was quantified using fat/water separation magnetic resonance imaging. Central volitional muscle activation of the plantarflexors was assessed using a burst superimposition technique. Results We found reduced spinal cord motor tract integrity, increased MFI of the neck and lower extremity muscles and significantly impaired voluntary plantarflexor muscle activation in five participants with chronic WAD. The lower extremity structural changes and volitional weakness in chronic WAD were comparable to participants with iSCI. Conclusion The results support the position that a subset of the chronic whiplash population may have sustained partial damage to the spinal cord. Sponsorship NIH R01HD079076-01A1, NIH T32 HD057845 and the Foundation for Physical Therapy Promotion of Doctoral Studies program.

  9. Surgical Outcomes of High-Grade Spinal Cord Gliomas

    PubMed Central

    Hida, Kazutoshi; Yano, Syunsuke; Aoyama, Takeshi; Koyanagi, Izumi; Houkin, Kiyohiro

    2015-01-01

    Study Design A retrospective study. Purpose The purpose of this study was to obtain useful information for establishing the guidelines for treating high-grade spinal cord gliomas. Overview of Literature The optimal management of high-grade spinal cord gliomas remains controversial. We report the outcomes of the surgical management of 14 high-grade spinal glioma. Methods We analyzed the outcomes of 14 patients with high-grade spinal cord gliomas who were surgically treated between 1989 and 2012. Survival was charted with the Kaplan-Meier plots and comparisons were made with the log-rank test. Results None of the patients with high-grade spinal cord gliomas underwent total resection. Subtotal resection was performed in two patients, partial resection was performed in nine patients, and open biopsy was performed in three patients. All patients underwent postoperative radiotherapy and six patients further underwent radiation cordotomy. The median survival time for patients with high-grade spinal cord gliomas was 15 months, with a 5-year survival rate of 22.2%. The median survival time for patients with World Health Organization grade III tumors was 25.5 months, whereas the median survival time for patients with glioblastoma multiforme was 12.5 months. Both univariate and multivariate Cox proportional hazards models demonstrated a significant effect only in the group that did not include cervical cord lesion as a factor associated with survival (p=0.04 and 0.03). Conclusions The surgical outcome of patients diagnosed with high-grade spinal cord gliomas remains poor. Notably, only the model which excluded cervical cord lesions as a factor significantly predicted survival. PMID:26713128

  10. Automated identification of spinal cord and vertebras on sagittal MRI

    NASA Astrophysics Data System (ADS)

    Zhou, Chuan; Chan, Heang-Ping; Dong, Qian; He, Bo; Wei, Jun; Hadjiiski, Lubomir M.; Couriel, Daniel

    2014-03-01

    We are developing an automated method for the identification of the spinal cord and the vertebras on spinal MR images, which is an essential step for computerized analysis of bone marrow diseases. The spinal cord segment was first enhanced by a newly developed hierarchical multiscale tubular (HMT) filter that utilizes the complementary hyper- and hypo- intensities in the T1-weighted (T1W) and STIR MRI sequences. An Expectation-Maximization (EM) analysis method was then applied to the enhanced tubular structures to extract candidates of the spinal cord. The spinal cord was finally identified by a maximum-likelihood registration method by analysis of the features extracted from the candidate objects in the two MRI sequences. Using the identified spinal cord as a reference, the vertebras were localized based on the intervertebral disc locations extracted by another HMT filter applied to the T1W images. In this study, 5 and 30 MRI scans from 35 patients who were diagnosed with multiple myeloma disease were collected retrospectively with IRB approval as training and test set, respectively. The vertebras manually outlined by a radiologist were used as reference standard. A total of 422 vertebras were marked in the 30 test cases. For the 30 test cases, 100% (30/30) of the spinal cords were correctly segmented with 4 false positives (FPs) mistakenly identified on the back muscles in 4 scans. A sensitivity of 95.0% (401/422) was achieved for the identification of vertebras, and 5 FPs were marked in 4 scans with an average FP rate of 0.17 FPs/scan.

  11. Potential associations between chronic whiplash and incomplete spinal cord injury

    PubMed Central

    Smith, Andrew C.; Parrish, Todd B.; Hoggarth, Mark A.; McPherson, Jacob G.; Tysseling, Vicki M.; Wasielewski, Marie; Kim, Hyosub E.; Hornby, T. George; Elliott, James M.

    2016-01-01

    Study Design This research utilized a cross-sectional design with control group inclusion. Objectives Preliminary evidence suggests that a portion of the patient population with chronic whiplash may have sustained spinal cord damage. Our hypothesis is that in some cases of chronic whiplash-associated disorders (WAD), observed muscle weakness in the legs will be associated with local signs of a partial spinal cord injury of the cervical spine. Setting University based laboratory in Chicago, IL, USA. Methods Five participants with chronic WAD were compared with five gender/age/height/weight/body mass index (BMI) control participants. For a secondary investigation, the chronic WAD group was compared with five unmatched participants with motor incomplete spinal cord injury (iSCI). Spinal cord motor tract integrity was assessed using magnetization transfer imaging. Muscle fat infiltration (MFI) was quantified using fat/water separation magnetic resonance imaging. Central volitional muscle activation of the plantarflexors was assessed using a burst superimposition technique. Results We found reduced spinal cord motor tract integrity, increased MFI of the neck and lower extremity muscles and significantly impaired voluntary plantarflexor muscle activation in five participants with chronic WAD. The lower extremity structural changes and volitional weakness in chronic WAD were comparable to participants with iSCI. Conclusion The results support the position that a subset of the chronic whiplash population may have sustained partial damage to the spinal cord. Sponsorship NIH R01HD079076-01A1, NIH T32 HD057845 and the Foundation for Physical Therapy Promotion of Doctoral Studies program. PMID:27630770

