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1

Spinal injury  

MedlinePLUS

... Pa: Elsevier Mosby; 2009:chap 40. Torg JS. Cervical Spine Injuries: 1. Cervical spine injuries in the adult. In: DeLee JC, Drez ... chap 16, section A. Pizzutillo PD, Herman MJ. Cervical spine injuries: 2. Cervical spine injuries in the child. ...

2

Bridging spinal cord injuries  

E-print Network

Minireview Bridging spinal cord injuries James W Fawcett Address: Cambridge University Centre for Brain Repair, Robinson Way, Cambridge CB2 0PY, UK. Email: jf108@cam.ac.uk Repair of the injured spinal cord has been one of the great quests... why not transplant Abstract One strategy for spinal cord injury repair is to make cellular bridges that support axon regeneration. However, the bridging cells often fail to integrate with host tissue and may lead to increased pain sensitivity. Recent...

2008-10-15

3

Spinal Cord Injury 101  

MedlinePLUS Videos and Cool Tools

... 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 ...

4

Tribal motor vehicle injury prevention programs for reducing disparities in motor vehicle-related injuries.  

PubMed

A previous analysis of National Vital Statistics System data for 2003-2007 that examined disparities in rates of motor vehicle-related death by race/ethnicity and sex found that death rates for American Indians/Alaska Natives were two to four times the rates of other races/ethnicities. To address the disparity in motor vehicle-related injuries and deaths among American Indians/Alaska Natives, CDC funded four American Indian tribes during 2004-2009 to tailor, implement, and evaluate evidence-based road safety interventions. During the implementation of these four motor vehicle-related injury prevention pilot programs, seat belt and child safety seat use increased and alcohol-impaired driving decreased. Four American Indian/Alaska Native tribal communities-the Tohono O'odham Nation, the Ho-Chunk Nation, the White Mountain Apache Tribe, and the San Carlos Apache Tribe-implemented evidence-based road safety interventions to reduce motor vehicle-related injuries and deaths. Each community selected interventions from the Guide to Community Preventive Services and implemented them during 2004-2009. Furthermore, each community took a multifaceted approach by incorporating several strategies, such as school and community education programs, media campaigns, and collaborations with law enforcement officers into their programs. Police data and direct observational surveys were the main data sources used to assess results of the programs. Results included increased use of seat belts and child safety seats, increased enforcement of alcohol-impaired driving laws, and decreased motor vehicle crashes involving injuries or deaths. CDC's Office of Minority Health and Health Equity selected the intervention analysis and discussion as an example of a program that might be effective for reducing motor vehicle-related injury disparities in the United States. The Guide to Community Preventive Services recognizes these selected interventions as effective; this report examines the feasibility and transferability for implementing the interventions in American Indian/Alaska Native tribal communities. The findings in this report underscore the effectiveness of community interventions to reduce motor vehicle crashes among selected American Indian/Alaska Native communities. PMID:24743664

West, Bethany A; Naumann, Rebecca B

2014-04-18

5

What Is Spinal Cord Injury?  

MedlinePLUS

... addition, there are two degrees of SCI severity : Complete injury is the situation when the injury is so ... National Spinal Cord Injury Association. Understanding spinal cord injury . Retrieved May 21, 2012, from http://www.spinalcord.org/resource-center/askus/index.php?pg=kb. ...

