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Sample records for acute spinal-cord ischemia

  1. Spinal cord ischemia secondary to hypovolemic shock.

    PubMed

    Oh, Jacob Yl; Kapoor, Siddhant; Koh, Roy Km; Yang, Eugene Wr; Hee, Hwan-Tak

    2014-12-01

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

  2. Current and emerging treatment options for spinal cord ischemia.

    PubMed

    Nardone, Raffaele; Pikija, Slaven; Mutzenbach, J Sebastian; Seidl, Martin; Leis, Stefan; Trinka, Eugen; Sellner, Johann

    2016-10-01

    Spinal cord infarction (SCI) is a rare but disabling disorder caused by a wide spectrum of conditions. Given the lack of randomized-controlled trials, contemporary treatment concepts are adapted from guidelines for cerebral ischemia, atherosclerotic vascular disease, and acute traumatic spinal cord injury. In addition, patients with SCI are at risk for several potentially life-threatening but preventable systemic and neurologic complications. Notably, there is emerging evidence from preclinical studies for the use of neuroprotection in acute ischemic injury of the spinal cord. In this review, we discuss the current state of the art for the therapy and prevention of SCI and highlight potential emerging treatment concepts awaiting translational adoption.

  3. 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

  4. Spinal cord ischemia resulting in paraplegia following extrapleural pneumonectomy.

    PubMed

    Ural, Kelly; Jakob, Kyle; Lato, Scott; Gilly, George; Landreneau, Rodney

    2014-08-01

    A patient undergoing radical extrapleural pneumonectomy for epithelioid malignant mesothelioma developed acute paraplegia postoperatively related to long-segment spinal cord ischemia. The usual area of concern for this complication is the T9 to T12 area where the artery of Adamkiewicz is most likely to originate. In this patient, there was ligation of only upper thoracic, ipsilateral segmental arteries from the T3 to T6 level, yet he still developed paraplegia. Our hypothesis is variant mid-thoracic vascular anatomy. Previously unreported, to our knowledge, this should be understood as a rare complication of this surgery.

  5. 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

  6. 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.

  7. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms.

    PubMed

    Tator, C H; Fehlings, M G

    1991-07-01

    In patients with spinal cord injury, the primary or mechanical trauma seldom causes total transection, even though the functional loss may be complete. In addition, biochemical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved for which numerous pathophysiological mechanisms have been postulated. This paper reviews the concept of secondary injury with special emphasis on vascular mechanisms. Evidence is presented to support the theory of secondary injury and the hypothesis that a key mechanism is posttraumatic ischemia with resultant infarction of the spinal cord. Evidence for the role of vascular mechanisms has been obtained from a variety of models of acute spinal cord injury in several species. Many different angiographic methods have been used for assessing microcirculation of the cord and for measuring spinal cord blood flow after trauma. With these techniques, the major systemic and local vascular effects of acute spinal cord injury have been identified and implicated in the etiology of secondary injury. The systemic effects of acute spinal cord injury include hypotension and reduced cardiac output. The local effects include loss of autoregulation in the injured segment of the spinal cord and a marked reduction of the microcirculation in both gray and white matter, especially in hemorrhagic regions and in adjacent zones. The microcirculatory loss extends for a considerable distance proximal and distal to the site of injury. Many studies have shown a dose-dependent reduction of spinal cord blood flow varying with the severity of injury, and a reduction of spinal cord blood flow which worsens with time after injury. The functional deficits due to acute spinal cord injury have been measured electrophysiologically with techniques such as motor and somatosensory evoked potentials and have been found proportional to the degree of posttraumatic ischemia. The histological effects

  8. Update on traumatic acute spinal cord injury. Part 1.

    PubMed

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

    2017-02-01

    Traumatic spinal cord injury requires a multidisciplinary approach both for specialized treatment of the acute phase and for dealing with the secondary complications. A suspicion or diagnosis of spinal cord injury is the first step for a correct management. A review is made of the prehospital management and characteristics of the acute phase of spinal cord injury. Respiratory monitoring for early selective intubation, proper identification and treatment of neurogenic shock are essential for the prevention of secondary spinal cord injury. The use of corticosteroids is currently not a standard practice in neuroprotective treatment, and hemodynamic monitoring and early surgical decompression constitute the cornerstones of adequate management. Traumatic spinal cord injury usually occurs as part of multiple trauma, and this can make diagnosis difficult. Neurological examination and correct selection of radiological exams prevent delayed diagnosis of spinal cord injuries, and help to establish the prognosis.

  9. Management of acute traumatic spinal cord injuries.

    PubMed

    Shank, C D; Walters, B C; Hadley, M N

    2017-01-01

    Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome.

  10. Update on traumatic acute spinal cord injury. Part 2.

    PubMed

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

    2017-02-01

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

  11. Spinal cord ischemia and left atrial myxoma.

    PubMed

    Hirose, G; Kosoegawa, H; Takado, M; Shimazaki, K; Murakami, E

    1979-07-01

    A 62-year-old man had an acute, transient, flaccid paraplegia. Examination showed a primary cardiac tumor with emboli to major branches of the aorta. A myxoma was removed from the left atrium, and normal function returned. Left atrial myxoma should be suspected as a cause for embolism to the CNS.

  12. Giant multinucleated macrophages occur in acute spinal cord injury.

    PubMed

    Leskovar, A; Turek, J; Borgens, R B

    2001-05-01

    Using a cell-isolation and -culture procedure specific for macrophages, we report the existence of giant (more than 50 microm diameter), multinucleated macrophages within an acute, 5-day-old adult rat spinal cord injury. The size and multinuclearity of these isolated giant cells was confirmed using transmission electron microscopy. Giant macrophages are markers for long-term infection, disease, and chronic injury in other soft tissues and are unexpected in the acute inflammatory stage of central nervous system injury. To our knowledge, this descriptive report is the first confirming the existence of giant macrophages in any injured nervous tissue, with additional data suggesting some of these cells to be multinucleated.

  13. Lipoxin A4 ameliorates ischemia/reperfusion induced spinal cord injury in rabbit model

    PubMed Central

    Liu, Zhi-Qiang; Zhang, Hong-Bin; Wang, Jian; Xia, Li-Jian; Zhang, Wei

    2015-01-01

    Ischemia/reperfusion (I/R) induced spinal cord injury is an important pathologic mechanism leading to the paraplegia observed after surgery to repairaortic aneurysms. This study aims to investigate the neuroprotective effects of Lipoxin A4 and its potential mechanism in a rabbit model with I/R spinal cord injury. Forty-five rabbits were randomly divided into three groups: sham group, I/R group and Lipoxin A4 group. Rabbits were subject to 30 min aortic occlusion to induce transient spinal cord ischemia. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, as well as local malondialdehyde (MDA) and total superoxide dismutase (SOD) activity analysis. All animals in the I/R group became paraplegic. While after 48-hour treatment, compared with I/R group, Lipoxin A4 significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). These results suggest that Lipoxin A4 can ameliorate I/R induced spinal cord injury in Rabbit through its antiapoptosis and antioxidant activity. PMID:26550197

  14. Acute Pharmacological DVT Prophylaxis after Spinal Cord Injury

    PubMed Central

    Thibault-Halman, Ginette; Casha, Steven

    2011-01-01

    Abstract A systematic review of the literature was performed to address pertinent clinical questions regarding deep vein thrombosis (DVT) prophylaxis in the setting of acute spinal cord injury (SCI). Deep vein thromboses are a common occurrence following SCI. Administration of low-molecular-weight heparin (LMWH) within 72 h of injury is recommended to minimize the occurrence of DVT. Furthermore, when surgical intervention is required, LMWH should be held the morning of surgery, and resumed within 24 h post-operatively. PMID:20795870

  15. Acute spinal cord injury: tetraplegia and paraplegia in small animals.

    PubMed

    Granger, Nicolas; Carwardine, Darren

    2014-11-01

    Spinal cord injury (SCI) is a common problem in animals for which definitive treatment is lacking, and information gained from its study has benefit for both companion animals and humans in developing new therapeutic approaches. This review provides an overview of the main concepts that are useful for clinicians in assessing companion animals with severe acute SCI. Current available advanced ancillary tests and those in development are reviewed. In addition, the current standard of care for companion animals following SCI and recent advances in the development of new therapies are presented, and new predictors of recovery discussed.

  16. Spinal Cord Ischemia Secondary to Epidural Metastasis from Small Cell Lung Carcinoma

    PubMed Central

    Yasui, Hirotoshi; Ozawa, Naoya; Mikami, Satoshi; Shimizu, Kenji; Hatta, Takahiro; Makino, Nami; Fukushima, Mayu; Baba, Satoshi; Makino, Yasushi

    2017-01-01

    Patient: Male, 56 Final Diagnosis: Small cell lung carcinoma Symptoms: Back pain • paralysis Medication: — Clinical Procedure: MRI Specialty: Pulmonology Objective: Unusual clinical course Background: Spinal cord ischemia is an uncommon event that is mainly caused by dissociation of the ascending aorta as a complication after aortic surgery. Spinal arteries can develop collateral circulation; therefore, the frequency of spinal infarction is about 1% of that in the brain. Few cases of spinal cord ischemia developing in the course of lung cancer have been reported. Case Report: We presented the case of a 56-year-old man with small cell lung carcinoma, cT4N2M1a (stage IV). He was treated with irradiation and 2 courses of platinum and etoposide combination chemotherapy. He complained of back pain followed by quadriplegia and sensory disturbance after cessation of chemotherapy. With a diagnosis of spinal cord metastasis, steroids were administered. However, diaphragmatic paralysis appeared a few hours later. He was started on palliative care and died after 6 days. Autopsy showed epidural metastasis and spinal ischemia at the C5 level. Conclusions: Epidural metastasis can compress the spinal artery and cause circulatory disorders. Spinal cord ischemia should be considered in patients with rapid paralysis in the course of lung cancer. PMID:28302996

  17. Spinal Cord Ischemia Secondary to Epidural Metastasis from Small Cell Lung Carcinoma.

    PubMed

    Yasui, Hirotoshi; Ozawa, Naoya; Mikami, Satoshi; Shimizu, Kenji; Hatta, Takahiro; Makino, Nami; Fukushima, Mayu; Baba, Satoshi; Makino, Yasushi

    2017-03-17

    BACKGROUND Spinal cord ischemia is an uncommon event that is mainly caused by dissociation of the ascending aorta as a complication after aortic surgery. Spinal arteries can develop collateral circulation; therefore, the frequency of spinal infarction is about 1% of that in the brain. Few cases of spinal cord ischemia developing in the course of lung cancer have been reported. CASE REPORT We presented the case of a 56-year-old man with small cell lung carcinoma, cT4N2M1a (stage IV). He was treated with irradiation and 2 courses of platinum and etoposide combination chemotherapy. He complained of back pain followed by quadriplegia and sensory disturbance after cessation of chemotherapy. With a diagnosis of spinal cord metastasis, steroids were administered. However, diaphragmatic paralysis appeared a few hours later. He was started on palliative care and died after 6 days. Autopsy showed epidural metastasis and spinal ischemia at the C5 level. CONCLUSIONS Epidural metastasis can compress the spinal artery and cause circulatory disorders. Spinal cord ischemia should be considered in patients with rapid paralysis in the course of lung cancer.

  18. Riluzole improves outcome following ischemia-reperfusion injury to the spinal cord by preventing delayed paraplegia.

    PubMed

    Wu, Y; Satkunendrarajah, K; Fehlings, M G

    2014-04-18

    The spinal cord is vulnerable to ischemic injury due to trauma, vascular malformations and correction of thoracic aortic lesions. Riluzole, a sodium channel blocker and anti-glutamate drug has been shown to be neuroprotective in a model of ischemic spinal cord injury, although the effects in clinically relevant ischemia/reperfusion models are unknown. Here, we examine the effect of riluzole following ischemia-reperfusion injury to the spinal cord. Female rats underwent high thoracic aortic balloon occlusion to produce an ischemia/reperfusion injury. Tolerance to ischemia was evaluated by varying the duration of occlusion. Riluzole (8mg/kg) was injected intraperitoneally 4h after injury. Locomotor function (Basso, Beattie and Bresnahan (BBB) scale) was assessed at 4h, 1day, and 5days post-ischemia. Spinal cords were extracted and evaluated for neuronal loss using immunohistology (choline acetyltransferase (ChAT) and neuronal nuclei (NeuN)), inflammation (CD11b), astrogliosis (glial fibrillary acidic protein - GFAP) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Ischemic injury lasting between 5.5 and 6.75min resulted in delayed paraplegia, whereas longer ischemia induced immediate paraplegia. When riluzole was administered to rats that underwent 6min of occlusion, delayed paraplegia was prevented. The BBB score of riluzole-treated rats was 11.14±4.85 compared with 1.86±1.07 in control animals. Riluzole also reduced neuronal loss, infiltration of microglia/macrophages and astrogliosis in the ventral horn and intermediate zone of the gray matter. In addition, riluzole reduced apoptosis of neurons in the dorsal horn of the gray matter. Riluzole has a neuroprotective effect in a rat model of spinal cord injury/reperfusion when administered up to 4h post-injury, a clinically relevant therapeutic time window.

  19. Propofol protects against blood-spinal cord barrier disruption induced by ischemia/reperfusion injury

    PubMed Central

    Xie, Li-jie; Huang, Jin-xiu; Yang, Jian; Yuan, Fen; Zhang, Shuang-shuang; Yu, Qi-jing; Hu, Ji

    2017-01-01

    Propofol has been shown to exert neuroprotective effects on the injured spinal cord. However, the effect of propofol on the blood-spinal cord barrier (BSCB) after ischemia/reperfusion injury (IRI) is poorly understood. Therefore, we investigated whether propofol could maintain the integrity of the BSCB. Spinal cord IRI (SCIRI) was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Propofol, 30 mg/kg, was intravenously infused 10 minutes before aortic clamping as well as at the onset of reperfusion. Then, 48 hours later, we performed histological and mRNA/protein analyses of the spinal cord. Propofol decreased histological damage to the spinal cord, attenuated the reduction in BSCB permeability, downregulated the mRNA and protein expression levels of matrix metalloprotease-9 (MMP-9) and nuclear factor-κB (NF-κB), and upregulated the protein expression levels of occludin and claudin-5. Our findings suggest that propofol helps maintain BSCB integrity after SCIRI by reducing MMP-9 expression, by inhibiting the NF-κB signaling pathway, and by maintaining expression of tight junction proteins. PMID:28250758

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

    PubMed Central

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

    2013-01-01

    Background Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. Objective To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. Methods A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3–L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Results Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). Conclusions The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury. PMID:23809530

  1. Key genes expressed in different stages of spinal cord ischemia/reperfusion injury

    PubMed Central

    Li, Jian-an; Zan, Chun-fang; Xia, Peng; Zheng, Chang-jun; Qi, Zhi-ping; Li, Chun-xu; Liu, Zhi-gang; Hou, Ting-ting; Yang, Xiao-yu

    2016-01-01

    The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24-hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed four differentially expressed microRNAs (miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p) and their common target genes (Tmem69 and Cxcl10). Compared with the sham group, miR-22-3p was continuously upregulated in all three ischemia groups but was highest in the group with no reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury. PMID:28123428

  2. 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.

  3. Selective occlusion of lumbar arteries as a spinal cord ischemia model in rabbits.

    PubMed

    Maeda, Tomoyuki; Mori, Koichi; Shiraishi, Yoshimitsu; Tatebayashi, Kyoko; Kawai, Yasuaki

    2003-02-01

    Paraplegia is a devastating complication of operations requiring transient occlusion of the descending thoracic aorta. Many animal models of spinal cord ischemia have been utilized to examine the efficacy of various neuroprotective methods. In this study, we establish a rabbit model of spinal cord ischemia by selective temporary occlusion of lumbar arteries and examine the protective effects of systemic mild hypothermia in this model. Animals were divided into the following four groups: sham group (group A, n = 6); 10 min ischemia, normothermia (39 degrees C) (group B, n = 6); 20 min ischemia, normothermia (group C, n = 6); and 30 min ischemia, mild hypothermia (35 degrees C) (group D, n = 6). After 7 d of reperfusion, three rabbits in group B and five rabbits in group C developed paraplegia (Tarlov's score = 0). In contrast, all rabbits preserved hindlimb motor function (Tarlov's score = 4) in groups A and D. Histological findings indicated that the number of motor neurons in the anterior horns in group C were significantly fewer than in group A. A large number of motor neurons were preserved in group D. Hypothermia is known to be an effective and reliable method of neuroprotection, but the risk of complications rises at deep hypothermia. Our current results confirm that systemic, mild hypothermia is a safe and effective neuroprotective method during ischemia-reperfusion injury of the spinal cord.

  4. 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

  5. Inhibition of nitric oxide synthesis accelerates the recovery of polysynaptic reflex potentials after transient spinal cord ischemia in cats.

    PubMed

    Nemoto, T; Sekikawa, T; Suzuki, T; Moriya, H; Nakaya, H

    1997-04-01

    Nitric Oxide (NO) has been implicated as a mediator of neuronal injury in vascular stroke. On the other hand, NO is suggested to play a neuroprotective role by increasing blood flow during cerebral ischemia. In order to evaluate the role of NO in the spinal cord ischemia, effects of nitric oxide synthase (NOS) inhibition on the recovery of reflex potentials after a transient spinal cord ischemia were examined in urethane-chloralose anesthetized spinal cats. Spinal cord ischemia was produced by occlusion of the thoracic aorta and the both internal mammary arteries for 10 min. Regional blood flow (RBF) in the spinal cord was continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials elicited by electrical stimulation of the tibial nerve, were recorded from the L7 or S1 ventral root. The recovery process of spinal reflex potentials was reproducible when the oclusion was repeated twice at an interval of 120 min. Pretreatment with N(G)-monomethyl-L-arginine (L-NMMA, 10 mg/kg), a NOS inhibitor significantly accelerated the recovery of PSR potentials after spinal cord ischemia. The accelerating effect of L-NMMA on the recovery of PSR potentials was abolished by co-administration of L-arginine (1 mg/kg/min) but not by that of D-arginine (1 mg/kg/min). L-NMMA failed to improve RBF in the spinal cord during ischemia and reperfusion. Nitroprusside (10 microg/kg/min), a NO donor, retarded the recovery of PSR potentials after spinal cord ischemia. These results suggest that NO production has a significant influence on the functional recovery after transient spinal cord ischemia.

  6. The Impact of Surgical Timing in Acute Traumatic Spinal Cord Injury

    DTIC Science & Technology

    2014-10-01

    1 AWARD NUMBER: W81XWH-13-1-0396 TITLE: The impact of surgical timing in acute traumatic spinal ...TYPE Annual 3. DATES COVERED 30 Sep 2013 – 29 Sep 2014 4. TITLE AND SUBTITLE The impact of surgical timing in acute traumatic spinal cord...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The optimal surgical timing following a traumatic spinal cord injury (SCI) remains controversial

  7. Development of an Animal Model of Thoracolumbar Burst Fracture Induced Acute Spinal Cord Injury

    DTIC Science & Technology

    2015-05-01

    AWARD NUMBER: W81XWH-14-2-0013 TITLE: DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE - INDUCED ACUTE SPINAL CORD INJURY...2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE -INDUCED ACUTE SPINAL CORD INJURY 5b...leads to permanent disability following traumatic spine injury. A dramatic increase in blast related spinal burst fracture has been observed in

  8. Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy.

    PubMed

    Yin, Fei; Meng, Chunyang; Lu, Rifeng; Li, Lei; Zhang, Ying; Chen, Hao; Qin, Yonggang; Guo, Li

    2014-09-15

    Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after transplantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-associated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Furthermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neurofilament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mesenchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury.

  9. Acute and Chronic Changes in Aquaporin 4 Expression After Spinal Cord Injury

    PubMed Central

    Nesic, Olivera; Lee, Julieann; Ye, Zaiming; Unabia, Geda C.; Rafati, Danny; Hulsebosch, Claire E.; Perez-Polo, J. Regino

    2007-01-01

    The effect of spinal cord injury (SCI) on the expression levels and distribution of water channel aquaporin 4 (AQP4) has not been studied. We have found AQP4 in gray and white matter astrocytes in both uninjured and injured rat spinal cords. AQP4 was detected in astrocytic processes that were tightly surrounding neurons and blood vessels, but more robustly in glia limitans externa and interna, which were forming an interface between spinal cord parenchyma and cerebrospinal fluid (CSF). Such spatial distribution of AQP4 suggests a critical role that astrocytes expressing AQP4 play in the transport of water from blood/CSF to spinal cord parenchyma and vice versa. SCI induced biphasic changes in astrocytic AQP4 levels, including its early down-regulation and subsequent persistent up-regulation. However, changes in AQP4 expression did not correlate well with the onset and magnitude of astrocytic activation, when measured as changes in GFAP expression levels. It appears that reactive astrocytes began expressing increased levels of AQP4 after migrating to the wound area (thoracic region) two weeks after SCI, and AQP4 remained significantly elevated for months after SCI. We also showed that increased levels of AQP4 spread away from the lesion site to cervical and lumbar segments, but only in chronically injured spinal cords. Although overall AQP4 expression levels increased in chronically-injured spinal cords, AQP4 immunolabeling in astrocytic processes forming glia limitans externa was decreased, which may indicate impaired water transport through glia limitans externa. Finally, we also showed that SCI-induced changes in AQP4 protein levels correlate, both temporally and spatially, with persistent increases in water content in acutely and chronically injured spinal cords. Although correlative, this finding suggests a possible link between AQP4 and impaired water transport/edema/syringomyelia in contused spinal cords. PMID:17074445

  10. Fluoro-Jade B evidence of induced ischemic tolerance in the rat spinal cord ischemia: physiological, neurological and histopathological consequences.

    PubMed

    Orendácová, J; Ondrejcák, T; Kuchárová, K; Cízková, D; Jergová, S; Mitrusková, B; Raceková, E; Vanický, I; Marsala, J

    2005-03-01

    Fluoro-Jade B, a marker of degenerating neurons, was used to label histopathological changes in the rat spinal cord after transient ischemia and ischemic preconditioning (IPC). To characterize postischemic neurodegenerations and consequent neurological changes, a particular attention was paid to the standardization of ischemic conditions in animals of both groups. 1. The control ischemic rats were submitted to a reversible occlusion of descending aorta by insertion and subsequent inflation of a 2F Fogarty catheter for 12 min. 2. In the IPC rats, an episode of short 3 min occlusion and 30 min reperfusion preceded the 12 min ischemia. Postischemic motor function testing (ambulation and stepping) was provided repeatedly for evaluation of neurological status 2 h and 24 h after surgery and at the end of postischemic survival, i.e. after 48 h. Fluoro-Jade B staining was used to demonstrate degenerated neurons. In the control rats, neurological consequences of histopathological changes in lumbosacral spinal cord, manifested as paraplegia, were present after 12 min ischemia. Thus, numbers of degenerated Fluoro-Jade B positive cells were visible in gray matter of the most injured L(4)-S(2) spinal cord segments. Slight motor function impairment, consequential from significant decreasing in Fluoro-Jade B-positivity in the L(4)-S(2) spinal cord segments of the IPC rats, was considered the pathomorpfological evidence that IPC induces spinal cord tolerance to ischemia. Our results are consistent with the previously published silver impregnation method for histopathological demonstration of ischemic degeneration.

  11. 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

  12. iNOS participates in apoptosis of spinal cord neurons via p-BAD dephosphorylation following ischemia/reperfusion (I/R) injury in rat spinal cord.

    PubMed

    Li, Yiming; Gu, Jun; Liu, Yuwen; Long, Hao; Wang, Guannan; Yin, Guoyong; Fan, Jin

    2013-06-17

    The pro-apoptotic effect of nitric oxide (NO) has been reported both in vivo and in vitro. Previous studies have revealed that NO, especially which produced by inducible nitric oxide synthase (iNOS), has an important effect on apoptosis of neurons in spinal cord ischemia/reperfusion (I/R) injury. To investigate the role of iNOS in this process, a randomized, controlled study was designed using a classical rat model of ischemic spinal cord injury. Fifty-four male Sprague-Dawley rats were randomly divided into three different groups: a sham-operated group (n=6), a vehicle group (I/R, n=24), and an iNOS inhibitor (aminoguanidine: AG) group (I/R+AG, n=24). Rats were sacrificed 6, 12, 24 and 72 h after reperfusion. We examined neurological motor function evaluated by 'Tarlov's score', assessed alterations in the morphology of spinal cord neurons by transmission electron microscopy (TEM), analyzed expression of iNOS at the levels of mRNA and protein, evaluated local concentrations and cellular locations of other key regulatory proteins, and investigated protein-protein interactions. In the vehicle group, iNOS expression, dephosphorylation of p-BAD (Ser 136), disassociation of BAD from p-BAD/14-3-3 dimers, and release of cytochrome c were all increased compared with the sham group. But in the AG group, all the performances above were decreased compared with the vehicle group. Similarly, rats in the sham group got a maximum score of 5 by Tarlov's motor scores evaluation. While the scores were higher in the AG group compared to the vehicle group because iNOS was inhibited. These results indicate that the activity of iNOS plays a critical role in the apoptosis of spinal cord neurons by influencing the dephosphorylation of p-BAD (Ser 136) and the interaction between BAD and 14-3-3.

  13. Third place winner of the Conrad Jobst Award in the gold medal paper competition. Prevention of spinal cord dysfunction in a new model of spinal cord ischemia.

    PubMed

    Lopez, S; Manahan, E; Evans, J R; Kao, R L; Browder, W

    1995-01-01

    Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Free radicals in rabbit spinal cord ischemia: electron spin resonance spectroscopy and correlation with SOD activity.

    PubMed

    Lombardi, V; Valko, L; Stolc, S; Valko, M; Ondrejicková, O; Horáková, L; Placek, J; Troncone, A

    1998-08-01

    1. In nonanesthetized rabbits temporal occlusion of the abdominal aorta was used to induce oxidative stress in the lower part of the body including distal segments of the spinal cord. 2. Spinal cord samples were taken from the animals exposed to 25-min aortic occlusion (AO) or to occlusion followed by 1- or 2-hr reperfusion (AO/R1 or AO/R2, respectively) or from sham-operated animals (C). The presence of free radicals (FR) in the spinal cord samples frozen in liquid N2 was assessed by ESR spectroscopy without spin trapping. Moreover, superoxide dismutase (SOD) activity and conjugated diene (CD) levels were measured in the samples. 3. In the AO group FR were detected in the spinal cord regions close to the occlusion (lower thoracic and distal segments) along with a decrease in SOD activity. The calculated g value (g = 2.0291) indicated that the paramagnetic signal recorded might be attributed to superoxide radicals. FR were absent in the AO/R1 group. Concurrently, the SOD activity revealed a significant tendency to return to the control level. FR appeared again in the AO/R2 group, mostly in the upper and middle lumbar regions, along with a decrease in SOD activity. No sample from the C group revealed FR. A significant increase in CD levels was observed in the thoracolumbar region only in the AO/R2 group. The temporary absence of FR in the AO/R1 group suggests activation of defense antioxidant mechanisms (e.g., specific enzymatic systems such as SOD), which might have been exhausted later. 4. Changes in SOD activity similar to those observed in the thoracolumbar region, though less noticeable, occurred in the obviously noncompromised tissue (upper cervical region). This points to a kind of generalized response of the animal to aortic occlusion. 5. Direct ESR spectroscopy revealed the presence of FR as well as their time course in the spinal cord during the early phase of ischemia/reperfusion injury and the inverse relationship between FR and SOD activity.

  15. 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.

  16. Changes of blood flow, oxygen tension, action potential and vascular permeability induced by arterial ischemia or venous congestion on the spinal cord in canine model.

    PubMed

    Kobayashi, Shigeru; Yoshizawa, Hidezo; Shimada, Seiichiro; Guerrero, Alexander Rodríguez; Miyachi, Masaya

    2013-01-01

    It is generally considered that the genesis of myelopathy associated with the degenerative conditions of the spine may result from both mechanical compression and circulatory disturbance. Many references about spinal cord tissue ischemic damage can be found in the literature, but not detailed studies about spinal cord microvasculature damage related to congestion or blood permeability. This study investigates the effect of ischemia and congestion on the spinal cord using an in vivo model. The aorta was clamped as an ischemia model of the spinal cord and the inferior vena cava was clamped as a congestion model at the 6th costal level for 30 min using forceps transpleurally. Measurements of blood flow, partial oxygen pressure, and conduction velocity in the spinal cord were repeated over a period of 1 h after release of clamping. Finally, we examined the status of blood-spinal cord barrier under fluorescence and transmission electron microscope. Immediately after clamping of the inferior vena cava, the central venous pressure increased by about four times. Blood flow, oxygen tension and action potential were more severely affected by the aorta clamping; but this ischemic model did not show any changes of blood permeability in the spinal cord. The intramedullar edema was more easily produced by venous congestion than by arterial ischemia. In conclusions, venous congestion may be a preceding and essential factor of circulatory disturbance in the compressed spinal cord inducing myelopathy.

  17. Protective effect of Crocus sativus L. (Saffron) extract on spinal cord ischemia-reperfusion injury in rats

    PubMed Central

    Farjah, Gholam Hossein; Salehi, Shadi; Ansari, Mohammad Hasan; Pourheidar, Bagher

    2017-01-01

    Objective(s): Ischemia/reperfusion (I/R) injury of spinal cord is leading to the paraplegia observed. In this study, we investigated the protective effect of the saffron extract on spinal cord I/R injury. Materials and Methods: Thirty five male Sprague-Dawley rats were divided into 5 groups: intact, sham surgery, normal saline (NS), low dose saffron aqua extract, high dose saffron aqua extract. Results: The mean motor deficit index (MDI) scores were significantly lower in the saffron extract groups than in the NS group at 48 hr after spinal cord ischemia (P<0.001). Saffron extract groups significantly decreased plasma level of malondialdehyde than in the NS Group (P<0.05). The number of motor normal neurons was significantly greater in the high saffron extract group than in the NS and low saffron group (P<0.05). Conclusion: These data suggest that a saffron extract may protect spinal cord neurons from I/R injury. PMID:28392907

  18. Co-application of ischemic preconditioning and postconditioning provides additive neuroprotection against spinal cord ischemia in rabbits.

    PubMed

    Jiang, Xiaojing; Shi, Enyi; Li, Liwen; Nakajima, Yoshiki; Sato, Shigehito

    2008-03-12

    Postconditioning can induce cardioprotection against ischemia. However, the data on postconditioning of the spinal cord is very limited. We investigated here whether co-application of ischemic preconditioning (IPC) and postconditioning can provide additive neuroprotection against prolonged spinal cord ischemia. Spinal cord ischemia was produced in rabbits by infrarenal aortic occlusion with a balloon catheter for 30 min. The four treatment groups were control (n=10): no intervention; IPC (n=10): a 5-minute aortic occlusion was performed 20 min before the prolonged ischemia; Postcon (n=10): postconditioning comprised of four cycles of 1-minute occlusion/1-minute reperfusion was applied one minute after the start of reperfusion. IPC+postcon (n=11): both IPC and postconditioning were applied. Functional evaluation with Tarlov score was performed during a 14-day observation period. Neurologic impairment was noticeably attenuated in the IPC+postcon group (compared with the control group, P<0.01, at day 1, day 2, day 7 and day 14, respectively), but not in either the IPC or Postcon group. Plasma malondialdehyde levels after reperfusion were significantly decreased to a similar extent in the IPC, Postcon and IPC+Postcon groups (compared with the control group (P<0.01). In the IPC+Postcon group, many more large motor neurons were preserved than in the control group (P<0.05) and white matter injury was also markedly attenuated as evidenced by reduction of the vacuolation area of the white matter (P<0.01) and decreased amyloid precursor protein immunoreactivity (P<0.01). From this, we conclude that the combination of IPC and postconditioning induces additive neuroprotective effects for spinal cord against ischemia and reperfusion injuries.

  19. ICF Based Comprehensive Evaluation for Post-Acute Spinal Cord Injury

    PubMed Central

    Nam, Hyung Seok; Kim, Kwang Dong

    2012-01-01

    Objective To evaluate the feasibility of the ICF for initial comprehensive evaluation of early post-acute spinal cord injury. Method A comprehensive evaluation of 62 early post-acute spinal cord injury (SCI) patients was conducted by rehabilitation team members, such as physicians, physical therapists, occupational therapists, nutritionists, medical social-workers, and nurses. They recorded each of their evaluation according to the ICF first level classification. The contents of the comprehensive evaluation were linked to the ICF second level categories, retrospectively. The linked codes were analyzed descriptively and were also compared with the brief ICF core set for early post-acute SCI. Results In the evaluation of early post-acute SCI patients based on the ICF first level categories, 19 items from the body functions domain, such as muscle power functions (b730) and urination functions (b620), 15 items from the body structures domain, including spinal cord and related structures (s120), 11 items from the activities and participation domain, such as transferring oneself (d420) and walking (d450), and 9 items from the environmental factors domain, e.g., health professionals (e355), were linked to the ICF second level categories. In total, 82.4% of all contents were linked to the brief ICF core set. Prognosis insight, a personal factor not linkable to an ICF code, was mentioned in 29.0% of all patients. Conclusion First level ICF categories can provide a structural base for a comprehensive evaluation in early post-acute spinal cord injury. However, frequently linked items, including the brief core set, as well as personal factors should be considered via a checklist in order to prevent the omission of significant contents. PMID:23342313

  20. Continuous intrathecal fluid infusions elevate nerve growth factor levels and prevent functional deficits after spinal cord ischemia.

    PubMed

    Bowes, M; Tuszynski, M H; Conner, J; Zivin, J A

    2000-11-17

    Continuous intracerebroventricular or intrathecal infusions of neurotrophic factors have been reported to prevent neuronal degeneration, stimulate axonal sprouting and ameliorate behavioral deficits in various models of CNS injury and aging. In the present study, the ability of intrathecal infusions of recombinant human nerve growth factor (NGF) to reduce functional deficits following spinal cord ischemia was investigated. Adult rabbits underwent intrathecal cannulation and continuous infusions of either 300 microg/ml recombinant human NGF or artificial CSF (vehicle) at a rate of 143 microl/day for 7 days prior to induction of spinal cord ischemia. Continuous infusions were maintained after induction of ischemia. Four days later, both NGF-treated and vehicle-infused subjects showed a significant amelioration of functional motor deficits compared to lesioned, non-infused subjects (P<0.05). The average duration of tolerated ischemia increased from 23.4+/-1.8 min in lesioned, non-infused subjects to 35.5+/-3.1 min in lesioned, artificial CSF-infused subjects and 35.6+/-4.7 min in NGF-infused subjects (mean+/-S.E.M.). Significantly elevated NGF protein levels were attained within the spinal cords of both NGF-treated subjects and artificial CSF-infused subjects, although levels were substantially higher in NGF-treated subjects (9.8+/-3.8 ng/g in NGF-infused vs. 2.0+/-0.4 ng/g in vehicle-infused and only 0.4+/-0.2 ng/g in lesioned, non-infused animals). These findings indicate that the process of intrathecal cannulation and fluid infusion elicits alterations in the spinal cord environment that are neuroprotective, including spontaneous elevations in NGF levels.

  1. Acute sports-related spinal cord injury: contemporary management principles.

    PubMed

    Kim, David H; Vaccaro, Alexander R; Berta, Scott C

    2003-07-01

    Improvements in helmet and equipment design have led to significant decreases in overall injury incidence, but no available helmet can prevent catastrophic injury to the neck and cervical spine. The most effective strategy for preventing this type of injury appears to be careful instruction, training, and regulations designed to eliminate head-first contact. The incidence of football-related quadriplegia has decreased from a peak of 13 cases per one million players between 1976 and 1980 to 3 per million from 1991 to 1993, mostly as a result of systematic research and an organized effort to eliminate high-risk behavior. An episode of transient quadriparesis does not appear to be a risk factor for catastrophic spinal cord injury. Torg reported that 0 of 117 quadriplegics in the National Football Head and Neck Injuries Registry recalled a prior episode of transient quadriparesis, and 0 of the 45 patients originally studied in his transient quadriparesis cohort have subsequently suffered quadriplegia. The significance of developmental spinal stenosis is unclear. Plain radiographic identification of a narrow spinal canal in a player sustaining cervical cord neurapraxia warrants further evaluation by MRI to rule out functional stenosis. The presence of actual cord deformation or compression on MRI should preclude participation in high-risk contact or collision sports.

  2. A Multicenter, Randomized Controlled Trial of Cerebrospinal Fluid Drainage in Acute Spinal Cord Injury

    DTIC Science & Technology

    2015-10-01

    purpose of this randomized clinical trial is to evaluate the safety and efficacy of cerebrospinal fluid drainage (CSFD) and to provide a preliminary... clinical efficacy evaluation of the combination of CSFD and elevation of mean arterial pressure (MAP) in patients with acute spinal cord injury...and society that are expected to increase with better long term care technologies. The purpose of this randomized clinical trial is to evaluate the

  3. 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

  4. 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

  5. Electroacupuncture preconditioning and postconditioning inhibit apoptosis and neuroinflammation induced by spinal cord ischemia reperfusion injury through enhancing autophagy in rats.

    PubMed

    Fang, Bo; Qin, Meiman; Li, Yun; Li, Xiaoqian; Tan, Wenfei; Zhang, Ying; Ma, Hong

    2017-03-06

    Electroacupuncture (EA) has beneficial effects on spinal cord ischemia reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. This study aimed to investigate the role of autophagy in the protection of EA preconditioning and postconditioning against spinal cord I/R injury. For this, spinal cord I/R injury was induced by 14min occlusion of the aortic arch, and rats were treated with EA for 20min before or after the surgery. The expression of autophagy components, light chain 3 and Beclin 1, was assessed by Western blot. The hind-limb motor function was assessed using the Basso-Beattie-Bresnahan (BBB) criteria, and motor neurons in the ventral gray matter were counted by histological examination. The apoptosis of neurocyte was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and matrix metalloproteinase-9 (MMP-9) was also measured using Western blot or enzyme-linked immunosorbent assay (ELISA). Either EA preconditioning or postconditioning enhanced autophagy, and minimized the neuromotor dysfunction and histopathological deficits after spinal cord I/R injury. In addition, EA suppressed I/R-induced apoptosis and increased in the expression of TNF-α, IL-1β, and MMP-9. In contrast, the autophagic inhibitor (3-methyladenine, 3-MA) inhibited the neuroprotective effects of EA. Moreover, 3-MA increased the apoptosis and the expression of TNF-α, IL-1β, and MMP-9. In summary, these findings suggested that EA preconditioning and postconditioning could alleviate spinal cord I/R injury, which was partly mediated by autophagy upregulation-induced inhibition of apoptosis and neuroinflammation.

  6. Exercise pressor reflex function following acute hemi-section of the spinal cord in cats

    PubMed Central

    Murphy, Megan N.; Ichiyama, Ronaldo M.; Iwamoto, Gary A.; Mitchell, Jere H.; Smith, Scott A.