  12. Spinal ischemia following abdominal aortic surgery.

    PubMed

    Ferguson, L R; Bergan, J J; Conn, J; Yao, J S

    1975-03-01

    Serious spinal cord ischemia may follow infrarenal abdominal aortic surgery. Five cases are summarized and added to the 23 previously published cases in order to identify this syndrome, emphasize its importance, and draw attention to the possibility of spontaneous recovery which may occur. The multifactorial complex which comprises each patient's clinical picture clouds a precise and specific cause for paraplegia in these cases. However, neither hypotension, steal phenomena nor emboli are necessary for completion of the syndrome. The relevant spinal cord arterial anatomy indicates that the common anomalies which occur favor development of spinal cord ischemia in the arteriosclerotic population which requires aortic surgery. No means of prevention is possible at this time.

  13. Treadmill training after spinal cord injury: it's not just about the walking.

    PubMed

    Hicks, Audrey L; Ginis, Kathleen A Martin

    2008-01-01

    Body weight-supported treadmill training (BWSTT) is being used throughout the world as a method for improving functional ambulation after spinal cord injury (SCI). This therapy, however, is very labor-intensive, and recent evidence suggests that it may not be superior to other more conventional forms of rehabilitation for improving locomotor ability. Recognizing that the value of BWSTT may extend well beyond its potential to improve functional ambulation is important, and the physiological and psychological benefits associated with this whole-body upright exercise may justify its use in both the acute and chronic SCI populations.

  14. Cell therapy for spinal cord injury informed by electromagnetic waves.

    PubMed

    Finnegan, Jack; Ye, Hui

    2016-10-01

    Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

  15. Rodent Models and Behavioral Outcomes of Cervical Spinal Cord Injury

    PubMed Central

    Geissler, Sydney A.; Schmidt, Christine E.; Schallert, Timothy

    2014-01-01

    Rodent spinal cord injury (SCI) models have been developed to examine functional and physiological deficits after spinal cord injury with the hope that these models will elucidate information about human SCI. Models are needed to examine possible treatments and to understand histopathology after SCI; however, they should be considered carefully and chosen based on the goals of the study being performed. Contusion, compression, transection, and other models exist and have the potential to reveal important information about SCI that may be related to human SCI and the outcomes of treatment and timing of intervention. PMID:25309824

  16. Spinal cord response to laser treatment of injured peripheral nerve

    SciTech Connect

    Rochkind, S.; Vogler, I.; Barr-Nea, L. )

    1990-01-01

    The authors describe the changes occurring in the spinal cord of rats subjected to crush injury of the sciatic nerve followed by low-power laser irradiation of the injured nerve. Such laser treatment of the crushed peripheral nerve has been found to mitigate the degenerative changes in the corresponding neurons of the spinal cord and induce proliferation of neuroglia both in astrocytes and oligodendrocytes. This suggests a higher metabolism in neurons and a better ability for myelin production under the influence of laser treatment.

  17. Exercise and sport for persons with spinal cord injury.

    PubMed

    Martin Ginis, Kathleen A; Jörgensen, Sophie; Stapleton, Jessica

    2012-11-01

    This review article provides an overview of the evidence that links exercise and sports participation to physical and psychological well-being among people with spinal cord injury. Two aspects of physical well-being are examined, including the prevention of chronic disease and the promotion of physical fitness. Multiple aspects of psychosocial well-being are discussed, including mental health, social participation, and life satisfaction. The review concludes with future research recommendations and a discussion of challenges and opportunities for using exercise and sports to promote health and well-being among people living with spinal cord injury.

  18. [Spinal cord stimulation for the management of chronic pain].

    PubMed

    Perruchoud, Christophe; Mariotti, Nicolas

    2016-06-22

    Neuromodulation techniques modify the activity of the central or peripheral nervous system. Spinal cord stimulation is a reversible and minimally invasive treatment whose efficacy and cost effectiveness are recognized for the treatment of chronic neuropathic pain or ischemic pain. Spinal cord stimulation is not the option of last resort and should be considered among other options before prescribing long-term opioids or considering reoperation. The selection and regular follow-up of patients are crucial to the success of the therapy. PMID:27506068

  19. Cell therapy for spinal cord injury informed by electromagnetic waves.

    PubMed

    Finnegan, Jack; Ye, Hui

    2016-10-01

    Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments. PMID:27599240

  20. Expression of Lymphatic Markers in the Adult Rat Spinal Cord

    PubMed Central

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A.; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  1. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    PubMed

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expressio