6

DISCUSSION ON SPINAL INJURIES  

PubMed Central

(1).—Varieties of spinal injuries, the three groups of common usage: fractures, dislocations, fracture-dislocations. Shall not refer in detail to fractures of the spinous or transverse processes. (2) Mechanics of injury to vertebræ. Two variables: (1) the nature of the bones; (2) the qualities of the force. Spinal injury usually caused by indirect violence. (3) The different results of injuries applied to the head; may break skull, failing that, the neck. Atlas fracture. Difference in qualities of the force causing atlas fracture and low cervical dislocation. (4) The compound nature of the vertebral body. The two columns, anterior, spongy; posterior, compact. The nature of wedge-compression of the vertebral body. Variations in the shape of the wedge. Reasons. Occur at all levels, including cervical spine. (5) Frequency of injury at different levels of vertebral column. “Localization” of injury. The two places of the graph of injury. The cervical at C. 5. Reason. The thoracic-lumbar peak at T. 12, L. 1 industrial. Is there a third peak at C. 2? (6) The effects of violent flexion of the spine: cervical flexion causes luxation at C. 5 or so. Extension causes fracture of odontoid. Violent flexion and extension therefore cause injury at very different levels. Thoracic region, why is there no “peak” of injury at T.6, 7? Lumbar region. (7) Displacement of fragments. Continuation of violence after the essential injury has been effected. Kümmell's disease, no inflammatory process involved. (8) Injury to the intervertebral discs, essential for displacement. Imperfect rupture a cause for difficulty in reducing luxations. The worst cases those in which it is most easily done, but most of these have cord damage. (9) Spinal injury from minimal violence. Examples of trivial cases, diving, brushing hair and so forth. Vertebral displacement in disease a much more serious thing. (10) Curious stability of many cervical luxations. Reasons. Locking of the inferior zygaphophyses. (11) Injury to nervous elements left principally to other speakers. Cord compression very rare. Immediate and irremediable damage. Root injuries. Falling mortality of modern statistics due to better diagnosis. (12) Primary operation for fractures of spine relegated to oblivion. Rarity of indications for open operation. Reduction the best treatment. ImagesFig. 5Fig. 6 PMID:19986314

1928-01-01

7

Attitudes Towards Individuals with Spinal Cord Injuries  

ERIC Educational Resources Information Center

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…

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

2010-01-01

8

Adjustment to Spinal Cord Injury  

MedlinePLUS

... to adjusting to spinal cord injury is personal motivation . Individuals who are newly injured are often motivated ... to find purpose in your life and the motivation to achieve your goals. It may help to ...

9

Spinal Myoclonus After Spinal Cord Injury  

PubMed Central

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, or thigh; in 4 of these subjects, treatment of the pathology eliminated the involuntary movements. Conclusion: The timing, distribution, and reliance upon hip angle suggest that these movement patterns reflect some elements of a central pattern generator for stepping. Emergence of these movements in persons with chronic spinal cord injury is extremely rare and appears to depend upon a combination of the more rostrally placed injury and a pathologic process leading to a further enhancement of excitability in the caudal spinal cord. PMID:17044393

Calancie, Blair

2006-01-01

10

Evaluation of spinal cord injury animal models  

PubMed Central

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

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

2014-01-01

11

SPINAL CORD INJURY (SCI) DATABASE  

EPA Science Inventory

The National Spinal Cord Injury Database has been in existence since 1973 and captures data from SCI cases in the United States. Since its inception, 24 federally funded Model SCI Care Systems have contributed data to the National SCI Database. Statistics are derived from this da...

12

Rehabilitation of spinal cord injuries.  

PubMed

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

Nas, Kemal; Yazmalar, Levent; ?ah, Volkan; Ayd?n, Abdulkadir; Öne?, Kadriye

2015-01-18

13

Rehabilitation of spinal cord injuries  

PubMed Central

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

Nas, Kemal; Yazmalar, Levent; ?ah, Volkan; Ayd?n, Abdulkadir; Öne?, Kadriye

2015-01-01

14

Pain Management Following Spinal Cord Injury  

MedlinePLUS

... signals are Rehabilitation Research and Training Center on Secondary Conditions of SCI & Model SCI Care Center Spinal Cord Injury InfoSheet 10 Level - Consumer Pain Management following Spinal ...

15

Testosterone Plus Finasteride Treatment After Spinal Cord Injury  

ClinicalTrials.gov

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

2014-09-22

16

Melatonin lowers edema after spinal cord injury  

PubMed Central

Melatonin has been shown to diminish edema in rats. Melatonin can be used to treat spinal cord injury. This study presumed that melatonin could relieve spinal cord edema and examined how it might act. Our experiments found that melatonin (100 mg/kg, i.p.) could reduce the water content of the spinal cord, and suppress the expression of aquaporin-4 and glial fibrillary acidic protein after spinal cord injury. This suggests that the mechanism by which melatonin alleviates the damage to the spinal cord by edema might be related to the expression of aquaporin-4 and glial fibrillary acidic protein.