    2013-01-01

    Cardiovascular disease is a leading cause of morbidity and mortality in patients post spinal cord injury (SCI). The prescription of exercise as a therapeutic modality for disease prevention in this population is promising. It is logical to suggest that the sooner an exercise program can begin the more benefit the patient will receive from the therapy. However, the time point after injury at which the requisite circulatory responses needed to support exercise are viable remains largely unknown. The skeletal muscle exercise pressor reflex (EPR) significantly contributes to cardiovascular control during exercise in healthy individuals. Experiments in patients with a chronic lateral hemi-section of the spinal cord (Brown-Séquard syndrome) suggest that the EPR, although blunted, is operational when examined months to years post injury. However, whether this critically important reflex remains functional immediately after lateral SCI or, in contrast, experiences a period of reduced capacity due to spinal shock has not been established. This study was designed to assess EPR function after acute lateral transection of the spinal cord. The EPR was selectively activated in seven decerebrate cats via electrically stimulated static contraction of the triceps surae muscles of each hindlimb before and after lateral hemi-section of the T13–L2 region of the spinal cord. Compared to responses prior to injury, increases in mean arterial pressure (MAP) were significantly decreased when contracting the hindlimb either ipsilateral to the lesion (MAP = 17 ± 3 mmHg before and 9 ± 2 mmHg after) or contralateral to the lesion (MAP = 22 ± 5 mmHg before and 12 ± 4 mmHg after). The heart rate (HR) response to stimulation of the EPR was largely unaffected by induction of acute SCI. The findings suggest that the EPR maintains the ability to importantly contribute to cardiovascular regulation during exercise immediately following a Brown-Séquard-like injury. PMID:23403764

  7. Staged Hybrid Repair to Reduce the Risk of Spinal Cord Ischemia After Extensive Thoracic Aortic Aneurysm Repair.

    PubMed

    Canaud, Ludovic; Gandet, Thomas; Ozdemir, Baris Ata; D'Annoville, Thomas; Marty-Ané, Charles; Alric, Pierre

    2016-01-01

    We hypothesized that staged repair of extensive thoracic aneurysms might mitigate the incidence and severity of spinal ischemia by facilitating structural remodeling of the spinal cord vasculature. Staged hybrid repair (in two or three stages) was undertaken in 7 patients with extensive thoracic aortic aneurysms. The 30-day mortality and spinal ischemia rates were 0%. The conceptual basis of staging extensive aortic repairs is the maintenance of adequate flow to a sufficient number of spinal arteries and that spinal perfusion is preserved during the early postoperative period when the patient is most vulnerable to hypotension, by deliberately allowing interval distal type I endoleak.

  8. 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

  9. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury.

    PubMed

    Yin, Fei; Guo, Li; Meng, Chun-yang; Liu, Ya-juan; Lu, Ri-feng; Li, Peng; Zhou, Yu-bo

    2014-05-02

    It is unknown whether transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can repair spinal cord ischemia-reperfusion injury (SCII) in a rat model through an anti-apoptotic effect. Adult rats were divided into untreated or sham-operated controls, untreated models of SCII (uSCII) and BM-MSC-transplanted models of SCII (tSCII; labeled with CM-Dill transplanted at 1 h and 24 h after reperfusion). According to evaluation of hind-limb motor function, the motor functions of tSCII rats were significantly better than those of uSCII rats by the seventh day. H&E and TUNEL staining showed that the spinal cords of uSCII rats contained damaged neural cells with nuclear pyknosis and congestion of blood vessels, with a high percentage of apoptotic neural cells, while the spinal cords of tSCII rats were nearly normal with significantly fewer apoptotic neural cells. Immunohistochemistry and double immunofluorescence staining revealed that in tSCII rats CASP3 and neurofilament-H (NF-H) levels were 14.57% and 174% those of uSCII rats, respectively, and in tSCII rats the ratio of BAX to BCL2 was reduced by nearly 50%. The differentiation of transplanted CM-Dil-labeled BM-MSCs into neurons and astrocytes was observed in the spinal cords of the tSCII rats under laser scanning confocal microscopy. These results showed that transplantation of BM-MSCs improved functional recovery after SCII via anti-apoptosis.

  10. Nicotinamide Adenine Dinucleotide Protects against Spinal Cord Ischemia Reperfusion Injury-Induced Apoptosis by Blocking Autophagy

    PubMed Central

    Yu, Sifei; Wang, Zhenfei; Yang, Kai; Liu, Zhuochao

    2017-01-01

    The role of autophagy, neuroprotective mechanisms of nicotinamide adenine dinucleotide (NAD+), and their relationship in spinal cord ischemic reperfusion injury (SCIR) was assessed. Forty-eight Sprague-Dawley rats were divided into four groups: sham, ischemia reperfusion (I/R), 10 mg/kg NAD+, and 75 mg/kg NAD+. Western blotting, immunofluorescence, and immunohistochemistry were used to assess autophagy and apoptosis. Basso, Beattie, and Bresnahan (BBB) scores were used to assess neurological function. Expression levels of Beclin-1, Atg12-Atg5, LC3B-II, cleaved caspase 3, and Bax were upregulated in the I/R group and downregulated in the 75 mg/kg NAD+ group; p-mTOR, p-AKT, p62, and Bcl-2 were downregulated in the I/R group and upregulated in the 75 mg/kg NAD+ group. Numbers of LC3B-positive, caspase 3-positive, Bax-positive, and TUNEL-positive cells were significantly increased in the I/R group and decreased in the 75 mg/kg NAD+ group. The mean integrated option density of Bax increased and that of Nissl decreased in the I/R group, and it decreased and increased, respectively, in the 75 mg/kg NAD+ group. BBB scores significantly increased in the 75 mg/kg NAD+ group relative to the I/R group. No difference was observed between I/R and 10 mg/kg NAD+ groups for these indicators. Therefore, excessive and sustained autophagy aggravates SCIR; administration of NAD+ alleviates injury. PMID:28367271

  11. Electroacupuncture pretreatment attenuates spinal cord ischemia-reperfusion injury via inhibition of high-mobility group box 1 production in a LXA4 receptor-dependent manner.

    PubMed

    Zhu, Xiao-Ling; Chen, Xin; Wang, Wei; Li, Xu; Huo, Jia; Wang, Yu; Min, Yu-Yuan; Su, Bin-Xiao; Pei, Jian-Ming

    2017-03-15

    Paraplegia caused by spinal cord ischemia is a severe complication following surgeries in the thoracic aneurysm. HMGB1 has been recognized as a key mediator in spinal inflammatory response after spinal cord injury. Electroacupuncture (EA) pretreatment could provide neuroprotection against cerebral ischemic injury through inhibition of HMGB1 release. Therefore, the present study aims to test the hypothesis that EA pretreatment protects against spinal cord ischemia-reperfusion (I/R) injury via inhibition of HMGB1 release. Animals were pre-treated with EA stimulations 30min daily for 4 successive days, followed by 20-min spinal cord ischemia induced by using a balloon catheter placed into the aorta. We found that spinal I/R significantly increased mRNA and cytosolic protein levels of HMGB1 after reperfusion in the spinal cord. The EA-pretreated animals displayed better motor performance after reperfusion along with the decrease of apoptosis, HMGB1, TNF-α and IL-1β expressions in the spinal cord, whereas these effects by EA pretreatment was reversed by rHMGB1 administration. Furthermore, EA pretreatment attenuated the down-regulation of LXA4 receptor (ALX) expression induced by I/R injury, while the decrease of HMGB1 release in EA-pretreated rats was reversed by the combined BOC-2 (an inhibitor of LXA4 receptor) treatment. In conclusion, EA pretreatment may promote spinal I/R injury through the inhibition of HMGB1 release in a LXA4 receptor-dependent manner. Our data may represent a new therapeutic technique for treating spinal cord ischemia-reperfusion injury.

  12. Variability in the treatment of acute spinal cord injury in the United Kingdom: results of a national survey.

    PubMed

    Werndle, Melissa C; Zoumprouli, Argyro; Sedgwick, Philip; Papadopoulos, Marios C

    2012-03-20

    The aim of this study was to examine how traumatic spinal cord injury is managed in the United Kingdom via a questionnaire survey of all neurosurgical units. We contacted consultant neurosurgeons and neuroanesthetists in all neurosurgical centers that manage patients with acute spinal cord injury. Two clinical scenarios-of complete and incomplete cervical spinal cord injuries-were given to determine local treatment policies. There were 175 responders from the 33 centers (36% response rate). We ascertained neurosurgical views on urgency of transfer, timing of surgery, nature and aim of surgery, as well as neuroanesthetic views on type of anesthetic, essential intraoperative monitoring, drug treatment, and intensive care management. Approximately 70% of neurosurgeons will admit patients with incomplete spinal cord injury immediately, but only 40% will admit patients with complete spinal cord injury immediately. There is no consensus on the timing or even the role of surgery for incomplete or complete injuries. Most (96%) neuroanesthetists avoid anesthetics known to elevate intracranial pressure. What was deemed essential intraoperative monitoring, however, varied widely. Many (22%) neuroanesthetists do not routinely measure arterial blood pressure invasively, central venous pressure (85%), or cardiac output (94%) during surgery. There is no consensus among neuroanesthetists on the optimal levels of arterial blood pressure, or oxygen and carbon dioxide partial arterial pressure. We report wide variability among U.K. neurosurgeons and neuroanesthetists in their treatment of acute traumatic spinal cord injury. Our findings reflect the lack of Class 1 evidence that early surgical decompression and intensive medical management of patients with spinal cord injury improves neurological outcome.

  13. Breakdown of Blood-Brain and Blood-Spinal Cord Barriers During Acute Methamphetamine Intoxication: Role of Brain Temperature.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2016-01-01

    Methamphetamine (METH) is a powerful and often-abused stimulant with potent addictive and neurotoxic properties. While it is generally believed that structural brain damage induced by METH results from oxidative stress, in this work we present data suggesting robust disruption of blood-brain and blood-spinal cord barriers during acute METH intoxication in rats. We demonstrate the relationships between METH-induced brain hyperthermia and widespread but structure-specific barrier leakage, acute glial cell activation, changes in brain water and ionic homeostasis, and structural damage of different types of cells in the brain and spinal cord. Therefore, METH-induced leakage of the blood-brain and blood-spinal cord barriers is a significant contributor to different types of functional and structural brain abnormalities that determine acute toxicity of this drug and possibly neurotoxicity during its chronic use.

  14. FAQs about Spinal Cord Injury (SCI)

    MedlinePlus

    ... spinal cord injury? Where is the nearest SCI Model System of Care? Emergency Medical Services Hospital (Acute) Care Rehabilitation More ... spinal cord injury? Where is the nearest SCI Model System of Care? Follow Us! Get Email Updates Questions & Comments Suggest ...

  15. Biodegradable scaffolds promote tissue remodeling and functional improvement in non-human primates with acute spinal cord injury.

    PubMed

    Slotkin, Jonathan R; Pritchard, Christopher D; Luque, Brian; Ye, Janice; Layer, Richard T; Lawrence, Mathew S; O'Shea, Timothy M; Roy, Roland R; Zhong, Hui; Vollenweider, Isabel; Edgerton, V Reggie; Courtine, Grégoire; Woodard, Eric J; Langer, Robert

    2017-04-01

    Tissue loss significantly reduces the potential for functional recovery after spinal cord injury. We previously showed that implantation of porous scaffolds composed of a biodegradable and biocompatible block copolymer of Poly-lactic-co-glycolic acid and Poly-l-lysine improves functional recovery and reduces spinal cord tissue injury after spinal cord hemisection injury in rats. Here, we evaluated the safety and efficacy of porous scaffolds in non-human Old-World primates (Chlorocebus sabaeus) after a partial and complete lateral hemisection of the thoracic spinal cord. Detailed analyses of kinematics and muscle activity revealed that by twelve weeks after injury fully hemisected monkeys implanted with scaffolds exhibited significantly improved recovery of locomotion compared to non-implanted control animals. Twelve weeks after injury, histological analysis demonstrated that the spinal cords of monkeys with a hemisection injury implanted with scaffolds underwent appositional healing characterized by a significant increase in remodeled tissue in the region of the hemisection compared to non-implanted controls. The number of glial fibrillary acidic protein immunopositive astrocytes was diminished within the inner regions of the remodeled tissue layer in treated animals. Activated macrophage and microglia were present diffusely throughout the remodeled tissue and concentrated at the interface between the preserved spinal cord tissue and the remodeled tissue layer. Numerous unphosphorylated neurofilament H and neuronal growth associated protein positive fibers and myelin basic protein positive cells may indicate neural sprouting inside the remodeled tissue layer of treated monkeys. These results support the safety and efficacy of polymer scaffolds in a primate model of acute spinal cord injury. A device substantially similar to the device described here is the subject of an ongoing human clinical trial.

  16. A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent

    PubMed Central

    Moonen, Gray; Satkunendrarajah, Kajana; Wilcox, Jared T.; Badner, Anna; Mothe, Andrea; Foltz, Warren; Fehlings, Michael G.

    2016-01-01

    Abstract Traumatic injury to the lumbar spinal cord results in complex central and peripheral nervous tissue damage causing significant neurobehavioral deficits and personal/social adversity. Although lumbar cord injuries are common in humans, there are few clinically relevant models of lumbar spinal cord injury (SCI). This article describes a novel lumbar SCI model in the rat. The effects of moderate (20 g), moderate-to-severe (26 g) and severe (35 g, and 56 g) clip impact-compression injuries at the lumbar spinal cord level L1-L2 (vertebral level T11-T12) were assessed using several neurobehavioral, neuroanatomical, and electrophysiological outcome measures. Lesions were generated after meticulous anatomical landmarking using microCT, followed by laminectomy and extradural inclusion of central and radicular elements to generate a traumatic SCI. Clinically relevant outcomes, such as MR and ultrasound imaging, were paired with robust morphometry. Analysis of the lesional tissue demonstrated that pronounced tissue loss and cavitation occur throughout the acute to chronic phases of injury. Behavioral testing revealed significant deficits in locomotion, with no evidence of hindlimb weight-bearing or hindlimb-forelimb coordination in any injured group. Evaluation of sensory outcomes revealed highly pathological alterations including mechanical allodynia and thermal hyperalgesia indicated by increasing avoidance responses and decreasing latency in the tail-flick test. Deficits in spinal tracts were confirmed by electrophysiology showing increased latency and decreased amplitude of both sensory and motor evoked potentials (SEP/MEP), and increased plantar H-reflex indicating an increase in motor neuron excitability. This is a comprehensive lumbar SCI model and should be useful for evaluation of translationally oriented pre-clinical therapies. PMID:26414192

  17. 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

  18. Protective effect of nicotinamide adenine dinucleotide (NAD(+)) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis.

    PubMed

    Xie, Lei; Wang, Zhenfei; Li, Changwei; Yang, Kai; Liang, Yu

    2017-02-01

    As previous studies demonstrate that oxidative stress and apoptosis play crucial roles in ischemic pathogenesis and nicotinamide adenine dinucleotide (NAD(+)) treatment attenuates oxidative stress-induced cell death among primary neurons and astrocytes as well as significantly reduce cerebral ischemic injury in rats. We used a spinal cord ischemia injury (SCII) model in rats to verify our hypothesis that NAD(+) could ameliorate oxidative stress-induced neuronal apoptosis. Adult male rats were subjected to transient spinal cord ischemia for 60min, and different doses of NAD(+) were administered intraperitoneally immediately after the start of reperfusion. Neurological function was determined by Basso, Beattie, Bresnahan (BBB) scores. The oxidative stress level was assessed by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The degree of apoptosis was analyzed by deoxyuridinetriphosphate nick-end labeling (TUNEL) staining and protein levels of cleaved caspase-3 and AIF (apoptosis inducing factor). The results showed that NAD(+) at 50 or 100mg/kg significantly decreased the oxidative stress level and neuronal apoptosis in the spinal cord of ischemia-reperfusion rats compared with saline, as accompanied with the decreased oxidative stress, NAD(+) administration significantly restrained the neuronal apoptosis after ischemia injury while improved the neurological and motor function. These findings suggested that NAD(+) might protect against spinal cord ischemia-reperfusion via reducing oxidative stress-induced neuronal apoptosis.

  19. PRDM5 Expression and Essential Role After Acute Spinal Cord Injury in Adult Rat.

    PubMed

    Liu, Jie; Wu, Weijie; Hao, Jie; Yu, Mingchen; Liu, Jin; Chen, Xinlei; Qian, Rong; Zhang, Feng

    2016-12-01

    PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products that modulate cellular processes such as differentiation, cell growth and apoptosis. PRDM5 is a recently identified family member that functions as a transcriptional repressor and behaves as a putative tumor suppressor in different types of cancer. However, the expression and function of PRDM5 in spinal cord injury (SCI) are still unknown. In the present study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of PRDM5 expression in the spinal cord. We found that PRDM5 protein levels gradually increased, reaching a peak at day 5 and then gradually declined to a normal level at day 14 after SCI with Western blot analysis. Double immunofluorescence staining showed that PRDM5 immunoreactivity was found in neurons, astrocytes and microglia. However, the expression of PRDM5 was increased predominantly in neurons. Additionally, colocalization of PRDM5/active caspase-3 was been respectively detected in neurons. In vitro, we found that depletion of PRDM5 by short interfering RNA, obviously decreases neuronal apoptosis. In summary, this is the first description of PRDM5 expression in SCI. Our results suggested that PRDM5 might play crucial roles in CNS pathophysiology after SCI and this research will provide new drug targets for clinical treatment of SCI.

  20. Altered activation patterns by triceps surae stretch reflex pathways in acute and chronic spinal cord injury.

    PubMed

    Frigon, Alain; Johnson, Michael D; Heckman, C J

    2011-10-01

    Spinal reflexes are modified by spinal cord injury (SCI) due the loss of excitatory inputs from supraspinal structures and changes within the spinal cord. The stretch reflex is one of the simplest pathways of the central nervous system and was used presently to evaluate how inputs from primary and secondary muscle spindles interact with spinal circuits before and after spinal transection (i.e., spinalization) in 12 adult decerebrate cats. Seven cats were spinalized and allowed to recover for 1 mo (i.e., chronic spinal state), whereas 5 cats were evaluated before (i.e., intact state) and after acute spinalization (i.e., acute spinal state). Stretch reflexes were evoked by stretching the left triceps surae (TS) muscles. The force evoked by TS muscles was recorded along with the activity of several hindlimb muscles. Stretch reflexes were abolished in the acute spinal state due to an inability to activate TS muscles, such as soleus (Sol) and lateral gastrocnemius (LG). In chronic spinal cats, reflex force had partly recovered but Sol and LG activity remained considerably depressed, despite the fact that injecting clonidine could recruit these muscles during locomotor-like activity. In contrast, other muscles not recruited in the intact state, most notably semitendinosus and sartorius, were strongly activated by stretching TS muscles in chronic spinal cats. Therefore, stretch reflex pathways from TS muscles to multiple hindlimb muscles undergo functional reorganization following spinalization, both acute and chronic. Altered activation patterns by stretch reflex pathways could explain some sensorimotor deficits observed during locomotion and postural corrections after SCI.

  1. A Brief Analysis of Traditional Chinese Medical Elongated Needle Therapy on Acute Spinal Cord Injury and Its Mechanism

    PubMed Central

    Du, Mengxuan; Chen, Rongliang; Quan, Renfu; Zhang, Liang; Xu, Jinwei; Yang, Zhongbao; Yang, Disheng

    2013-01-01

    Acute spinal cord injury is one of the most common and complicated diseases among human spinal injury. We aimed to explore the effect of point-through-point acupuncture therapy with elongated needles on acute spinal cord injury in rabbits and its possible mechanism. Adult rabbits were randomly divided into a model group, elongated needle therapy group, and blank group. Immunohistochemical staining showed that the protein levels of Fas and caspase-3 in the model group were significantly higher than those in the blank group at each time point (P < 0.05) and significantly lower than those in the elongated needle therapy group on the 3rd and 5th days after operation (P < 0.05). RT-PCR showed that Fas and caspase-3 mRNA levels in the model group and elongated needle therapy group were significantly higher than those in the blank group (P < 0.05, 0.01). The mRNA levels of Fas and caspase-3 in the elongated needle therapy group were significantly lower than those in model group on the 3rd day (P < 0.05, 0.01). Therefore, we confirmed that elongated needle therapy has an obvious effect on acute spinal cord injury in rabbits. Its mechanism is made possible by inhibiting the expression of the Fas→caspase-3 cascade, thereby inhibiting cell apoptosis after spinal cord injury. PMID:24348723

  2. A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury.

    PubMed

    Coleman, W P; Benzel, D; Cahill, D W; Ducker, T; Geisler, F; Green, B; Gropper, M R; Goffin, J; Madsen, P W; Maiman, D J; Ondra, S L; Rosner, M; Sasso, R C; Trost, G R; Zeidman, S

    2000-06-01

    From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical

  3. 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

  4. An injectable, calcium responsive composite hydrogel for the treatment of acute spinal cord injury.

    PubMed

    McKay, Christopher A; Pomrenke, Rebecca D; McLane, Joshua S; Schaub, Nicholas J; DeSimone, Elise K; Ligon, Lee A; Gilbert, Ryan J

    2014-02-12

    Immediately following spinal cord injury, further injury can occur through several secondary injury cascades. As a consequence of cell lysis, an increase in extracellular Ca(2+) results in additional neuronal loss by inducing apoptosis. Thus, hydrogels that reduce extracellular Ca(2+) concentration may reduce secondary injury severity. The goal of this study was to develop composite hydrogels consisting of alginate, chitosan, and genipin that interact with extracellular Ca(2+) to enable in situ gelation while maintaining an elastic modulus similar to native spinal cord (∼1000 Pa). It was hypothesized that incorporation of genipin and chitosan would regulate hydrogel electrostatic characteristics and influence hydrogel porosity, degradation, and astrocyte behavior. Hydrogel composition was varied to create hydrogels with statistically similar mechanical properties (∼1000 Pa) that demonstrated tunable charge characteristics (6-fold range in free amine concentration) and degradation rate (complete degradation between 7 and 28 days; some blends persist after 28 days). Hydrogels demonstrate high sensitivity to Ca(2+) concentration, as a 1 mM change during fabrication induced a significant change in elastic modulus. Additionally, hydrogels incubated in a Ca(2+)-containing solution exhibited an increased linear viscoelastic limit (LVE) and an increased elastic modulus above the LVE limit in a time dependent manner. An extension of the LVE limit implies a change in hydrogel cross-linking structure. Attachment assays demonstrated that addition of chitosan/genipin to alginate hydrogels induced up to a 4-fold increase in the number of attached astrocytes and facilitated astrocyte clustering on the hydrogel surface in a composition dependent manner. Furthermore, Western blots demonstrated tunable glial fibrillary acid protein (GFAP) expression in astrocytes cultured on hydrogel blends, with some hydrogel compositions demonstrating no significant increase in GFAP expression

  5. An Injectable, Calcium Responsive Composite Hydrogel for the Treatment of Acute Spinal Cord Injury

    PubMed Central

    2015-01-01

    Immediately following spinal cord injury, further injury can occur through several secondary injury cascades. As a consequence of cell lysis, an increase in extracellular Ca2+ results in additional neuronal loss by inducing apoptosis. Thus, hydrogels that reduce extracellular Ca2+ concentration may reduce secondary injury severity. The goal of this study was to develop composite hydrogels consisting of alginate, chitosan, and genipin that interact with extracellular Ca2+ to enable in situ gelation while maintaining an elastic modulus similar to native spinal cord (∼1000 Pa). It was hypothesized that incorporation of genipin and chitosan would regulate hydrogel electrostatic characteristics and influence hydrogel porosity, degradation, and astrocyte behavior. Hydrogel composition was varied to create hydrogels with statistically similar mechanical properties (∼1000 Pa) that demonstrated tunable charge characteristics (6-fold range in free amine concentration) and degradation rate (complete degradation between 7 and 28 days; some blends persist after 28 days). Hydrogels demonstrate high sensitivity to Ca2+ concentration, as a 1 mM change during fabrication induced a significant change in elastic modulus. Additionally, hydrogels incubated in a Ca2+-containing solution exhibited an increased linear viscoelastic limit (LVE) and an increased elastic modulus above the LVE limit in a time dependent manner. An extension of the LVE limit implies a change in hydrogel cross-linking structure. Attachment assays demonstrated that addition of chitosan/genipin to alginate hydrogels induced up to a 4-fold increase in the number of attached astrocytes and facilitated astrocyte clustering on the hydrogel surface in a composition dependent manner. Furthermore, Western blots demonstrated tunable glial fibrillary acid protein (GFAP) expression in astrocytes cultured on hydrogel blends, with some hydrogel compositions demonstrating no significant increase in GFAP expression compared

  6. 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.

  7. 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

  8. Spinal Cord Injury

    MedlinePlus

    ... Types of illnesses and disabilities Spinal cord injury Spinal cord injury Read advice from Dr. Jeffrey Rabin , a ... your health on a daily basis. Living with spinal cord injury — your questions answered top What are pediatric ...

  9. Spinal Cord Injury Map

    MedlinePlus

    ... Counseling About Blog Facing Disability Jeff Shannon Donate Spinal Cord Injury Map Loss of function depends on what ... control. Learn more about spinal cord injuries. A spinal cord injury affects the entire family FacingDisability is designed ...

  10. Spinal Cord Tumor

    MedlinePlus

    Spinal cord tumor Overview By Mayo Clinic Staff A spinal tumor is a growth that develops within your ... as vertebral tumors. Tumors that begin within the spinal cord itself are called spinal cord tumors. There are ...

  11. 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.

  12. Lipoprotein(a)-hyperlipoproteinemia as cause of chronic spinal cord ischemia resulting in progressive myelopathy - successful treatment with lipoprotein apheresis.

    PubMed

    Heigl, Franz; Hettich, Reinhard; Mauch, Erich; Klingel, Reinhard; Fassbender, Cordula

    2017-03-01

    High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life.Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.

  13. Optimizing Hemodynamic Support of Acute Spinal Cord Injury Based on Injury Mechanism

    DTIC Science & Technology

    2015-10-01

    1 sheds light on the dynamic changes that occur with oxygenation , blood flow, and metabolic responses in the penumbra of the traumatic spinal cord...critical reduction of substrate (glucose/ oxygen ) delivery. Following decompression only partially recovery was observed for blood flow, oxygen and glucose...and persisted for several hours. Distal to the injury we also observed a decrease in spinal cord oxygenation although more progressive over time

  14. 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

  15. Calorie and Protein Intake in Acute Rehabilitation Inpatients with Traumatic Spinal Cord Injury Versus Other Diagnoses

    PubMed Central

    2013-01-01

    Background: Obesity and its consequences affect patients with spinal cord injury (SCI). There is a paucity of data with regard to the dietary intake patterns of patients with SCI in the acute inpatient rehabilitation setting. Our hypothesis is that acute rehabilitation inpatients with SCI consume significantly more calories and protein than other inpatient rehabilitation diagnoses. Objective: To compare calorie and protein intake in patients with new SCI versus other diagnoses (new traumatic brain injury [TBI], new stroke, and Parkinson’s disease [PD]) in the acute inpatient rehabilitation setting. Methods: The intake of 78 acute rehabilitation inpatients was recorded by registered dieticians utilizing once-weekly calorie and protein intake calculations. Results: Mean ± SD calorie intake (kcal) for the SCI, TBI, stroke, and PD groups was 1,967.9 ± 611.6, 1,546.8 ± 352.3, 1,459.7 ± 443.2, and 1,459.4 ± 434.6, respectively. ANOVA revealed a significant overall group difference, F(3, 74) = 4.74, P = .004. Mean ± SD protein intake (g) for the SCI, TBI, stroke, and PD groups was 71.5 ± 25.0, 61.1 ± 12.8, 57.6 ± 16.6, and 55.1 ± 19.1, respectively. ANOVA did not reveal an overall group difference, F(3, 74) = 2.50, P = .066. Conclusions: Given the diet-related comorbidities and energy balance abnormalities associated with SCI, combined with the intake levels demonstrated in this study, education with regard to appropriate calorie intake in patients with SCI should be given in the acute inpatient rehabilitation setting. PMID:23960707

  16. Effect of acute lateral hemisection of the spinal cord on spinal neurons of postural networks.

    PubMed

    Zelenin, P V; Lyalka, V F; Orlovsky, G N; Deliagina, T G

    2016-12-17

    In quadrupeds, acute lateral hemisection of the spinal cord (LHS) severely impairs postural functions, which recover over time. Postural limb reflexes (PLRs) represent a substantial component of postural corrections in intact animals. The aim of the present study was to characterize the effects of acute LHS on two populations of spinal neurons (F and E) mediating PLRs. For this purpose, in decerebrate rabbits, responses of individual neurons from L5 to stimulation causing PLRs were recorded before and during reversible LHS (caused by temporal cold block of signal transmission in lateral spinal pathways at L1), as well as after acute surgical LHS at L1. Results obtained after Sur-LHS were compared to control data obtained in our previous study. We found that acute LHS caused disappearance of PLRs on the affected side. It also changed a proportion of different types of neurons on that side. A significant decrease and increase in the proportion of F- and non-modulated neurons, respectively, was found. LHS caused a significant decrease in most parameters of activity in F-neurons located in the ventral horn on the lesioned side and in E-neurons of the dorsal horn on both sides. These changes were caused by a significant decrease in the efficacy of posture-related sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to both F- and E-neurons. These distortions in operation of postural networks underlie the impairment of postural control after acute LHS, and represent a starting point for the subsequent recovery of postural functions.

  17. The cross-talk between autophagy and endoplasmic reticulum stress in blood-spinal cord barrier disruption after spinal cord injury

    PubMed Central

    He, Zili; Zou, Shuang; Wang, Qingqing; Li, Jiawei; Zheng, Zengming; Chen, Jian; Wu, Fenzan; Gong, Fanhua; Zhang, Hongyu; Xu, Huazi; Xiao, Jian

    2017-01-01

    Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in

  18. The cross-talk between autophagy and endoplasmic reticulum stress in blood-spinal cord barrier disruption after spinal cord injury.

    PubMed

    Zhou, Yulong; Wu, Yanqing; Liu, Yanlong; He, Zili; Zou, Shuang; Wang, Qingqing; Li, Jiawei; Zheng, Zengming; Chen, Jian; Wu, Fenzan; Gong, Fanhua; Zhang, Hongyu; Xu, Huazi; Xiao, Jian

    2017-01-03

    Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro. ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in

  19. Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury

    PubMed Central

    Anderson, Kimberly M.; Welsh, C. Jane; Young, Colin; Levine, Gwendolyn J.; Kerwin, Sharon C.; Boudreau, C. Elizabeth; Reyes, Ismael; Mondragon, Armando; Griffin, John F.; Cohen, Noah D.

    2015-01-01

    Abstract Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target. PMID:26186466

  20. Spinal cord astrocytoma mimicking multifocal myelitis

    PubMed Central

    Neutel, Dulce; Teodoro, Tiago; Coelho, Miguel; Pimentel, José; Albuquerque, Luísa

    2014-01-01

    Introduction Differential diagnosis of acute/subacute intrinsic spinal cord lesions can be challenging. In addition, intramedullary neoplasms typically show gadolinium enhancement, mass effect, and cord expansion. Case report We report a patient with spinal cord and brain stem lesions resembling multifocal myelitis. Magnetic resonance imaging showed no spinal cord enlargement or gadolinium enhancing. Treatment of myelitis was undertaken without stopping the progression of the disease. Biopsy was made and led to a histological diagnosis of astrocytoma. Discussion Astrocytoma must remain as a possible diagnosis of spinal cord lesions, even without typical characteristics of neoplasms. Furthermore, biopsy should always be considered when diagnosis is uncertain. PMID:24621037

  1. Elevated serum lactoferrin and neopterin are associated with postoperative infectious complications in patients with acute traumatic spinal cord injury

    PubMed Central

    Du, Gang; Wei, Chengshou; Gu, Song; Tang, Jun

    2013-01-01

    Introduction Several studies have shown that lactoferrin (LF) and neopterin (NT) are correlated with infection. The aim of this study is to determine whether serum levels of LF and NT are associated with postoperative infectious complications in patients with acute traumatic spinal cord injury. Material and methods A total of 268 patients with acute traumatic spinal cord injury who underwent spinal surgery were enrolled in this study. Serum levels of LF, NT, and C-reactive protein (CRP), in addition to white blood cell count (WBC) and erythrocyte sedimentation rate (ESR), were measured preoperatively and 24 h postoperatively. Results In total, 22 of 268 patients (8.2%) developed postoperative infectious complications. The levels of serum LF, NT, and CRP were significantly higher in the infected patients than in the non-infected patients. No significant differences were observed in postoperative WBC count and ESR between the two groups. Multivariate logistic regression revealed that LF (OR: 1.004 (1.002–1.007)), NT (OR: 1.137 (1.054–1.227)), and CRP (OR: 1.023 (1.002–1.044)) were significantly associated with the presence of postoperative infectious complications. The area under receiver operating characteristic curves for LF, NT, and CRP was 0.709, 0.779, and 0.629, respectively. Conclusions Elevated serum concentrations of LF and NT are associated with early infection after surgery. Compared to CRP, elevated levels of LF and NT are better indicators for predicting postoperative infectious complications in patients with acute traumatic spinal cord injury. PMID:24273571

  2. 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

  3. Spinal Cord Injury

    MedlinePlus

    ... care for people with spinal cord injuries and aggressive treatment and rehabilitation can minimize damage to the ... care for people with spinal cord injuries and aggressive treatment and rehabilitation can minimize damage to the ...

  4. Value of MRI and DTI as Biomarkers for Classifying Acute Spinal Cord Injury

    DTIC Science & Technology

    2014-10-29

    trajectories. Results: Spinal cord hemorrhage and edema on anatomic MRI, and FA, ADC, RD and AD indices derived from DTI data correlate significantly to...features is reproducible among observers. MRI provides excellent definition of intramedullary hemorrhage and edema in animal models. The combination of...prognosis. Cord edema alone (Type II pattern of injury) was found in patients with mild to moderate initial neurologic deficits who subsequently showed

  5. 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

  6. 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, ...

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

    PubMed

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

    2016-05-16

    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 biomarker 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 [(18)F] Fluorodeoxyglucose (FDG) was performed prior to injury and at 6 and 24h and 15days post-injury (dpi). FDG-PET imaging revealed significantly depressed glucose uptake at 6h post-injury at the lesion epicenter that returned to sham/naïve levels at 24h 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Enhancement of brain plasticity and recovery of locomotive function after lumbar spinal cord stimulation in combination with gait training with partial weight support in rats with cerebral ischemia.

    PubMed

    Choi, Yoon-Hee; Lee, Shi-Uk

    2017-02-22

    Lumbar spinal cord stimulation (LSCS) is reportedly effective for the recovery of locomotive intraspinal neural network, motor cortex and basal ganglia in animals with complete spinal cord injury and parkinsonism. We evaluated the effect of LSCS in combination with gait training on the recovery of locomotive function and brain plasticity using a rat model of brain ischemia. Adult male Sprague Dawley rats with ischemia were randomly assigned into one of four groups: sham treatment (group 1), LSCS only (group 2), LSCS with gait training and 50% (group 3) and 80% (group 4) of body weight support. Evaluations before randomization and 4 weeks after intervention included motor scoring index, real-time PCR and Western blot. Motor scoring index was significantly improved after the intervention in groups 2 and 3. The ratio of phospho-Protein Kinase C (PKC) to PKC measured in the infarcted area tended to be higher in groups 3 and 4. Protein expression of mGluR2 and mRNA expression of mGluR1 measured in the contralateral cortex were lower in groups 3 and 4. The ratio of phospho-Akt to Akt and mRNA expression of vascular endothelial growth factor measured in the ischemic border zone were higher in group 2. The mRNA expression of MAP1b measured in the infarcted area was significantly higher in group 2. The findings suggest that LSCS and gait training with an adequate amount of body weight support may promote brain plasticity and facilitate the functional recovery.

  13. [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.

  14. 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.

  15. Parallel Metabolomic Profiling of Cerebrospinal Fluid and Serum for Identifying Biomarkers of Injury Severity after Acute Human Spinal Cord Injury

    PubMed Central

    Wu, Yiman; Streijger, Femke; Wang, Yining; Lin, Guohui; Christie, Sean; Mac-Thiong, Jean-Marc; Parent, Stefan; Bailey, Christopher S.; Paquette, Scott; Boyd, Michael C.; Ailon, Tamir; Street, John; Fisher, Charles G.; Dvorak, Marcel F.; Kwon, Brian K.; Li, Liang

    2016-01-01

    Suffering an acute spinal cord injury (SCI) can result in catastrophic physical and emotional loss. Efforts to translate novel therapies in acute clinical trials are impeded by the SCI community’s singular dependence upon functional outcome measures. Therefore, a compelling rationale exists to establish neurochemical biomarkers for the objective classification of injury severity. In this study, CSF and serum samples were obtained at 3 time points (~24, 48, and 72 hours post-injury) from 30 acute SCI patients (10 AIS A, 12 AIS B, and 8 AIS C). A differential chemical isotope labeling liquid chromatography mass spectrometry (CIL LC-MS) with a universal metabolome standard (UMS) was applied to the metabolomic profiling of these samples. This method provided enhanced detection of the amine- and phenol-containing submetabolome. Metabolic pathway analysis revealed dysregulations in arginine-proline metabolism following SCI. Six CSF metabolites were identified as potential biomarkers of baseline injury severity, and good classification performance (AUC > 0.869) was achieved by using combinations of these metabolites in pair-wise comparisons of AIS A, B and C patients. Using the UMS strategy, the current data set can be expanded to a larger cohort for biomarker validation, as well as discovering biomarkers for predicting neurologic outcome. PMID:27966539

  16. 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

  17. 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 Central

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

    2014-01-01

    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 are 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 noninvasive approach to increase the levels of GFLs in the spinal cord is through exercise (Ex), and to date exercise training is the only ameliorative, nonpharmacological treatment for SCI-induced neuropathic pain. The purpose of this study was three 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 20 minutes, 5d/week starting at 5 days post injury (dpi), continuing until 9 or 37 dpi. 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

  18. 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

  19. Paralysis caused by acute myelitis in Theiler's murine encephalomyelitis virus strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal cord.

    PubMed

    Kohanawa, M; Asano, M; Min, Y; Minagawa, T; Nakane, A

    1995-09-01

    Intravenous infection by Theiler's murine encephalomyelitis virus strain GD VII causes acute encephalomyelitis and paralysis in infected mice. However, nude mice and cyclophosphamide-treated ddY mice did not show paralysis when they were able to survive until day 20 post-infection (p.i.). Of ddY mice infected with 5 x 10(7) p.f.u./mouse, 70-80% showed symptoms of paralysis on day 20 p.i. The viral titres in the brain and spinal cord in infected mice were not significantly different between paralytic and non-paralytic mice. In all of the mice infected with the virus, CD4+ lymphocytes and CD8+ lymphocytes had infiltrated the brain on days 10, 12, 14 and 20 p.i. as demonstrated by flow cytometric analysis. In contrast, few T lymphocytes infiltrated the spinal cord in the non-paralytic mice. Administration of an anti-CD4 monoclonal antibody (MAb) or anti-T cell receptor-alpha beta MAb on day 6 p.i. inhibited paralysis until day 20 p.i., though 20% of the MAb-treated mice and 80% of the control mice showed paralysis. Administration of anti-CD8 MAb was not effective in the suppression of paralysis. The MAb treatment did not significantly augment viral replication in the spinal cord, although the viral titres in the brain of the MAb-treated mice increased significantly. After the transfer of spleen cells from infected C3H mice, the recipient mice infected with a small amount of the virus showed paralysis, though uninfected mice did not. This transfer could be blocked by CD4+ lymphocyte depletion of the donor mice. These results indicate that paralysis caused by acute myelitis in Theiler's virus strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal cord.

  20. Efficacy of Acute Intermittent Hypoxia on Physical Function and Health Status in Humans with Spinal Cord Injury: A Brief Review

    PubMed Central

    Astorino, Todd A.; Harness, Eric T.; White, Ailish C.