Li, Cheng; Chen, Xiao; Qiao, Suchi; Liu, Xinwei; Liu, Chang; Zhu, Degang; Su, Jiacan; Wang, Zhiwei

2014-01-01

17

Spinal cord injury rehabilitation in Nepal.  

PubMed

Spinal cord injury is a major trauma, with its short and long term effects and consequences to the patient, his friends and family. Spinal cord injury is addressed in the developed countries with standard trauma care system commencing immediately after injury and continuing to the specialized rehabilitation units. Rehabilitation is important to those with spinal injury for both functional and psychosocial reintegration. It has been an emerging concept in Nepal, which has been evident with the establishment of the various hospitals with rehabilitation units, rehabilitation centres and physical therapy units in different institutions. However, the spinal cord injury rehabilitation setting and scenario is different in Nepal from those in the developed countries since spinal cord injury rehabilitation care has not been adequately incorporated into the health care delivery system nor its importance has been realized within the medical community of Nepal. To name few, lack of human resource for the rehabilitation care, awareness among the medical personnel and general population, adequate scientific research evidence regarding situation of spinal injury and exorbitant health care policy are the important hurdles that has led to the current situation. Hence, it is our responsibility to address these apparent barriers to successful implementation and functioning of rehabilitation so that those with spinal injury would benefit from enhanced quality of life. PMID:24362674

Shah, Nabina; Shrestha, Binav; Subba, Kamana

2013-01-01

18

Causes of Spinal Cord Injury  

PubMed Central

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

2013-01-01

19

CHRONIC PAIN FOLLOWING SPINAL CORD INJURY  

PubMed Central

Most patients with insults to the spinal cord or central nervous system suffer from excruciating, unrelenting, chronic pain that is largely resistant to treatment. This condition affects a large percentage of spinal cord injury patients, and numerous patients with multiple sclerosis, stroke and other conditions. Despite the recent advances in basic science and clinical research the pathophysiological mechanisms of pain following spinal cord injury remain unknown. Here we describe a novel mechanism of loss of inhibition within the thalamus that may predispose for the development of this chronic pain and discuss a potential treatment that may restore inhibition and ameliorate pain. PMID:23281514

Masri, Radi; Keller, Asaf

2013-01-01

20

Spinal trauma. Pathophysiology and management of traumatic spinal injuries.  

PubMed

Spinal trauma can originate from internal or external sources. Injuries to the spinal cord can be classified as either concussive or compressive and concussive. The pathophysiologic events surrounding spinal cord injury include the primary injury (compression, concussion) and numerous secondary injury mechanisms (vascular, biochemical, electrolyte), which are mediated by excessive oxygen free radicles, neurotransmitter and electrolyte alterations in cell membrane permeability, excitotoxic amino acids, and various other biochemical factors that collectively result in reduced SCBF, ischemia, and eventual necrosis of the gray and white matter. Management of acute spinal cord injuries includes the use of a high-dose corticosteroid regimen within the initial 8 hours after trauma. Sodium prednisolone and methylprednisolone, at recommended doses, act as oxygen radical scavengers and are anti-inflammatory. Additional considerations are the stability of the vertebral column, other conditions associated with trauma (i.e., pneumothorax), and the presence or absence of spinal cord compression, which may warrant surgical therapy. Vertebral fractures or luxations can occur in any area of the spine but most commonly occur at the junction of mobile and immobile segments. Dorsal and dorsolateral surgical approaches are applicable to the lumbosacral and thoracolumbar spine and dorsal and ventral approaches to the cervical spine. Indications for surgical intervention include spinal cord compression and vertebral instability. Instability can be determined from the type of fracture, how many of the three compartments of the vertebrae are disrupted, and on occasion, by carefully positioned stress studies of fluoroscopy. Decompression (dorsal laminectomy, hemilaminectomy, or ventral cervical slot) is employed when compression of the spinal cord exists. The hemilaminectomy (unilateral or bilateral) causes less instability than dorsal laminectomy and therefore should be used when practical. The preferred approach for atlantoaxial subluxation is ventral, and the cross pinning, vertebral fusion technique is used for stabilization. Fracture luxations of C-2 are repaired with small plates on the ventral vertebral body. The thoracic and upper lumbar spine is stabilized with dorsal fixation techniques or combined dorsal spinal plate/vertebral body plate fixation. Several methods of fixation can be used with lower lumbar or lumbosacral fractures, including the modified segmental technique and the combined dorsal spinal plate/Kirschner-Ehmer technique. PMID:1641921