    2015-01-01

    Spinal cord injury (SCI) results in a loss of motor and sensory function and is consequent with reductions in locomotion, leading to a relatively sedentary lifestyle which predisposes individuals to premature morbidity and mortality. Many exercise modalities have been employed to improve physical function and health status in SCI, yet they are typically expensive, require many trained clinicians to implement, and are thus relegated to specialized rehabilitation centers. These characteristics of traditional exercise-based rehabilitation in SCI make their application relatively impractical considering the time-intensive nature of these regimens and patients' poor access to exercise. A promising approach to improve physical function in persons with SCI is exposure to acute intermittent hypoxia (IH) in the form of a small amount of sessions of brief, repeated exposures to low oxygen gas mixtures interspersed with normoxic breathing. This review summarizes the clinical application of IH in humans with SCI, describes recommended dosing and potential side effects of IH, and reviews existing data concerning the efficacy of relatively brief exposures of IH to modify health and physical function. Potential mechanisms explaining the effects of IH are also discussed. Collectively, IH appears to be a safe, time-efficient, and robust approach to enhance physical function in chronic, incomplete SCI. PMID:26167303

  1. von Frey anesthesiometry to assess sensory impairment after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs.

    PubMed

    Song, R B; Basso, D M; da Costa, R C; Fisher, L C; Mo, X; Moore, S A

    2016-03-01

    Sensory threshold (ST) was measured using an electric von Frey anesthesiometer (VFA) in all limbs of 20 normal dogs and 29 dogs with acute thoracolumbar spinal cord injury (SCI) caused by spontaneous intervertebral disc extrusion. ST values were measured at three separate time points in normal dogs and on days 3, 10 and 30 following decompressive surgery in dogs with SCI. ST values were compared between groups and correlated with locomotor recovery in SCI-affected dogs. ST values were significantly higher (consistent with hypoalgesia) in the pelvic limbs of SCI-affected dogs at day 3, day 10 and day 30 when compared to normal dogs (P <0.05), while no significant difference in thoracic limb ST values was observed between groups. A progressive decrease in pelvic limb ST values occurred in SCI-affected dogs over time, consistent with improvement toward normal sensation or development of allodynia. This finding correlated inversely with locomotor score at 3 and 10 days after surgery. A significant decline in ST values across testing sessions was observed for all limbs of normal and SCI-affected dogs and may be related to patient acclimation, operator training effect, or effect of analgesic medications. This study supports the feasibility of VFA to assess differences in ST between normal and SCI-affected dogs. However, future studies must focus on techniques to minimize or compensate for clinical, environmental and behavioral factors which may impact ST values in the clinical setting.

  2. 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

  3. Spinal cord trauma

    MedlinePlus

    ... Oh's Intensive Care Manual . 7th ed. Philadelphia, PA: Elsevier; 2014:chap 78. Bryce TN. Spinal cord injury. ... Physical Medicine and Rehabilitation . 5th ed. Philadelphia, PA: Elsevier; 2016:chap 49. Dalzell K, Nouri A, Fehlings ...

  4. Tethered Spinal Cord Syndrome

    MedlinePlus

    ... the movement of the spinal cord within the spinal column. Attachments may occur congenitally at the base of ... or may be due to narrowing of the spinal column (stenosis) with age. Tethering may also develop after ...

  5. Spinal Cord Injury 101

    MedlinePlus Videos and Cool Tools

    ... 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 ...

  6. 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.

  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, subacute and chronic effect of cyclosporin-A on mean arterial pressure of rats with severe spinal cord contusion.

    PubMed

    Romero, Samanta E; Bravo, Guadalupe; Hong, Enrique; Rojas, Guillermo; Ibarra, Antonio

    2008-11-07

    Cyclosporin-A (CsA) protects and regenerates the neural tissue after spinal cord (SC) injury. These beneficial effects are achieved when CsA is administered at a dose of 2.5mg/kg/12h during the first 2 days after lesion. In view of these observations, it is realistic to envision that, CsA could be tested in SC-clinical trials. Since CsA is a drug strongly related to hypertension, results imperative to evaluate experimentally the effect of the above CsA-dose regimen on blood pressure. For this purpose, one hundred and twenty adult rats were subjected (10 groups) or not (10 groups) to SC-injury. Five injured and five Sham-operated groups received CsA. The remaining groups received only vehicle. Mean arterial pressure (MAP) was recorded from these animals at acute (6 and 24h post surgery; p.s.), subacute (96h), or chronic (30 days) stages of injury. In the latter, the therapy (CsA or vehicle) was administered only during the first 2 days p.s. or daily during 30 days of follow-up. The results of this study showed that SC-injury by itself induces a significant decrease of MAP during the acute and subacute phases of injury. CsA therapy was able to reestablish MAP parameters to control values in these phases. Regardless the therapy, a reestablishment of MAP was observed in chronic stages. Only the daily administration of CsA induced a significant increase in MAP, however; such variation remained into the normal ranges of MAP for rats. The potential benefits offered by CsA support its usefulness after SC-injury.

  9. Canine spinal cord glioma.

    PubMed

    Rissi, Daniel R; Barber, Renee; Burnum, Annabelle; Miller, Andrew D

    2017-01-01

    Spinal cord glioma is uncommonly reported in dogs. We describe the clinicopathologic and diagnostic features of 7 cases of canine spinal cord glioma and briefly review the veterinary literature on this topic. The median age at presentation was 7.2 y. Six females and 1 male were affected and 4 dogs were brachycephalic. The clinical course lasted from 3 d to 12 wk, and clinical signs were progressive and associated with multiple suspected neuroanatomic locations in the spinal cord. Magnetic resonance imaging of 6 cases revealed T2-weighted hyperintense lesions with variable contrast enhancement in the spinal cord. All dogs had a presumptive clinical diagnosis of intraparenchymal neoplasia or myelitis based on history, advanced imaging, and cerebrospinal fluid analysis. Euthanasia was elected in all cases because of poor outcome despite anti-inflammatory or immunosuppressive treatment or because of poor prognosis at the time of diagnosis. Tumor location during autopsy ranged from C1 to L6, with no clear predilection for a specific spinal cord segment. The diagnosis was based on histopathology and the immunohistochemistry expression of glial fibrillary acidic protein, oligodendrocyte lineage transcription factor 2, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, neuron-specific enolase, synaptophysin, and Ki-67. Diagnoses consisted of 4 cases of oligodendroglioma, 2 cases of gliomatosis cerebri, and 1 astrocytoma. This case series further defines the clinicopathologic features of canine spinal glioma and highlights the need for comprehensive immunohistochemistry in addition to routine histopathology to confirm the diagnosis of these tumors.

  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. Living with Spinal Cord Injury

    MedlinePlus

    ... to send and receive messages to and from the brain. About 200,000 people in the United States have spinal cord injuries. Most injuries occur from a traumatic event, according to the National Spinal Cord Injury ...

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

    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. PMID:25847920

  14. 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

  15. Surgical Neurostimulation for Spinal Cord Injury

    PubMed Central

    Chari, Aswin; Hentall, Ian D.; Papadopoulos, Marios C.; Pereira, Erlick A. C.

    2017-01-01

    Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress in scientific understanding, regenerative therapies are lacking. In this review, we outline the current state and future potential of invasive and non-invasive neuromodulation strategies including deep brain stimulation (DBS), spinal cord stimulation (SCS), motor cortex stimulation (MCS), transcutaneous direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in the context of SCI. We consider the ability of these therapies to address pain, sensorimotor symptoms and autonomic dysregulation associated with SCI. In addition to the potential to make important contributions to SCI treatment, neuromodulation has the added ability to contribute to our understanding of spinal cord neurobiology and the pathophysiology of SCI. PMID:28208601

  16. Time-Dependent Increases in Protease Activities for Neuronal Apoptosis in Spinal Cords of Lewis Rats During Development of Acute Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Das, Arabinda; Guyton, M. Kelly; Matzelle, Denise D.; Ray, Swapan K.; Banik, Naren L.

    2008-01-01

    Multiple sclerosis (MS) is characterized by axonal demyelination and neurodegeneration, the latter having been inadequately explored in the MS animal model experimental autoimmune encephalomyelitis (EAE). The purpose of this study was to examine the time-dependent correlation between increased calpain and caspase activities and neurodegeneration in spinal cord tissues from Lewis rats with acute EAE. An increase in TUNEL-positive neurons and internucleosomal DNA fragmentation in EAE spinal cords suggested that neuronal death was a result of apoptosis on days 8–10 following induction of EAE. Increases in calpain expression in EAE correlated with activation of pro-apoptotic proteases, leading to apoptotic cell death beginning on day 8 of EAE, which occurred before the appearance of visible clinical symptoms. Increases in calcineurin expression and decreases in phospho-Bad (p-Bad) suggested Bad activation in apoptosis during acute EAE. Increases in the Bax:Bcl-2 ratio and activation of caspase-9 showed the involvement of mitochondria in apoptosis. Further, caspase-8 activation suggested induction of the death receptor–mediated pathway for apoptosis. Endoplasmic reticulum stress leading to caspase-3 activation was also observed, indicating that multiple apoptotic pathways were activated following EAE induction. In contrast, cell death was mostly a result of necrosis on the later day (day 11), when EAE entered a severe stage. From these findings, we conclude that increases in calpain and caspase activities play crucial roles in neuronal apoptosis during the development of acute EAE. PMID:18521931

  17. Acute Neuropathic Orchalgia and Scrotalgia After Percutaneous Spinal Cord Stimulator Lead Placement: Two Cases with an Unusual Complication

    PubMed Central

    Desai, Virendra R; Ho, David; Simpson, Richard K

    2017-01-01

    Spinal cord stimulation is an effective adjunct to the treatment of a variety of chronic pain syndromes. Complications are relatively low in morbidity and are most often secondary to hardware malfunction/malposition. Infection and undesired dysesthesias represent only a minority of complications. Neuropathic orchalgia and scrotalgia after placement of epidural spinal cord stimulator is a previously unreported morbidity. While alarming, this condition is physiologically benign, causing no neurological or urological dysfunction. The two cases we encountered both occurred during uncomplicated percutaneous trial stimulator placement. Corticosteroid treatment and stimulator activation facilitated resolution of the dysesthesia and allowed completion of the trial in one case, while the other case was refractory and resulted in termination of the trial. PMID:28286722

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

    PubMed Central

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

    2017-01-01

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

  19. Clinical Trial of AC105 (Mg/PEG) for Treatment of Acute Spinal Cord Injury (SCI). Phase 2

    DTIC Science & Technology

    2013-10-01

    505-9. Kwon BK, Roy J, Lee JH, Okon E, Zhang H, Marx JC, Kindy MS. (2009) Magnesium chloride in a polyethylene glycol formulation as a...13. SUPPLEMENTARY NOTES 14. ABSTRACT Acorda Therapeutics, Inc. is developing the polymer formulation of magnesium , known as AC-105...15. SUBJECT TERMS AC-105, Magnesium , Mg, Spinal Cord Injury, SCI 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

  20. A new pattern of spinal-cord demyelination in guinea pigs with acute experimental allergic encephalomyelitis mimicking multiple sclerosis.

    PubMed Central

    Colover, J.

    1980-01-01

    A technique is described for producing large demyelinating lesions of the spinal cord in the guinea pig. Guinea pigs were pretreated by immunization with ovalbumin and water-soluble adjuvant (N-acetyl-muramyl L-alanyl D-isoglutamine, MDP) in water-in-oil emulsion (Freund's incomplete adjuvant). They were given a large dose (10 mg) of ovalbumin i.p. one month later. After a few weeks the animals were sensitized with guinea-pig basic protein in Freund's complete adjuvant. Five out of 11 animals developed large, distinctive, sharply demarcated, symmetrical demyelinating lesions within 30 days. These lesions occurred in the dorsal and anterior columns, root entry zones and subpial region of the spinal cord. Histology showed a considerable amount of free lipids. There were also infiltrative lesions of classical experimental allergic encephalomyelitis (EAE) of normal severity in the same animals. The demyelinating lesions resembled those seen in multiple sclerosis in their location and extent in the spinal cord and in the presence of free lipids. Control experiments indicated that pretreatment with ovalbumin/MDP and the second injection of ovalbumin was necessary for all the demyelination; moreover guinea pigs immunized with basic protein in Freund's complete adjuvant or Freund's incomplete adjuvant plus MDP without pretreatment only developed classical EAE with minimal or no demyelination. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:7426390

  1. 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

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

    PubMed Central

    Gomes-Osman, Joyce; Cortes, Mar; Guest, James

    2016-01-01

    Abstract 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

  3. Effect of spinal cord compression on local vascular blood flow and perfusion capacity by Alshareef M, Krishna V, Ferdous J, Aishareef A, Kindy M, Kolachalama VB, et al.

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: Different degrees of blood flow/vascular compromise occur with anterior, posterior, or circumferential spinal cord compression/spinal cord injury (SCI). SCI is also divided into primary and secondary injury. Primary SCI refers to the original neurological damage to tissues, whereas secondary injury reflects interruption of normal blood flow leading to further inflammatory response/other local changes which contribute to additional neurological injury. Methods: The authors developed a quantitative “3-D finite element fluid structure interaction model” of spinal cord blood flow to better document the mechanisms of secondary ischemic damage occurring in the spinal cord anteriorly, posteriorly, or circumferentially. This included assessment of the anterior spinal artery (ASA) and five arterial branches (L1, L2, L3, R1, R2), but excluded the microvasculature. Results: Different locations of cord compression resulted in alternative patterns of spinal cord ischemia. Anterior spinal artery (ASA) flow was substantially reduced by direct anterior compression, but resulted in the least vascular compromise. Alternatively, posterior compression resulted in a significant and critical reduction of distal ASA blood flow and, therefore, correlated with the greatest susceptibility to acute ischemia. Counterintuitively, they concluded “at equivalent degrees of dural occlusion, the loss of branch blood flow under anterior posterior compression was intermediate to predictions for purely posterior or anterior loading.” Conclusion: Utilizing a computational three-dimensional model, Alshareef et al. observed that anterior cervical cord compression resulted in the least severe compromise of ASA blood flow to the spinal cord, whereas posterior cord compression/SCI maximally reduced distal ASA blood flow potentiating acute ischemia. Therefore, the latter warranted the earliest surgical intervention. PMID:27843686

  4. Metabolic profile of injured human spinal cord determined using surface microdialysis.

    PubMed

    Chen, Suliang; Phang, Isaac; Zoumprouli, Argyro; Papadopoulos, Marios C; Saadoun, Samira

    2016-12-01

    The management of patients having traumatic spinal cord injury would benefit from understanding and monitoring of spinal cord metabolic states. We hypothesized that the metabolism of the injured spinal cord could be visualized using Kohonen self-organizing maps. Sixteen patients with acute, severe spinal cord injuries were studied. Starting within 72 h of the injury, and for up to a week, we monitored the injury site hourly for tissue glucose, lactate, pyruvate, glutamate, and glycerol using microdialysis as well as intraspinal pressure and spinal cord perfusion pressure. A Kohonen map, which is an unsupervised, self-organizing topology-preserving neural network, was used to analyze 3366 h of monitoring data. We first visualized the different spinal cord metabolic states. Our data show that the injured cord assumes one or more of four metabolic states. On the basis of their metabolite profiles, we termed these states near-normal, ischemic, hypermetabolic, and distal. We then visualized how patients' intraspinal pressure and spinal cord perfusion pressure affect spinal cord metabolism. This revealed that for more than 60% of the time, spinal cord metabolism is patient-specific; periods of high intraspinal pressure or low perfusion pressure are not associated with specific spinal cord metabolic patterns. Finally, we determined relationships between spinal cord metabolism and neurological status. Patients with complete deficits have shorter periods of near-normal spinal cord metabolic states (7 ± 4% vs. 58 ± 12%, p < 0.01, mean ± standard error) and more variable injury site metabolic responses (metabolism spread in 70 ± 11 vs. 40 ± 6 hexagons, p < 0.05), compared with patients who have incomplete neurological deficits. We conclude that Kohonen maps allow us to visualize the metabolic responses of the injured spinal cord and may thus aid us in treating patients with acute spinal cord injuries.

  5. 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.

  6. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

    PubMed Central

    2013-01-01

    Introduction Intraspinal grafting of human neural stem cells represents a promising approach to promote recovery of function after spinal trauma. Such a treatment may serve to: I) provide trophic support to improve survival of host neurons; II) improve the structural integrity of the spinal parenchyma by reducing syringomyelia and scarring in trauma-injured regions; and III) provide neuronal populations to potentially form relays with host axons, segmental interneurons, and/or α-motoneurons. Here we characterized the effect of intraspinal grafting of clinical grade human fetal spinal cord-derived neural stem cells (HSSC) on the recovery of neurological function in a rat model of acute lumbar (L3) compression injury. Methods Three-month-old female Sprague–Dawley rats received L3 spinal compression injury. Three days post-injury, animals were randomized and received intraspinal injections of either HSSC, media-only, or no injections. All animals were immunosuppressed with tacrolimus, mycophenolate mofetil, and methylprednisolone acetate from the day of cell grafting and survived for eight weeks. Motor and sensory dysfunction were periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds and myogenic motor evoked potentials. The presence of spasticity was measured by gastrocnemius muscle resistance and electromyography response during computer-controlled ankle rotation. At the end-point, gait (CatWalk), ladder climbing, and single frame analyses were also assessed. Syrinx size, spinal cord dimensions, and extent of scarring were measured by magnetic resonance imaging. Differentiation and integration of grafted cells in the host tissue were validated with immunofluorescence staining using human-specific antibodies. Results Intraspinal grafting of HSSC led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at

  7. Fitness and Spinal Cord Injuries

    PubMed Central

    Mackie, J. William; McCormack, Rebecca; Campbell, Duncan

    1989-01-01

    Activity for many disabled persons often begins as therapy, but the additional rewards derived from exercise must be appreciated. Public attitudes toward disabled persons have changed during the last few decades, recently focusing on abilities rather than on disabilities. The family physician of patients with spinal cord injuries will assist in managing acute medical problems and the association with loss of some degree of physical capacity. Physicians also can guide these individuals to choose a life that remains active and interesting over a “house-bound,” but safe, existence. Sensitivity and timing play key roles in establishing exercise as an intergral part of a disabled individuals' altered lifestyle. The physician can advocate increased access to wheelchairs and other facilities that make life easier for disabled individuals. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:21248871

  8. 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

  9. Responses of the Acutely Injured Spinal Cord to Vibration that Simulates Transport in Helicopters or Mine-Resistant Ambush-Protected Vehicles.

    PubMed

    Streijger, Femke; Lee, Jae H T; Manouchehri, Neda; Melnyk, Angela D; Chak, Jason; Tigchelaar, Seth; So, Kitty; Okon, Elena B; Jiang, Shudong; Kinsler, Rachel; Barazanji, Khalid; Cripton, Peter A; Kwon, Brian K

    2016-12-15

    In the military environment, injured soldiers undergoing medical evacuation via helicopter or mine-resistant ambush-protected vehicle (MRAP) are subjected to vibration and shock inherent to the transport vehicle. We conducted the present study to assess the consequences of such vibration on the acutely injured spinal cord. We used a porcine model of spinal cord injury (SCI). After a T10 contusion-compression injury, animals were subjected to 1) no vibration (n = 7-8), 2) whole body vibration at frequencies and amplitudes simulating helicopter transport (n = 8), or 3) whole body vibration simulating ground transportation in an MRAP ambulance (n = 7). Hindlimb locomotor function (using Porcine Thoracic Injury Behavior Scale [PTIBS]), Eriochrome Cyanine histochemistry and biochemical analysis of inflammatory and neural damage markers were analyzed. Cerebrospinal fluid (CSF) expression levels for monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-8, and glial fibrillary acidic protein (GFAP) were similar between the helicopter or MRAP group and the unvibrated controls. Spared white/gray matter tended to be lower in the MRAP-vibrated animals than in the unvibrated controls, especially rostral to the epicenter. However, spared white/gray matter in the helicopter-vibrated group appeared normal. Although there was a relationship between the extent of sparing and the extent of locomotor recovery, no significant differences were found in PTIBS scores between the groups. In summary, exposures to vibration in the context of ground (MRAP) or aeromedical (helicopter) transportation did not significantly impair functional outcome in our large animal model of SCI. However, MRAP vibration was associated with increased tissue damage around the injury site, warranting caution around exposure to vehicle vibration acutely after SCI.

  10. 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

    Dvorak, Marcel F; 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

    2015-05-01

    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.

  11. 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

  12. Targeted Iron Chelation Will Improve Recovery after Spinal Cord Injury

    DTIC Science & Technology

    2014-10-01

    Treatment with the flavonoid quercetin starting 1 h after compression SCI in rats had a var- iable effect on improving locomotor function in that a...Kendall, E., Kamencic, H., Ghong, Z., Griebel, R.W., Juurlink, B.H., 2003. Quercetin promotes functional recovery following acute spinal cord injury. J...Neurotrauma 20 (6), 583-591. Schultke, E., Griebel, R.W., Juurlink, B.H., 2010a. Quercetin attenuates inflammatory pro- cesses after spinal cord

  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. 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

  15. 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.

  16. 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…

  17. The dura causes spinal cord compression after spinal cord injury.

    PubMed

    Saadoun, Samira; Werndle, Melissa C; Lopez de Heredia, Luis; Papadopoulos, Marios C

    2016-10-01

    MR scans from 65 patients with traumatic spinal cord injury were analysed; on admission 95% had evidence of cord compression - in 26% due to the dura, and in the remaining 74% due to extradural factors. Compression due to dural factors resolved with a half-life of 5.5 days. These findings suggest that bony decompression alone may not relieve spinal cord compression in the quarter of patients in whom dural factors are significant.

  18. Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

    PubMed Central

    Li, JingLun; Deng, JiaoJiao; Yuan, JinXian; Fu, Jie; Li, XiaoLing; Tong, AiPing; Wang, YueLong; Chen, YangMei; Guo, Gang

    2017-01-01

    Spinal cord injury (SCI) commonly leads to lifelong disability due to the limited regenerative capacity of the adult central nervous system. Nanomicelles can be used as therapeutic systems to provide effective treatments for SCI. In this study, a novel triblock monomethyl poly(ethylene glycol)-poly(l-lactide)-poly(trimethylene carbonate) copolymer was successfully synthesized. Next, polymeric nanomicelles loaded with zonisamide (ZNS), a Food and Drug Administration-approved antiepileptic drug, were prepared and characterized. The ZNS-loaded micelles (ZNS-M) were further utilized for the treatment of SCI in vitro and in vivo. The obtained ZNS-M were ~50 nm in diameter with good solubility and dispersibility. Additionally, these controlled-release micelles showed significant antioxidative and neuron-protective effects in vitro. Finally, our results indicated that ZNS-M treatment could promote motor function recovery and could increase neuron and axon density in a hemisection SCI model. In summary, these results may provide an experimental basis for the use of ZNS-M as a clinically applicable therapeutic drug for the treatment of SCI in the future.

  19. How to prevent spinal cord injury during endovascular repair of thoracic aortic disease.

    PubMed

    Uchida, Naomichi

    2014-07-01

    The incidence of spinal cord injury in thoracic endovascular aortic repair (TEVAR) has been 3-5 % from recent major papers where sacrifice of the critical intercostal arteries is inevitable by a stent graft. Hemodynamic stability, which depends on a network of blood vessels around the cord is most important not only during but also after stent-graft deployment. High risk factors of spinal cord injury during endovascular aortic repair are (1) coverage of the left subclavian artery, (2) extensive coverage of long segments of the thoracic aorta, (3) prior downstream aortic repair, (4) compromising important intercostal (T8-L1), vertebral, pelvic and hypogastric collaterals, and (5) shaggy aorta. Preoperative, intraoperative, and postoperative managements have been required to prevent spinal cord injury with TEVAR. For imaging assessment of blood supply to spinal cord including Adamkiewicz artery, prophylactic cerebrospinal fluid drainage is mandatory, and monitoring motor-evoked potential is recommended for high risk factors of spinal cord injury. Mean arterial pressure should be maintained over 90 mmHg after stent-graft placement for a while to prevent delayed spinal cord ischemia in high-risk patients of spinal cord ischemia. Finally, because spinal cord injury during TEVAR is not rare and negligible, perioperative care during TEVAR should be strictly performed according to the protocol proposed by each cardiovascular team.

  20. Early radiation-induced endothelial cell loss and blood-spinal cord barrier breakdown in the rat spinal cord.

    PubMed

    Li, Yu-Qing; Chen, Paul; Jain, Vipan; Reilly, Raymond M; Wong, C Shun

    2004-02-01

    Using a rat spinal cord model, this study was designed to characterize radiation-induced vascular endothelial cell loss and its relationship to early blood-brain barrier disruption in the central nervous system. Adult rats were given a single dose of 0, 2, 8, 19.5, 22, 30 or 50 Gy to the cervical spinal cord. At various times up to 2 weeks after irradiation, the spinal cord was processed for histological and immunohistochemical analysis. Radiation-induced apoptosis was assessed by morphology and TdT-mediated dUTP nick end labeling combined with immunohistochemical markers for endothelial and glial cells. Image analysis was performed to determine endothelial cell and microvessel density using immunohistochemistry with endothelial markers, namely endothelial barrier antigen, glucose transporter isoform 1, laminin and zonula occludens 1. Blood-spinal cord barrier permeability was assessed using immunohistochemistry for albumin and (99m)Tc-diethylenetriamine pentaacetic acid as a vascular tracer. Endothelial cell proliferation was assessed using in vivo BrdU labeling. During the first 24 h after irradiation, apoptotic endothelial cells were observed in the rat spinal cord. The decrease in endothelial cell density at 24 h after irradiation was associated with an increase in albumin immunostaining around microvessels. The decrease in the number of endothelial cells persisted for 7 days and recovery of endothelial density was apparent by day 14. A similar pattern of blood-spinal cord barrier disruption and recovery of permeability was observed over the 2 weeks, and an increase in BrdU-labeled endothelial cells was seen at day 3. These results are consistent with an association between endothelial cell death and acute blood-spinal cord barrier disruption in the rat spinal cord after irradiation.

  1. Paraplegia Due to Spinal Cord Infarction After Coronary Artery Bypass Graft Surgery.

    PubMed

    Sevuk, Utkan; Kaya, Sedat; Ayaz, Firat; Aktas, Ulas

    2016-01-01

    Paraplegia is an extremely rare complication after coronary artery bypass grafting (CABG) and the underlying mechanisms remain poorly understood. We report a patient who developed paraplegia after CABG and review the literature on spinal cord ischemia following CABG surgery.

  2. Overview of Spinal Cord Disorders

    MedlinePlus

    ... cord consists of gray matter shaped like a butterfly: The front "wings" (anterior or motor horns) contain ... In the center of the spinal cord, a butterfly-shaped area of gray matter helps relay impulses ...

  3. Depression and Spinal Cord Injury

    MedlinePlus

    ... colleagues, with an educational grant from Pfizer Inc. University of Washington-operated SCI Clinics: Harborview Medical Center ... Spinal Cord Injury Clinic nurses: 206-744-5862 University of Washington Medical Center Rehabilitation Medicine Clinic 1959 ...

  4. Spinal cord compression from Wegener’s granulomatosis: an unusual presentation

    PubMed Central

    Roy, Deb; Phan, Kevin; Mobbs, Ralph J.; Selby, Michael

    2016-01-01

    Wegener’s granulomatosis (WG) causing spinal cord compression is very rare with only few cases reported in literature. We present a case report with review of literature. A 55-year-old lady with known WG presented with acute on chronic spinal cord compression. MRI scan revealed spinal cord compression anteriorly and posteriorly at T2–T5 level. Patient underwent urgent surgical decompression with excision of the posterior dural lesion with synthetic duraplasty. Patient made good neurological recovery. Histopathology revealed features consistent with WG. A rare case of spinal cord compression from WG is presented. Urgent surgical decompression with duraplasty resulted in good neurological outcome. PMID:28097250

  5. 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

  6. Effects of electromyostimulation on muscle and bone in men with acute traumatic spinal cord injury: A randomized clinical trial

    PubMed Central

    Arija-Blázquez, Alfredo; Ceruelo-Abajo, Silvia; Díaz-Merino, María S.; Godino-Durán, Juan Antonio; Martínez-Dhier, Luís; Martin, José L. R.; Florensa-Vila, José

    2014-01-01

    Objective To study the effect of 14 weeks of electromyostimulation (EMS) training (47 minutes/day, 5 days/week) on both muscle and bone loss prevention in persons with recent, complete spinal cord injury (SCI). Design Prospective, experimental, controlled, single-blind randomized trial with external blind evaluation by third parties. Methods Eight men with recent SCI (8 weeks from injury; ASIA Impairment Scale (AIS) “A”) were randomized into the intervention or the control groups. Cross-sectional area of the quadriceps femoris (QF) muscle was quantified using magnetic resonance imaging. Bone mineral density changes were assessed with a dual-energy X-ray absorptiometry. Several bone biomarkers (i.e. total testosterone, cortisol, growth hormone, insulin-growth factor I, osteocalcin, serum type I collagen C-telopeptide), lipid, and lipoprotein profiles were quantified. A standard oral glucose tolerance test was performed before and after the 14-week training. All analyses were conducted at the beginning and after the intervention. Results The intervention group showed a significant increase in QF muscle size when compared with the control group. Bone losses were similar in both groups. Basal levels of bone biomarkers did not change over time. Changes in lipid and lipoprotein were similar in both groups. Glucose and insulin peaks moved forward after the training in the intervention group. Conclusions This study indicates that skeletal muscle of patients with complete SCI retains the ability to grow in response to a longitudinal EMS training, while bone does not respond to similar external stimulus. Increases in muscle mass might have induced improvements in whole body insulin-induced glucose uptake. PMID:24090427

  7. Magnetic resonance imaging and motor-evoked potentials in spinal cord infarction: report of two cases.

    PubMed

    Nardone, Raffaele; Bergmann, Jürgen; Kronbichler, Martin; Lochner, Piergiorgio; Caleri, Francesca; Tezzon, Frediano; Ladurner, Gunther; Golaszewski, Stefan

    2010-08-01

    Because in the early phases of spinal cord ischemia magnetic resonance imaging (MRI) can be normal, its clinical diagnosis is often difficult. We aimed to explore if motor-evoked potentials (MEPs) recordings may contribute to earlier diagnosis of spinal cord stroke. The clinical, MRI, and MEP findings in one case each of cervical and lumbar spinal cord infarction were reported. Spinal MRI at admission was unremarkable in both patients. At this time, MEPs were abnormal in both patients, to the upper and lower limbs in the first patient, exclusively to the lower limbs in the second. Follow-up MRI examinations documented an infarction in the territory of the anterior spinal artery and of the Adamkiewicz artery, respectively. MEP study can be useful in demonstrating spinal cord involvement also when radiological evidence for spinal cord damage is absent or equivocal. Early diagnosis may allow earlier intervention and contribute to improved patient management.

  8. RNA-Seq Characterization of Spinal Cord Injury Transcriptome in Acute/Subacute Phases: A Resource for Understanding the Pathology at the Systems Level

    PubMed Central

    Chen, Kenian; Deng, Shuyun; Lu, Hezuo; Zheng, Yiyan; Yang, Guodong; Kim, Dong; Cao, Qilin; Wu, Jia Qian

    2013-01-01

    Spinal cord injury (SCI) is a devastating neurological disease without effective treatment. To generate a comprehensive view of the mechanisms involved in SCI pathology, we applied RNA-Sequencing (RNA-Seq) technology to characterize the temporal changes in global gene expression after contusive SCI in mice. We sequenced tissue samples from acute and subacute phases (2 days and 7 days after injury) and systematically characterized the transcriptomes with the goal of identifying pathways and genes critical in SCI pathology. The top enriched functional categories include “inflammation response,” “neurological disease,” “cell death and survival” and “nervous system development.” The top enriched pathways include LXR/RXR Activation and Atherosclerosis Signaling, etc. Furthermore, we developed a systems-based analysis framework in order to identify key determinants in the global gene networks of the acute and sub-acute phases. Some candidate genes that we identified have been shown to play important roles in SCI, which demonstrates the validity of our approach. There are also many genes whose functions in SCI have not been well studied and can be further investigated by future experiments. We have also incorporated pharmacogenomic information into our analyses. Among the genes identified, the ones with existing drug information can be readily tested in SCI animal models. Therefore, in this study we have described an example of how global gene profiling can be translated to identifying genes of interest for functional tests in the future and generating new hypotheses. Additionally, the RNA-Seq enables splicing isoform identification and the estimation of expression levels, thus providing useful information for increasing the specificity of drug design and reducing potential side effect. In summary, these results provide a valuable reference data resource for a better understanding of the SCI process in the acute and sub-acute phases. PMID:23951329

  9. Open Access Platforms in Spinal Cord Injury.

    PubMed

    Kramer, John L K; Geisler, Fred; Ramer, Leanne; Plunet, Ward; Cragg, Jacquelyn J

    2017-01-01

    Recovery from acute spinal cord injury (SCI) is characterized by extensive heterogeneity, resulting in uncertain prognosis. Reliable prediction of recovery in the acute phase benefits patients and their families directly, as well as improves the likelihood of detecting efficacy in clinical trials. This issue of heterogeneity is not unique to SCI. In fields such as traumatic brain injury, Parkinson's disease, and amyotrophic lateral sclerosis, one approach to understand variability in recovery has been to make clinical trial data widely available to the greater research community. We contend that the SCI community should adopt a similar approach in providing open access clinical trial data.

  10. Alterations in cardiac autonomic control in spinal cord injury.

    PubMed

    Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan; Malmqvist, Lasse; Wecht, Jill Maria; Krassioukov, Andrei

    2017-02-15

    A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury.

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

    DTIC Science & Technology

    2015-10-01

    ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite this fact...that stretching for short periods of time (4-5 weeks ) allows substantial recovery to occur once stretching is stopped, and both acute and chronic...4hours after one stretching session and then on Friday afternoon 3-4hours after the final stretching session of the week (the lowest scores). As seen

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

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-12-1-0587 TITLE: Directing Spinal Cord Plasticity: The Impact of Stretch ...Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury. 5b. GRANT NUMBER W81XWH-12-1...ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite

  13. Timing of Surgery After Spinal Cord Injury.

    PubMed

    Piazza, Matthew; Schuster, James

    2017-01-01

    Although timing for surgical intervention after spinal cord injury remains controversial, there is accumulating evidence suggesting that early surgery may improve neurologic outcomes, particularly with incomplete spinal cord injury, and may reduce non-neurologic complications and health care resource utilization. Moreover, even in patients with complete spinal cord injury, minor improvement in neurologic function can lead to significant changes in quality of life. This article reviews the experimental and clinical data examining surgical timing after spinal cord injury.

  14. Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease.

    PubMed

    Henke, D; Vandevelde, M; Doherr, M G; Stöckli, M; Forterre, F

    2013-10-01

    The outcome of spinal surgery in dogs with absent voluntary motor function and nociception following intervertebral disc (IVD) herniation is highly variable, which likely attests to differences in the severity of spinal cord damage. This retrospective study evaluated the extent to which neurological signs correlated with histologically detected spinal cord damage in 60 dogs that were euthanased because of thoracolumbar IVD herniation. Clinical neurological grades correlated significantly with the extent of white matter damage (P<0.001). However, loss of nociception also occurred in 6/31 (19%) dogs with relatively mild histological changes. The duration of clinical signs, Schiff-Sherrington posture, loss of reflexes and pain on spinal palpation were not significantly associated with the severity of spinal cord damage. Although clinical-pathological correlation was generally good, some clinical signs frequently thought to indicate severe cord injury did not always correlate with the degree of cord damage, suggesting functional rather than structural impairment in some cases.

  15. Aquaporins in the Spinal Cord

    PubMed Central

    Oklinski, Michal K.; Skowronski, Mariusz T.; Skowronska, Agnieszka; Rützler, Michael; Nørgaard, Kirsten; Nieland, John D.; Kwon, Tae-Hwan; Nielsen, Søren

    2016-01-01

    Aquaporins (AQPs) are water channel proteins robustly expressed in the central nervous system (CNS). A number of previous studies described the cellular expression sites and investigated their major roles and function in the brain and spinal cord. Among thirteen different mammalian AQPs, AQP1 and AQP4 have been mainly studied in the CNS and evidence has been presented that they play important roles in the pathogenesis of CNS injury, edema and multiple diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, amyotrophic lateral sclerosis, glioblastoma multiforme, Alzheimer’s disease and Parkinson’s disease. The objective of this review is to highlight the current knowledge about AQPs in the spinal cord and their proposed roles in pathophysiology and pathogenesis related to spinal cord lesions and injury. PMID:27941618

  16. [Surgical anatomy of spinal cord tumors].

    PubMed

    Peltier, J; Chenin, L; Hannequin, P; Page, C; Havet, É; Foulon, P; Le Gars, D

    2015-08-03

    In this article, we respectively describe the morphology of the spinal cord, spinal meningeal layers, main fiber tracts, and both arterial and venous distribution in order to explain signs of spinal cord compression. We will then describe a surgical technique for spinal cord tumor removal.

  17. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2014-04-01

    in order to minimize scarring and injected dissociated adult DRGs rostral to a dorsal column transection of the spinal cord. From the sensory... columns were dissected and post-fixed overnight in 4% paraformaldehyde, and then spinal cords were dissected from spinal columns and cryoprotected...AD______________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered Nervous Tissue

  18. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... Search Search En Español Category Cancer A-Z Brain and Spinal Cord Tumors in Adults If you have a brain or spinal cord tumor or are close to ... cope. Here you can find out all about brain and spinal cord tumors in adults, including risk ...

  19. 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

  20. 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

  1. Role of histamine in posttraumatic spinal cord hyperemia and the luxury perfusion syndrome.

    PubMed

    Kobrine, A I; Doyle, T F

    1976-01-01

    The authors studied the effect of pretreatment of monkeys with antihistamines on hyperemia observed in the lateral funiculus of the spinal cord after severe experimental spinal cord trauma. After administration of Chlorpheniramine and Metiamide, the spinal cords were traumatized with a 600 gm-cm injury. Blood flow in the lateral funiculus at the injury site was then determined hourly for 6 hours. The blood flow at this site remained in the normal range at all times in all animals. Neither a hyperemia nor an ischemia could be demonstrated. This finding reaffirms the authors' previous observation that ischemia does not exist in the lateral funiculus after severe experimental spinal cord trauma, and explains the previous observation of hyperemia as a histamine-related phenomenon, easily blocked by the administration of Chlorpheniramine and Metiamide, potent antihistamines which together block both the H1 and H2 receptor sites.

  2. Cervical Spinal Cord Compression: A Rare Presentation of Hepatocellular Carcinoma

    PubMed Central

    Chime, Chukwunonso; Arjun, Shiva; Reddy, Pavithra; Niazi, Masooma

    2017-01-01

    Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver. Distant metastasis to various organs is well known. Skeletal metastasis is also reported to various locations. Vertebral metastasis has been reported mostly to thoracic spine. However, cervical spinal cord involvement leading to cord compression has been reported very rarely in literature. We present a case of 58-year-old male with liver cirrhosis presenting as neck pain. Further work-up revealed metastatic HCC to cervical spinal cord resulting in acute cord compression. Patient has been treated with neurosurgical intervention. PMID:28299213

  3. Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury

    PubMed Central

    Ryu, Hak-Hyun; Lim, Ji-Hey; Byeon, Ye-Eun; Park, Jeong-Ran; Seo, Min-Soo; Lee, Young-Won; Kim, Wan Hee

    2009-01-01

    In this study, we evaluated if the implantation of allogenic adipose-derived stem cells (ASCs) improved neurological function in a canine spinal cord injury model. Eleven adult dogs were assigned to three groups according to treatment after spinal cord injury by epidural balloon compression: C group (no ASCs treatment as control), V group (vehicle treatment with PBS), and ASC group (ASCs treatment). ASCs or vehicle were injected directly into the injured site 1 week after spinal cord injury. Pelvic limb function after transplantation was evaluated by Olby score. Magnetic resonance imaging, somatosensory evoked potential (SEP), histopathologic and immunohistichemical examinations were also performed. Olby scores in the ASC group increased from 2 weeks after transplantation and were significantly higher than C and V groups until 8 weeks (p < 0.05). However, there were no significant differences between the C and V groups. Nerve conduction velocity based on SEP was significantly improved in the ASC group compared to C and V groups (p < 0.05). Positive areas for Luxol fast blue staining were located at the injured site in the ASC group. Also, GFAP, Tuj-1 and NF160 were observed immunohistochemically in cells derived from implanted ASCs. These results suggested that improvement in neurological function by the transplantation of ASCs in dogs with spinal cord injury may be partially due to the neural differentiation of implanted stem cells. PMID:19934591

  4. Activation of Lysophosphatidic Acid Receptor Type 1 Contributes to Pathophysiology of Spinal Cord Injury

    PubMed Central

    Santos-Nogueira, Eva; López-Serrano, Clara; Hernández, Joaquim; Lago, Natalia; Astudillo, Alma M.; Balsinde, Jesús; Estivill-Torrús, Guillermo; de Fonseca, Fernando Rodriguez; Chun, Jerold

    2015-01-01

    Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions that signals through six known G-protein-coupled receptors (LPA1–LPA6). A wide range of LPA effects have been identified in the CNS, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and development of neuropathic pain. However, little is known about the involvement of LPA in CNS pathologies. Herein, we demonstrate for the first time that LPA signaling via LPA1 contributes to secondary damage after spinal cord injury. LPA levels increase in the contused spinal cord parenchyma during the first 14 d. To model this potential contribution of LPA in the spinal cord, we injected LPA into the normal spinal cord, revealing that LPA induces microglia/macrophage activation and demyelination. Use of a selective LPA1 antagonist or mice lacking LPA1 linked receptor-mediated signaling to demyelination, which was in part mediated by microglia. Finally, we demonstrate that selective blockade of LPA1 after spinal cord injury results in reduced demyelination and improvement in locomotor recovery. Overall, these results support LPA–LPA1 signaling as a novel pathway that contributes to secondary damage after spinal cord contusion in mice and suggest that LPA1 antagonism might be useful for the treatment of acute spinal cord injury. SIGNIFICANCE STATEMENT This study reveals that LPA signaling via LPA receptor type 1 activation causes demyelination and functional deficits after spinal cord injury. PMID:26180199

  5. Pain following spinal cord injury.

    PubMed

    Ullrich, Philip M

    2007-05-01

    Pain is one of the most common, severe, and treatment-resistant complications that follows SCI. Recent years have seen a surge of research on methods for assessing and treating spinal cord injury pain. In this article, pain after SCI is reviewed in terms of nature, scope, assessment techniques, and treatment strategies.

  6. Effect of carnosine, methylprednisolone and their combined application on irisin levels in the plasma and brain of rats with acute spinal cord injury.

    PubMed

    Albayrak, Serdal; Atci, İbrahim Burak; Kalayci, Mehmet; Yilmaz, Musa; Kuloglu, Tuncay; Aydin, Suna; Kom, Mustafa; Ayden, Omer; Aydin, Suleyman

    2015-08-01

    Spinal cord injury (SCI) might occur to anybody at any time and any age. In its treatment, methylprednisolone (MP) is a first choice worldwide, but there is still no significant breakthrough in truly beneficial treatment due to SCI's complex pathophysiology. We investigated the effect of carnosine, methylprednisolone (MP) and its combination on irisin levels in the plasma, brain and medulla spinalis tissues in SCI using a rat model. The rats were divided into 6 groups: I (Control, saline); II (sham animals with laminectomy without cross-clamping); III (SCI); IV (SCI treated with 150mg/kg carnosine); V (SCI treated with 30mg/kg methylprednisolone); and VI (SCI treated with a combination of carnosine and MP). The animals were given traumatic SCI after laminectomy, using 70-g closing force aneurysm clips (Yasargil FE 721). Irisin concentration was measured by ELISA. The distribution of irisin in brain and spinal cord tissues was examined by immunochemistry. Irisin was mainly expressed in the astrocytes and microglia of brain tissues, and multipolar neurones of the anterior horn of spinal cord tissue in rats of all groups, indicating that irisin is physiologically indispensable. MP and carnosine and the combination of the two, significantly increased irisin in plasma and were accompanied by a significant rise in irisin immunoreactivity of brain and spinal cord tissues of the injured rats compared with control and sham. This finding raises the possibility that methylprednisolone and carnosine regulate the brain and spinal cord tissues in SCI by inducing irisin expression, and may therefore offer a better neurological prognosis.

  7. 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

    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.

  8. 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.

  9. Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

    PubMed Central

    Gong, Gu; Yuan, Li-bang; Hu, Ling; Wu, Wei; Yin, Liang; Hou, Jing-li; Liu, Ying-hai; Zhou, Le-shun

    2012-01-01

    Aim: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process. Methods: Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia. The motor functions of the animals were assessed according to the modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2–L4) was taken out for histopathological examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA. Results: Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores, and reduced the number of apoptotic neurons, which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level correlated well with the serum TNF-α, IL-1β and IL-6 levels during the time period of reperfusion. Conclusion: The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1. PMID:22158106

  10. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2011-10-01

    funded grant, we demonstrated proof-of-concept success of bridging a lateral hemisection of the rat spinal cord with engineered (“stretch-grown...AD_________________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered...5a. CONTRACT NUMBER Spinal Cord Repair with Engineered Nervous Tissue 5b. GRANT NUMBER W81XWH-10-1-0941 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  11. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2012-10-01

    success of bridging a lateral hemisection in the rat spinal cord with engineered (“stretch-grown”) living nervous tissue constructs 2 . For the current...AD_________________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered...SUBTITLE Spinal Cord Repair with Engineered Nervous Tissue 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-1-0941 5c. PROGRAM ELEMENT NUMBER 6

  12. Survival Rates for Selected Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... Diagnosis, and Staging Survival Rates for Selected Childhood Brain and Spinal Cord Tumors Survival rates are often ... Childhood Brain and Spinal Cord Tumors More In Brain and Spinal Cord Tumors in Children About Brain ...

  13. Testosterone Plus Finasteride Treatment After Spinal Cord Injury

    ClinicalTrials.gov

    2017-01-24

    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

  14. 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

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

    PubMed

    Kjell, Jacob; Olson, Lars

    2016-10-01

    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.

  16. 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

  17. The shortened spinal cord in tetraodontiform fishes.

    PubMed

    Uehara, Masato; Hosaka, Yoshinao Z; Doi, Hiroyuki; Sakai, Harumi

    2015-03-01

    In teleosts, the spinal cord generally extends along the entire vertebral canal. The Tetraodontiformes, in which the spinal cord is greatly reduced in length with a distinct long filum terminale and cauda equina, have been regarded as an aberration. The aims of this study are: 1) to elucidate whether the spinal cord in all tetraodontiform fishes shorten with the filum terminale, and 2) to describe the gross anatomical and histological differences in the spinal cord among all families of the Tetraodontiformes. Representative species from all families of the Tetraodontiformes, and for comparison the carp as a common teleost, were investigated. In the Triacanthodidae, Triacanthidae, and Triodontidae, which are the more ancestral taxa of the Tetraodontiformes, the spinal cord extends through the entire vertebral canal. In the Triacanthidae and Triodontidae, the caudal half or more spinal segments of the spinal cord, however, lack gray matter and consist largely of nerve fibers. In the other tetraodontiform families, the spinal cord is shortened forming a filum terminale with the cauda equina, which is prolonged as far as the last vertebra. The shortened spinal cord is divided into three groups. In the Ostraciidae and Molidae, the spinal cord tapers abruptly at the cranium or first vertebra forming a cord-like filum terminale. In the Monacanthidae, Tetraodontidae, and Diodontidae, it abruptly flattens at the rostral vertebrae forming a flat filum terminale. The spinal cord is relatively longer in the Monacanthidae than that in the other two families. It is suggested by histological features of the flat filum terminale that shortening of the spinal cord in this group progresses in order of the Monacanthidae, Tetraodontidae, and Diodontidae. In the Balistidae and Aracanidae, the cord is relatively long and then gradually decreased in dorso-ventral thickness.

  18. [Spinal cord toxoplasmosis in HIV infection].

    PubMed

    Pittner, Y; Dufour, J-F; David, G; Boibieux, A; Peyramond, D

    2009-06-01

    We report the case of an atypical localization of a spinal cord "toxoplasmic abscess". The 46-year-old patient, HIV-1 positive, was admitted for acute urine retention and gait disorders. MRI revealed a T12-L1 medullary lesion suggesting a tumoral, inflammatory and infectious pathology. The radiological aspect and immunosuppression lead to the initiation of a treatment against Toxoplasma gondii, following the same treatment principles as for cerebral toxoplasmosis. The diagnosis can only be proved by data from autopsy or surgical biopsy, but toxoplasmosis PCR on CSF seems to be an interesting alternative to confirm the diagnosis. According to the literature, PCR is not sensitive enough as a diagnostic tool. Improvement after treatment supported the diagnosis confirmed by PCR.

  19. 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

  20. Cardiac dysfunctions following spinal cord injury

    PubMed Central

    Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

    2009-01-01

    The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following

  1. 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...

  2. 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)

  3. Part 1: recognizing neonatal spinal cord injury.

    PubMed

    Brand, M Colleen

    2006-02-01

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

  4. Galactorrhea: a complication of spinal cord injury.

    PubMed

    Yarkony, G M; Novick, A K; Roth, E J; Kirschner, K L; Rayner, S; Betts, H B

    1992-09-01

    Galactorrhea, a secretion of milk or milk-like products from the breast in the absence of parturition, has been reported to occur in women with spinal cord injuries in association with amenorrhea and hyperprolactinemia. Four cases of galactorrhea in association with spinal cord injury are reported. Galactorrhea developed in four spinal cord injured women who had thoracic paraplegia. The onset of galactorrhea was from one month to five months after injury. Although the onset of galactorrhea may have been related to prescribed medications in all four cases, insufficient data exist to draw conclusions. The three women whose galactorrhea persisted declined treatment and galactorrhea continuing for more than two years in one instance. We conclude that galactorrhea with or without amenorrhea may develop after a spinal cord injury and that spinal cord injured women may have an enhanced sensitivity to medication-induced galactorrhea.

  5. 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.

  6. Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration

    PubMed Central

    Krityakiarana, Warin; Zhao, Paul M.; Nguyen, Kevin; Gomez-Pinilla, Fernando; Kotchabhakdi, Naiphinich; de Vellis, Jean; Espinosa-Jeffrey, Araceli

    2017-01-01

    Trophic factor treatment has been shown to improve the recovery of brain and spinal cord injury (SCI). In this study, we examined the effects of TSC1 (a combination of insulin-like growth factor 1 and transferrin) 4 and 8 h after SCI at the thoracic segment level (T12) in nestin-GFP transgenic mice. TSC1 treatment for 4 and 8 h increased the number of nestin-expressing cells around the lesion site and prevented Wallerian degeneration. Treatment with TSC1 for 4 h significantly increased heat shock protein (HSP)-32 and HSP-70 expression 1 and 2 mm from lesion site (both, caudal and rostral). Conversely, the number of HSP-32 positive cells decreased after an 8-h TSC1 treatment, although it was still higher than in both, non-treated SCI and intact spinal cord animals. Furthermore, TSC1 increased NG2 expressing cell numbers and preserved most axons intact, facilitating remyelination and repair. These results support our hypothesis that TSC1 is an effective treatment for cell and tissue neuroprotection after SCI. An early intervention is crucial to prevent secondary damage of the injured SC and, in particular, to prevent Wallerian degeneration. PMID:26883642

  7. 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

  8. Rehabilitation of spinal cord injuries.

    PubMed

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

    2015-01-18

    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.

  9. Care of the Spinal Cord-Injured Patient

    PubMed Central

    Boxall, Jan

    1989-01-01

    Family physicians are often unfamiliar with the care of patients with spinal cord injuries because they may have only one such patient in their practice. Urinary tract infections, constipation, and decubitus ulcers are the most common problems, and autonomic dysreflexia the most serious emergency that family physicians treat in this population. This article addresses these areas, as well as spasticity, sexuality, depression, and the acute abdomen. PMID:20469504

  10. Spinal cord injuries in older children: is there a role for high-dose methylprednisolone?

    PubMed

    Arora, Bhawana; Suresh, Srinivasan

    2011-12-01

    We present a retrospective case series of 15 children (aged 8-16 years) with blunt traumatic spinal cord injury who were treated with methylprednisolone as per the National Acute Spinal Cord Injury Study protocol. Of all patients, 12 (80%) were male. Causes were sports injuries (n = 9), motor vehicle crashes (n = 2), and falls (n = 4). Most injuries were nonskeletal (n = 14), and all patients had incomplete injury of the spinal cord. The most common location of tenderness was cervical (n = 7). Of the 15 patients, methylprednisolone was initiated within 3 hours in 13 patients and between 3 and 8 hours in 2 patients. All patients received the medication for 23 hours as per the National Acute Spinal Cord Injury Study protocol. Of the 15 patients, 13 recovered completely by 24 hours and were discharged with a diagnosis of spinal cord concussion. One patient had compression fracture of T5 and T3-T5 spinal contusion but no long-term neurological deficit. One patient was discharged with diagnosis of C1-C3 spinal cord contusion (by magnetic resonance imaging) and had partial recovery at 2 years after injury. All patients with a diagnosis of cord concussion had normal plain films of the spine and computed tomographic and magnetic resonance imaging findings. None of the patients had any associated major traumatic injuries to other organ systems. The high-dose steroid therapy did not result in any serious bacterial infections.

  11. 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.

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

    PubMed Central

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

    2016-01-01

    Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient’s environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS (‘immune paralysis’), sufficient to propagate clinically relevant infection in an injury level dependent manner. PMID:26754788

  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. Oestrogen regulates mitochondrial respiratory chain enzyme transcription in the mouse spinal cord.

    PubMed

    Johann, S; Dahm, M; Kipp, M; Beyer, C; Arnold, S

    2010-08-01

    The regulation of mitochondrial energy metabolism is not only important for normal functioning of neurones, but also appears to be essential during acute damage and neurodegeneration in the central nervous system. This makes mitochondria an interesting regulatory target for therapeutic approaches. Oestrogen is well-recognised as a protective hormone in the central nervous system under pathological threats. In the present study, we analysed the influence of oestrogen on the expression of mitochondria-encoded genes and mitochondrial activity in spinal cord cells both in vitro and vivo. Hormone application increased the transcription of mitochondrial respiratory chain enzymes (MRCE). This effect was observed in cultured spinal cord neurones, where it was inhibited by a nuclear oestrogen receptor (ER) antagonist and mainly mediated by the activation of ERbeta. No effect of oestrogen was observed in cultured spinal cord astroglia. In addition, the mitochondrial transcription factor A and nuclear respiratory factor 1 were up-regulated by oestrogen in a similar way as MRCE in vitro, and ATP levels were elevated after the application of the specific ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile in cultured spinal cord nerve cells. The exposure of young male mice to oestrogen yielded increased levels of MRCE transcripts in the spinal cord. These data clearly show that systemic application of oestrogen stimulates MRCE expression in the spinal cord and predominantly in neurones. Further studies are required to demonstrate the potency of oestrogen to counteract pathological damage by stabilising mitochondrial performance.

  15. VOLUNTARY EXERCISE INCREASES OLIGODENDROGENESIS IN SPINAL CORD

    PubMed Central

    Krityakiarana, W.; Espinosa-Jeffrey, A.; Ghiani, C.A.; Zhao, P. M.; Gomez-Pinilla, F.; Yamaguchi, M.; Kotchabhakdi, N.; de Vellis, J.

    2009-01-01

    Exercise has been shown to increase hippocampal neurogenesis, but the effects of exercise on oligodendrocyte generation have not yet been reported. In this study, we evaluated the hypothesis that voluntary exercise may affect neurogenesis, and more in particular, oligodendrogenesis, in the thoracic segment of the intact spinal cord of adult nestin-GFP transgenic mice. Voluntary exercise for 7 and 14 days increased nestin-GFP expression around the ependymal area. In addition, voluntary exercise for 7 days significantly increased nestin-GFP expression in both the white and gray matter of the thoracic segment of the intact spinal cord, whereas, 14 days-exercise decreased nestin-GFP expression. Markers for immature oligodendrocytes (Transferrin and CNPase) were significantly increased after 7 days of voluntary exercise. These results suggest that voluntary exercise positively influences oligodendrogenesis in the intact spinal cord, emphasizing the beneficial effect of voluntary exercise as a possible co-treatment for spinal cord injury. PMID:20374076

  16. [Osteoporosis associated with spinal cord lesion].

    PubMed

    Miladinović, Ksenija; Vavra-Hadziahmetović, Narcisa; Muftić, Mirsad; Sakota, Slavica

    2007-01-01

    One of the complications caused by spinal lesion is osteoporosis which development is induced by lesion itself, and its mechanism is not explained enough. Risk factor of this kind of osteoporosis is fracture which management is difficult and is cause of further complications which aggravate already damaged quality of life of patients with spinal cord injury, and demand additional health insurance expenses. Importance of prevention and treatment of spinal cord injury induced osteoporosis is enlightened by case report.

  17. [Traumatic recurrence of idiopathic spinal cord herniation].

    PubMed

    Lorente-Muñoz, Asís; Cortés-Franco, Severiano; Moles-Herbera, Jesús; Casado-Pellejero, Juan; Rivero-Celada, David; Alberdi-Viñas, Juan

    2013-01-01

    Idiopathic spinal cord herniation is a rare cause of thoracic myelopathy and its recurrence is even more infrequent. Cord herniation is through an anterior dural defect in thoracic spine with unknown causes. Symptomatic cases must be surgically treated to reduce the hernia and seal the defect to prevent recurrences. We report a patient presenting a Brown-Séquard syndrome secondary to a D5 spinal cord herniation treated successfully and its posterior traumatic recurrence.

  18. 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

  19. 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

  20. Spinal cord transection in the larval zebrafish.

    PubMed

    Briona, Lisa K; Dorsky, Richard I

    2014-05-21

    Mammals fail in sensory and motor recovery following spinal cord injury due to lack of axonal regrowth below the level of injury as well as an inability to reinitiate spinal neurogenesis. However, some anamniotes including the zebrafish Danio rerio exhibit both sensory and functional recovery even after complete transection of the spinal cord. The adult zebrafish is an established model organism for studying regeneration following spinal cord injury, with sensory and motor recovery by 6 weeks post-injury. To take advantage of in vivo analysis of the regenerative process available in the transparent larval zebrafish as well as genetic tools not accessible in the adult, we use the larval zebrafish to study regeneration after spinal cord transection. Here we demonstrate a method for reproducibly and verifiably transecting the larval spinal cord. After transection, our data shows sensory recovery beginning at 2 days post-injury (dpi), with the C-bend movement detectable by 3 dpi and resumption of free swimming by 5 dpi. Thus we propose the larval zebrafish as a companion tool to the adult zebrafish for the study of recovery after spinal cord injury.

  1. 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.

  2. 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.

  3. Process benchmarking appraisal of surgical decompression of spinal cord following traumatic cervical spinal cord injury: opportunities to reduce delays in surgical management.

    PubMed

    Furlan, Julio C; Tung, Kayee; Fehlings, Michael G

    2013-03-15

    Prior pre-clinical and clinical studies indicate that early decompression of the spinal cord (≤ 24 h post-trauma) may have benefits regarding clinical outcomes and neurological recovery after spinal cord injury (SCI). This study examines the benchmarking of management of patients with acute traumatic cervical SCI in order to determine the potential barriers and ideal timelines for each step to early surgical decompression. We reviewed patient charts and the Surgical Trial in Acute Spinal Cord Injury Study (STASCIS) forms regarding the time and reasons for delay of each step in the management of patients with SCI. The reasons for delays were classified into: 1) health care-related ("extrinsic") factors and 2) patient-related ("intrinsic") factors. The cases were grouped into patients who underwent early surgical decompression of spinal cord (early-surgery group) and individuals who underwent later decompression (later-surgery group). Whereas both groups showed comparable time periods related to intrinsic factors, patients in the early surgery group had a significantly shorter time period associated with extrinsic factors when compared with the later surgery group. Both groups were comparable regarding pre-hospital time, time in a second general hospital prior to transfer to a spine center, and time in the trauma emergency department. Patients in the early surgery group had a significantly shorter waiting time, shorter waiting time for assessment by a spine surgeon, and a shorter waiting time for a surgical decision than did the later surgery group. Our benchmarking analysis suggests that health-related factors are key determinants of the timing from SCI to spinal cord decompression. Time in the general hospital and time of waiting for a surgical decision were the most important causes of delay of surgical spinal cord decompression. Early surgery is possible in the vast majority of the cases.

  4. 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.

  5. 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

  6. [Postoperative spinal cord ischemia in thoracoabdominal aneurysms].

    PubMed

    Latorre, J; Rosendo, A; Vidal, J; Sarrias, M

    1991-01-01

    At the present article, 12 cases of paraplegia secondary to the surgical treatment of thoracoabdominal aneurysms are presented. Study includes patients admitted between 1973-1987 for treatment and rehabilitation of its medular injury. Factors of risk, surgical technics practiced, peroperative complications and type of medular injury are analyzed. The most common medular injury was an anterior medular syndrome (rather than 60%). In the same way, preventive methods are analyzed and somatosensory evoked potentials (SEP) and motor evoked potentials (MEP), both in developing phase at the present moment, are recommended as the most viable method for detecting changes during the surgical procedure.

  7. Residual Spinal Cord Compression Following Hemilaminectomy and Mini-Hemilaminectomy in Dogs: A Prospective Randomized Study

    PubMed Central

    Svensson, Gustaf; Simonsson, Ulrika S. H.; Danielsson, Fredrik; Schwarz, Tobias

    2017-01-01

    The aim of this study was to compare the reduction of spinal cord compression after surgical treatment of dogs with acute thoracolumbar intervertebral disc (IVD) extrusion achieved using hemilaminectomy versus mini-hemilaminectomy techniques. This was a prospective randomized study with client-owned dogs presented with acute IVD extrusion that were allocated to surgical treatment using hemilaminectomy (n = 15) or mini-hemilaminectomy (n = 15) techniques. Plain and intravenous-contrast computed tomography was performed pre- and postoperatively. The preoperative minimal cross-sectional dimension of the spinal cord (MDSCpre) and the postoperative minimal cross-sectional dimension of the spinal cord (MDSCpost) were measured at the level of greatest compression. The minimal diameter of the uncompressed spinal cord was measured in a similar way both pre- (MDUSCpre) and postoperatively (MDUSCpost). Dogs in the mini-hemilaminectomy group had significantly greater reduction of compression (RC) (p < 0.01) after surgery compared to dogs in the hemilaminectomy group. The mean RC in the hemilaminectomy group was 34.6% and in the mini-hemilaminectomy group 62.6%. Our results showed a significantly greater reduction of spinal cord compression for mini-hemilaminectomy compared to hemilaminectomy. Additionally, mini-hemilaminectomy could be a preferred method due to its minimal invasiveness and easier access to lateral fenestration. PMID:28386545

  8. Managing chronic pain with spinal cord stimulation.

    PubMed

    Epstein, Lawrence J; Palmieri, Marco

    2012-01-01

    Since its introduction as a procedure of last resort in a terminally ill patient with intractable cancer-related pain, spinal cord stimulation has been used to effectively treat chronic pain of varied origins. Spinal cord stimulation is commonly used for control of pain secondary to failed back surgery syndrome and complex regional pain syndrome, as well as pain from angina pectoris, peripheral vascular disease, and other causes. By stimulating one or more electrodes implanted in the posterior epidural space, the patient feels paresthesias in their areas of pain, which reduces the level of pain. Pain is reduced without the side effects associated with analgesic medications. Patients have improved quality of life and improved function, with many returning to work. Spinal cord stimulation has been shown to be cost effective as compared with conservative management alone. There is strong evidence for efficacy and cost effectiveness of spinal cord stimulation in the treatment of pain associated with intractable angina, failed back surgery syndrome, and complex regional pain syndrome. In this article, we review the history and pathophysiology of spinal cord stimulation, and the evidence (or lack thereof) for efficacy in common clinical practice.

  9. Diagnosis and management of spinal cord emergencies.

    PubMed

    Flanagan, E P; Pittock, S J

    2017-01-01

    Most spinal cord injury is seen with trauma. Nontraumatic spinal cord emergencies are discussed in this chapter. These myelopathies are rare but potentially devastating neurologic disorders. In some situations prior comorbidity (e.g., advanced cancer) provides a clue, but in others (e.g., autoimmune myelopathies) it may come with little warning. Neurologic examination helps distinguish spinal cord emergencies from peripheral nervous system emergencies (e.g., Guillain-Barré), although some features overlap. Neurologic deficits are often severe and may quickly become irreversible, highlighting the importance of early diagnosis and treatment. Emergent magnetic resonance imaging (MRI) of the entire spine is the imaging modality of choice for nontraumatic spinal cord emergencies and helps differentiate extramedullary compressive causes (e.g., epidural abscess, metastatic compression, epidural hematoma) from intramedullary etiologies (e.g., transverse myelitis, infectious myelitis, or spinal cord infarct). The MRI characteristics may give a clue to the diagnosis (e.g., flow voids dorsal to the cord in dural arteriovenous fistula). However, additional investigations (e.g., aquaporin-4-IgG) are often necessary to diagnose intramedullary etiologies and guide treatment. Emergency decompressive surgery is necessary for many extramedullary compressive causes, either alone or in combination with other treatments (e.g., radiation) and preoperative neurologic deficit is the best predictor of outcome.

  10. Sudden myelopathy secondary to therapeutic total-body hyperthermia after spinal-cord irradiation

    SciTech Connect

    Douglas, M.A.; Parks, L.C.; Bebin, J.

    1981-03-05

    Hyperthermia is a new method of treatment receiving increasing clinical attention in cancer therapy. Its efficacy has been well demonstrated in animals, but its indications, contraindications, and appropriate place in cancer therapy have yet to be defined. We report three cases of acute myelopathy in patients undergoing hyperthermia after spinal-cord irradiation within the preceding two months. Post-mortem examination in one case revealed findings similar to those seen in myelopathy resulting from long-term irradiation. Several neurologic side effects have been reported previously with total-body hyperthermia - most commonly peripheral neuropathy, but not myelopathy. The mechanism of action of hyperthermia in cancer therapy (with or without prior irradiation) is unknown. The experience reported suggests that in some patients hyperthermia may potentiate radiation-induced damage to the spinal cord or otherwise interact to cause acute spinal-cord necrosis.

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

    MedlinePlus

    ... Children Early Detection, Diagnosis, and Staging 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 ...

  12. 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)

  13. Vascular dysfunctions following spinal cord injury

    PubMed Central

    Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

    2010-01-01

    The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as

  14. Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response

    PubMed Central

    Sutherland, Theresa C.; Mathews, Kathryn J.; Mao, Yilin; Nguyen, Tara; Gorrie, Catherine A.

    2017-01-01

    There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury (n = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; however

  15. 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

  16. 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

  17. 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…

  18. 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.

  19. 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…

  20. 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.

  1. MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma

    PubMed Central

    2011-01-01

    Background Glutamergic excitotoxicity has been shown to play a deleterious role in the pathophysiology of spinal cord injury (SCI). The aim of this study was to investigate the neuroprotective effect of dizocilpine maleate, MK801 (2 mg/Kg, 30 min and 6 hours after injury) in a mice model of SCI. The spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. Results Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis. In this study we clearly demonstrated that administration of MK801 attenuated all inflammatory parameters. In fact 24 hours after injury, the degree of spinal cord inflammation and tissue injury (evaluated as histological score), infiltration of neutrophils, NF-κB activation, iNOS, cytokines levels (TNF-α and IL-1β), neurotrophin expression were markedly reduced by MK801 treatment. Moreover, in a separate set of experiments, we have demonstrated that MK801 treatment significantly improved the recovery of locomotory function. Conclusions Blockade of NMDA by MK801 lends support to the potential importance of NMDA antagonists as therapeutic agents in the treatment of acute spinal cord injury. PMID:21492450

  2. Spinal cord injury secondary to electrocution in a dog.

    PubMed

    Ros, C; de la Fuente, C; Pumarola, M; Añor, S

    2015-10-01

    A 13-year-old, female spayed, crossbreed dog of 32 kg was presented for evaluation of peracute onset of non-ambulatory tetraparesis after chewing an electrical wire. Neurological examination was consistent with a C1-C5 myelopathy. Magnetic resonance imaging revealed a focal intramedullary lesion over the C2-C3 vertebral bodies, which was confirmed to be an acute focal necrotising poliomyelopathy with subarachnoid and subdural haemorrhages on postmortem examination. This report describes the clinical, imaging and histopathological findings of this unusual type of spinal cord injury, and the effects of electrocution in the central nervous system of dogs.

  3. Spinal cord stimulation: uses and applications.

    PubMed

    Golovac, Stanley

    2010-05-01

    Spinal cord stimulation has been used successfully for more than 40 years. The application of an electrical impulse field on to the spinal cord is used with a battery generator source and a variety of either cylindrical or paddle/plate leads. Energy is delivered from either a conventional internal programmable generator or a rechargeable style battery. Many clinical conditions such as complex regional pain syndrome, failed back spinal syndrome, and extremity neuropathic pain involving the trunk and limbs are approved for its use. This device allows patients to live a successful life without pain.

  4. Dropped-head syndrome resulting from injury to the central spinal cord at the upper cervical level.

    PubMed

    Rust, C L; Ching, A C; Hart, R A

    2011-04-01

    There are many causes of paraspinal muscle weakness which give rise to the dropped-head syndrome. In the upper cervical spine the central portion of the spinal cord innervates the cervical paraspinal muscles. Dropped-head syndrome resulting from injury to the central spinal cord at this level has not previously been described. We report two patients who were treated acutely for this condition. Both presented with weakness in the upper limbs and paraspinal cervical musculature after a fracture of C2. Despite improvement in the strength of the upper limbs, the paraspinal muscle weakness persisted in both patients. One ultimately underwent cervicothoracic fusion to treat her dropped-head syndrome. While the cause of the dropped-head syndrome cannot be definitively ascribed to the injuries to the spinal cord, this pattern is consistent with the known patho-anatomical mechanisms of both injury to the central spinal cord and dropped-head syndrome.

  5. Toxoplasmosis of spinal cord in acquired immunodeficiency syndrome patient presenting as paraparesis: a rare entity.

    PubMed

    Agrawal, Sachin R; Singh, Vinita; Ingale, Sheetal; Jain, Ajeet Prasad

    2014-10-01

    Although brain has been the most common site for toxoplasma infection in acquired immunodeficiency syndrome patients, involvement of spinal cord by toxoplasma has been rarely found. Spinal cord toxoplasmosis can present as acute onset weakness in both lower limbs associated with sensory and bladder dysfunction. A presumptive diagnosis can be made in patients with CD4 count <100/mm(3) based on a positive serum Toxoplasma gondii IgG antibodies, no recent prophylaxis against toxoplasmosis, intramedullary ring enhancing lesion in spinal cord supported by similar lesions in brain parenchyma. Institutions of antitoxoplasma treatment in such patients result in prompt clinical response and therefore avoiding the need of unnecessary invasive diagnostic tests. Here, we report a case of toxoplasmic myelitis in immunocompromised patient presenting as myelopathy who showed significant clinical improvement after starting antitoxoplasma treatment. Hence toxoplasmic myelitis should be considered in toxoplasma seropositive immunocompromised patients presenting as myelopathy and imaging studies showing ring enhancing intramedullary lesion.

  6. [The use micro-polarization in spinal cord lesions].

    PubMed

    Sheliakin, A M; Preobrazhenskaia, I G; Komantsev, V N; Makarovskiĭ, A N; Bogdanov, O V

    1998-01-01

    Transdermal micropolarization of the spinal cord was made in patients with consequences of the spinal cord injury or tuberculous spondylitis. Changes in clinical and electrophysiologic status were evaluated. It was found that local direct current through dermal electrodes promotes an improvement of both motor and autonomic functions in such patients. This corresponded to a positive dynamics both of the spinal cord state and cardiac activity. Possible mechanisms of influence of the direct current on the spinal cord as well as perspectives of application of micropolarization in spinal cord's damage are outlined.

  7. Effects of NO Synthase Blocker L-NAME on Functional State of the Neuromotor System during Traumatic Disease of the Spinal Cord.

    PubMed

    Yafarova, G G; Andrianov, V V; Yagudin, R Kh; Shaikhytdinov, I I; Gainutdinov, Kh L

    2017-01-01

    Functional state of the neuromotor system after administration of a nonspecific NO synthase blocker L-NAME was studied on the model of experimental contusion of the spinal cord. Electron paramagnetic resonance measurements of NO production in the damaged segment of the spinal cord were performed for estimation of the dynamics of intensity of NO production during traumatic disease of the spinal cord and selection of optimal period for L-NAME administration. The status of the neuromotor system was evaluated by stimulation electromyography. Treatment with L-NAME during the acute period of traumatic injury to the spinal cord sharply reduced the intensity of evoked motor responses and more pronounced increase in excitability of peripheral motor structures. The results suggest that NO system is a factor of regulation of the stress-induced and adaptive responses of the body at the early stage of spinal cord injury.

  8. 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)

  9. Anorgasmia in anterior spinal cord syndrome.

    PubMed

    Berić, A; Light, J K

    1993-05-01

    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.

  10. Alleviating Autonomic Dysreflexia after Spinal Cord Injury

    DTIC Science & Technology

    2015-10-01

    develop from 1) aberrant plasticity and 2) the loss of tonic input onto sympathetic preganglionic neurons (SPN) in the spinal cord that drive...life. Another cause of autonomic dysreflexia is aberrant plasticity of spinal circuits that increase activity of the sympathetic preganglionic neurons...modulatory circuitry and pharmacological mitigation of hyperexcitability resulting from aberrant plasticity will result in greater mitigation of

  11. Spinal cord compression due to vertebral hemangioma.

    PubMed

    Aksu, Gorkem; Fayda, Merdan; Saynak, Mert; Karadeniz, Ahmet

    2008-02-01

    This article presents a case of multiple vertebral hemangiomas in a 58-year-old man with pain in the dorsal region and bilateral progressive foot numbness. Magnetic resonance imaging revealed multiple vertebral hemangiomas. One hemangioma at the T7 level demonstrated epidural extension, causing spinal cord compression. After treatment with radiotherapy, the patient's symptoms improved significantly.

  12. 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)

  13. 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.

  14. 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.

  15. Exercise modulates chloride homeostasis after spinal cord injury.

    PubMed

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

    2014-07-02

    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.

  16. 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.

  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. 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

  19. Vasospastic Limb Ischemia Presenting Acute and Chronic Limb Ischemia

    PubMed Central

    2014-01-01

    Vasospastic limb ischemia might have been underappreciated compared to vasospasm in other territories such as heart and brain. However, an increasing awareness of this vascular disorder can be translated to an improved patients’ care. Herein, we report a case of vasospasm presenting acute and chronic limb ischemia in four extremities. PMID:24995065

  20. Reduced inflammatory cell recruitment and tissue damage in spinal cord injury by acellular spinal cord scaffold seeded with mesenchymal stem cells.

    PubMed

    Wang, Yu-Hai; Chen, Jian; Zhou, Jing; Nong, Feng; Lv, Jin-Han; Liu, Jia

    2017-01-01

    Therapy using acellular spinal cord (ASC) scaffolds seeded with bone marrow stromal cells (BMSCs) has previously been shown to restore function of the damaged spinal cord and improve functional recovery in a rat model of acute hemisected spinal cord injury (SCI). The aim of the present study was to determine whether BMSCs and ASC scaffolds promote the functional recovery of the damaged spinal cord in a rat SCI model through regulation of apoptosis and immune responses. Whether this strategy regulates secondary inflammation, which is characterized by the infiltration of immune cells and inflammatory mediators to the lesion site, in SCI repair was investigated. Basso, Beattie, and Bresnahan scores revealed that treatment with BMSCs seeded into an ASC scaffold led to a significant improvement in motor function recovery compared with treatment with an ASC scaffold alone or untreated controls at 2 and 8 weeks after surgery (P<0.05). Two weeks after transplantation, the BMSCs seeded into an ASC scaffold significantly decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, as compared with the ASC scaffold only and control groups. These results suggested that the use of BMSCs decreased the apoptosis of neural cells and thereby limited tissue damage at the lesion site. Notably, the use of BMSCs with an ASC scaffold also decreased the recruitment of macrophages (microglia; P<0.05) and T lymphocytes (P<0.05) around the SCI site, as indicated by immunofluorescent markers. By contrast, there was no inhibition of the inflammatory response in the control and ASC scaffold only groups. BMSCs regulated inflammatory cell recruitment to promote functional recovery. However, there was no significant difference in IgM-positive expression among the three groups (P>0.05). The results of this study demonstrated that BMSCs seeded into ASC scaffolds for repair of spinal cord hemisection defects promoted functional recovery through the early

  1. Reduced inflammatory cell recruitment and tissue damage in spinal cord injury by acellular spinal cord scaffold seeded with mesenchymal stem cells

    PubMed Central

    Wang, Yu-Hai; Chen, Jian; Zhou, Jing; Nong, Feng; Lv, Jin-Han; Liu, Jia

    2017-01-01

    Therapy using acellular spinal cord (ASC) scaffolds seeded with bone marrow stromal cells (BMSCs) has previously been shown to restore function of the damaged spinal cord and improve functional recovery in a rat model of acute hemisected spinal cord injury (SCI). The aim of the present study was to determine whether BMSCs and ASC scaffolds promote the functional recovery of the damaged spinal cord in a rat SCI model through regulation of apoptosis and immune responses. Whether this strategy regulates secondary inflammation, which is characterized by the infiltration of immune cells and inflammatory mediators to the lesion site, in SCI repair was investigated. Basso, Beattie, and Bresnahan scores revealed that treatment with BMSCs seeded into an ASC scaffold led to a significant improvement in motor function recovery compared with treatment with an ASC scaffold alone or untreated controls at 2 and 8 weeks after surgery (P<0.05). Two weeks after transplantation, the BMSCs seeded into an ASC scaffold significantly decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, as compared with the ASC scaffold only and control groups. These results suggested that the use of BMSCs decreased the apoptosis of neural cells and thereby limited tissue damage at the lesion site. Notably, the use of BMSCs with an ASC scaffold also decreased the recruitment of macrophages (microglia; P<0.05) and T lymphocytes (P<0.05) around the SCI site, as indicated by immunofluorescent markers. By contrast, there was no inhibition of the inflammatory response in the control and ASC scaffold only groups. BMSCs regulated inflammatory cell recruitment to promote functional recovery. However, there was no significant difference in IgM-positive expression among the three groups (P>0.05). The results of this study demonstrated that BMSCs seeded into ASC scaffolds for repair of spinal cord hemisection defects promoted functional recovery through the early

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Respiratory problems and management in people with spinal cord injury

    PubMed Central

    Wadsworth, Brooke; Ross, Jack

    2016-01-01

    Spinal cord injury (SCI) is characterised by profound respiratory compromise secondary to the level of loss of motor, sensory and autonomic control associated with the injury. This review aims to detail these anatomical and physiological changes after SCI, and outline their impact on respiratory function. Injury-related impairments in strength substantially alter pulmonary mechanics, which in turn affect respiratory management and care. Options for treatments must therefore be considered in light of these limitations. Key points Respiratory impairment following spinal cord injury (SCI) is more severe in high cervical injuries, and is characterised by low lung volumes and a weak cough secondary to respiratory muscle weakness. Autonomic dysfunction and early-onset sleep disordered breathing compound this respiratory compromise. The mainstays of management following acute high cervical SCI are tracheostomy and ventilation, with noninvasive ventilation and assisted coughing techniques being important in lower cervical and thoracic level injuries. Prompt investigation to ascertain the extent of the SCI and associated injuries, and appropriate subsequent management are important to improve outcomes. Educational aims To describe the anatomical and physiological changes after SCI and their impact on respiratory function. To describe the changes in respiratory mechanics seen in cervical SCI and how these changes affect treatments. To discuss the relationship between injury level and respiratory compromise following SCI, and describe those at increased risk of respiratory complications. To present the current treatment options available and their supporting evidence. PMID:28270863

  7. Muscular, skeletal, and neural adaptations following spinal cord injury.

    PubMed

    Shields, Richard K

    2002-02-01

    Spinal cord injury is associated with adaptations to the muscular, skeletal, and spinal systems. Experimental data are lacking regarding the extent to which rehabilitative methods may influence these adaptations. An understanding of the plasticity of the muscular, skeletal, and spinal systems after paralysis may be important as new rehabilitative technologies emerge in the 21st century. Moreover, individuals injured today may become poor candidates for future scientific advancements (cure) if their neuromusculoskeletal systems are irreversibly impaired. The primary purpose of this paper is to explore the physiological properties of skeletal muscle as a result of spinal cord injury; secondarily, to consider associated changes at the skeletal and spinal levels. Muscular adaptations include a transformation to faster myosin, increased contractile speeds, shift to the right on the torque-frequency curve, increased fatigue, and enhanced doublet potentiation. These muscular adaptations may be prevented in individuals with acute paralysis and partially reversed in individuals with chronic paralysis. Moreover, the muscular changes may be coordinated with motor unit and spinal circuitry adaptations. Concurrently, skeletal adaptations, as measured by bone mineral density, show extensive loss within the first six months after paralysis. The underlying science governing neuromusculoskeletal adaptations after paralysis will help guide professionals as new rehabilitation strategies evolve in the future.