Shores, A

1992-07-01

21

The Impact Biomechanics of Spinal Column Injuries  

Microsoft Academic Search

The vertebral column is the central bony pillar of the body and serves to protect the spinal cord from injury. Vertebrae show\\u000a regional differences but they all possess a common pattern. Analysis of the biomechanics of individual components of the spine\\u000a allows one to predict how the spinal column behaves during impact. Although many forces and moments in different directions

M. J. Shelly; A. R. Poynton

22

Serotonergic transmission after spinal cord injury.  

PubMed

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. PMID:24866695

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

2015-02-01

23

Acute hydrocephalus following cervical spinal cord injury.  

PubMed

We present a case of acute hydrocephalus secondary to cervical spinal cord injury in a patient with diffuse ossification of the posterior longitudinal ligament (OPLL). A 75-year-old male patient visited the emergency department with tetraparesis and spinal shock. Imaging studies showed cervical spinal cord injury with hemorrhage and diffuse OPLL from C1 to C4. We performed decompressive laminectomy and occipitocervical fusion. Two days after surgery, his mental status had deteriorated to drowsiness with dilatation of the right pupil. Findings on brain computed tomography revealed acute hydrocephalus and subarachnoid hemorrhage in the cerebellomedullary cistern, therefore, extraventricular drainage was performed immediately. Acute hydrocephalus as a complication of cervical spine trauma is rare, however, it should be considered if the patient shows deterioration of neurologic symptoms. PMID:24175033

Son, Seong; Lee, Sang Gu; Park, Chan Woo; Kim, Woo Kyung

2013-08-01

24

Endogenous Repair after Spinal Cord Contusion Injuries in the Rat  

Microsoft Academic Search

Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center

M. S. Beattie; J. C. Bresnahan; J. Komon; C. A. Tovar; M. Van Meter; D. K. Anderson; A. I. Faden; C. Y. Hsu; L. J. Noble; S. Salzman; W. Young

1997-01-01

25

Vascular dysfunctions following spinal cord injury  

PubMed Central

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 deep vein thrombosis and long–term risk for coronary heart disease and systemic atherosclerosis are also described. Proper prophylaxis, including non–pharmacologic and pharmacological strategies, diminishes the occurrence of the vascular dysfunction following SCI. Each vascular disturbance requires a specific treatment. PMID:20945818

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

2010-01-01

26

Gene therapy approaches for spinal cord injury  

NASA Astrophysics Data System (ADS)

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

Bright, Corinne

27

Pediatric spinal cord injury: a review by organ system.  

PubMed

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

Powell, Aaron; Davidson, Loren

2015-02-01

28

Current therapeutic strategies for inflammation following traumatic spinal cord injury?  

PubMed Central

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.

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

2012-01-01

29

Anemia after traumatic spinal cord injury.  

PubMed

The incidence and natural history of anemia in patients with spinal cord injuries (SCI) were investigated in a prospective study of 68 patients consecutively admitted to a regional acute SCI unit. Fifty had SCI and 18 had spine injuries (SI) without neurologic deficit. Thirty-six of 41 males (88%) and six of nine females (67%) with SCI were anemic on at least one occasion. In the first two weeks after injury, in females and in males, there was no significant difference in mean hemoglobin level between SI and SCI patients. At six weeks, no male with SI was anemic, and males with SCI had significantly lower mean hemoglobin levels than those with SI (121.6 g/L vs 145.4 g/L, p less than .001). Identified early causes of anemia were blood loss due to bony soft tissue or visceral injury, gastrointestinal bleeding, and surgery. In the postacute phase (more than six weeks after injury), anemia occurred in 25 of 41 male and three of nine female SCI patients, and its occurrence was associated with the presence of an identified chronic disease, especially urinary tract infection. PMID:1998453

Hirsch, G H; Menard, M R; Anton, H A

1991-03-01

30

Spinal clearance in unconscious children following traumatic brain injury.  