  8. Relationship between Spinal Cord Volume and Spinal Cord Injury due to Spinal Shortening

    PubMed Central

    Qiu, Feng; Yang, Jin-Cheng; Ma, Xiang-Yang; Xu, Jun-Jie; Yang, Qing-Lei; Zhou, Xin; Xiao, Yao-Sheng; Hu, Hai-Sheng; Xia, Li-Hui

    2015-01-01

    Vertebral column resection is associated with a risk of spinal cord injury. In the present study, using a goat model, we aimed to investigate the relationship between changes in spinal cord volume and spinal cord injury due to spinal shortening, and to quantify the spinal cord volume per 1-mm height in order to clarify a safe limit for shortening. Vertebral column resection was performed at T10 in 10 goats. The spinal cord was shortened until the somatosensory-evoked potential was decreased by 50% from the baseline amplitude or delayed by 10% relative to the baseline peak latency. A wake-up test was performed, and the goats were observed for two days postoperatively. Magnetic resonance imaging was used to measure the spinal cord volume, T10 height, disc height, osteotomy segment height, and spinal segment height pre- and postoperatively. Two of the 10 goats were excluded, and hence, only data from eight goats were analyzed. The somatosensory-evoked potential of these eight goats demonstrated meaningful changes. With regard to neurologic function, five and three goats were classified as Tarlov grades 5 and 4 at two days postoperatively. The mean shortening distance was 23.6 ± 1.51 mm, which correlated with the d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment (r = 0.95, p < 0.001) and with the height of the T10 body (r = 0.79, p = 0.02). The mean d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment was 142.87 ± 0.59 mm3 (range, 142.19–143.67 mm3). The limit for shortening was approximately 106% of the vertebral height. The mean volumes of the osteotomy and spinal segments did not significantly change after surgery (t = 0.310, p = 0.765 and t = 1.241, p = 0.255, respectively). Thus, our results indicate that the safe limit for shortening can be calculated using the change in spinal cord volume per 1-mm height. PMID:26001196

  9. Radiation-induced spinal cord hemorrhage (hematomyelia).

    PubMed

    Agarwal, Amit; Kanekar, Sangam; Thamburaj, Krishnamurthy; Vijay, Kanupriya

    2014-10-23

    Intraspinal hemorrhage is very rare and intramedullary hemorrhage, also called hematomyelia, is the rarest form of intraspinal hemorrhage, usually related to trauma. Spinal vascular malformations such intradural arteriovenous malformations are the most common cause of atraumatic hematomyelia. Other considerations include warfarin or heparin anticoagulation, bleeding disorders, spinal cord tumors. Radiation-induced hematomyelia of the cord is exceedingly rare with only one case in literature to date. We report the case of an 8 year old girl with Ewing's sarcoma of the thoracic vertebra, under radiation therapy, presenting with hematomyelia. We describe the clinical course, the findings on imaging studies and the available information in the literature. Recognition of the clinical pattern of spinal cord injury should lead clinicians to perform imaging studies to evaluate for compressive etiologies.

  10. Hydrogels in Spinal Cord Injury Repair Strategies

    PubMed Central

    2011-01-01

    Nowadays there are at present no efficient therapies for spinal cord injury (SCI), and new approaches have to be proposed. Recently, a new regenerative medicine strategy has been suggested using smart biomaterials able to carry and deliver cells and/or drugs in the damaged spinal cord. Among the wide field of emerging materials, research has been focused on hydrogels, three-dimensional polymeric networks able to swell and absorb a large amount of water. The present paper intends to give an overview of a wide range of natural, synthetic, and composite hydrogels with particular efforts for the ones studied in the last five years. Here, different hydrogel applications are underlined, together with their different nature, in order to have a clearer view of what is happening in one of the most sparkling fields of regenerative medicine. PMID:22816020

  11. Neural plasticity after spinal cord injury☆

    PubMed Central

    Liu, Jian; Yang, Xiaoyu; Jiang, Lianying; Wang, Chunxin; Yang, Maoguang

    2012-01-01

    Plasticity changes of uninjured nerves can result in a novel neural circuit after spinal cord injury, which can restore sensory and motor functions to different degrees. Although processes of neural plasticity have been studied, the mechanism and treatment to effectively improve neural plasticity changes remain controversial. The present study reviewed studies regarding plasticity of the central nervous system and methods for promoting plasticity to improve repair of injured central nerves. The results showed that synaptic reorganization, axonal sprouting, and neurogenesis are critical factors for neural circuit reconstruction. Directed functional exercise, neurotrophic factor and transplantation of nerve-derived and non-nerve-derived tissues and cells can effectively ameliorate functional disturbances caused by spinal cord injury and improve quality of life for patients. PMID:25774179

  12. Metastatic carcinoid tumour with spinal cord compression.

    PubMed

    Scott, Si; Antwi-Yeboah, Y; Bucur, Sd

    2012-07-01

    Carcinoid tumours are rare with an incidence of 5.25/100,000. They predominantly originate in the gastrointestinal tract (50-60%) or bronchopulmonary system (25-30%). Common sites of metastasis are lymph nodes, liver, lungs and bone. Spinal metastasis are rare, but has been reported in patients with symptoms of spinal cord compression including neurological deficits. We report a rare case of carcinoid metastasis with spinal cord compression, in a 63-year-old man, presenting with a one-year history of back pain without any neurological symptoms. The patient underwent a two-level decompressive laminectomy of T10 and T11 as well as piecemeal tumour resection. Post-operatively the patient made a good recovery without complications.

  13. Metastatic carcinoid tumour with spinal cord compression

    PubMed Central

    Scott, SI; Antwi-Yeboah, Y; Bucur, SD

    2012-01-01

    Carcinoid tumours are rare with an incidence of 5.25/100,000. They predominantly originate in the gastrointestinal tract (50-60%) or bronchopulmonary system (25-30%). Common sites of metastasis are lymph nodes, liver, lungs and bone. Spinal metastasis are rare, but has been reported in patients with symptoms of spinal cord compression including neurological deficits. We report a rare case of carcinoid metastasis with spinal cord compression, in a 63-year-old man, presenting with a one-year history of back pain without any neurological symptoms. The patient underwent a two-level decompressive laminectomy of T10 and T11 as well as piecemeal tumour resection. Post-operatively the patient made a good recovery without complications. PMID:24960730

  14. Shoulder biomechanics and muscle plasticity: implications in spinal cord injury.

    PubMed

    Lee, Thay Q; McMahon, Patrick J

    2002-10-01

    After spinal cord injury, excessive burden falls on the upper extremity, especially the shoulder. Overall, 51% of persons with spinal cord injury have shoulder problems. Common shoulder problems in persons with spinal cord injury begin with muscle imbalance that can lead to glenohumeral instability, impingement disease, rotator cuff tears, and subsequent degenerative joint disease. These problems can be attributed to the functional demands placed on the shoulder that are specific to patients with spinal cord injury, including overhead activities, wheelchair use, and transfers. Despite preventive exercises, shoulder problems in persons with spinal cord injury remain a significant problem, causing pain and functional limitations. The biomechanics of the shoulder for persons with spinal cord injury resulting from changes in muscle plasticity will be elucidated. Specifically, the effects of scapular protraction that can result from muscle imbalance, the age-dependent properties of the anterior band of the inferior glenohumeral ligament, and the influence of the dynamic restraints around the shoulder will be addressed.

  15. Tracking Changes following Spinal Cord Injury

    PubMed Central

    Curt, Armin; Friston, Karl; Thompson, Alan

    2013-01-01

    Traumatic spinal cord injury is often disabling and recovery of function is limited. As a consequence of damage, both spinal cord and brain undergo anatomical and functional changes. Besides clinical measures of recovery, biomarkers that can detect early anatomical and functional changes might be useful in determining clinical outcome—during the course of rehabilitation and recovery—as well as furnishing a tool to evaluate novel treatment interventions and their mechanisms of action. Recent evidence suggests an interesting three-way relationship between neurological deficit and changes in the spinal cord and of the brain and that, importantly, noninvasive magnetic resonance imaging techniques, both structural and functional, provide a sensitive tool to lay out these interactions. This review describes recent findings from multimodal imaging studies of remote anatomical changes (i.e., beyond the lesion site), cortical reorganization, and their relationship to clinical disability. These developments in this field may improve our understanding of effects on the nervous system that are attributable to the injury itself and will allow their distinction from changes that result from rehabilitation (i.e., functional retraining) and from interventions affecting the nervous system directly (i.e., neuroprotection or regeneration). PMID:22730072

  16. Serotonergic transmission after spinal cord injury.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Thomschewski, Aljoscha; Höller, Peter; Lochner, Piergiorgio; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2015-02-01

    Changes in descending serotonergic innervation of spinal neural activity have been implicated in symptoms of paralysis, spasticity, sensory disturbances and pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury, including SCI. Current research suggests that serotonine (5-HT) release within the ventral horn of the spinal cord plays a critical role in motor function, and activation of 5-HT receptors mediates locomotor control. 5-HT originating from the brain stem inhibits sensory afferent transmission and associated spinal reflexes; by abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission. 5-HT denervation supersensitivity is one of the key mechanisms underlying the increased motoneuron excitability that occurs after SCI, and this hyperexcitability has been demonstrated to underlie the pathogenesis of spasticity after SCI. Moreover, emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. There are functional relevant connections between the descending serotonergic system from the rostral ventromedial medulla in the brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain facilitation after tissue and nerve injury. This narrative review focussed on the most important studies that have investigated the above-mentioned effects of impaired 5-HT-transmission in humans after SCI. We also briefly discussed the promising therapeutical approaches with serotonergic drugs, monoclonal antibodies and intraspinal cell transplantation.

  17. Spinal cord grey matter segmentation challenge.

    PubMed

    Prados, Ferran; Ashburner, John; Blaiotta, Claudia; Brosch, Tom; Carballido-Gamio, Julio; Cardoso, Manuel Jorge; Conrad, Benjamin N; Datta, Esha; Dávid, Gergely; Leener, Benjamin De; Dupont, Sara M; Freund, Patrick; Wheeler-Kingshott, Claudia A M Gandini; Grussu, Francesco; Henry, Roland; Landman, Bennett A; Ljungberg, Emil; Lyttle, Bailey; Ourselin, Sebastien; Papinutto, Nico; Saporito, Salvatore; Schlaeger, Regina; Smith, Seth A; Summers, Paul; Tam, Roger; Yiannakas, Marios C; Zhu, Alyssa; Cohen-Adad, Julien

    2017-03-07

    An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication.

  18. Fluoro-Jade B staining following zymosan microinjection into the spinal cord white matter.

    PubMed

    Saganová, Kamila; Burda, Jozef; Orendácová, Judita; Cízková, Dása; Vanický, Ivo

    2006-01-01

    1. The fluorescein derivate Fluoro-Jade B (FJB), which primarily labels dead or dying neurons, was used to study the acute focal inflammation in the spinal cord white matter. Inflammation was induced by microinjection of the yeast particulate zymosan to evaluate the biological effects of intraspinal macrophages activation without the confounding effects of physical trauma. 2. A single bolus of zymosan (Sigma, 75 nL) was stereotaxically injected at the thoracic level into the lateral white matter of rat spinal cord. A standard Fluoro-Jade B staining protocol was applied to spinal cord sections at 6, 12, 24 h and 2, 4 days postinjection. Neutral Red, NADPH-diaphorase, Iba1-IR, and DAPI staining protocols accomplished examination of the cells participating in the acute inflammatory response. 3. Zymosan caused formation of clearly delineated inflammation lesions localized in the lateral white matter of the spinal cord. Fluoro-Jade B stained cells in the area of inflammation were not observed at 12 h postinjection while mild FJB staining appeared at 24 h and intense staining was observed at 2 and 4 days postinjection. 4. This study shows that the acute response to zymosan-induced inflammation in the rat spinal cord white matter causes a gradual appearance of phagocytic microglia/macrophages and delayed FJB staining of the inflammatory cells. 5. FJB, a reliable marker of dying neurons, is a more universal agent than formerly believed. One possible explanation for the gradual appearance of FJB-stained cells in the area of inflammation is that specific time is required for sufficient levels of proteins and/or myelin debris of axonal origin to appear in the cytoplasm of phagocytic microglia/macrophages.

  19. Review of Epidural Spinal Cord Stimulation for Augmenting Cough after Spinal Cord Injury

    PubMed Central

    Hachmann, Jan T.; Calvert, Jonathan S.; Grahn, Peter J.; Drubach, Dina I.; Lee, Kendall H.; Lavrov, Igor A.

    2017-01-01

    Spinal cord injury (SCI) remains a debilitating condition for which there is no cure. In addition to loss of somatic sensorimotor functions, SCI is also commonly associated with impairment of autonomic function. Importantly, cough dysfunction due to paralysis of expiratory muscles in combination with respiratory insufficiency can render affected individuals vulnerable to respiratory morbidity. Failure to clear sputum can aggravate both risk for and severity of respiratory infections, accounting for frequent hospitalizations and even mortality. Recently, epidural stimulation of the lower thoracic spinal cord has been investigated as novel means for restoring cough by evoking expiratory muscle contraction to generate large positive airway pressures and expulsive air flow. This review article discusses available preclinical and clinical evidence, current challenges and clinical potential of lower thoracic spinal cord stimulation (SCS) for restoring cough in individuals with SCI.

  20. Experiences of Living with Pain after a Spinal Cord Injury

    DTIC Science & Technology

    2014-09-01

    Spinal Cord Injury PRINCIPAL INVESTIGATOR: Eva G. Widerström-Noga, DDS, PhD CONTRACTING ORGANIZATION: University of Miami REPORT...AND SUBTITLE Experiences of Living with Pain after a Spinal Cord Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0465 5c. PROGRAM...after a spinal cord injury (SCI), with about two-thirds of persons with SCI reporting persistent pain despite available treatments. There is a risk

  1. Noninvasive respiratory management of high level spinal cord injury

    PubMed Central

    Bach, John R.

    2012-01-01

    This article describes noninvasive acute and long-term management of the respiratory muscle paralysis of high spinal cord injury (SCI). This includes full-setting, continuous ventilatory support by noninvasive intermittent positive pressure ventilation (NIV) to support inspiratory muscles and mechanically assisted coughing (MAC) to support inspiratory and expiratory muscles. The NIV and MAC can also be used to extubate or decannulate ‘unweanable’ patients with SCI, to prevent intercurrent respiratory tract infections from developing into pneumonia and acute respiratory failure (ARF), and to eliminate tracheostomy and resort to costly electrophrenic/diaphragm pacing (EPP/DP) for most ventilator users, while permitting glossopharyngeal breathing (GPB) for security in the event of ventilator failure. PMID:22525322

  2. Noninvasive respiratory management of high level spinal cord injury.

    PubMed

    Bach, John R

    2012-03-01

    This article describes noninvasive acute and long-term management of the respiratory muscle paralysis of high spinal cord injury (SCI). This includes full-setting, continuous ventilatory support by noninvasive intermittent positive pressure ventilation (NIV) to support inspiratory muscles and mechanically assisted coughing (MAC) to support inspiratory and expiratory muscles. The NIV and MAC can also be used to extubate or decannulate 'unweanable' patients with SCI, to prevent intercurrent respiratory tract infections from developing into pneumonia and acute respiratory failure (ARF), and to eliminate tracheostomy and resort to costly electrophrenic/diaphragm pacing (EPP/DP) for most ventilator users, while permitting glossopharyngeal breathing (GPB) for security in the event of ventilator failure.

  3. 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

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

    MedlinePlus

    ... in Adults What Are the Key Statistics About Brain and Spinal Cord Tumors? The American Cancer Society’s ... Spinal Cord Tumor Research and Treatment? More In Brain And Spinal Cord Tumors In Adults About Brain ...

  5. SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data.

    PubMed

    De Leener, Benjamin; Lévy, Simon; Dupont, Sara M; Fonov, Vladimir S; Stikov, Nikola; Louis Collins, D; Callot, Virginie; Cohen-Adad, Julien

    2017-01-15

    For the past 25 years, the field of neuroimaging has witnessed the development of several software packages for processing multi-parametric magnetic resonance imaging (mpMRI) to study the brain. These software packages are now routinely used by researchers and clinicians, and have contributed to important breakthroughs for the understanding of brain anatomy and function. However, no software package exists to process mpMRI data of the spinal cord. Despite the numerous clinical needs for such advanced mpMRI protocols (multiple sclerosis, spinal cord injury, cervical spondylotic myelopathy, etc.), researchers have been developing specific tools that, while necessary, do not provide an integrative framework that is compatible with most usages and that is capable of reaching the community at large. This hinders cross-validation and the possibility to perform multi-center studies. In this study we introduce the Spinal Cord Toolbox (SCT), a comprehensive software dedicated to the processing of spinal cord MRI data. SCT builds on previously-validated methods and includes state-of-the-art MRI templates and atlases of the spinal cord, algorithms to segment and register new data to the templates, and motion correction methods for diffusion and functional time series. SCT is tailored towards standardization and automation of the processing pipeline, versatility, modularity, and it follows guidelines of software development and distribution. Preliminary applications of SCT cover a variety of studies, from cross-sectional area measures in large databases of patients, to the precise quantification of mpMRI metrics in specific spinal pathways. We anticipate that SCT will bring together the spinal cord neuroimaging community by establishing standard templates and analysis procedures.

  6. Congenital malformations of the spinal cord without early symptoms.

    PubMed

    Moffie, D; Stefanko, S Z; Makkink, B

    1986-01-01

    Description of 11 patients with congenital malformations of the spinal cord. Six of them were males, five females and the age varied from 7 to 70 years. Most of these cases produced clinical neurological signs indicating spinal cord disease in later life during an intercurrent disease. It was thought that changes in the bloodvessels and/or perfusion of the area of the spinal cord malformation was the ultimate cause of the neurological symptoms. An exact explanation of the origin of these developmental disturbances of the spinal cord remains unknown. Different hypotheses proposed in the literature, concerning these malformations, are not satisfactory.

  7. The spinal cord: a review of functional neuroanatomy.

    PubMed

    Bican, Orhan; Minagar, Alireza; Pruitt, Amy A

    2013-02-01

    The spinal cord controls the voluntary muscles of the trunk and limbs and receives sensory input from these areas. It extends from the medulla oblongata to the lower border of the first lumbar vertebra. A basic knowledge of spinal cord anatomy is essential for interpretation of clinical signs and symptoms and for understanding of pathologic processes involving the spinal cord. In this article, anatomic structures are correlated with relevant clinical signs and symptoms and a step-wise approach to spinal cord diagnosis is outlined.

  8. Subacute combined degeneration mimicking traumatic spinal cord injury.

    PubMed

    Paul, Ian; Reichard, R Ross

    2009-03-01

    Subacute combined degeneration (SCD) of the spinal cord is the most common neurologic manifestation of vitamin B12 (cobalamin) deficiency and is usually secondary to autoimmune gastritis, but may also be seen in malnutrition syndromes such as chronic alcoholism, strict vegetarianism, gastrectomy, and also in nitrous oxide abuse. Although traumatic spinal cord injury is routinely encountered in the medical examiner's office, medical causes of spinal cord abnormalities such as SCD should be considered in the appropriate clinical setting. We report a case of alcohol-associated SCD mimicking traumatic spinal cord injury.

  9. Spinal Myoclonus After Spinal Cord Injury

    PubMed Central

    Calancie, Blair

    2006-01-01

    Background/Objective: In the course of examining spinal motor function in many hundreds of people with traumatic spinal cord injury, we encountered 6 individuals who developed involuntary and rhythmic contractions in muscles of their legs. Although there are many reports of unusual muscle activation patterns associated with different forms of myoclonus, we believe that certain aspects of the patterns seen with these 6 subjects have not been previously reported. These patterns share many features with those associated with a spinal central pattern generator for walking. Methods: Subjects in this case series had a history of chronic injury to the cervical spinal cord, resulting in either complete (ASIA A; n = 4) or incomplete (ASIA D; n = 2) quadriplegia. We used multi-channel electromyography recordings of trunk and leg muscles of each subject to document muscle activation patterns associated with different postures and as influenced by a variety of sensory stimuli. Results: Involuntary contractions spanned multiple leg muscles bilaterally, sometimes including weak abdominal contractions. Contractions were smooth and graded and were highly reproducible in rate for a given subject (contraction rates were 0.3–0.5 Hz). These movements did not resemble the brief rapid contractions (ie, "jerks") ascribed to some forms of spinal myoclonus. For all subjects, the onset of involuntary muscle contraction was dependent upon hip angle; contractions did not occur unless the hips (and knees) were extended (ie, subjects were supine). In the 4 ASIA A subjects, contractions occurred simultaneously in all muscles (agonists and antagonists) bilaterally. In sharp contrast, contractions in the 2 ASIA D subjects were reciprocal between agonists and antagonists within a limb and alternated between limbs, such that movements in these 2 subjects looked just like repetitive stepping. Finally, each of the 6 subjects had a distinct pathology of their spinal cord, nerve roots, distal trunk

  10. CD36 deletion improves recovery from spinal cord injury

    PubMed Central

    Myers, Scott A.; Andres, Kariena R.; Hagg, Theo; Whittemore, Scott R.

    2014-01-01

    CD36 is a pleiotropic receptor involved in several pathophysiological conditions, including cerebral ischemia, neurovascular dysfunction and atherosclerosis, and recent reports implicate its involvement in the endoplasmic reticulum stress response (ERSR). We hypothesized that CD36 signaling contributes to the inflammation and microvascular dysfunction following spinal cord injury. Following contusive injury, CD36−/− mice demonstrated improved hindlimb functional recovery and greater white matter sparing than CD36+/+ mice. CD36−/− mice exhibited a reduced macrophage, but not neutrophil, infiltration into the injury epicenter. Fewer infiltrating macrophages were either apoptotic or positive for the ERSR marker, phospho-ATF4. CD36−/− mice also exhibited significant improvements in injury heterodomain vascularity and function. These microvessels accumulated less of the oxidized lipid product 4-hydroxy-trans-2-nonenal (4HNE) and exhibited a reduced ERSR, as detected by vascular phospho-ATF4, CHOP and CHAC-1 expression. In cultured primary endothelial cells, deletion of CD36 diminished 4HNE-induced phospho-ATF4 and CHOP expression. A reduction in phospho-eIF2α and subsequent increase in KDEL-positive, ER-localized proteins suggest that 4HNE-CD36 signaling facilitates the detection of misfolded proteins upstream of eIF2α phosphorylation, ultimately leading to CHOP-induced apoptosis. We conclude that CD36 deletion modestly, but significantly, improves functional recovery from spinal cord injury by enhancing vascular function and reducing macrophage infiltration. These phenotypes may, in part, stem from reduced ER stress-induced cell death within endothelial and macrophage cells following injury. PMID:24690303

  11. [Potential biochemical factors for the development of urolithiasis in patients with spinal cord injuries].

    PubMed

    Stogov, M V; Shchurova, E N; Bliudenov, D N

    2014-01-01

    A comparative analysis of biochemical parameters of blood serum and daily urine in patients with urolithiasis developed after spinal cord injury (study group--35 patients) and patients without development of the disease (comparison group--20 patients) was performed. It was found that patients after spinal cord injury have developed productive azotemia, which led to the disruption of renal excretory function (accumulation of urea and creatinine in blood, and lowering their clearance). Against this background, there is violation of excretion of uric acid, magnesium, decreased sensitivity of the renal tubules to aldosterone (in patients with nephrolithiasis K/Na ratio in urine was lower). As a result, patients have decreased reabsorption of sodium and water retention, increased urine osmolality; against the background of electrolyte imbalance in urine, this leads to the formation of stones. In patients with spinal cord injuries, main trigger mechanism of formation of urinary stones was excessive posttraumatic azotemia. The high concentration of the products of protein-nitrogen catabolism in the serum of patients in the acute and early periods of spinal cord injury may be unfavorable criterion determining the significant risk of developing of kidney stones.

  12. Early gene expression during natural spinal cord regeneration in the salamander Ambystoma mexicanum.

    PubMed

    Monaghan, James R; Walker, John A; Page, Robert B; Putta, Srikrishna; Beachy, Christopher K; Voss, S Randal

    2007-04-01

    In contrast to mammals, salamanders have a remarkable ability to regenerate their spinal cord and recover full movement and function after tail amputation. To identify genes that may be associated with this greater regenerative ability, we designed an oligonucleotide microarray and profiled early gene expression during natural spinal cord regeneration in Ambystoma mexicanum. We sampled tissue at five early time points after tail amputation and identified genes that registered significant changes in mRNA abundance during the first 7 days of regeneration. A list of 1036 statistically significant genes was identified. Additional statistical and fold change criteria were applied to identify a smaller list of 360 genes that were used to describe predominant expression patterns and gene functions. Our results show that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal cord regeneration. We also report gene expression similarities and differences between our study and studies that have profiled gene expression after spinal cord injury in rat. Our study illustrates the utility of a salamander model for identifying genes and gene functions that may enhance regenerative ability in mammals.

  13. 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.

  14. 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.

  15. 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

  16. Upregulation of complement inhibitors in association with vulnerable cells following contusion-induced spinal cord injury.

    PubMed

    Anderson, Aileen J; Najbauer, Joseph; Huang, Wencheng; Young, Wise; Robert, Stephanie

    2005-03-01

    We have previously described the activation of the classical, alternative, and terminal complement cascade pathways after acute contusion spinal cord injury using the New York University (NYU) weight-drop impactor. In the present study, we examined the induction of protein regulators of the complement cascade, factor H (FH), and clusterin, in the same experimental paradigm. The spinal cord of laminectomized adult rats was subjected to mild or severe injury using impactor weight-drop heights of 12.5 and 50 mm, respectively. The spinal cords of control and injured animals were evaluated at 1, 7, and 42 days after injury. Immunocytochemistry revealed a robust increase in the numbers and intensity of staining of FH, and clusterin-positive cells in the injured cord at all three time points, with the highest increases observed at 1 and 42 days after injury. FH and clusterin-positive cells were observed among neurons as well as oligodendrocytes. The increased expression was detected both rostrally and caudally from the injury site, in the latter case at distances up to 20 mm. The precise biological significance of injury-induced upregulation of these proteins remains to be determined. However, FH and clusterin are potent regulators of complement activity targeting upstream (FH) and downstream (clusterin) molecules of the pro-inflammatory cascade, which could be of vital importance in preventing a "runaway" inflammatory reaction in the injured spinal cord.

  17. Nrf2 Activation in Astrocytes Contributes to Spinal Cord Ischemic Tolerance Induced by Hyperbaric Oxygen Preconditioning

    PubMed Central

    Xu, Jiajun; Huang, Guoyang; Zhang, Kun; Sun, Jinchuan; Xu, Tao; Li, Runping

    2014-01-01

    Abstract In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtime-polymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, γ-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury. HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in

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

    DTIC Science & Technology

    2013-10-01

    Louisville, KY After spinal cord injury (SCI) patients commonly develop spasticity and contractures as secondary complications of “upper motor neuron...lesions. Physical therapists use stretching maneuvers to maintain extensibility of soft tissues and to manage spasticity . Previous studies in our lab

  19. 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.

  20. 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,…

  1. 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.…

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

    PubMed

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

    2016-09-05

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

  3. 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

  4. Vascular Imaging Techniques of the Spinal Cord.

    PubMed

    Vargas, Maria Isabel; Barnaure, Isabelle; Gariani, Joanna; Boto, José; Pellaton, Alain; Dietemann, Jean-Louis; Kulcsar, Zsolt

    2017-04-01

    The various imaging techniques used to depict vascular lesions of the spinal cord are described in this article with particular emphasis on magnetic resonance imaging (MRI), vascular sequences, and advantages of high-field MRI. Technical vascular protocols are discussed in computed tomography, MRI, and conventional angiography. The diverse magnetic resonance angiography protocols are presented as well as their findings, specificities, and pitfalls. A review of the vascular anatomy and the most common pathologies analyzed by magnetic resonance angiography and conventional angiography is described.

  5. Epidemiologic Change of Patients With Spinal Cord Injury

    PubMed Central

    Shin, Ji Cheol; Yu, Su Jin; Yang, Hea Eun; Yoon, Seo Yeon

    2013-01-01

    Objective To evaluate the epidemiologic change of patients with spinal cord injury who were admitted to a Rehabilitation Hospital, Yonsei University College of Medicine, during 1987-1996 and 2004-2008. Methods Medical records of 629 patients with spinal cord injury admitted to the Rehabilitation Hospital, Yonsei University College of Medicine, from 2004 to 2008 were collected and reviewed retrospectively. Results The male-to-female ratio decreased to 2.86:1, the mean age at injury increased, nontraumatic etiology increased, traffic accident remained to be the most common in traumatic spinal cord injury, and falling increased significantly. Tumor was the most common etiology in nontraumatic spinal cord injury, tetraplegia and incomplete injuries occurred more than paraplegia and complete injuries, indwelling catheter was the most common voiding method, and the duration of hospitalization decreased. Conclusion Many trends changed in epidemiology of spinal cord injury. PMID:23525183

  6. Motoneuron differentiation of immortalized human spinal cord cell lines.

    PubMed

    Li, R; Thode, S; Zhou, J; Richard, N; Pardinas, J; Rao, M S; Sah, D W

    2000-02-01

    Human motoneuron cell lines will be valuable tools for spinal cord research and drug discovery. To create such cell lines, we immortalized NCAM(+)/neurofilament(+) precursors from human embryonic spinal cord with a tetracycline repressible v-myc oncogene. Clonal NCAM(+)/neurofilament(+) cell lines differentiated exclusively into neurons within 1 week. These neurons displayed extensive processes, exhibited immunoreactivity for mature neuron-specific markers such as tau and synaptophysin, and fired action potentials upon current injection. Moreover, a clonal precursor cell line gave rise to multiple types of spinal cord neurons, including ChAT(+)/Lhx3(+)/Lhx4(+) motoneurons and GABA(+) interneurons. These neuronal restricted precursor cell lines will expedite the elucidation of molecular mechanisms that regulate the differentiation, maturation and survival of specific subsets of spinal cord neurons, and the identification and validation of novel drug targets for motoneuron diseases and spinal cord injury.

  7. 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

  8. Spinal cord pattern generators for locomotion.

    PubMed

    Dietz, V

    2003-08-01

    It is generally accepted that locomotion in mammals, including humans, is based on the activity of neuronal circuits within the spinal cord (the central pattern generator, CPG). Afferent information from the periphery (i.e. the limbs) influences the central pattern and, conversely, the CPG selects appropriate afferent information according to the external requirement. Both the CPG and the reflexes that mediate afferent input to the spinal cord are under the control of the brainstem. There is increasing evidence that in central motor diseases, a defective utilization of afferent input, in combination with secondary compensatory processes, is involved in typical movement disorders, such as spasticity and Parkinson's disease. Recent studies indicate a plastic behavior of the spinal neuronal circuits following a central motor lesion. This has implications for any rehabilitative therapy that should be directed to take advantage of the plasticity of the central nervous system. The significance of this research is in a better understanding of the pathophysiology underlying movement disorders and the consequences for an appropriate treatment.

  9. The Temporal Pattern, Flux, and Function of Autophagy in Spinal Cord Injury

    PubMed Central

    Zhou, Kailiang; Sansur, Charles A.; Xu, Huazi; Jia, Xiaofeng

    2017-01-01

    Previous studies have indicated that autophagy plays a critical role in spinal cord injury (SCI), including traumatic spinal cord injury (TSCI) and ischemia-reperfusion spinal cord injury (IRSCI). However, while the understanding of mechanisms underlying autophagy in SCI has progressed, there remain several controversial points: (1) temporal pattern results of autophagic activation after SCI are not consistent across studies; (2) effect of accumulation of autophagosomes due to the blockade or enhancement of autophagic flux is uncertain; (3) overall effect of enhanced autophagy remains undefined, with both beneficial and detrimental outcomes reported in SCI literature. In this review, the temporal pattern of autophagic activation, autophagic flux, autophagic cell death, relationship between autophagy and apoptosis, and pharmacological intervention of autophagy in TSCI (contusion injury, compression injury and hemisection injury) and IRSCI are discussed. Types of SCI and severity appear to contribute to differences in outcomes regarding temporal pattern, flux, and function of autophagy. With future development of specific strategies on autophagy intervention, autophagy may play an important role in improving functional recovery in patients with SCI. PMID:28230791

  10. Acute mesenteric ischemia in young adults.

    PubMed

    Ozturk, Gurkan; Aydinli, Bulent; Atamanalp, S Selcuk; Yildirgan, M Ilhan; Ozoğul, Bünyami; Kısaoğlu, Abdullah

    2012-08-01

    Acute mesenteric ischemia is commonly seen in old patients. This study was undertaken to show that mesenteric ischemia might be seen in individuals under 40 years of age and that its diagnosis is challenging. Twenty-six patients with acute mesenteric ischemia under the age of 40 were studied. The main symptom on admission was abdominal pain. Symptom duration varied between 12 h and 5 days. The medical history of the patients revealed that 9 had no previous diseases. Other 17 had predisposing factors in the first evaluation. None of the patients had any history of narcotic or drug abuse. Ten patients presented with signs and symptoms of sepsis and septic shock. Preoperative diagnosis was acute intestinal ischemia only in 6 patients. Preoperatively, all the patients had intestinal or colonic ischemia and necrosis; one had additional ischemia of the liver, stomach, duodenum, and pancreas. Six patients had massive intestinal necrosis. The overall postoperative complication and overall mortality rates were 61.5 and 26.9 %, respectively. Complications and mortality were determined to be associated with previous pulmonary disease, acidosis, presence of septic shock, acute renal failure, extent of the ischemia and extent of resection, second look operations, previous cardiac events, and the kind of affected bowel (colon involvement).

  11. 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

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Anti-NGF Local Therapy for Autonomic Dysreflexia in Spinal Cord Injury

    DTIC Science & Technology

    2013-10-01

    pathophysiological basis of neurogenic detrusor overactivity with spinal cord injury (SCI). However, the... bladder distention after SCI. Using adult female rats with chronic spinal cord injury induced by Th4 spinal cord transection, we will investigate: (1...autonomic dysreflexia during bladder distention in rats with spinal cord injury . 111th Annual Meeting AUA, Abstract No. 34, San Diego, May 4-8, 2013.

  18. 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

  19. 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

  20. 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…

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

    PubMed

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

    2016-11-01

    Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)(+) neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)(-) and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH(+) neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal 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.

  2. Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

    PubMed

    Kumar, Hemant; Ropper, Alexander E; Lee, Soo-Hong; Han, Inbo

    2016-05-18

    The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

  3. Neuromyelitis optica mimics the morphology of spinal cord tumors.

    PubMed

    Erol, İlknur; Özkale, Murat; Savaş, Tülin; Alkan, Özlem; Çekinmez, Melih; Erbay, Ayşe

    2016-01-01

    Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, that predominantly affects the spinal cord and the optic nerve. Its key features include transverse myelitis, commonly associated with extensive inflammation spanning three or more consecutive vertebral segments. Longitudinal extensive spinal cord lesions can also occur in systemic autoimmune diseases, infections, vascular and metabolic disorders, subsequent to irradiation, intramedullary tumors and paraneoplastic myelopathies. We present a case study of an 8-year-old girl seropositive for antibodies against the aquaporin 4 who displayed longitudinal extensive spinal cord lesions, that was initially misdiagnosed as an intramedullary tumor.

  4. Risks associated with pregnancy in spinal cord-injured women.

    PubMed

    Baker, E R; Cardenas, D D; Benedetti, T J

    1992-09-01

    We reviewed the experience with pregnancy in spinal cord-injured women at the University of Washington over the past 10 years. During that time, 11 women with spinal cord injury had 13 pregnancies. Infant outcome was uniformly good. No major obstetric complication occurred. The mothers experienced medical problems including urinary tract infection in ten and pyelonephritis in three. Autonomic hyperreflexia occurred in three of five subjects with lesions at or above the sixth thoracic vertebra. Pregnancy in the spinal cord-injured patient involves medical risk for the mother, but with careful management, an excellent outcome for both mother and infant may be anticipated.

  5. Partial agonistic action of endomorphins in the mouse spinal cord.

    PubMed

    Mizoguchi, H; Wu, H E; Narita, M

    2001-09-07

    The partial agonistic properties of endogenous mu-opioid peptides endomorphin-1 and endomorphin-2 for G-protein activation were determined in the mouse spinal cord, monitoring the increases in guanosine-5'-o-(3-[35S]thio)triphosphate binding. The G-protein activation induced by endogenous opioid peptide beta-endorphin in the spinal cord was significantly, but partially, attenuated by co-incubation with endomorphin-1 or endomorphin-2. The data indicates that endomorphin-1 and endomorphin-2 are endogenous partial agonists for mu-opioid receptor in the mouse spinal cord.

  6. Current therapeutic strategies for inflammation following traumatic spinal cord injury☆

    PubMed Central

    Singh, Priyanka L.; Agarwal, Nitin; Barrese, James C.; Heary, Robert F.

    2012-01-01

    Damage from spinal cord injury occurs in two phases – the trauma of the initial mechanical insult and a secondary injury to nervous tissue spared by the primary insult. Apart from damage sustained as a result of direct trauma to the spinal cord, the post-traumatic inflammatory response contributes significantly to functional motor deficits exacerbated by the secondary injury. Attenuating the detrimental aspects of the inflammatory response is a promising strategy to potentially ameliorate the secondary injury, and promote significant functional recovery. This review details how the inflammatory component of secondary injury to the spinal cord can be treated currently and in the foreseeable future. PMID:25624806

  7. 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

  8. 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

  9. 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

  10. Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats.

    PubMed

    Karalija, Amar; Novikova, Liudmila N; Kingham, Paul J; Wiberg, Mikael; Novikov, Lev N

    2012-01-01

    Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the

  11. NBQX treatment improves mitochondrial function and reduces oxidative events after spinal cord injury.

    PubMed

    Mu, Xiaojun; Azbill, Robert D; Springer, Joe E

    2002-08-01

    The purpose of this study was to examine the effects of inhibiting ionotropic glutamate receptor subtypes on measures of oxidative stress events at acute times following traumatic spinal cord injury (SCI). Rats received a moderate contusion injury and 15 min later were treated with one of two doses of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulfonamide disodium (NBQX), MK-801, or the appropriate vehicle. At 4 h following injury, spinal cords were removed and a crude synaptosomal preparation obtained to examine mitochondrial function using the MTT assay, as well as measures of reactive oxygen species (ROS), lipid peroxidation, and glutamate and glucose uptake. We report here that intraspinal treatment with either 15 or 30 nmol of NBQX improves mitochondrial function and reduces the levels of ROS and lipid peroxidation products. In contrast, MK-801, given intravenously at doses of 1.0 or 5.0 mg/kg, was without effect on these same measures. Neither drug treatment had an effect on glutamate or glucose uptake, both of which are reduced at acute times following SCI. Previous studies have documented that drugs acting on non-N-methyl-D-aspartate (NMDA) receptors exhibit greater efficacy compared to NMDA receptor antagonists on recovery of function and tissue sparing following traumatic spinal cord injury. The results of this study provide a potential mechanism by which blockade of the non-NMDA ionotropic receptors exhibit positive effects following traumatic SCI.

  12. 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.

  13. 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

  14. Chronic GABAergic blockade in the spinal cord in vivo induces motor alterations and neurodegeneration.

    PubMed

    Ramírez-Jarquín, Uri Nimrod; Tapia, Ricardo

    2017-05-01

    Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord. We show that acute glycinergic blockade with strychnine or GABAergic blockade with bicuculline had no significant effects on motor activity and on motor neuron survival. However, chronic bicuculline infusion, but not strychnine, induced ipsilateral gait alterations, phalange flaccidity and significant motor neuron loss, and these effects were prevented by AMPA receptor blockade with CNQX but not by NMDA receptor blockade with MK801. In addition, we demonstrate that the chronic infusion of bicuculline enhanced the excitotoxic effect of AMPA, causing faster bilateral paralysis and increasing motor neuron loss. These findings indicate a relevant role of GABAergic inhibitory circuits in the regulation of motor neuron excitability and suggest that their alterations may be involved in the neurodegeneration processes characteristic of motor neuron diseases such as amyotrophic lateral sclerosis.

  15. 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.

  16. 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

  17. Spinal Cord Injury and Related Clinical Trials

    PubMed Central

    Ha, Kee-Yong; Kim, Sang-Il

    2017-01-01

    Spinal cord injury (SCI) has been considered an incurable condition and it often causes devastating sequelae. In terms of the pathophysiology of SCI, reducing secondary damage is the key to its treatment. Various researches and clinical trials have been performed, and some of them showed promising results; however, there is still no gold standard treatment with sufficient evidence. Two therapeutic concepts for SCI are neuroprotective and neuroregenerative strategies. The neuroprotective strategy modulates the pathomechanism of SCI. The purpose of neuroprotective treatment is to minimize secondary damage following direct injury. The aim of neuroregenerative treatment is to enhance the endogenous regeneration process and to alter the intrinsic barrier. With advancement in biotechnology, cell therapy using cell transplantation is currently under investigation. This review discusses the pathophysiology of SCI and introduces the therapeutic candidates that have been developed so far. PMID:28261421

  18. Steroids, spinal cord and pain sensation.

    PubMed

    Patte-Mensah, Christine; Meyer, Laurence; Mensah-Nyagan, Ayikoe Guy

    2011-10-01

    During the whole life, the nervous system is continuously submitted to the actions of different categories of hormones, including steroids. Therefore, the interactions between hormonal compounds and neural tissues are subjected to intense investigations. While a majority of studies focus on the brain, the spinal cord (SC) has received little attention, although this structure is also an important part of the central nervous system, controlling motor and sensory functions. To point out the importance of interactions between hormones and the SC in the regulation of neurobiological activities, we recapitulated and discussed herein various key data, revealing that the pivotal role played by the SC in nociception and pain modulation, directly depends on the SC ability to metabolize and synthesize steroidal molecules. The paper suggests that future investigations aiming to develop effective strategies against chronic pain, must integrate regulatory effects exerted by hormonal steroids on the SC activity, as well as the actions of endogenous neurosteroids locally synthesized in spinal neural networks.

  19. 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

  20. Endogenous neurogenesis in adult mammals after spinal cord injury.

    PubMed

    Duan, Hongmei; Song, Wei; Zhao, Wen; Gao, Yudan; Yang, Zhaoyang; Li, Xiaoguang

    2016-12-01

    During the whole life cycle of mammals, new neurons are constantly regenerated in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles. Thanks to emerging methodologies, great progress has been made in the characterization of spinal cord endogenous neural stem cells (ependymal cells) and identification of their role in adult spinal cord development. As recently evidenced, both the intrinsic and extrinsic molecular mechanisms of ependymal cells control the sequential steps of the adult spinal cord neurogenesis. This review introduces the concept of adult endogenous neurogenesis, the reaction of ependymal cells after adult spinal cord injury (SCI), the heterogeneity and markers of ependymal cells, the factors that regulate ependymal cells, and the niches that impact the activation or differentiation of ependymal cells.

  1. 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

  2. Syrinx of the Spinal Cord and Brain Stem

    MedlinePlus

    ... the Spinal Cord and Brain Stem Symptoms Diagnosis Treatment Medical Dictionary Also of Interest (Quiz) Horner Syndrome (Video) Overview of the Nervous System (News) Youth With Type 2 Diabetes Often Face Complications (News) Study Tracks Bleeding Risk ...

  3. 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.

  4. 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 ...

  5. General Information about 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 ...

  6. 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

  7. Corticospinal circuit plasticity in motor rehabilitation from spinal cord injury.

    PubMed

    Serradj, Najet; Agger, Sydney F; Hollis, Edmund R

    2016-12-06

    Restoring corticospinal function after spinal cord injury is a significant challenge as the corticospinal tract elicits no substantive, spontaneous regeneration, and its interruption leaves a permanent deficit. The corticospinal circuit serves multiple motor and sensory functions within the mammalian nervous system as the direct link between isocortex and spinal cord. Maturation of the corticospinal circuit involves the refinement of projections within the spinal cord and a subsequent refinement of motor maps within the cortex. The plasticity of these cortical motor maps mirrors the acquisition of skilled motor learning, and both the maps and motor skills are disrupted following injury to the corticospinal tract. The motor cortex exhibits the capacity to incorporate changes in corticospinal projections induced by both spontaneous and therapeutic-mediated plasticity of corticospinal axons through appropriate rehabilitation. An understanding of the mechanisms of corticospinal plasticity in motor learning will undoubtedly help inform strategies to improve motor rehabilitation after spinal cord injury.

  8. 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

  9. Radiation myelopathy of cervical spinal cord simulating intramedullary neoplasm

    PubMed Central

    Fogelholm, R.; Haltia, M.; Andersson, L. C.

    1974-01-01

    Radiation myelopathy is a well-known complication of irradiation therapy of neoplasms in the vicinity of the spinal cord. Most earlier authors have stressed the association of a normal myelogram and normal CSF protein level with this condition. One case of radiation myelopathy with a myelogram simulating intramedullary neoplasm and with extremely high CSF protein concentration is presented. Six months after myelography necropsy revealed severe atrophy of the previously thickened lower cervical spinal cord. The pathogenetic mechanisms are discussed. Images PMID:4443812

  10. Cystic Abnormalities of the Spinal Cord and Vertebral Column.

    PubMed

    da Costa, Ronaldo C; Cook, Laurie B

    2016-03-01

    Cystic lesions of the vertebral column and spinal cord are important differential diagnoses in dogs with signs of spinal cord disease. Synovial cysts are commonly associated with degenerative joint disease and usually affect the cervical and lumbosacral regions. Arachnoid diverticulum (previously known as cyst) is seen in the cervical region of large breed dogs and thoracolumbar region of small breed dogs. This article reviews the causes, diagnosis, and treatment of these and other, less common, cystic lesions.

  11. Central pattern generators of the mammalian spinal cord.

    PubMed

    Frigon, Alain

    2012-02-01

    Neuronal networks within the spinal cord of mammals are responsible for generating various rhythmic movements, such as walking, running, swimming, and scratching. The ability to generate multiple rhythmic movements highlights the complexity and flexibility of the mammalian spinal circuitry. The present review describes features of some rhythmic motor behaviors generated by the mammalian spinal cord and discusses how the spinal circuitry is able to produce different rhythmic movements with their own sets of goals and demands.

  12. [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.

  13. Magnetic resonance imaging in the diagnosis of spinal cord diseases.

    PubMed Central

    Aichner, F; Poewe, W; Rogalsky, W; Wallnöfer, K; Willeit, J; Gerstenbrand, F

    1985-01-01

    Experience with magnetic resonance imaging in 22 patients with diseases of the spinal cord is reported. Important additional diagnostic information as compared to conventional neuroradiological techniques (myelography, spinal CT) was gained especially in cases of hydrosyringomyelia, intraspinal tumour and multiple sclerosis. It is suggested that magnetic resonance imaging may become the method of choice in the diagnosis of structural spinal cord diseases. Images PMID:3936900

  14. Robust, accurate and fast automatic segmentation of the spinal cord.

    PubMed

    De Leener, Benjamin; Kadoury, Samuel; Cohen-Adad, Julien

    2014-09-01

    Spinal cord segmentation provides measures of atrophy and facilitates group analysis via inter-subject correspondence. Automatizing this procedure enables studies with large throughput and minimizes user bias. Although several automatic segmentation methods exist, they are often restricted in terms of image contrast and field-of-view. This paper presents a new automatic segmentation method (PropSeg) optimized for robustness, accuracy and speed. The algorithm is based on the propagation of a deformable model and is divided into three parts: firstly, an initialization step detects the spinal cord position and orientation using a circular Hough transform on multiple axial slices rostral and caudal to the starting plane and builds an initial elliptical tubular mesh. Secondly, a low-resolution deformable model is propagated along the spinal cord. To deal with highly variable contrast levels between the spinal cord and the cerebrospinal fluid, the deformation is coupled with a local contrast-to-noise adaptation at each iteration. Thirdly, a refinement process and a global deformation are applied on the propagated mesh to provide an accurate segmentation of the spinal cord. Validation was performed in 15 healthy subjects and two patients with spinal cord injury, using T1- and T2-weighted images of the entire spinal cord and on multiecho T2*-weighted images. Our method was compared against manual segmentation and against an active surface method. Results show high precision for all the MR sequences. Dice coefficients were 0.9 for the T1- and T2-weighted cohorts and 0.86 for the T2*-weighted images. The proposed method runs in less than 1min on a normal computer and can be used to quantify morphological features such as cross-sectional area along the whole spinal cord.

  15. Effect of Combination of Non-Invasive Spinal Cord Electrical Stimulation and Serotonin Receptor Activation in Patients with Chronic Spinal Cord Lesion.

    PubMed

    Moshonkina, T R; Shapkova, E Yu; Sukhotina, I A; Emeljannikov, D V; Gerasimenko, Yu P

    2016-10-01

    We analyzed the efficiency of percutaneous electrical stimulation of the spinal cord and serotonin receptor activation in rehabilitation of paralyzed patients. Four-week course of spinal cord electrical stimulation combined with mechanotherapy produced positive shifts in the status of chronically paralyzed patients. Serotonin receptor activation potentiated the effect of spinal cord stimulation and can be regarded as an additional neurorehabilitation option.

  16. Spinal cord lesions and disability in Hispanics with multiple sclerosis

    PubMed Central

    Amezcua, L.; Lerner, A.; Ledezma, K.; Conti, D.; Law, M.; Weiner, L.; Langer-Gould, A.

    2013-01-01

    Background Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. Objective To describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. Methods Cross-sectional study of 164 patients with complete MRIs. Spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale ≥4.0) was adjusted for age, disease duration and sex using logistic regression. Results 125/164(73%) MS patients had spinal cord lesions (sSCLs, 57%; LESCLs, 19%) but only 11(7%) had OSMS. LESCLs were associated with disability (p<0.0001), longer disease duration (p<0.0001) and MS (n=21 vs. n=10 OSMS; p<0.0001). LESCLs was associated with the greatest risk to disability (OR 7.3, 95% CIs1.9-26.5; p=0.003; sSCLs OR 2.5, 95% CIs0.9-7.1; p=0.09) compared with noSCLs. Conclusion LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population. PMID:23912723

  17. GABA and Central Neuropathic Pain following Spinal Cord Injury

    PubMed Central

    Gwak, Young S.; Hulsebosch, Claire E.

    2012-01-01

    Spinal cord injury induces maladaptive synaptic transmission in the somatosensory system that results in chronic central neuropathic pain. Recent literature suggests that glial-neuronal interactions are important modulators in synaptic transmission following spinal cord injury. Neuronal hyperexcitability is one of the predominant phenomenon caused by maladaptive synaptic transmission via altered glial-neuronal interactions after spinal cord injury. In the somatosensory system, spinal inhibitory neurons counter balance the enhanced synaptic transmission from peripheral input. For a decade, the literature suggests that hypofunction of GABAergic inhibitory tone is an important factor in the enhanced synaptic transmission that often results in neuronal hyperexcitability in dorsal horn neurons following spinal cord injury. Neurons and glial cells synergistically control intracellular chloride ion gradients via modulation of chloride transporters, extracellular glutamate and GABA concentrations via uptake mechanisms. Thus, the intracellular “GABA-glutamate-glutamine cycle” is maintained for normal physiological homeostasis. However, hyperexcitable neurons and glial activation after spinal cord injury disrupts the balance of chloride ions, glutamate and GABA distribution in the spinal dorsal horn and results in chronic neuropathic pain. In this review, we address spinal cord injury induced mechanisms in hypofunction of GABAergic tone that results in chronic central neuropathic pain. PMID:21216257

  18. Anomalous vertebral artery compression of the spinal cord at the cervicomedullary junction

    PubMed Central

    Ball, Bret Gene; Krueger, Bruce R; Piepgras, David G

    2011-01-01

    Background: Myelopathy from ectatic vertebral artery compression of the spinal cord at the cervicomedullary junction is a rare condition. Case Description: A 63-year-old female was originally diagnosed with occult hydrocephalus syndrome after presenting with symptoms of ataxia and urinary incontinence. Ventriculoperitoneal shunting induced an acute worsening of the patient′s symptoms as she immediately developed a sensory myelopathy. An MR scan demonstrated multiple congenital abnormalities including cervicomedullary stenosis with anomalous vertebral artery compression of the dorsal spinal cord at the cervicomedullary junction. The patient was taken to surgery for a suboccipital craniectomy, C1-2 laminectomy, vertebral artery decompression, duraplasty, and shunt ligation. Intraoperative findings confirmed preoperative radiography with ectactic vertebral arteries deforming the dorsal aspect of the spinal cord. There were no procedural complications and at a 6-month follow-up appointment, the patient had experienced a marked improvement in her preoperative signs and symptoms. Conclusion: Myelopathy from ectatic vertebral artery compression at the cervicomedullary junction is a rare disorder amenable to operative neurovascular decompression. PMID:21886876

  19. TCTP Expression After Rat Spinal Cord Injury: Implications for Astrocyte Proliferation and Migration.

    PubMed

    Ren, Jianbing; Mao, Xingxing; Chen, Minghao; Zhang, Weidong; Liu, Yang; Duan, Chengwei; Zhang, Haiyan; Sun, Chi; Wu, Weijie; Zhu, Xinjian; Ge, Jianbing; Tao, Weidong; Wang, Youhua; Lu, Hongjian

    2015-11-01

    Translationally controlled tumor protein (TCTP) is a ubiquitous and highly conserved protein which plays a role in cell proliferation and growth, apoptosis, and cell cycle regulation. However, its expression and function in spinal cord injury (SCI) are still unknown. Here, we demonstrated that expression of TCTP was dynamic changed after acute spinal cord injury. Our results showed that TCTP gradually increased, reached a peak at 3 day, and then declined to basal levels at 14 days after spinal cord injury. Upregulation of TCTP was accompanied with an increase in the levels of proliferation proteins such as PCNA. Immunofluorescent labeling also showed that TCTP located in astrocytes and traumatic SCI induced TCTP colocalizated with PCNA. These results indicated that TCTP might play an important role in astrocyte proliferation. To further probe the role of TCTP, TCTP-specific siRNA-transfected astrocytes showed significant decrease of primary astrocyte proliferation. Surprisingly, TCTP knockdown also reduced primary astrocyte migration, as the reorganization of microtubules and F-actin was disturbed after siRNA transfection. All above indicated that TCTP might play a crucial role in astrocyte proliferation and migration. Collectively, our data suggested that TCTP might play important roles in CNS pathophysiology after SCI.

  20. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice.

    PubMed

    Liu, Tong; Berta, Temugin; Xu, Zhen-Zhong; Park, Chul-Kyu; Zhang, Ling; Lü, Ning; Liu, Qin; Liu, Yang; Gao, Yong-Jing; Liu, Yen-Chin; Ma, Qiufu; Dong, Xinzhong; Ji, Ru-Rong

    2012-06-01

    Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs) that coexpress the itch signaling pathway components transient receptor potential subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a TLR3 agonist induces inward currents and action potentials in DRG neurons and elicited scratching in WT mice but not Tlr3(-/-) mice. Furthermore, excitatory synaptic transmission in spinal cord slices and long-term potentiation in the intact spinal cord were impaired in Tlr3(-/-) mice but not Tlr7(-/-) mice. Consequently, central sensitization-driven pain hypersensitivity, but not acute pain, was impaired in Tlr3(-/-) mice. In addition, TLR3 knockdown in DRGs also attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was substantially reduced in Tlr3(-/-) mice. Our findings demonstrate a critical role of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic transmission, and central sensitization. TLR3 may serve as a new target for developing anti-itch treatment.

  1. Deficiency of TREK-1 potassium channel Exacerbates Secondary Injury Following Spinal Cord Injury in Mice.

    PubMed

    Fang, Yongkang; Huang, Xiaojiang; Wan, Yue; Tian, Hao; Tian, Yeye; Wang, Wei; Zhu, Suiqiang; Xie, Minjie

    2017-02-13

    Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI. TREK-1 was widely expressed in mice spinal cord, including astrocytes and neurons. Deficiency of TREK-1 significantly exacerbated focal inflammatory responses as indicated by the increased accumulation of microglia/macrophage as well as pro-inflammatory factor interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) expression. Meanwhile, TREK-1 knockout (KO) mice showed enhanced reactive astrogliosis, chondroitin sulphate proteoglycans (CSPGs) production and decreased glutamate transporter-1(GLT-1) expression compared to the wide type mice after SCI. Furthermore, TREK-1 deficiency promoted neurons and oligodendrocytes apoptosis, aggravated demyelination, cavity formation and retarded motor recovery. In summary, our findings provide the first in vivo evidence suggesting that TREK-1 may thereby constitute a promising therapeutic target to treat acute SCI. This article is protected by copyright. All rights reserved.

  2. 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

  3. 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.

  4. Imaging and clinical properties of inflammatory demyelinating pseudotumor in the spinal cord

    PubMed Central

    Wang, Ying; Wang, Min; Liang, Hui; Yu, Quntao; Yan, Zhihui; Kong, Min

    2013-01-01

    Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea-tures of 36 cases of inflammatory demyelinating pseudotumor in the spinal cord were retrospec-tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensorimotor disorder. Among them, six cases were misdiagnosed as having intra-dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologi-cally confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were com-mon. Magnetic resonance imaging revealed edema and space-occupying lesions to varying grees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like forcement (open-loop sign). Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re-sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement (open-ring sign) on magnetic resonance imaging is the predominant property of inflammatory myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional pa-logical properties. PMID:25206559

  5. Airway complications in traumatic lower cervical spinal cord injury: A retrospective study

    PubMed Central

    Niedeggen, Andreas; Estel, Barbara; Seidl, Rainer O.

    2015-01-01

    Objective To investigate risk factors for pneumonia in patients with traumatic lower cervical spinal cord injury. Design Observational study, retrospective study. Setting Spinal cord unit in a maximum care hospital. Methods Thirty-seven patients with acute isolated traumatic spinal cord injury at levels C4–C8 and complete motor function injury (AIS A, B) treated from 2004 to 2010 met the criteria for inclusion in our retrospective analysis. The following parameters were considered: ventilation-specific parameters, re-intubation, creation of a tracheostomy, pneumonia, antibiotic treatment, and length of intensive care unit (ICU) stay and total hospitalization. Results Among the patients, 81% had primary invasive ventilation. In 78% of cases a tracheostomy was created; 3% of these cases were discharged with invasive ventilation and 28% with a tracheostomy without ventilation. Pneumonia according to Centers for Disease Control criteria occurred in 51% of cases within 21 ± 32 days of injury, and in 3% at a later date. The number of pre-existing conditions was significantly associated with pneumonia. Length of ICU stay was 25 ± 34 days, and average total hospital duration was 230 ± 144 days. Significant factors affecting the duration of ventilation were the number of pre-existing conditions and tetraplegia-specific complications. Conclusions Our results confirm that patients with traumatic lower cervical spinal cord injuries defined by lesion level and AIS constitute a homogeneous group. This group is characterized by a high rate of pneumonia during the first 4 weeks after injury. The number of pre-existing general conditions and spinal injury-specific comorbidities are the only risk factors identified for the development of pneumonia and/or duration of ventilation. PMID:25117865

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

    PubMed Central

    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

  7. 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

  8. 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

  9. 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

    2015-11-06

    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.

  10. Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury

    PubMed Central

    Koehn, Liam M.; Noor, Natassya M.; Dong, Qing; Er, Sing-Yan; Rash, Lachlan D.; King, Glenn F.; Dziegielewska, Katarzyna M.; Saunders, Norman R.; Habgood, Mark D.

    2016-01-01

    Tissue loss after spinal trauma is biphasic, with initial mechanical/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a “ treatment window” through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies. PMID:28105306

  11. Acute small bowel ischemia: CT imaging findings.

    PubMed

    Segatto, Enrica; Mortelé, Koenraad J; Ji, Hoon; Wiesner, Walter; Ros, Pablo R

    2003-10-01

    Small bowel ischemia is a disorder related to a variety of conditions resulting in interruption or reduction of the blood supply of the small intestine. It may present with various clinical and radiologic manifestations, and ranges pathologically from localized transient ischemia to catastrophic necrosis of the intestinal tract. The primary causes of insufficient blood flow to the small intestine are various and include thromboembolism (50% of cases), nonocclusive causes, bowel obstruction, neoplasms, vasculitis, abdominal inflammatory conditions, trauma, chemotherapy, radiation, and corrosive injury. Computed tomography (CT) can demonstrate changes because of ischemic bowel accurately, may be helpful in determining the primary cause of ischemia, and can demonstrate important coexistent findings or complications. However, common CT findings in acute small bowel ischemia are not specific and, therefore, it is often a combination of clinical, laboratory and radiologic signs that may lead to a correct diagnosis. Understanding the pathogenesis of various conditions leading to mesenteric ischemia and being familiar with the spectrum of diagnostic CT signs may help the radiologist recognize ischemic small bowel disease and avoid delayed diagnosis. The aim of this article is to provide a review of the pathogenesis and various causes of acute small bowel ischemia and to demonstrate the contribution of CT in the diagnosis of this complex disease.

  12. TLR4 Deficiency Impairs Oligodendrocyte Formation in the Injured Spinal Cord

    PubMed Central

    Church, Jamie S.; Kigerl, Kristina A.; Lerch, Jessica K.; Popovich, Phillip G.

    2016-01-01

    Acute oligodendrocyte (OL) death after traumatic spinal cord injury (SCI) is followed by robust neuron–glial antigen 2 (NG2)-positive OL progenitor proliferation and differentiation into new OLs. Inflammatory mediators are prevalent during both phases and can influence the fate of NG2 cells and OLs. Specifically, toll-like receptor (TLR) 4 signaling induces OL genesis in the naive spinal cord, and lack of TLR4 signaling impairs white matter sparing and functional recovery after SCI. Therefore, we hypothesized that TLR4 signaling may regulate oligodendrogenesis after SCI. C3H/HeJ (TLR4-deficient) and control (C3H/HeOuJ) mice received a moderate midthoracic spinal contusion. TLR4-deficient mice showed worse functional recovery and reduced OL numbers compared with controls at 24 h after injury through chronic time points. Acute OL loss was accompanied by reduced ferritin expression, which is regulated by TLR4 and needed for effective iron storage. TLR4-deficient injured spinal cords also displayed features consistent with reduced OL genesis, including reduced NG2 expression, fewer BrdU-positive OLs, altered BMP4 signaling and inhibitor of differentiation 4 (ID4) expression, and delayed myelin phagocytosis. Expression of several factors, including IGF-1, FGF2, IL-1β, and PDGF-A, was altered in TLR4-deficient injured spinal cords compared with wild types. Together, these data show that TLR4 signaling after SCI is important for OL lineage cell sparing and replacement, as well as in regulating cytokine and growth factor expression. These results highlight new roles for TLR4 in endogenous SCI repair and emphasize that altering the function of a single immune-related receptor can dramatically change the reparative responses of multiple cellular constituents in the injured CNS milieu. SIGNIFICANCE STATEMENT Myelinating cells of the CNS [oligodendrocytes (OLs)] are killed for several weeks after traumatic spinal cord injury (SCI), but they are replaced by resident

  13. Acute limb ischemia due to ergotism.

    PubMed

    Naz, Iram; Sophie, Ziad

    2006-08-01

    Acute ischemia of an extremity potentially threatens limb loss and occasionally the life of the patient. We are reporting two cases of extremity ischemia secondary to ergot poisoning. The first patient was a 60 years old woman, who presented with a 15 days history of ischemia of the left arm with gangrene of the fingers and pain in the resting right hand for one day. Right brachial artery catheterization showed severe spasm of the artery which was resolved by passage of the inflated balloon catheter. She underwent amputation for gangrene of the left hand. The second patient presented with bilateral symmetrical ischemia of the lower extremities which improved upon withdrawal of the ergot containing medicine. She responded to nifedipine.

  14. Nanoparticle Estrogen in Rat Spinal Cord Injury Elicits Rapid Anti-Inflammatory Effects in Plasma, Cerebrospinal Fluid, and Tissue

    PubMed Central

    Varma, Abhay; Barry, John; Vertegel, Alexey; Banik, Naren

    2015-01-01

    Abstract Persons with spinal cord injury (SCI) are in need of effective therapeutics. Estrogen (E2), as a steroid hormone, is a highly pleiotropic agent; with anti-inflammatory, anti-apoptotic, and neurotrophic properties, it is ideal for use in treatment of patients with SCI. Safety concerns around the use of high doses of E2 have limited clinical application, however. To address these concerns, low doses of E2 (25 μg and 2.5 μg) were focally delivered to the injured spinal cord using nanoparticles. A per-acute model (6 h after injury) was used to assess nanoparticle release of E2 into damaged spinal cord tissue; in addition, E2 was evaluated as a rapid anti-inflammatory. To assess inflammation, 27-plex cytokine/chemokine arrays were conducted in plasma, cerebrospinal fluid (CSF), and spinal cord tissue. A particular focus was placed on IL-6, GRO-KC, and MCP-1 as these have been identified from CSF in human studies as potential biomarkers in SCI. S100β, an additional proposed biomarker, was also assessed in spinal cord tissue only. Tissue concentrations of E2 were double those found in the plasma, indicating focal release. E2 showed rapid anti-inflammatory effects, significantly reducing interleukin (IL)-6, GRO-KC, MCP-1, and S100β in one or all compartments. Numerous additional targets of rapid E2 modulation were identified including: leptin, MIP-1α, IL-4, IL-2, IL-10, IFNγ, tumor necrosis factor-α, etc. These data further elucidate the rapid anti-inflammatory effects E2 exerts in an acute rat SCI model, have identified additional targets of estrogen efficacy, and suggest nanoparticle delivered estrogen may provide a safe and efficacious treatment option in persons with acute SCI. PMID:25845398

  15. 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.

  16. The Therapeutic Effectiveness of Delayed Fetal Spinal Cord Tissue Transplantation on Respiratory Function Following Mid-Cervical Spinal Cord Injury.

    PubMed

    Lin, Chia-Ching; Lai, Sih-Rong; Shao, Yu-Han; Chen, Chun-Lin; Lee, Kun-Ze

    2017-01-17

    Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and γ-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.

  17. 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.

  18. p53 participates in the protective effects of ischemic post-conditioning against OGD-reperfusion injury in primary cultured spinal cord neurons.

    PubMed

    Li, Jinquan; Chen, Gong; Gao, Xinjie; Shen, Chao; Zhou, Ping; Wu, Xing; Che, Xiaoming; Xie, Rong

    2017-01-18

    Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury.

  19. Acute mesenteric ischemia: current multidisciplinary approach.

    PubMed

    Savlania, Ajay; Tripathi, Ramesh K

    2017-04-01

    The aim of this review was to describe and discuss the mechanisms of acute mesenteric ischemia (AMI) and the rationale and conduct of currently available endovascular and open surgical techniques in its management. We also propose an algorithm to support the current multidisciplinary approach in decision-making for mesenteric revascularization to manage this high-risk entity.

  20. 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

  1. 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

  2. Clinical indicators of paraplegia underplay universal spinal cord neuronal injury from transient aortic occlusion.

    PubMed

    Bell, Marshall T; Puskas, Ferenc; Bennett, Daine T; Cleveland, Joseph C; Herson, Paco S; Mares, Joshua M; Meng, Xainzhong; Weyant, Michael J; Fullerton, David A; Brett Reece, T

    2015-08-27

    Paraplegia following complex aortic intervention relies on crude evaluation of lower extremity strength such as whether the patient can lift their legs or flex the ankle. Little attention has been given to the possible long-term neurologic sequelae following these procedures in patients appearing functionally normal. We hypothesize that mice subjected to minimal ischemic time will have functional and histological changes despite the gross appearance of normal function. Male mice underwent 3 min of aortic occlusion (n=14) or sham surgery (n=4) via a median sternotomy. Neurologic function was graded by Basso Motor Score (BMS) preoperatively and at 24h intervals after reperfusion. Mice appearing functionally normal and sham mice were placed on a walking beam and recorded on high-definition, for single-frame motion analysis. After 96 hrs, spinal cords were removed for histological analysis. Following 3 min of ischemia, functional outcomes were split evenly with either mice displaying almost normal function n=7 or near complete paraplegia n=7. Additionally, single-frame motion analysis revealed significant changes in gait. Histologically, there was a significant stepwise reduction of neuronal viability, with even the normal function ischemic group demonstrating significant loss of neurons. Despite the appearance of normal function, temporary ischemia induced marked cyto-architectural changes and neuronal degeneration. Furthermore high-definition gait analysis revealed significant changes in gait and activity following thoracic aortic occlusion. These data suggest that all patients undergoing procedures, even with short ischemic times, may have spinal cord injury that is not evident clinically.

  3. Stress-resistant neural stem cells positively influence regional energy metabolism after spinal cord injury in mice.

    PubMed

    Schwerdtfeger, Karsten; Mautes, Angelika E M; Bernreuther, Christian; Cui, Yifang; Manville, Jérôme; Dihné, Marcel; Blank, Simon; Schachner, Melitta

    2012-02-01

    The importance of stem cells to ameliorate the devastating consequences of traumatic injuries in the adult mammalian central nervous system calls for improvements in the capacity of these cells to cope, in particular, with the host response to the injury. We have previously shown, however, that in the acutely traumatized spinal cord local energy metabolism led to decreased ATP levels after neural stem cell (NSC) transplantation. As this might counteract NSC-mediated regenerative processes, we investigated if NSC selected for increased oxidative stress resistance are better suited to preserve local energy content. For this purpose, we exposed wild-type (WT) NSC to hydrogen peroxide prior to transplantation. We demonstrate here that transplantation of WT-NSC into a complete spinal cord compression injury model even lowers the ATP content beyond the level detected in spinal cord injury-control animals. Compared to WT-NSC, stress-resistant (SR) NSC did not lead to a further decrease in ATP content. These differences between WT- and SR-NSC were observed 4 h after the lesion with subsequent transplantation. At 24 h after lesioning, these differences were no more as obvious. Thus, in contrast to native NSC, transplantation of NSC selected for oxidative stress resistance can positively influence local energy metabolism in the first hours after spinal cord compression. The functional relevance of this observation has to be tested in further experiments.

  4. Gene Expression Changes in the Injured Spinal Cord Following Transplantation of Mesenchymal Stem Cells or Olfactory Ensheathing Cells

    PubMed Central

    Torres-Espín, Abel; Hernández, Joaquim; Navarro, Xavier

    2013-01-01

    Transplantation of bone marrow derived mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) have demonstrated beneficial effects after spinal cord injury (SCI), providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI. PMID:24146830

  5. Fibrocartilaginous embolism: a comprehensive review of an under-studied cause of spinal cord infarction and proposed diagnostic criteria

    PubMed Central

    Mowla, Ashkan; Farooq, Salman; Silvestri, Nicholas; Sawyer, Robert; Wolfe, Gil

    2016-01-01

    Background Most spinal cord infarctions are due to aortic pathologies and aortic surgeries. Fibrocartilaginous Embolism (FCE) has been reported to represent 5.5% of spinal cord infarctions. Some believe that FCE is more common than presumed and is rather under-diagnosed due to vagueness surrounding its clinical presentation. Method A literature search was conducted for case reports of FCE published before August 2014. PubMed, the Cochrane Central Register and Google Scholar were searched for different combinations of the key words "fibrocartilaginous, "nucleus pulposus", "embolism", "spinal cord", "inter-vertebral disc", "infarction", "stroke", "paraplegia", "quadriplegia", "myelopathy". Result Fifty-five case articles were reviewed, ten of which were translated from foreign languages. A total of 67 cases of FCE were found, 41 tissue-confirmed and 26 clinically suspected. A comprehensive summary of the clinical anatomy, patho-physiologic mechanisms, epidemiology, diagnosis and treatment of FCE is described, along with the conflicting opinions on its incidence and relevance after reviewing all of the related literature. The 41 tissue proven cases are summarized and a schematic approach to the clinical diagnosis of FCE, deducted from their clinical findings, is presented. Conclusion FCE of the spinal cord, often mis-diagnosed as transverse myelitis, may be more common than presumed. Future research into FCE, including the development of a chondrolytic therapy that can be given empirically upon its clinical suspicion to acutely reverse its symptoms, may be of value. PMID:26833287

  6. 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

  7. New rehabilitation interventions in spinal cord injury.

    PubMed

    Kirshblum, Steven

    2004-01-01

    Progress in the care of people with spinal cord injury (SCI) spans every aspect, from research in neuroregeneration to pharmacologic interventions. This article focuses on advances in rehabilitation interventions, which have employed bioengineering, computerization, and advanced therapeutic techniques. These interventions are being applied to functional deficits of the bladder, bowel, upper extremities, and respiratory system, as well as to improvements in ambulation and mobility. Functional electrical stimulation (FES) is being used to augment the function of the lower extremities, the upper extremities (Freehand System), and the bowel and bladder (Vocare System). Tendon transfer is a reconstructive technique used to improve upper extremity function; it is sometimes combined with FES. Body weight-supported treadmill training is being used to improve ambulation in people with incomplete SCI, and advances in wheelchair technology are expanding options for mobility. Cushion design and pressure mapping are modalities being used to reduce the high risk for pressure ulcers in the SCI population. Research on shoulder stressors is being applied to transfer techniques, exercise regimens, adaptive equipment and wheelchair mechanics to minimize shoulder pain, another common complication. The effectiveness of rehabilitation interventions needs to be documented by evidence-based research. Researchers are focusing on the identification of outcomes measures that will form the basis for established standards of care for individuals with SCI. Perhaps the combination of conventional and newer therapies may enhance neurological recovery. Well-designed studies are needed before we can make this determination.

  8. Stem cell therapy for spinal cord injury.

    PubMed

    Kan, E M; Ling, E A; Lu, J

    2010-01-01

    Spinal cord injury (SCI) damages axons and disrupts myelination interrupting sensory and motor neuronal transmission to and from the brain. Patients suffering from SCI although continue to survive, are often left chronically disabled and with no promise of a cure. Advances in stem cell biology has opened up doors for the use of human embryonic, adult neural and induced pluripotent stem cell strategies for SCI. Despite great promise from animal research, clinical trials have been limited and the jury is still out on its safety and efficacy. This review discusses the advantages and disadvantages of the various stem cell types, barriers hindering translation from animal to humans, and the need for established guidelines for standardization of clinical trials ensuring subsequent implementation. Ultimately, unrealistic expectations of stem cell therapy (SCT) as the elixir for SCI should be managed. The success of SCT for SCI lies in the network of research scientists, medical professionals and patients working cooperatively to build up a knowledge-intensive platform for a comprehensive risk-benefit assessment of SCT for SCI.

  9. Venous Thromboembolism Following Spinal Cord Injury

    PubMed Central

    Teasell, R.W.; Hsieh, T.J.; Aubut, JA. L.; Eng, J.J.; Krassioukov, A.; Tu, L.

    2011-01-01

    Objective To systematically review the published literature on the treatment of deep venous thromboembolism post-spinal cord injury (SCI). Data Sources MEDLINE/Pubmed, CINAHL, EMBASE, and PsycINFO databases were searched for articles addressing the treatment of deep venous thromboembolism post-SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database Scale, while non-RCTs were assessed using the Downs and Black evaluation tool. Study Selection Studies included RCTs, non-RCTS, cohort, case-control, case series, pre-post, and postinterventional studies. Case studies were included only when no other studies were available. Data Extraction Data extracted included demographics, the nature of the study intervention, and study results. Data Synthesis Levels of evidence were assigned to the interventions using a modified Sackett scale. Conclusions Twenty-three studies met inclusion criteria. Thirteen studies examined various pharmacologic interventions for the treatment or prevention of deep venous thrombosis in SCI patients. There was strong evidence to support the use of low molecular weight heparin in reducing venous thrombosis events, and a higher adjusted dose of unfractionated heparin was found to be more effective than 5000 units administered every 12 hours, although bleeding complication was more common. Nonpharmacologic treatments were also reviewed, but again limited evidence was found to support these treatments. PMID:19236977

  10. Spinal cord involvement in patients with cirrhosis.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Storti, Monica; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2014-03-14

    A severe spinal cord involvement may rarely occur in patients with cirrhosis and other chronic liver diseases; this complication is usually associated with overt liver failure and surgical or spontaneous porto-systemic shunt. Hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while sensory and sphincter disturbances have rarely been described and are usually less important. The diagnosis is assigned in the appropriate clinical setting on clinical grounds after the exclusion of other clinical entities leading to spastic paraparesis. Magnetic resonance imaging is often unremarkable; however, also intracerebral corticospinal tract abnormalities have been reported recently. The study of motor evoked potentials may disclose central conduction abnormalities even before HM is clinically manifest. HM responds poorly to blood ammonia-lowering and other conservative medical therapy. Liver transplantation represents a potentially definitive treatment for HM in patients with decompensated cirrhosis of Child-Pugh B and C grades. Other surgical treatment options in HM include surgical ligation, shunt reduction, or occlusion by interventional procedures.