PubMed

Spinal clearance in unconscious children following traumatic brain injury is an area of controversy. The risk of significant injury in this high-risk group needs to be balanced against that of prolonged spinal immobilization and all its implications. No national or international guideline exists to aid clinicians faced with such a scenario. This article reviews traumatic spinal injury in children looking at prevalence, risk factors, anatomical considerations, and radiological investigation. Spinal immobilization is discussed along with the use of appropriate and targeted radiological investigations to aid clearance. PMID:24697966

Cullen, Aidan; Terris, Mark; Ford, Ruth

2014-07-01

31

Automated Analysis of Remyelination Therapy for Spinal Cord Injury  

E-print Network

­ is a prominent fea- ture in many neurological disorders including multiple sclerosis (MS) and spinal cord injury disorders resulting in spinal cord injury (SCI). The lost myelin sheath can be replaced by remyelination to be Permission to make digital or hard copies of all or part of this work for personal or classroom use

Meenakshisundaram, Gopi

32

Cellular/Molecular Enhanced Oligodendrocyte Survival after Spinal Cord Injury  

E-print Network

Cellular/Molecular Enhanced Oligodendrocyte Survival after Spinal Cord Injury in Bax-Deficient Mice Medical School, Boston, Massachusetts 02115 Mechanisms of oligodendrocyte death after spinal cord injury Bax (Bax / ). In the lateral white-matter tracts, substantial oligodendrocyte death was evident

Steinbach, Joe Henry

33

Cellular therapies for treating pain associated with spinal cord injury  

PubMed Central

Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing. PMID:22394650

2012-01-01

34

Surgical correction of spinal deformities following spinal cord injury occurring in childhood.  

PubMed

This article reports on the surgical treatment of 14 consecutive patients with paralytic spinal deformities secondary to spinal cord injury occurring in childhood. Eleven patients underwent a posterior spinal fusion and three patients underwent a combined anterior and posterior spinal arthrodesis. Luque rods were used in all but one patient. The spinal fusion extended to the sacrum in 10 patients. No patient developed postoperative wound infections or medical complications. Four patients (28.6%) who underwent initially a posterior spinal arthrodesis developed pseudarthrosis. This was treated successfully by a combined anterior and posterior spinal fusion in two patients. The remaining patients underwent a revision posterior spinal fusion with recurrence of the nonunion in one patient. A combined anterior and posterior spinal arthrodesis could be considered the treatment of choice for patients with severe deformities who can tolerate anterior surgery. If pseudarthrosis develops following posterior spinal fusion, this can be best treated by a combined anterior and posterior revision procedure with instrumentation. PMID:18053399

Tsirikos, Athanasios I; Markham, Philip; McMaster, Michael J

2007-01-01

35

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

Federal Register 2010, 2011, 2012, 2013

...Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review...Title: Spinal Cord Injury Patient Care Survey, VA Form 10-0515...used to determine spinal cord patients' satisfaction with VA rehabilitation and...

2011-11-18

36

Spinal cord injury (SCI)--prehospital management.  

PubMed

Up to 20,000 patients annually suffer from spinal cord injury (SCI) and 20% of these die before being admitted to the hospital in the United States as well as in the European Union. Prehospital management of SCI is of critical importance since 25% of SCI damage may occur or be aggravated after the initial event. Prehospital management includes examination of the patient, spinal immobilisation, careful airway management (intubation, if indicated, using manual in-line stabilisation), and cardiovascular support (maintenance of mean arterial blood pressure above 90 mm Hg) and blood glucose levels within the normal range. It is still not known whether additional specific therapy is useful. Studies have not demonstrated convincingly that methylprednisolone (MPS) or other pharmacological agents really have clinically significant and important benefits for patients suffering from SCI. Recently published statements from the United States also do not support the therapeutic use of MPS in patients suffering from SCI in the prehospital setting any more. Moreover, at this stage, it is not known whether therapeutic hypothermia or any further pharmacological intervention has beneficial effects or not. Therefore, networks for clinical studies in SCI patients should be established, as a basic requirement for further improvement in outcome in such patients. PMID:15950358