  11. 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

  12. Enrichment of spinal cord cell cultures with motoneurons

    PubMed Central

    1978-01-01

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

  13. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    PubMed Central

    Abdelalim, Essam M.; Bellier, Jean-Pierre; Tooyama, Ikuo

    2016-01-01

    Brain natriuretic peptide (BNP) exerts its functions through NP receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn (DH) of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and dorsal root ganglion (DRG). BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the DH of the spinal cord and in the neurons of the intermediate column (IC) and ventral horn (VH). Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I–II) labeled with calcitonin gene-related peptide (CGRP), suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase (ChAT) in the motor neurons of the VH. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NP receptor-A (NPR-A) and/or NP receptor-B (NPR-B) at the spinal cord level. PMID:27994541

  14. 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

  15. Translational spinal cord injury research: preclinical guidelines and challenges.

    PubMed

    Reier, Paul J; Lane, Michael A; Hall, Edward D; Teng, Y D; Howland, Dena R

    2012-01-01

    Advances in the neurobiology of spinal cord injury (SCI) have prompted increasing attention to opportunities for moving experimental strategies towards clinical applications. Preclinical studies are the centerpiece of the translational process. A major challenge is to establish strategies for achieving optimal translational progression while minimizing potential repetition of previous disappointments associated with clinical trials. This chapter reviews and expands upon views pertaining to preclinical design reported in recently published opinion surveys. Subsequent discussion addresses other preclinical considerations more specifically related to current and potentially imminent cellular and pharmacological approaches to acute/subacute and chronic SCI. Lastly, a retrospective and prospective analysis examines how guidelines currently under discussion relate to select examples of past, current, and future clinical translations. Although achieving definition of the "perfect" preclinical scenario is difficult to envision, this review identifies therapeutic robustness and independent replication of promising experimental findings as absolutely critical prerequisites for clinical translation. Unfortunately, neither has been fully embraced thus far. Accordingly, this review challenges the notion "everything works in animals and nothing in humans", since more rigor must first be incorporated into the bench-to-bedside translational process by all concerned, whether in academia, clinical medicine, or corporate circles.

  16. 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.

  17. Rapid diaphragm atrophy following cervical spinal cord hemisection.

    PubMed

    Gill, L C; Ross, H H; Lee, K Z; Gonzalez-Rothi, E J; Dougherty, B J; Judge, A R; Fuller, D D

    2014-02-01

    A cervical (C2) hemilesion (C2Hx), which disrupts ipsilateral bulbospinal inputs to the phrenic nucleus, was used to study diaphragm plasticity after acute spinal cord injury. We hypothesized that C2Hx would result in rapid atrophy of the ipsilateral hemidiaphragm and increases in mRNA expression of proteolytic biomarkers. Diaphragm tissue was harvested from male Sprague-Dawley rats at 1 or 7 days following C2Hx. Histological analysis demonstrated reduction in cross-sectional area (CSA) of type I and IIa fibers in the ipsilateral hemidiaphragm at 1 but not 7 days. Type IIb/x fibers, however, had reduced CSA at 1 and 7 days. A targeted gene array was used to screen mRNA changes for genes associated with skeletal muscle myopathy and myogenesis; this was followed by qRT-PCR validation. Changes in diaphragm gene expression suggested that profound myoplasticity is initiated immediately following C2Hx including activation of both proteolytic and myogenic pathways. We conclude that an immediate myoplastic response occurs in the diaphragm after C2Hx with atrophy occurring in ipsilateral myofibers within 1 day.

  18. Endovascular management of acute limb ischemia.

    PubMed

    Peeters, P; Verbist, J; Keirse, K; Deloose, K; Bosiers, M

    2010-06-01

    Acute limb ischemia (ALI) refers to a rapid worsening of limb perfusion resulting in rest pain, ischemic ulcers or gangrene. With an estimated incidence of 140 million/year, ALI is serious limb-threatening and life-threatening medical emergency demanding prompt action. Three prospective, randomized clinical trials provide data on trombolytic therapy versus surgical intervention in patients with acute lower extremity ischemia. Although they did not give us the final answer, satisfactory results are reported for percutaneous thrombolysis compared with surgery. Moreover, they suggest an important advantage of thrombolysis in acute bypass graft occlusions. Therefore, we believe thrombolytic therapy should be a part of the vascular surgeon's armamentarium to safely and successfully treat ALI patients.

  19. 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. PMID:27683710

  20. Heme Oxygenase-1 Protects Neurons from Ischemic Damage by Upregulating Expression of Cu,Zn-Superoxide Dismutase, Catalase, and Brain-Derived Neurotrophic Factor in the Rabbit Spinal Cord.

    PubMed

    Jung, Hyo Young; Kim, Dae Won; Yim, Hee Sun; Yoo, Dae Young; Kim, Jong Whi; Won, Moo-Ho; Yoon, Yeo Sung; Choi, Soo Young; Hwang, In Koo

    2016-04-01

    In the present study, we investigated the protective effects of heme oxygenase (HO-1) against ischemic damage in motor neurons of the rabbit spinal cord. A PEP-1-HO-1 fusion protein was made to and confirmed the effective the penetration of HO-1 into spinal cord neurons at 8 h after treatment. Transient spinal cord ischemia was induced by occlusion of the abdominal aorta for 15 min. Vehicle (glycerol) or 0.375 mg/kg PEP-1-HO-1 was administered intraperitoneally to rabbits immediately after ischemia/reperfusion. Animals were sacrificed 15 min after reperfusion to measure lactate levels; 24 h after reperfusion to measure caspase 3 and myeloperoxidase levels, lipid peroxidation, and the activity of Cu,Zn-superoxide dismutase (SOD1) and catalase (CAT); or 72 h after reperfusion to assess neuronal survival and measure the levels of brain-derived neurotrophic factor (BDNF) in spinal cord homogenates. Administration of PEP-1-HO-1 did not significantly alter arterial blood gases (PaCO2 and PaO2), pH, or blood glucose levels before ischemia, 10 min after occlusion, or 10 min after reperfusion. Mean arterial pressure was selectively reduced 10 min after occlusion. Administration of PEP-1-HO-1 improved the rabbit Tarlov scores, and increased neuronal survival, as assessed by NeuN immunohistochemical staining 72 h after ischemia/reperfusion. In addition, administration of PEP-1-HO-1 significantly ameliorated lactate accumulation 15 min after reperfusion, and the increases in caspase 3, myeloperoxidase, and lipid peroxidation 24 h after reperfusion. PEP-1-HO-1 administration significantly mitigated the decrease in SOD1 and CAT 24 h after reperfusion, and reversed the decrease in BDNF levels in spinal cord homogenates 72 h after ischemia/reperfusion. These results suggest that PEP-1-HO-1 can protect against neuronal damage after transient spinal cord ischemia by limiting early lactic acidosis and increasing SOD1, CAT, and BDNF levels.

  1. Intrinsically organized resting state networks in the human spinal cord

    PubMed Central

    Kong, Yazhuo; Eippert, Falk; Beckmann, Christian F.; Andersson, Jesper; Finsterbusch, Jürgen; Büchel, Christian; Tracey, Irene; Brooks, Jonathan C. W.

    2014-01-01

    Spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signals of the brain have repeatedly been observed when no task or external stimulation is present. These fluctuations likely reflect baseline neuronal activity of the brain and correspond to functionally relevant resting-state networks (RSN). It is not known however, whether intrinsically organized and spatially circumscribed RSNs also exist in the spinal cord, the brain’s principal sensorimotor interface with the body. Here, we use recent advances in spinal fMRI methodology and independent component analysis to answer this question in healthy human volunteers. We identified spatially distinct RSNs in the human spinal cord that were clearly separated into dorsal and ventral components, mirroring the functional neuroanatomy of the spinal cord and likely reflecting sensory and motor processing. Interestingly, dorsal (sensory) RSNs were separated into right and left components, presumably related to ongoing hemibody processing of somatosensory information, whereas ventral (motor) RSNs were bilateral, possibly related to commissural interneuronal networks involved in central pattern generation. Importantly, all of these RSNs showed a restricted spatial extent along the spinal cord and likely conform to the spinal cord’s functionally relevant segmental organization. Although the spatial and temporal properties of the dorsal and ventral RSNs were found to be significantly different, these networks showed significant interactions with each other at the segmental level. Together, our data demonstrate that intrinsically highly organized resting-state fluctuations exist in the human spinal cord and are thus a hallmark of the entire central nervous system. PMID:25472845

  2. Spinal Cord Injury Immediately Changes the State of the Brain

    PubMed Central

    Humanes-Valera, Desiré; Alonso-Calviño, Elena; Yague, Josué G.; Moxon, Karen A.; Oliviero, Antonio

    2010-01-01

    Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury. PMID:20519527

  3. 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.

  4. Spinal cord regeneration in a tail autotomizing urodele.

    PubMed

    Dawley, Ellen M; O Samson, Shoji; Woodard, Kenton T; Matthias, Kathryn A

    2012-02-01

    Adult urodele amphibians possess extensive regenerative abilities, including lens, jaws, limbs, and tails. In this study, we examined the cellular events and time course of spinal cord regeneration in a species, Plethodon cinereus, that has the ability to autotomize its tail as an antipredator strategy. We propose that this species may have enhanced regenerative abilities as further coadaptations with this antipredator strategy. We examined the expression of nestin, vimentin, and glial fibrillary acidic protein (GFAP) after autotomy as markers of neural precursor cells and astroglia; we also traced the appearance of new neurons using 5-bromo-2'-deoxyuridine/neuronal nuclei (BrdU/NeuN) double labeling. As expected, the regenerating ependymal tube was a major source of new neurons; however, the spinal cord cranial to the plane of autotomy showed significant mitotic activity, more extensive than what is reported for other urodeles that cannot autotomize their tails. In addition, this species shows upregulation of nestin, vimentin, and GFAP within days after tail autotomy; further, this expression is upregulated within the spinal cord cranial to the plane of autotomy, not just within the extending ependymal tube, as reported in other urodeles. We suggest that enhanced survival of the spinal cord cranial to autotomy allows this portion to participate in the enhanced recovery and regeneration of the spinal cord.

  5. 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.

  6. The spinal cord supports of vertebrae in the crown-group salamanders (Caudata, Urodela).

    PubMed

    Skutschas, Pavel P; Baleeva, Nataly V

    2012-09-01

    The development of spinal cord supports (bony thickenings which extend into the vertebral canal of vertebrae) in primitive (Salamandrella keyserlingii) and derived (Lissotriton vulgaris) salamanders were described. The spinal cord supports develop as the protuberances of periostal bone of the neural arches in the anteroproximal part of the septal collagenous fibers which connect a transverse myoseptum with the notochord and spinal cord, in the septal bundle inside the vertebral canal. Spinal cord supports were also found in some teleostean (Salmo salar, Oncorhynchus mykiss) and dipnoan (Protopterus sp.) fishes. The absence of the spinal cord supports in vertebrates with cartilaginous vertebrae (lampreys, chondrichthyan, and chondrostean fishes) corresponds to the fact that the spinal cord supports are bone structures. The absence of the spinal cord supports in frogs correlates with the lack of the well developed septal bundles inside the vertebral canal. The spinal cord supports are, presumably, a synapomorphic character for salamanders which originated independently of those observed in teleostean and dipnoan fishes.

  7. 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:...

  8. Distinct roles of oxidative stress and antioxidants in the nucleus dorsalis and red nucleus following spinal cord hemisection.

    PubMed

    Xu, Mei; Yip, George Wai-Cheong; Gan, Le-Ting; Ng, Yee-Kong

    2005-09-07

    Oxidative stress plays an important role in the pathogenesis of neurodegeneration after the acute central nervous system injury. We reported previously that increased nitric oxide (NO) production following spinal cord hemisection tends to lead to neurodegeneration in neurons of the nucleus dorsalis (ND) that normally lacks expression of neuronal NO synthase (nNOS) in opposition to those in the red nucleus (RN) that constitutively expresses nNOS. We wondered whether oxidative stress could be a mechanism underlying this NO involved neurodegeneration. In the present study, we examined oxidative damage evaluated by the presence of 4-hydroxynonenal (HNE) and iron accumulation and expression of putative antioxidant enzymes heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) in neurons of the ND and RN after spinal cord hemisection. We found that HNE expression was induced in neurons of the ipsilateral ND from 1 to 14 days following spinal cord hemisection. Concomitantly, iron staining was seen from 7 to 14 days after lesion. HO-1, however, was only transiently induced in ipsilateral ND neurons between 3 and 7 days after lesion. In contrast to the ND neurons, HNE was undetectable and iron level was unaltered in the RN neurons after spinal cord hemisection. HO-1, SOD-Cu/Zn and SOD-Mn were constitutively expressed in RN neurons, and lesion to the spinal cord did not change their expression. These results suggest that oxidative stress is involved in the degeneration of the lesioned ND neurons; whereas constitutive antioxidant enzymes may protect the RN neurons from oxidative damage.

  9. Protease-Activated Receptor-1 Supports Locomotor Recovery by Biased Agonist Activated Protein C after Contusive Spinal Cord Injury

    PubMed Central

    Whetstone, William D.; Walker, Breset; Trivedi, Alpa; Lee, Sangmi; Noble-Haeusslein, Linda J.; Hsu, Jung-Yu C.

    2017-01-01

    Thrombin-induced secondary injury is mediated through its receptor, protease activated receptor-1 (PAR-1), by "biased agonism." Activated protein C (APC) acts through the same PAR-1 receptor but functions as an anti-coagulant and anti-inflammatory protein, which counteracts many of the effects of thrombin. Although the working mechanism of PAR-1 is becoming clear, the functional role of PAR-1 and its correlation with APC in the injured spinal cord remains to be elucidated. Here we investigated if PAR-1 and APC are determinants of long-term functional recovery after a spinal cord contusive injury using PAR-1 null and wild-type mice. We found that neutrophil infiltration and disruption of the blood-spinal cord barrier were significantly reduced in spinal cord injured PAR-1 null mice relative to the wild-type group. Both locomotor recovery and ability to descend an inclined grid were significantly improved in the PAR-1 null group 42 days after injury and this improvement was associated with greater long-term sparing of white matter and a reduction in glial scarring. Wild-type mice treated with APC acutely after injury showed a similar level of improved locomotor recovery to that of PAR-1 null mice. However, improvement of APC-treated PAR-1 null mice was indistinguishable from that of vehicle-treated PAR-1 null mice, suggesting that APC acts through PAR-1. Collectively, our findings define a detrimental role of thrombin-activated PAR-1 in wound healing and further validate APC, also acting through the PAR-1 by biased agonism, as a promising therapeutic target for spinal cord injury. PMID:28122028

  10. 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.

  11. [Electrophysiological testing in spinal cord tumors].

    PubMed

    André-Obadia, N; Mauguière, F

    2017-02-01

    Evoked potentials (EPs) are useful to evaluate the functional impairment of motor and somatosensory pathways in spinal cord tumors. Conduction through pyramidal tracts is evaluated by motor EPs (MEPs) elicited by transcranial stimulation, magnetic for awake patients or electric in the operating room. Somatosensory EPs (SEPs) and laser EPs (LEPs) are complementary procedures to explore conduction in dorsal columns and spinothalamic tracts, respectively. MEPs as well as SEPs show conduction abnormalities in about 60% of cases with a sensitivity that increases up to 70% when both procedures are carried out. Abnormalities are observed in the absence of any clinical sign in respectively 7% and 15% of cases for MEPs and SEPs. Multilevel stimulations for SEPs recordings permit to detect segmental dysfunction in 70% in case of cervical TIM, even in the absence of clinical signs. LEPs are useful in specific clinical situations: they allow a dermatomal stimulation and are correlated to segmental thermoalgic anaesthesia. Electrophysiological testing plays an important role in the diagnostic and therapeutic strategy: before surgery, MEPs and SEPs objectively evaluate the functional impairment directly related to the lesion. They also help by permitting a follow-up, either before surgery when the surgical decision is delayed because of a good clinical tolerance of the lesion, or after operation to evaluate the functional evolution. Intraoperative monitoring of MEPs and SEPs allows informing the surgeon about the impact on each surgical manipulation. No prospective randomized study has been performed to date to compare clinical evolution after surgery with or without monitoring. Nevertheless, a wide consensus became established in favor of monitoring to limit the risk of postoperative definite deficit and to permit an optimal surgical resection without risk when responses are preserved.

  12. 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.

  13. 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.

  14. Malnutrition in Spinal Cord Injury: More Than Nutritional Deficiency

    PubMed Central

    Dionyssiotis, Yannis

    2012-01-01

    Denervation of the spinal cord below the level of injury leads to complications producing malnutrition. Nutritional status affects mortality and pathology of injured subjects and it has been reported that two thirds of individuals enrolled in rehabilitation units are malnourished. Therefore, the aim should be either to maintain an optimal nutritional status, or supplement these subjects in order to overcome deficiencies in nutrients or prevent obesity. This paper reviews methods of nutritional assessment and describes the physiopathological mechanisms of malnutrition based on the assumption that spinal cord injured subjects need to receive adequate nutrition to promote optimal recovery, placing nutrition as a first line treatment and not an afterthought in the rehabilitation of spinal cord injury. PMID:22870169

  15. Exercise Training Promotes Functional Recovery after Spinal Cord Injury

    PubMed Central

    Fu, Juanjuan; Deng, Lingxiao; Li, Jianan

    2016-01-01

    The exercise training is an effective therapy for spinal cord injury which has been applied to clinic. Traditionally, the exercise training has been considered to improve spinal cord function only through enhancement, compensation, and replacement of the remaining function of nerve and muscle. Recently, accumulating evidences indicated that exercise training can improve the function in different levels from end-effector organ such as skeletal muscle to cerebral cortex through reshaping skeletal muscle structure and muscle fiber type, regulating physiological and metabolic function of motor neurons in the spinal cord and remodeling function of the cerebral cortex. We compiled published data collected in different animal models and clinical studies into a succinct review of the current state of knowledge. PMID:28050288

  16. 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

  17. Spinal cord electrophysiology II: extracellular suction electrode fabrication.

    PubMed

    Garudadri, Suresh; Gallarda, Benjamin; Pfaff, Samuel; Alaynick, William

    2011-02-20

    Development of neural circuitries and locomotion can be studied using neonatal rodent spinal cord central pattern generator (CPG) behavior. We demonstrate a method to fabricate suction electrodes that are used to examine CPG activity, or fictive locomotion, in dissected rodent spinal cords. The rodent spinal cords are placed in artificial cerebrospinal fluid and the ventral roots are drawn into the suction electrode. The electrode is constructed by modifying a commercially available suction electrode. A heavier silver wire is used instead of the standard wire given by the commercially available electrode. The glass tip on the commercial electrode is replaced with a plastic tip for increased durability. We prepare hand drawn electrodes and electrodes made from specific sizes of tubing, allowing consistency and reproducibility. Data is collected using an amplifier and neurogram acquisition software. Recordings are performed on an air table within a Faraday cage to prevent mechanical and electrical interference, respectively.

  18. Pelvic nerve input mediates descending modulation of homovisceral processing in the thoracolumbar spinal cord of the rat

    PubMed Central

    Wang, Gexin; Tang, Bin; Traub, Richard J.

    2007-01-01

    Background and aims Colonic afferents project to the lumbosacral and thoracolumbar spinal cord via the pelvic and hypogastric/lumbar colonic nerves, respectively. Both spinal regions process inflammatory colonic stimuli. The role of thoracolumbar segments in processing acute colorectal pain is questionable, however, since the lumbosacral spinal cord appears sufficient to process reflex responses to acute pain. Here we demonstrate that activity in pelvic nerve colonic afferents actively modulates thoracolumbar dorsal horn neuron processing of the same colonic stimulus via a supraspinal loop: homovisceral descending modulation. Methods Dorsal horn neurons were recorded in the rat thoracolumbar spinal cord following acute or chronic pelvic neurectomy and cervical cold block. Results Acute pelvic neurectomy or lidocaine inhibition of lumbosacral dorsal roots facilitated the excitatory response of thoracolumbar dorsal horn neurons to colorectal distention (CRD) and decreased the percentage of neurons inhibited by CRD, suggesting colonic input over the pelvic nerve inhibits thoracolumbar processing of the same stimulus. Ectopic activity developed in the proximal pelvic nerve following chronic neurectomy reactivating the inhibitory circuit, inhibiting thoracolumbar neurons. Cervical cold block alleviated the inhibition in intact or chronic neurectomized rats. However, the facilitated response following acute pelvic neurectomy was inhibited by cervical cold block exposing an underlying descending facilitation. Inhibiting pelvic nerve input following cervical cold block had minimal effect. Conclusion These data demonstrate that input over the pelvic nerve modulates the response of thoracolumbar spinal neurons to CRD via a supraspinal loop, and that increasing thoracolumbar processing increases visceral hyperalgesia. PMID:17916357

  19. Developing a Meaningful Life: Social Reintegration of Service-Members and Veterans with Spinal Cord Injury

    DTIC Science & Technology

    2013-10-01

    Reintegration of Service-Members and Veterans with Spinal Cord Injury PRINCIPAL INVESTIGATOR: Seth D. Messinger...SUBTITLE Developing a Meaningful Life: Social Reintegration of Service- Social Reintegration of Service Me Members and Veterans with Spinal Cord...communities and cultural identities that is key to long-term success . 15. SUBJECT TERMS Spinal Cord Injury, Community Reintegration , Qualitative

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

    PubMed

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

    2007-01-01

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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. Anti-NGF Local Therapy for Autonomic Dysreflexia in Spinal Cord Injury

    DTIC Science & Technology

    2012-10-01

    bladder distention between spinal intact and spinal cord injury ...excitability of bladder afferent neurons in rats with spinal cord injury : a role of A-type voltage-gated potassium channels. 110th Annual Meeting AUA...Increased excitability of bladder afferent neurons in rats with spinal cord injury : a role of A-type voltage-gated potassium channels. 110th Annual

  8. Nogo-A expression dynamically varies after spinal cord injury

    PubMed Central

    Wang, Jian-wei; Yang, Jun-feng; Ma, Yong; Hua, Zhen; Guo, Yang; Gu, Xiao-lin; Zhang, Ya-feng

    2015-01-01

    The mechanism involved in neural regeneration after spinal cord injury is unclear. The myelin-derived protein Nogo-A, which is specific to the central nervous system, has been identified to negatively affect the cytoskeleton and growth program of axotomized neurons. Studies have shown that Nogo-A exerts immediate and chronic inhibitory effects on neurite outgrowth. In vivo, inhibitors of Nogo-A have been shown to lead to a marked enhancement of regenerative axon extension. We established a spinal cord injury model in rats using a free-falling weight drop device to subsequently investigate Nogo-A expression. Nogo-A mRNA and protein expression and immunoreactivity were detected in spinal cord tissue using real-time quantitative PCR, immunohistochemistry and western blot analysis. At 24 hours after spinal cord injury, Nogo-A protein and mRNA expression was low in the injured group compared with control and sham-operated groups. The levels then continued to drop further and were at their lowest at 3 days, rapidly rose to a peak after 7 days, and then gradually declined again after 14 days. These changes were observed at both the mRNA and protein level. The transient decrease observed early after injury followed by high levels for a few days indicates Nogo-A expression is time dependent. This may contribute to the lack of regeneration in the central nervous system after spinal cord injury. The dynamic variation of Nogo-A should be taken into account in the treatment of spinal cord injury. PMID:25883620

  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. [Operative ultrasonography of the brain and spinal cord pathology].

    PubMed

    Machi, J; Sigel, B; Menoni, R; Jafar, J J; Beitler, J C; Crowell, R M

    1984-07-01

    B-mode real-time ultrasound using 5 or 7.5 MHz transducer has been employed during 21 operations for brain pathology and spinal cord lesions. Ultrasonic scanning was performed at the following operations: 10 brain tumors (4 glioblastomas multiforme, 2 astrocytomas, 1 medulloblastoma, 2 metastatic tumors), 2 brain cysts (arachnoid, epidermoid), 1 tuberculous abscess, 3 cerebral hematomas: 2 spinal cord tumors (malignant melanoma, glioma), 2 syringomyelias, 1 posterior longitudinal ligament thickening. Operative ultrasound was useful prior to dural incisions and particularly for subcortical lesions. In addition, ultrasound provided assistance at spinal cord surgery. Our experience has been reviewed and summarized in this report in terms of specific usefulness of assistance of this method which has proven helpful to the neurosurgeons. The types of assistance provided by operative ultrasonography include: Location of dural incision. Localization of brain and spinal cord lesions prior to biopsy. Diagnosis which has not been made preoperatively (e.g. necrosis or cystic area in tumor). Consistency of each lesion (e.g. solid or cystic, necrosis, loculation). Size, extent and depth of brain tumor, cyst, abscess and hematoma. Presence and extent of spinal cord syrinx. Relation of tumor to spinal cord and dura. Access route for biopsy and drainage (avoiding critical areas such as motor strip). Exclusion of bleeding or hematoma following biopsy. Confirmation of the effectiveness of drainage or resection of lesions. Relationship between pathology and surrounding anatomic structures. A number of important assistance by the utilization of ultrasound during neurological surgery have been identified.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Scratching activates microglia in the mouse spinal cord.

    PubMed

    Zhang, Ying; Dun, Siok L; Chen, Yi-Hung; Luo, Jin J; Cowan, Alan; Dun, Nae J

    2015-03-01

    This study tested the hypothesis that repetitive scratching provoked by two known pruritogens, compound 48/80 and 5'-guanidinonaltrindole (GNTI), is accompanied by activation of microglial cells in the mouse spinal cord. Immunohistochemical studies revealed that the complement receptor 3, also known as cluster determinant 11b (CD11b), a cell surface marker of microglial cells, was upregulated in the spinal cord 10-30 min after a subcutaneous (s.c.) injection of compound 48/80 (50 μg/100 μl) or GNTI (0.3 mg/kg) to the back of the mouse neck. Numerous intensely labeled CD11b-immunoreactive (CD11b-ir) cells, with the appearance of hypertrophic reactive microglia, were distributed throughout the gray and white matter. In contrast, weakly labeled CD11b-ir cells were distributed in the spinal cord from mice injected with saline. Western blots showed that CD11b expression levels were significantly increased in spinal cords of mice injected s.c. with either pruritogen, reached a peak response in about 30 min, and declined to about the basal level in the ensuing 60 min. In addition, phospho-p38 (p-p38) but not p38 levels were upregulated in spinal cords from mice injected with compound 48/80 or GNTI, with a time course parallel to that of CD11b expression. Pretreatment of the mice with nalfurafine (20 µg/kg; s.c.), a κ-opioid receptor agonist that has been shown to suppress scratching, reduced CD11b and p-p38 expression induced by either pruritogen. The results demonstrate, for the first time, that scratch behavior induced by the pruritogens GNTI and compound 48/80 is accompanied by a parallel activation of microglial cells in the spinal cord.

  12. 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.

  13. Potential associations between chronic whiplash and incomplete spinal cord injury

    PubMed Central

    Smith, AC; Parrish, TB; Hoggarth, MA; McPherson, JG; Tysseling, VM; Wasielewski, M; Kim, HE; Hornby, TG; Elliott, JM

    2015-01-01

    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

  14. Spinal cord lesions and disability in Hispanics with multiple sclerosis.

    PubMed

    Amezcua, L; Lerner, A; Ledezma, K; Conti, D; Law, M; Weiner, L; Langer-Gould, A

    2013-11-01

    Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. The purpose of this study is to describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. A cross-sectional study of 164 patients with complete MRIs was used. In each case the spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale ≥4.0) was adjusted for age, disease duration and sex using logistic regression. A total of 125/164 (73 %) MS patients had spinal cord lesions (sSCLs, 57 %; LESCLs, 19 %), but only 11 (7 %) had OSMS. LESCLs were associated with disability (p < 0.0001), longer disease duration (p < 0.0001) and MS (n = 21 vs. n = 10 OSMS; p < 0.0001). LESCLs were also associated with the greatest risk to disability (OR 7.3, 95 % CIs 1.9-26.5; p = 0.003; sSCLs OR 2.5, 95 % CIs 0.9-7.1; p = 0.09) compared with noSCLs. LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.

  15. Scratching activates microglia in the mouse spinal cord

    PubMed Central

    Zhang, Ying; Dun, Siok L.; Chen, Yi-Hung; Luo, Jin J.; Cowan, Alan; Dun, Nae J.

    2014-01-01

    The present study tested the hypothesis that repetitive scratching provoked by either of two known pruritogens, compound 48/80 and 5′-guanidinonaltrindole (GNTI), is accompanied by activation of microglia cells in the mouse spinal cord. Immunohistochemical studies revealed that CD11b, a cell surface marker of microglia cells, was up-regulated in the spinal cord 10–30 min post subcutaneous (s.c.) injection of compound 48/80 (50 μg/100 μl) or GNTI (0.3 mg/kg) to the back of the mouse neck. Numerous intensely labeled CD11b immunoreactive (irCD11b) cells, with the appearance of hypertrophic reactive microglia, were distributed throughout the gray and white matter. In contrast, weakly labeled irCD11b cells were distributed in the spinal cord from mice injected with saline. Western blots showed that CD11b expression levels were significantly increased in spinal cords of mice injected s.c. with either pruritogen, reached a peak response in about 30 min, and declined toward the basal level in the ensuing 60 min. In addition, phospho-p38 (p-p38), but not p38, levels were up-regulated in spinal cords from mice injected with compound 48/80 or GNTI, with a time course parallel to that of CD11b expression. Pretreatment of the mice with nalfurafine (20 μg/kg; s.c.), a κ opioid receptor agonist that has been shown to suppress scratching, reduced CD11b and p-p38 expression induced by either pruritogen. The result demonstrates, for the first time, that scratch behavior induced by pruritogens GNTI and compound 48/80 is accompanied by a parallel activation of microglia cells in the spinal cord. PMID:25354468

  16. Disability, atrophy and cortical reorganization following spinal cord injury.

    PubMed

    Freund, Patrick; Weiskopf, Nikolaus; Ward, Nick S; Hutton, Chloe; Gall, Angela; Ciccarelli, Olga; Craggs, Michael; Friston, Karl; Thompson, Alan J

    2011-06-01

    The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy

  17. Spinal cord stimulation for neuropathic pain: current perspectives

    PubMed Central

    Wolter, Tilman

    2014-01-01

    Neuropathic pain constitutes a significant portion of chronic pain. Patients with neuropathic pain are usually more heavily burdened than patients with nociceptive pain. They suffer more often from insomnia, anxiety, and depression. Moreover, analgesic medication often has an insufficient effect on neuropathic pain. Spinal cord stimulation constitutes a therapy alternative that, to date, remains underused. In the last 10 to 15 years, it has undergone constant technical advancement. This review gives an overview of the present practice of spinal cord stimulation for chronic neuropathic pain and current developments such as high-frequency stimulation and peripheral nerve field stimulation. PMID:25429237

  18. [Mortality structure following spine and spinal cord injuries].

    PubMed

    Bazilevskaia, Z V; Golovnykh, L L; Kirkinskaia, T A

    1980-01-01

    In a group of 520 patients with injury to the spine and spinal cord 125 died within 10 years. The highest fatality rate (76.0 +/0 3.8) is recorded in the first year after the injury. In the following 10 years the fatality rate was uniform and ranged between 1.6 and 4.1%. This value increases with the patient's age, the severity of the spinal cord injury, and the degree of damage to the spinal ligamento-bursal apparatus. Among the total number of injured, 76% have a survival period of more than 10 years.

  19. [Therapy progress of spinal cord compression by metastatic spinal tumor].

    PubMed

    Liu, Yao-sheng; He, Qi-zhen; Liu, Shu-bin; Jiang, Wei-gang; Lei, Ming-xing

    2016-01-01

    Metastatic epidural compression of the spinal cord is a significant source of morbidity in patients with systemic cancer. With improvment of oncotheray, survival period in the patients is improving and metastatic cord compression is en- countered increasingly often. Surgical management performed for early circumferential decompression for the spinal cord com- pression with spine instability, and spine reconstruction performed. Patients with radiosensitive tumours without spine instabili- ty, radiotherapy is an effective therapy. Spinal stereotactic radiosurgery and minimally invasive techniques, such as vertebro- plasty and kyphoplasty, percutaneous pedicle screw fixation, radiofrequency ablation are promising options for treatment of cer- tain selected patients with spinal metastases.

  20. Human spinal cord injury: new and emerging approaches to treatment.

    PubMed

    Johnston, L

    2001-11-01

    The World Health Organization together with the Iceland Ministry of Health and Social Security sponsored a conference entitled 'Human Spinal Cord Injury: New and Emerging Approaches to Treatment' held on May 31-June 2, 2001 in Reykjavik, Iceland. To help catalyze the development of new paradigms to address spinal cord injury, the conference's overall goal was to bring in a diversity of perspectives, ranging from state-of-the-art stem cell biology to the ancient wisdom of Eastern Medicine. The purpose of this paper is to summarize the presentations of the conference's 26 speakers.

  1. Spinal cord stimulation in pain management: a review.

    PubMed

    Jeon, Young Hoon

    2012-07-01

    Spinal cord stimulation has become a widely used and efficient alternative for the management of refractory chronic pain that is unresponsive to conservative therapies. Technological improvements have been considerable and the current neuromodulation devices are both extremely sophisticated and reliable in obtaining good results for various clinical situations of chronic pain, such as failed back surgery syndrome, complex regional pain syndrome, ischemic and coronary artery disease. This technique is likely to possess a savings in costs compared with alternative therapy strategies despite its high initial cost. Spinal cord stimulation continues to be a valuable tool in the treatment of chronic disabling pain.

  2. Rodent spinal cord injury models for studies of axon regeneration.

    PubMed

    Steward, Oswald; Willenberg, Rafer

    2017-01-01

    For over a century, axon regeneration has been considered the Holy Grail for spinal cord injury (SCI) repair. Although there are other factors that could contribute to improving function, restoring the long motor and sensory tracts that are interrupted by SCI has the greatest potential for actually reversing paralysis, restoring the brain's control of autonomic functions mediated by sympathetic and parasympathetic circuits of the spinal cord and restoring sensation. Accordingly and in keeping with the overall theme of this special issue, this review focuses narrowly on rodent SCI models for studies of axon regeneration.

  3. 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

  4. 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-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

  5. Complete rat spinal cord transection as a faithful model of spinal cord injury for translational cell transplantation

    PubMed Central

    Lukovic, Dunja; Moreno-Manzano, Victoria; Lopez-Mocholi, Eric; Rodriguez-Jiménez, Francisco Javier; Jendelova, Pavla; Sykova, Eva; Oria, Marc; Stojkovic, Miodrag; Erceg, Slaven

    2015-01-01

    Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Various animal models have been developed to mimic human SCI. Widely used animal models of SCI are complete or partial transection or experimental contusion and compression, with both bearing controversy as to which one more appropriately reproduces the human SCI functional consequences. Here we present in details the widely used procedure of complete spinal cord transection as a faithful animal model to investigate neural and functional repair of the damaged tissue by exogenous human transplanted cells. This injury model offers the advantage of complete damage to a spinal cord at a defined place and time, is relatively simple to standardize and is highly reproducible. PMID:25860664

  6. The Function of FGFR1 Signalling in the Spinal Cord: Therapeutic Approaches Using FGFR1 Ligands after Spinal Cord Injury

    PubMed Central

    Moon, Lawrence D. F.

    2017-01-01

    Extensive research is ongoing that concentrates on finding therapies to enhance CNS regeneration after spinal cord injury (SCI) and to cure paralysis. This review sheds light on the role of the FGFR pathway in the injured spinal cord and discusses various therapies that use FGFR activating ligands to promote regeneration after SCI. We discuss studies that use peripheral nerve grafts or Schwann cell grafts in combination with FGF1 or FGF2 supplementation. Most of these studies show evidence that these therapies successfully enhance axon regeneration into the graft. Further they provide evidence for partial recovery of sensory function shown by electrophysiology and motor activity evidenced by behavioural data. We also present one study that indicates that combination with additional, synergistic factors might further drive the system towards functional regeneration. In essence, this review summarises the potential of nerve and cell grafts combined with FGF1/2 supplementation to improve outcome even after severe spinal cord injury. PMID:28197342

  7. Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair.

    PubMed

    Tukmachev, Dmitry; Forostyak, Serhiy; Koci, Zuzana; Zaviskova, Kristyna; Vackova, Irena; Vyborny, Karel; Sandvig, Ioanna; Sandvig, Axel; Medberry, Christopher J; Badylak, Stephen F; Sykova, Eva; Kubinova, Sarka

    2016-02-01

    Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.

  8. Early metabolic reactivation versus antioxidant therapy after a traumatic spinal cord injury in adult rats.

    PubMed

    Torres, Sergio; Salgado-Ceballos, Hermelinda; Torres, José Luis; Orozco-Suarez, Sandra; Díaz-Ruíz, Araceli; Martínez, Angelina; Rivera-Cruz, Mario; Ríos, Camilo; Lara, Alicia; Collado, Carlos; Guizar-Sahagún, Gabriel

    2010-02-01

    Disability after traumatic spinal cord injury (TSCI) results from physical trauma and from "secondary mechanisms of injury" such as low metabolic energy levels, oxidative damage and lipid peroxidation. In order to prove if early metabolic reactivation is a better therapeutic option than antioxidant therapy in the acute phase of TSCI, spinal cord contusions were performed in adult rats using a well-characterized weight drop technique at thoracic 9 level. After TSCI, pyrophosphate of thiamine or non-degradable cocarboxylase (NDC) enzyme was used to maintain energy levels, antioxidants such as superoxide dismutase and catalase (ANT) were used to decrease oxidative damage and methylprednisolone (MP), which has both therapeutic properties, was used as a control. Rats were divided into one sham group and six with TSCI; one of them received no treatment, and the rest were treated with NDC, MP, NDC + MP, NDC + ANT or ANT. The ANT group decreased lactate and creatine phosphokinase levels and increased the amount of preserved tissue (morphometric analysis) as well as functional recovery (Basso, Beattie and Bresnahan or BBB motor scale). In contrast, NDC treatment increased lipid peroxidation, measured through thiobarbituric acid reactive substances (TBARS) levels, as well as spinal cord tissue destruction and functional deficit. Early metabolic reactivation after a TSCI may be deleterious, while natural early metabolic inhibition may not be a "secondary mechanism of injury" but a "secondary neuroprotective response". While increased antioxidant defence after a TSCI may currently be an ideal therapeutic strategy, the usefulness of metabolic reactivation should be tested in the sub-acute or chronic phases of TSCI and new strategies must continue to be tested for the early ones.

  9. Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

    PubMed Central

    Tukmachev, Dmitry; Forostyak, Serhiy; Koci, Zuzana; Zaviskova, Kristyna; Vackova, Irena; Vyborny, Karel; Sandvig, Ioanna; Sandvig, Axel; Medberry, Christopher J.; Badylak, Stephen F.; Sykova, Eva

    2016-01-01

    Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI. PMID:26729284

  10. Monoamine-containing fiber plexuses in the spinal cord of guinea pigs during paralysis, recovery and relapse stages of chronic relapsing experimental allergic encephalomyelitis.

    PubMed

    White, S R; Vyas, D; Bieger, D; Samathanam, G

    1989-05-01

    Immunohistochemical techniques were used to examine the morphology and distribution of monoamine- and substance P-containing fibers in the spinal cords of guinea pigs in acute paralytic, remission and relapse stages of chronic relapsing experimental allergic encephalomyelitis. During the initial paralytic attack, focal regions of axonal distortion appeared in the white matter of the cervical and thoracic cord; and axon terminal depletion in the gray matter of the caudal spinal cord was pronounced. This neuropathology persisted throughout remission and was exacerbated during relapse of paralysis. These results suggest that axonal damage is an important component of the pathophysiology of this autoimmune disease.