Bernhard, Michael; Gries, André; Kremer, Paul; Böttiger, Bernd W

2005-08-01

37

Current and future surgery strategies for spinal cord injuries  

PubMed Central

Spinal cord trauma is a prominent cause of mortality and morbidity. In developed countries a spinal cord injury (SCI) occurs every 16 min. SCI occurs due to tissue destruction, primarily by mechanical and secondarily ischemic. Primary damage occurs at the time of the injury. It cannot be improved. Following the primary injury, secondary harm mechanisms gradually result in neuronal death. One of the prominent causes of secondary harm is energy deficit, emerging from ischemia, whose main cause in the early stage, is impaired perfusion. Due to the advanced techniques in spinal surgery, SCI is still challenging for surgeons. Spinal cord doesn’t have a self-repair property. The main damage occurs at the time of the injury primarily by mechanical factors that cannot be improved. Secondarily mechanisms take part in the following sections. Spinal compression and neurological deficit are two major factors used to decide on surgery. According to advanced imaging techniques the classifications systems for spinal injury has been changed in time. Aim of the surgery is to decompress the spinal channel and to restore the spinal alinement and mobilize the patient as soon as possible. Use of neuroprotective agents as well as methods to achieve cell regeneration in addition to surgery would contribute to the solution.

Dalbayrak, Sedat; Yaman, Onur; Y?lmaz, Tevfik

2015-01-01

38

Current and future surgery strategies for spinal cord injuries.  

PubMed

Spinal cord trauma is a prominent cause of mortality and morbidity. In developed countries a spinal cord injury (SCI) occurs every 16 min. SCI occurs due to tissue destruction, primarily by mechanical and secondarily ischemic. Primary damage occurs at the time of the injury. It cannot be improved. Following the primary injury, secondary harm mechanisms gradually result in neuronal death. One of the prominent causes of secondary harm is energy deficit, emerging from ischemia, whose main cause in the early stage, is impaired perfusion. Due to the advanced techniques in spinal surgery, SCI is still challenging for surgeons. Spinal cord doesn't have a self-repair property. The main damage occurs at the time of the injury primarily by mechanical factors that cannot be improved. Secondarily mechanisms take part in the following sections. Spinal compression and neurological deficit are two major factors used to decide on surgery. According to advanced imaging techniques the classifications systems for spinal injury has been changed in time. Aim of the surgery is to decompress the spinal channel and to restore the spinal alinement and mobilize the patient as soon as possible. Use of neuroprotective agents as well as methods to achieve cell regeneration in addition to surgery would contribute to the solution. PMID:25621209

Dalbayrak, Sedat; Yaman, Onur; Y?lmaz, Tevfik

2015-01-18

39

Neuroprotection and its molecular mechanism following spinal cord injury?  

PubMed Central

Acute spinal cord injury initiates a complex cascade of molecular events termed ‘secondary injury’, which leads to progressive degeneration ranging from early neuronal apoptosis at the lesion site to delayed degeneration of intact white matter tracts, and, ultimately, expansion of the initial injury. These secondary injury processes include, but are not limited to, inflammation, free radical-induced cell death, glutamate excitotoxicity, phospholipase A2 activation, and induction of extrinsic and intrinsic apoptotic pathways, which are important targets in developing neuroprotective strategies for treatment of spinal cord injury. Recently, a number of studies have shown promising results on neuroprotection and recovery of function in rodent models of spinal cord injury using treatments that target secondary injury processes including inflammation, phospholipase A2 activation, and manipulation of the PTEN-Akt/mTOR signaling pathway. The present review outlines our ongoing research on the molecular mechanisms of neuroprotection in experimental spinal cord injury and briefly summarizes our earlier findings on the therapeutic potential of pharmacological treatments in spinal cord injury.

Liu, Nai-Kui; Xu, Xiao-Ming

2012-01-01

40

Acute complications of spinal cord injuries.  