  11. Non-traumatic acute paraplegia associated with a CT-guided needle biopsy in a silicotic nodule: A case report

    PubMed Central

    XU, LIYING; DING, XUN; LIAO, MEIYAN

    2016-01-01

    The present study reports the case of an adult patient with non-traumatic acute paraplegia following a computed tomography (CT)-guided automated cutting needle biopsy (ACNB). Multiple nodules and masses were revealed on performing chest radiography and CT on a 45-year-old man. In order to make a pathological diagnosis, a CT-guided biopsy using an automatic cutting needle was performed. However, 10 min after the biopsy, a weakness of the lower extremities occurred, and the patient collapsed to the ground, albeit with clear consciousness. Spinal magnetic resonance imaging (MRI) performed subsequently revealed no abnormal findings in the spinal cord. An MRI performed 24 h later, however, revealed swelling of the thoracic spinal cord and a high-signal-intensity lesion in T2-weighted images at the level of T7, T8 and T9. The patient subsequently received hyperbaric oxygen therapy for a few days, and rehabilitative treatment over the course of a few weeks. At 6 months following the biopsy, the patient was unable to walk, although the patient could stand for 10 min and defecate independently. Currently, the patient remains active in daily life, in spite of confinement to a wheelchair. The present case study was reported to raise the awareness of the possibility of spinal cord ischemia and acute paraplegia following a CT-guided ACNB of the lungs. The mechanism underlying spinal cord ischemia remains to be fully elucidated, although is thought to be multifactorial, involving air embolism. PMID:26998303

  12. Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats.

    PubMed

    Muradov, Johongir M; Ewan, Eric E; Hagg, Theo

    2013-11-01

    The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and an ~70% loss of the sensory axons by 24 h. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 h. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 μg/μl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 h. EB also caused an ~75% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R(2) = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons.

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

    PubMed Central

    Wieraszko, Andrzej

    2008-01-01

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

  14. The use of micropolarization in the treatment of spinal cord lesions.

    PubMed

    Shelyakin, A M; Preobrazhenskaya, I G; Komantsev, V N; Makarovskii, A N; Bogdanov, O V

    2000-01-01

    Transdermal micropolarization of the spinal cord was performed in patients suffering sequelae of spinal cord trauma and tuberculous spondylitis. Changes in clinical and electrophysiological status were monitored. These studies demonstrated that the use of local direct currents passed via skin electrodes promoted improvements in motor and autonomic functions in these patients, leading to positive changes in measures of the functional state of the spinal cord and heart activity. The possible mechanisms of the action of direct currents acting on the spinal cord are discussed, along with the potential for applying micropolarization in the treatment of spinal cord lesions.

  15. Geomapping of Traumatic Spinal Cord Injury in Canada and Factors Related to Triage Pattern.

    PubMed

    Cheng, Christiana L; Noonan, Vanessa K; Shurgold, Jayson; Chen, Jason; Rivers, Carly S; Hamedani, Hamid Khaleghi; Humphreys, Suzanne; Bailey, Christopher; Attabib, Najmedden; Mac-Thiong, Jean-Marc; Goytan, Michael; Paquet, Jérôme; Fox, Richard; Ahn, Henry; Kwon, Brian K; Fourney, Daryl R

    2017-03-22

    Current research indicates that more than half of patients with traumatic spinal cord injury (tSCI) experience delays in transfer and receive surgery more than 24 hours post-injury. The objectives of this study were to determine the geographic distribution of tSCI in Canada relative to specialized treatment facilities, to assess clinical and logistical factors at play for indirect admissions to those facilities, and to explore differences in current time to admission and simulated scenarios in an attempt to assess the potential impact of changes to triage protocols. This study included data from 876 patients with tSCI enrolled in the prospectively collected acute Rick Hansen Spinal Cord Injury Registry (RHSCIR) between January 1, 2010 and December 31, 2013 who had data on the location of their injury. Patients transported directly to a RHSCIR acute facility were more likely to reach the facility within 1 h of injury while those transported indirectly were more likely to arrive 7 h later. Considering the injuries occurring within 40 km of a RHSCIR acute facility (n=323), 249 patients (77%) were directly and 74 (23%) were indirectly admitted. In the multivariate regression analysis, only older age and longer road distance remained significantly associated with being indirectly admitted to a RHSCIR facility. Compared to the current status, the median time to admission decreased by 20% (3.5 h) in the 100% direct admission scenario; and increased by 102% (8.9 h) in the 100% indirect admission scenario.

  16. Methylprednisolone protects oligodendrocytes but not neurons following spinal cord injury

    PubMed Central

    Lee, Jin-Moo; Yan, Ping; Xiao, Qingli; Chen, Shawei; Lee, Kuang-Yung; Hsu, Chung Y.; Xu, Jan

    2009-01-01

    Methylprednisolone (MP) is used to treat a variety of neurological disorders involving white matter injury, including multiple sclerosis, acute disseminated encephalomyelitis, and spinal cord injury (SCI). While its mechanism of action has been attributed to anti-inflammatory or anti-oxidant properties, we examined the possibility that MP may have direct neuroprotective activities. Neurons and oligodendrocytes treated with AMPA (alpha-amino-3-hydroxy-5- methylisoxazole-4-propionate) or staurosporine died within 24 hrs after treatment. MP attenuated oligodendrocyte death in a dose-dependent manner; however, neurons were not rescued by the same doses of MP. This protective effect was reversed by the glucocorticoid receptor (GR) antagonist, RU486, and siRNA directed against GR, suggesting a receptor-dependent mechanism. MP reversed AMPA-induced decreases in the expression of antiapoptotic Bcl-xL, caspase-3 activation, and DNA laddering, suggesting anti-apoptotic activity in oligodendrocytes. To examine if MP demonstrated this selective protection in vivo, neuronal and oligodendrocyte survival was assessed in rats subjected to SCI; groups of rats were treated with or without MP in the presence or absence of RU486. Eight days after SCI, MP significantly increased oligodendrocytes (CC-1 immunoreactive cells) following SCI, but neuronal (NeuN immunoreactive cells) number remained unchanged; RU486 reversed this protective effect. MP also inhibited SCI-induced decreases in Bcl-xL and caspase-3 activation. Consistent with these findings, the volume of demyelination, assessed by Luxol Fast Blue staining, was attenuated by MP and reversed by RU486. These results suggest that MP selectively inhibits oligodendrocyte but not neuronal cell death via a receptor-mediated action, and may be a mechanism for its limited protective effect following SCI. PMID:18354017

  17. Impaired blood-brain/spinal cord barrier in ALS patients.

    PubMed

    Garbuzova-Davis, Svitlana; Hernandez-Ontiveros, Diana G; Rodrigues, Maria C O; Haller, Edward; Frisina-Deyo, Aric; Mirtyl, Santhia; Sallot, Sebastian; Saporta, Samuel; Borlongan, Cesario V; Sanberg, Paul R

    2012-08-21

    Vascular pathology, including blood-brain/spinal cord barrier (BBB/BSCB) alterations, has recently been recognized as a key factor possibly aggravating motor neuron damage, identifying a neurovascular disease signature for ALS. However, BBB/BSCB competence in sporadic ALS (SALS) is still undetermined. In this study, BBB/BSCB integrity in postmortem gray and white matter of medulla and spinal cord tissue from SALS patients and controls was investigated. Major findings include (1) endothelial cell damage and pericyte degeneration, (2) severe intra- and extracellular edema, (3) reduced CD31 and CD105 expressions in endothelium, (4) significant accumulation of perivascular collagen IV, and fibrin deposits (5) significantly increased microvascular density in lumbar spinal cord, (6) IgG microvascular leakage, (7) reduced tight junction and adhesion protein expressions. Microvascular barrier abnormalities determined in gray and white matter of the medulla, cervical, and lumbar spinal cord of SALS patients are novel findings. Pervasive barrier damage discovered in ALS may have implications for disease pathogenesis and progression, as well as for uncovering novel therapeutic targets.

  18. Spinal cord compression due to extramedullary haemopoiesis in myelofibrosis.

    PubMed Central

    Cook, G; Sharp, R A

    1994-01-01

    Extramedullary haemopoiesis resulting in spinal cord compression is rare. This report of extramedullary myeloid metaplasia in a patient with myelofibrosis serves to illustrate the value of magnetic resonance imaging (MRI) in the diagnosis and management of good neurological recovery. Images PMID:8027402

  19. Emerging concepts in myeloid cell biology after spinal cord injury.

    PubMed

    Hawthorne, Alicia L; Popovich, Phillip G

    2011-04-01

    Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte/macrophages. Because these myeloid cells can positively and negatively affect survival of neurons and glia, they are among the most commonly studied immune cells. However, the mechanisms that regulate myeloid cell activation and recruitment after SCI have not been adequately defined. In general, the dynamics and composition of myeloid cell recruitment to the injured spinal cord are consistent between mammalian species; only the onset, duration, and magnitude of the response vary. Emerging data, mostly from rat and mouse SCI models, indicate that resident and recruited myeloid cells are derived from multiple sources, including the yolk sac during development and the bone marrow and spleen in adulthood. After SCI, a complex array of chemokines and cytokines regulate myelopoiesis and intraspinal trafficking of myeloid cells. As these cells accumulate in the injured spinal cord, the collective actions of diverse cues in the lesion environment help to create an inflammatory response marked by tremendous phenotypic and functional heterogeneity. Indeed, it is difficult to attribute specific reparative or injurious functions to one or more myeloid cells because of convergence of cell function and difficulties in using specific molecular markers to distinguish between subsets of myeloid cell populations. Here we review each of these concepts and include a discussion of future challenges that will need to be overcome to develop newer and improved immune modulatory therapies for the injured brain or spinal cord.

  20. The spinal cord of the common marmoset (Callithrix jacchus).

    PubMed

    Watson, Charles; Sengul, Gulgun; Tanaka, Ikuko; Rusznak, Zoltan; Tokuno, Hironobu

    2015-04-01

    The marmoset spinal cord possesses all the characteristic features of a typical mammalian spinal cord, but with some interesting variation in the levels of origin of the limb nerves. In our study Nissl and ChAT sections of the each segment of the spinal cord in two marmosets (Ma5 and Ma8), we found that the spinal cord can be functionally and anatomically divided into six regions: the prebrachial region (C1 to C3); the brachial region (C4 to C8) - segments supplying the upper limb; the post-brachial region (T1 to L1) - containing the sympathetic outflow, and supplying the hypaxial muscles of the body wall; the crural region (L2 to L5) - segments supplying the lower limb; the postcrural region (L6) - containing the parasympathetic outflow; and the caudal region (L7 to Co4) - supplying the tail. In the rat, mouse, and rhesus monkey, the prebrachial region consists of segments C1 to C4 (with the phrenic nucleus located at the C4 segment), and the brachial region extends from C5 to T1 inclusive. The prefixing of the upper limb outflow in these two marmosets mirrors the finding in the literature that a large C4 contribution to the brachial plexus is common in humans.

  1. The Role of Hope in Spinal Cord Injury Rehabilitation.

    ERIC Educational Resources Information Center

    Heinemann, Allen; And Others

    Hope has motivational importance to individuals who have suffered a major physical loss. Theories of adjustment to a spinal cord injury take one of three approaches: (1) premorbid personality, which highlights the individual's past experiences, personal meanings, and body image; (2) typologies of injury reactions, which range from normal to…

  2. Clinical radiology of the spine and spinal cord

    SciTech Connect

    Banna, M.

    1985-01-01

    This book is a source of information about aspects of radiology of the spine and spinal column. It presents coverage of both normal and abnormal conditions. Contents: Spinal fractures and dislocations. Degenerative diseases of the spine. Gross anatomy of the spinal cord and meninges. Intraspinal mass lesions. Spinal dysraphism. Congenital anomalies. Tumors of the vertebral column, and more.

  3. Organisation of the sympathetic skin response in spinal cord injury

    PubMed Central

    Cariga, P; Catley, M; Mathias, C; Savic, G; Frankel, H; Ellaway, P

    2002-01-01

    Objectives: The sympathetic skin response (SSR) is a technique to assess the sympathetic cholinergic pathways, and it can be used to study the central sympathetic pathways in spinal cord injury (SCI). This study investigated the capacity of the isolated spinal cord to generate an SSR, and determined the relation between SSR, levels of spinal cord lesion, and supraspinal connections. Methods: Palmar and plantar SSR to peripheral nerve electrical stimulation (median or supraorbital nerve above the lesion, and peroneal nerve below the lesion) were recorded in 29 patients with SCI at various neurological levels and in 10 healthy control subjects. Results: In complete SCI at any neurological level, SSR was absent below the lesion. Palmar SSR to median nerve stimuli was absent in complete SCI with level of lesion above T6. Plantar SSR was absent in all patients with complete SCI at the cervical and thoracic level. In incomplete SCI, the occurrence of SSR was dependent on the preservation of supraspinal connections. For all stimulated nerves, there was no difference between recording from ipsilateral and contralateral limbs. Conclusions: No evidence was found to support the hypothesis that the spinal cord isolated from the brain stem could generate an SSR. The results indicate that supraspinal connections are necessary for the SSR, together with integrity of central sympathetic pathways of the upper thoracic segments for palmar SSR, and possibly all thoracic segments for plantar SSR. PMID:11861696

  4. [Intramedullary spinal cord cavernous hemangiomas: clinical features and surgical treatment].

    PubMed

    Ishii, Ken; Nakamura, Masaya

    2011-01-01

    Intramedullary spinal cord cavernous hemangiomas (angiomas) are occult vascular malformations characterized by rare lesions consisting of closely packed capillary-like vessels. In general, patients with this disease become symptomatic because of hemorrhage leads to progressive neurological deficits. Therefore, surgical tumor resection should be considered for symptomatic patients should be considered a surgical tumor resection.

  5. Substance Use by Persons with Recent Spinal Cord Injuries.

    ERIC Educational Resources Information Center

    Heinemann, Allen W.; And Others

    Substance use histories were obtained from 103 persons (16 to 63 years of age) with recent spinal cord injuries (SCI). Lifetime exposure to and current use of substances with abuse potential were substantially greater in this sample compared to a like-age national sample. Exposure to and recent use of substances with abuse potential was…

  6. Race-Ethnicity, Education, and Employment after Spinal Cord Injury

    ERIC Educational Resources Information Center

    Krause, James S.; Saunders, Lee; Staten, David

    2010-01-01

    The objective of this article was to identify the relationship between race-ethnicity and employment after spinal cord injury (SCI), while evaluating interrelationships with gender, injury severity, and education. The authors used a cohort design using the most current status from a post-injury interview from the National SCI Statistical Center.…

  7. Quality of Life in Patients with Spinal Cord Injury

    ERIC Educational Resources Information Center

    Gurcay, Eda; Bal, Ajda; Eksioglu, Emel; Cakci, Aytul

    2010-01-01

    The primary objective of this study was to assess the quality of life (QoL) in spinal cord injury (SCI) survivors. Secondary objectives were to determine the effects of various sociodemographic and clinical characteristics on QoL. This cross-sectional study included 54 patients with SCI. The Turkish version of the Short-Form-36 Health Survey was…

  8. Fibrocartilagenous embolism: an unusual cause of spinal cord infarction.

    PubMed

    Yousef, O M; Appenzeller, P; Kornfeld, M

    1998-12-01

    A 14-year-old girl experienced sudden onset of weakness progressing rapidly to paralysis. She died 7 days later from a massive pulmonary thromboembolus. Autopsy revealed extensive infarction of the spinal cord with a fibrocartilaginous embolus of the corresponding segment of the anterior spinal artery.

  9. Incidence of Secondary Complications in Spinal Cord Injury.

    ERIC Educational Resources Information Center

    Anson, C. A.; Shepherd, C.

    1996-01-01

    Data from 348 patients (mean age 37) with postacute spinal cord injury revealed that 95% reported at least 1 secondary problem, and 58% reported 3 or more. The number and severity of complications varied with time since the injury. Obesity, pain, spasticity, urinary tract infections, pressure sores, and lack of social integration were common…

  10. Cell Therapy Augments Functional Recovery Subsequent to Spinal Cord Injury under Experimental Conditions

    PubMed Central

    Sabapathy, Vikram; Tharion, George; Kumar, Sanjay

    2015-01-01

    The spinal cord injury leads to enervation of normal tissue homeostasis ultimately leading to paralysis. Until now there is no proper cure for the treatment of spinal cord injury. Recently, cell therapy in animal spinal cord injury models has shown some progress of recovery. At present, clinical trials are under progress to evaluate the efficacy of cell transplantation for the treatment of spinal cord injury. Different types of cells such as pluripotent stem cells derived neural cells, mesenchymal stromal cells, neural stem cells, glial cells are being tested in various spinal cord injury models. In this review we highlight both the advances and lacuna in the field of spinal cord injury by discussing epidemiology, pathophysiology, molecular mechanism, and various cell therapy strategies employed in preclinical and clinical injury models and finally we discuss the limitations and ethical issues involved in cell therapy approach for treating spinal cord injury. PMID:26240569

  11. Wnt/β-catenin signaling promotes regeneration after adult zebrafish spinal cord injury.

    PubMed

    Strand, Nicholas S; Hoi, Kimberly K; Phan, Tien M T; Ray, Catherine A; Berndt, Jason D; Moon, Randall T

    2016-09-02

    Unlike mammals, zebrafish can regenerate their injured spinal cord and regain control of caudal tissues. It was recently shown that Wnt/β-catenin signaling is necessary for spinal cord regeneration in the larval zebrafish. However, the molecular mechanisms of regeneration may or may not be conserved between larval and adult zebrafish. To test this, we assessed the role of Wnt/β-catenin signaling after spinal cord injury in the adult zebrafish. We show that Wnt/β-catenin signaling is increased after spinal cord injury in the adult zebrafish. Moreover, overexpression of Dkk1b inhibited Wnt/β-catenin signaling in the regenerating spinal cord of adult zebrafish. Dkk1b overexpression also inhibited locomotor recovery, axon regeneration, and glial bridge formation in the injured spinal cord. Thus, our data illustrate a conserved role for Wnt/β-catenin signaling in adult and larval zebrafish spinal cord regeneration.

  12. Management of severe spinal cord injury following hyperbaric exposure.

    PubMed

    Mathew, Bruce; Laden, Gerard

    2015-09-01

    There is an increasing body of evidence that drainage of lumbar cerebrospinal fluid (CSF) improves functional neurological outcome after reperfusion injury to the spinal cord that occasionally follows aortic reconstructive surgery. This beneficial effect is considered owing to lowering of the CSF pressure thereby normalising spinal cord blood flow and reducing the 'secondary' cord injury caused by vascular congestion and cord swelling in the relatively confined spinal canal. Whilst lacking definitive proof, there are convincing randomised controlled trials (RCTs), cohort data and systematic reviews supporting this intervention. The therapeutic window for lumbar CSF drainage requires further elucidation; however, it appears to be days rather than hours post insult. We contend that the same benefit is likely to be achieved following other primary spinal cord injuries that cause cord swelling and elicit the 'secondary' injury. Traditionally the concept of CSF drainage has been considered more applicable to the brain as contained in a 'closed box' by lowering intracranial pressure (ICP) to improve cerebral perfusion pressure (CPP). The control of CPP is intended to limit 'secondary' brain injury and is a key concept of brain injury management. Using microdialysis in the spinal cords of trauma patients, it has been shown that intraspinal pressure (ISP) needs to be kept below 20 mmHg and spinal cord perfusion pressure (SCPP) above 70 mmHg to avoid biochemical evidence of secondary cord damage. Vasopressor have also been used in spinal cord injury to improve perfusion, however complications are common, typically cardiac in nature, and require very careful monitoring; the evidence supporting this approach is notably less convincing. Decompression illness (DCI) of the spinal cord is treated with recompression, hyperbaric oxygen, various medications designed to reduce the inflammatory response and fluid administration to normalise blood pressure and haematocrit. These

  13. Pannexin 1: a novel participant in neuropathic pain signaling in the rat spinal cord.

    PubMed

    Bravo, David; Ibarra, Paula; Retamal, Jeffri; Pelissier, Teresa; Laurido, Claudio; Hernandez, Alejandro; Constandil, Luis

    2014-10-01

    Pannexin 1 (panx1) is a large-pore membrane channel expressed in many tissues of mammals, including neurons and glial cells. Panx1 channels are highly permeable to calcium and adenosine triphosphatase (ATP); on the other hand, they can be opened by ATP and glutamate, two crucial molecules for acute and chronic pain signaling in the spinal cord dorsal horn, thus suggesting that panx1 could be a key component for the generation of central sensitization during persistent pain. In this study, we examined the effect of three panx1 blockers, namely, 10panx peptide, carbenoxolone, and probenecid, on C-reflex wind-up activity and mechanical nociceptive behavior in a spared nerve injury neuropathic rat model involving sural nerve transection. In addition, the expression of panx1 protein in the dorsal horn of the ipsilateral lumbar spinal cord was measured in sural nerve-transected and sham-operated control rats. Sural nerve transection resulted in a lower threshold for C-reflex activation by electric stimulation of the injured hindpaw, together with persistent mechanical hypersensitivity to pressure stimuli applied to the paw. Intrathecal administration of the panx1 blockers significantly depressed the spinal C-reflex wind-up activity in both neuropathic and sham control rats, and decreased mechanical hyperalgesia in neuropathic rats without affecting the nociceptive threshold in sham animals. Western blotting showed that panx1 was similarly expressed in the dorsal horn of lumbar spinal cord from neuropathic and sham rats. The present results constitute the first evidence that panx1 channels play a significant role in the mechanisms underlying central sensitization in neuropathic pain.

  14. Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury

    PubMed Central

    Salgado, Iris K.; Torrado, Aranza I.; Santiago, Jose M.; Miranda, Jorge D.

    2015-01-01

    Spinal cord injury (SCI) is a devastating condition that produces significant changes in the lifestyle of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI: an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents (tamoxifen and a Src kinase family inhibitor known as PP2) that have been shown in our laboratory to produce neuroprotective (increase cell survival) and/or regenerative (axonal outgrowth) actions. The animal model used in our laboratory is adult female rat (~250 g) with a moderate contusion (12.5 mm) to the spinal cord at the T10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet (Innovative Research of America, Sarasota, FL, USA) or by intraperitoneal injections (1.5 mg/kg, every 3 days), respectively, to produce a long-term effect (28 days). Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regenerative activity in vertebrates with SCI. PMID:25878585

  15. CNS Cell Distribution and Axon Orientation Determine Local Spinal Cord Mechanical Properties

    PubMed Central

    Koser, David E.; Moeendarbary, Emad; Hanne, Janina; Kuerten, Stefanie; Franze, Kristian

    2015-01-01

    Mechanical signaling plays an important role in cell physiology and pathology. Many cell types, including neurons and glial cells, respond to the mechanical properties of their environment. Yet, for spinal cord tissue, data on tissue stiffness are sparse. To investigate the regional and direction-dependent mechanical properties of spinal cord tissue at a spatial resolution relevant to individual cells, we conducted atomic force microscopy (AFM) indentation and tensile measurements on acutely isolated mouse spinal cord tissue sectioned along the three major anatomical planes, and correlated local mechanical properties with the underlying cellular structures. Stiffness maps revealed that gray matter is significantly stiffer than white matter irrespective of directionality (transverse, coronal, and sagittal planes) and force direction (compression or tension) (Kg= ∼130 Pa vs. Kw= ∼70 Pa); both matters stiffened with increasing strain. When all data were pooled for each plane, gray matter behaved like an isotropic material under compression; however, subregions of the gray matter were rather heterogeneous and anisotropic. For example, in sagittal sections the dorsal horn was significantly stiffer than the ventral horn. In contrast, white matter behaved transversely isotropic, with the elastic stiffness along the craniocaudal (i.e., longitudinal) axis being lower than perpendicular to it. The stiffness distributions we found under compression strongly correlated with the orientation of axons, the areas of cell nuclei, and cellular in plane proximity. Based on these morphological parameters, we developed a phenomenological model to estimate local mechanical properties of central nervous system (CNS) tissue. Our study may thus ultimately help predicting local tissue stiffness, and hence cell behavior in response to mechanical signaling under physiological and pathological conditions, purely based on histological data. PMID:25954872

  16. Diagnosis and management of traumatic cervical central spinal cord injury: A review

    PubMed Central

    Epstein, Nancy E.; Hollingsworth, Renee

    2015-01-01

    Background: The classical clinical presentation, neuroradiographic features, and conservative vs. surgical management of traumatic cervical central spinal cord (CSS) injury remain controversial. Methods: CSS injuries, occurring in approximately 9.2% of all cord injuries, are usually attributed to significant hyperextension trauma combined with congenital/acquired cervical stenosis/spondylosis. Patients typically present with greater motor deficits in the upper vs. lower extremities accompanied by patchy sensory loss. T2-weighted magnetic resonance (MR) scans usually show hyperintense T2 intramedullary signals reflecting acute edema along with ligamentous injury, while noncontrast computed tomography (CT) studies typically show no attendant bony pathology (e.g. no fracture, dislocation). Results: CSS constitute only a small percentage of all traumatic spinal cord injuries. Aarabi et al. found CSS patients averaged 58.3 years of age, 83% were male and 52.4% involved accidents/falls in patients with narrowed spinal canals (average 5.6 mm); their average American Spinal Injury Association (ASIA) motor score was 63.8, and most pathology was at the C3-C4 and C4-C5 levels (71%). Surgery was performed within 24 h (9 patients), 24–48 h (10 patients), or after 48 h (23 patients). In the Brodell et al. study of 16,134 patients with CSS, 39.7% had surgery. In the Gu et al. series, those with CSS and stenosis/ossification of the posterior longitudinal ligament (OPLL) exhibited better outcomes following laminoplasty. Conclusions: Recognizing the unique features of CSS is critical, as the clinical, neuroradiological, and management strategies (e.g. conservative vs. surgical management: early vs. late) differ from those utilized for other spinal cord trauma. Increased T2-weighted MR images best document CSS, while CT studies confirm the absence of fracture/dislocation. PMID:26005576

  17. Chronic Oligodendrogenesis and Remyelination after Spinal Cord Injury in Mice and Rats

    PubMed Central

    Hesp, Zoe C.; Goldstein, Evan A.; Miranda, Carlos J.; Kaspar, Brain K.

    2015-01-01

    Adult progenitor cells proliferate in the acutely injured spinal cord and their progeny differentiate into new oligodendrocytes (OLs) that remyelinate spared axons. Whether this endogenous repair continues beyond the first week postinjury (wpi), however, is unknown. Identifying the duration of this response is essential for guiding therapies targeting improved recovery from spinal cord injury (SCI) by enhancing OL survival and/or remyelination. Here, we used two PDGFRα-reporter mouse lines and rats injected with a GFP-retrovirus to assess progenitor fate through 80 d after injury. Surprisingly, new OLs were generated as late as 3 months after injury and their processes ensheathed axons near and distal to the lesion, colocalized with MBP, and abutted Caspr+ profiles, suggesting newly formed myelin. Semithin sections confirmed stereotypical thin OL remyelination and few bare axons at 10 wpi, indicating that demyelination is relatively rare. Astrocytes in chronic tissue expressed the pro-OL differentiation and survival factors CNTF and FGF-2. In addition, pSTAT3+ NG2 cells were present through at least 5 wpi, revealing active signaling of the Jak/STAT pathway in these cells. The progenitor cell fate genes Sox11, Hes5, Id2, Id4, BMP2, and BMP4 were dynamically regulated for at least 4 wpi. Collectively, these data verify that the chronically injured spinal cord is highly dynamic. Endogenous repair, including oligodendrogenesis and remyelination, continues for several months after SCI, potentially in response to growth factors and/or transcription factor changes. Identifying and understanding spontaneous repair processes such as these is important so that beneficial plasticity is not inadvertently interrupted and effort is not exerted to needlessly duplicate ongoing spontaneous repair. PMID:25609641

  18. Rapamycin increases neuronal survival, reduces inflammation and astrocyte proliferation after spinal cord injury.

    PubMed

    Goldshmit, Yona; Kanner, Sivan; Zacs, Maria; Frisca, Frisca; Pinto, Alexander R; Currie, Peter D; Pinkas-Kramarski, Ronit

    2015-09-01

    Spinal cord injury (SCI) frequently leads to a permanent functional impairment as a result of the initial injury followed by secondary injury mechanism, which is characterised by increased inflammation, glial scarring and neuronal cell death. Finding drugs that may reduce inflammatory cell invasion and activation to reduce glial scarring and increase neuronal survival is of major importance for improving the outcome after SCI. In the present study, we examined the effect of rapamycin, an mTORC1 inhibitor and an inducer of autophagy, on recovery from spinal cord injury. Autophagy, a process that facilitates the degradation of cytoplasmic proteins, is also important for maintenance of neuronal homeostasis and plays a major role in neurodegeneration after neurotrauma. We examined rapamycin effects on the inflammatory response, glial scar formation, neuronal survival and regeneration in vivo using spinal cord hemisection model in mice, and in vitro using primary cortical neurons and human astrocytes. We show that a single injection of rapamycin, inhibited p62/SQSTM1, a marker of autophagy, inhibited mTORC1 downstream effector p70S6K, reduced macrophage/neutrophil infiltration into the lesion site, microglia activation and secretion of TNFα. Rapamycin inhibited astrocyte proliferation and reduced the number of GFAP expressing cells at the lesion site. Finally, it increased neuronal survival and axonogenesis towards the lesion site. Our study shows that rapamycin treatment increased significantly p-Akt levels at the lesion site following SCI. Similarly, rapamycin treatment of neurons and astrocytes induced p-Akt elevation under stress conditions. Together, these findings indicate that rapamycin is a promising candidate for treatment of acute SCI condition and may be a useful therapeutic agent.

  19. [The biological kinetics of biofilms of clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa separated from patients with bronchopulmonary complications under traumatic disease of spinal cord].

    PubMed

    Ul'ianov, V Iu; Opredelentseva, S V; Shvidenko, I G; Norkin, I A; Korshunov, G V; Gladkova, E V

    2014-08-01

    The capacity and intensity of formation of microbial biofilms was analyzed in 24 strains of Staphylococcus aureus and Pseudomonas aeruginosa in static conditions of cultivation during 24, 48, 72 and 96 yours. The microorganisms were separated from patients with bronchopulmonary infectious complications in acute and early periods of traumatic disease of spinal cord.

  20. Expectations of life and health among spinal cord injured adults.

    PubMed

    McColl, M A; Walker, J; Stirling, P; Wilkins, R; Corey, P

    1997-12-01

    While our understanding of aging and mortality in spinal cord injury is evolving, precise estimates are still not available for expectations of life and health following a spinal cord injury. In order to derive these estimates, information about mortality and health must be combined into a single estimate. Health expectancy estimates have been widely used in the literature of the last decade to try to understand the relationship between population health and survival, both in the general population and in special populations. This study brought the benefit of this methodology to the question of long-term survival following spinal cord injury. Specifically, the study aimed to calculate life and health expectancy in a population of spinal cord injured individuals; and to estimate the effect of factors associated with survival and health. The study involved a retrospective cohort, all of whom sustained a spinal cord injury between the ages of 25 and 34 years, and between 1945 and 1990. The study predicted a median survival time of 38 years post-injury, with 43% surviving at least 40 years. These findings suggest an increase in life expectancy of about 5 years over previous research on the same cohort. Factors affecting survival were age at injury, level and completeness of lesion. Expectations of health found in the present study are similar to those found in studies of the general population. This study showed seven remaining years of poor health expected at injury, and five remaining years expected at 40 years post injury, presumably occurring at the end of life.

  1. Electrophysiological and Anatomical Correlates of Spinal Cord Optical Coherence Tomography

    PubMed Central

    Valente, Maurizio; Krstajic, Nikola; Biella, Gabriele E. M.

    2016-01-01

    Despite the continuous improvement in medical imaging technology, visualizing the spinal cord poses severe problems due to structural or incidental causes, such as small access space and motion artifacts. In addition, positional guidance on the spinal cord is not commonly available during surgery, with the exception of neuronavigation techniques based on static pre-surgical data and of radiation-based methods, such as fluoroscopy. A fast, bedside, intraoperative real-time imaging, particularly necessary during the positioning of endoscopic probes or tools, is an unsolved issue. The objective of our work, performed on experimental rats, is to demonstrate potential intraoperative spinal cord imaging and probe guidance by optical coherence tomography (OCT). Concurrently, we aimed to demonstrate that the electromagnetic OCT irradiation exerted no particular effect at the neuronal and synaptic levels. OCT is a user-friendly, low-cost and endoscopy-compatible photonics-based imaging technique. In particular, by using a Fourier-domain OCT imager, operating at 850 nm wavelength and scanning transversally with respect to the spinal cord, we have been able to: 1) accurately image tissue structures in an animal model (muscle, spine bone, cerebro-spinal fluid, dura mater and spinal cord), and 2) identify the position of a recording microelectrode approaching and inserting into the cord tissue 3) check that the infrared radiation has no actual effect on the electrophysiological activity of spinal neurons. The technique, potentially extendable to full three-dimensional image reconstruction, shows prospective further application not only in endoscopic intraoperative analyses and for probe insertion guidance, but also in emergency and adverse situations (e.g. after trauma) for damage recognition, diagnosis and fast image-guided intervention. PMID:27050096

  2. Severe hypothermia in a patient with spinal cord injury without radiological abnormality

    PubMed Central

    Smith, Travis M; Berk, Alexander S; Upadhyay, Hiten

    2011-01-01

    We report a case of a 64-year-old caucasian male who was transported to the emergency department (ED) after being found unconscious on the side of the road. On arrival to the ED the patient went into ventricular fibrillation and advanced cardiac life support was started at that time. Thirty minutes into the resuscitation, after multiple rounds of code drugs and defibrillation attempts, the patient was found to be severely hypothermic with a rectal temperature of 24.9°C (76.9°F). Through the use of passive and active re-warming measures the patient's temperature increased enough to allow successful cardioversion and stabilization. Within minutes of cardiac stabilization the patient regained consciousness and was able to follow commands, but was found to be paralyzed from the neck down. Subsequent CT scans revealed no acute fractures, subluxations or acute spinal cord injury. This case represents the rare finding of severe hypothermia secondary to occult spinal cord injury. Case report was taken from case at Bayfront Hospital, St. Petersburg, Florida. PMID:21887040

  3. Phenylbutyrate prevents disruption of blood-spinal cord barrier by inhibiting endoplasmic reticulum stress after spinal cord injury

    PubMed Central

    Zhou, Yulong; Ye, Libing; Zheng, Binbin; Zhu, Sipin; Shi, Hongxue; Zhang, Hongyu; Wang, Zhouguang; Wei, Xiaojie; Chen, Daqing; Li, Xiaokun; Xu, Huazi; Xiao, Jian

    2016-01-01

    This study aims to investigate the role of endocytoplasmic reticulum (ER) stress induced by spinal cord injury (SCI) in blood-spinal cord barrier (BSCB) disruption and the effect of phenylbutyrate (PBA) on BSCB disruption after SCI. After a moderate contusion injury at the T9 level of spinal cord with a vascular clip, PBA was immediately administered into injured rat via intraperitoneal injection (100 mg/kg) and then further treated once a day for 2 weeks for behavior test. Spinal cord was collected at 1 day post-injury for evaluation of the effects of ER stress and PBA on BSCB disruption after SCI. PBA significantly attenuated BSCB permeability and degradation of tight junction molecules such as P120, β-catenin, Occludin and Claudin5 at 1 day after injury and improved functional recovery in the rat model of trauma. The BSCB protective effect of PBA is related to the inhibition of ER stress induced by SCI. In addition, PBA significantly inhibited the increase of ER stress markers and prevents loss of tight junction and adherens junction proteins in TG-treated human brain microvascular endothelial cells (HBMEC). Taken together, our data demonstrate that therapeutic strategies targeting ER stress may be suitable for the therapy of preserving BSCB integrity after SCI. PBA may be a new candidate as a therapeutic agent for protecting SCI by a compromised BSCB. PMID:27186310

  4. Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

    PubMed

    Hofstoetter, Ursula S; Krenn, Matthias; Danner, Simon M; Hofer, Christian; Kern, Helmut; McKay, William B; Mayr, Winfried; Minassian, Karen

    2015-10-01

    The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control.

  5. Translational potential of preclinical trials of neuroprotection through pharmacotherapy for spinal cord injury.

    PubMed

    Tator, Charles H; Hashimoto, Robin; Raich, Annie; Norvell, Daniel; Fehlings, Michael G; Harrop, James S; Guest, James; Aarabi, Bizhan; Grossman, Robert G

    2012-09-01

    There is a need to enhance the pipeline of discovery and evaluation of neuroprotective pharmacological agents for patients with spinal cord injury (SCI). Although much effort and money has been expended on discovering effective agents for acute and subacute SCI, no agents that produce major benefit have been proven to date. The deficiencies of all aspects of the pipeline, including the basic science input and the clinical testing output, require examination to determine remedial strategies. Where has the neuroprotective/pharmacotherapy preclinical process failed and what needs to be done to achieve success? These are the questions raised in the present review, which has 2 objectives: 1) identification of articles that address issues related to the translational readiness of preclinical SCI pharmacological therapies; and 2) examination of the preclinical studies of 5 selected agents evaluated in animal models of SCI (including blunt force trauma, penetrating trauma, or ischemia). The 5 agents were riluzole, glyburide, magnesium sulfate, nimodipine, and minocycline, and these were selected because of their promise of translational readiness as determined by the North American Clinical Trials Network Consortium. The authors found that there are major deficiencies in the effort that has been extended to coordinate and conduct preclinical neuroprotection/pharmacotherapy trials in the SCI field. Apart from a few notable exceptions such as the NIH effort to replicate promising strategies, this field has been poorly coordinated. Only a small number of articles have even attempted an overall evaluation of the neuroprotective/pharmacotherapy agents used in preclinical SCI trials. There is no consensus about how to select the agents for translation to humans on the basis of their preclinical performance and according to agreed-upon preclinical performance criteria. In the absence of such a system and to select the next agent for translation, the Consortium has developed a

  6. Olfactory Ensheathing Cell Transplantation after a Complete Spinal Cord Transection Mediates Neuroprotective and Immunomodulatory Mechanisms to Facilitate Regeneration

    PubMed Central

    Khankan, Rana R.; Griffis, Khris G.; Haggerty-Skeans, James R.; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

    2016-01-01

    Multiple neural and peripheral cell types rapidly respond to tissue damage after spinal cord injury to form a structurally and chemically inhibitory scar that limits axon regeneration. Astrocytes form an astroglial scar and produce chondroitin sulfate proteoglycans (CSPGs), activate microglia, and recruit blood-derived immune cells to the lesion for debris removal. One beneficial therapy, olfactory ensheathing cell (OEC) transplantation, results in functional improvements and promotes axon regeneration after spinal cord injury. The lack of an OEC-specific marker, however, has limited the investigation of mechanisms underlying their proregenerative effects. We compared the effects of enhanced green fluorescent protein-labeled fibroblast (FB) and OEC transplants acutely after a complete low-thoracic spinal cord transection in adult rats. We assessed the preservation of neurons and serotonergic axons, the levels of inhibitory CSPGs and myelin debris, and the extent of immune cell activation between 1 and 8 weeks postinjury. Our findings indicate that OECs survive longer than FBs post-transplantation, preserve axons and neurons, and reduce inhibitory molecules in the lesion core. Additionally, we show that OECs limit immune-cell activation and infiltration, whereas FBs alter astroglial scar formation and increase immune-cell infiltration and concomitant secondary tissue damage. Administration of cyclosporine-A to enhance graft survival demonstrated that immune suppression can augment OEC contact-mediated protection of axons and neurons during the first 2 weeks postinjury. Collectively, these data suggest that OECs have neuroprotective and immunomodulatory mechanisms that create a supportive environment for neuronal survival and axon regeneration after spinal cord injury. SIGNIFICANCE STATEMENT Spinal cord injury creates physical and chemical barriers to axon regeneration. We used a complete spinal cord transection model and olfactory ensheathing cell (OEC) or