PubMed

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

Hagen, Ellen Merete

2015-01-18

41

Acute complications of spinal cord injuries  

PubMed Central

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

Hagen, Ellen Merete

2015-01-01

42

Molecular basis of vascular events following spinal cord injury  

PubMed Central

The aim of this article is to analyze the effects of the molecular basis of vascular events following spinal cord injury and their contribution in pathogenesis. First of all, we reviewed the anatomy of spinal cord vessels. The pathophysiology of spinal cord injuries revealed two types of pathogenic mechanisms. The primary event, the mechanic trauma, results in a disruption of neural and vascular structures into the spinal cord. It is followed by secondary pathogenesis that leads to the progression of the initial lesion. We reviewed vascular responses following spinal cord injury, focusing on both primary and secondary events. The intraparenchymal hemorrhage is a direct consequence of trauma; it has a typical pattern of distribution into the contused spinal cord, inside the gray matter and, it is radially extended into the white matter. The intraparenchymal hemorrhage is restricted to the dorsal columns, into adjacent rostral and caudal spinal segments. Distribution of chronic lesions overlaps the pattern of the early intraparenchymal hemorrhage. We described the mechanisms of action, role, induction and distribution of the heme oxygenase isoenzymes 1 and 2. Posttraumatic inflammatory response contributes to secondary pathogenesis. We analyzed the types of cells participating in the inflammatory response, the moment of appearance after the injury, the decrease in number, and the nature of their actions. The disruption of the blood–spinal cord barrier is biphasic. It exposes the spinal cord to inflammatory cells and to toxic effects of other molecules. Endothelin 1 mediates oxidative stress into the spinal cord through the modulation of spinal cord blood flow. The role of matrix metalloproteinases in blood–spinal cord barrier disruption, inflammation, and angiogenesis are reviewed. PMID:20945816

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

2010-01-01

43

Spinal Cord Injury: Facts and Figures at a Glance  

MedlinePLUS

... National SCI Database. The National Spinal Cord Injury Database has been in existence since 1973 and captures ... Systems have contributed data to the National SCI Database. As of December 2011, the database contained information ...

44

Characterization of Morphine Self-Administration Following Spinal Cord Injury  

E-print Network

spinal injury. These experiments used a clinically relevant self-administration paradigm to examine both addiction and functional recovery after morphine administration. To assess morphine administration in the acute phase of SCI, animals were placed...

Woller, Sarah Ann

2013-07-16

45

Nanomedicine strategies for treatment of secondary spinal cord injury  

PubMed Central

Neurological injury, such as spinal cord injury, has a secondary injury associated with it. The secondary injury results from the biological cascade after the primary injury and affects previous uninjured, healthy tissue. Therefore, the mitigation of such a cascade would benefit patients suffering a primary injury and allow the body to recover more quickly. Unfortunately, the delivery of effective therapeutics is quite limited. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Incorporating nanomedicine into the treatment of neuronal injury and disease would likely push nanomedicine into a new light. This review highlights the various pathological issues involved in secondary spinal cord injury, current treatment options, and the improvements that could be made using a nanomedical approach.

White-Schenk, Désirée; Shi, Riyi; Leary, James F

2015-01-01

46

Recovery of airway protective behaviors after spinal cord injury  

PubMed Central

Pulmonary morbidity is high following spinal cord injury and is due, in part, to impairment of airway protective behaviors. These airway protective behaviors include augmented breaths, the cough reflex, and expiration reflexes. Functional recovery of these behaviors has been reported after spinal cord injury. In humans, evidence for functional recovery is restricted to alterations in motor strategy and changes in the frequency of occurrence of these behaviors. In animal models, compensatory alterations in motor strategy have been identified. Crossed descending respiratory motor pathways at the thoracic spinal cord levels exist that are composed of crossed premotor axons, local circuit interneurons, and propriospinal neurons. These pathways can collectively form a substrate that supports maintenance and/or recovery of function, especially after asymmetric spinal cord injury. Local sprouting of premotor axons in the thoracic spinal cord also can occur following chronic spinal cord injury. These mechanisms may contribute to functional resiliency of the cough reflex that has been observed following chronic spinal cord injury in the cat. PMID:19635591

Bolser, Donald C.; Jefferson, Stephanie C.; Rose, Melanie J.; Tester, Nicole J.; Reier, Paul J.; Fuller, David D.; Davenport, Paul W.; Howland, Dena R.

2009-01-01

47

Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury  

PubMed Central

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

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

2014-01-01

48

Cooling athletes with a spinal cord injury.  

PubMed

Cooling strategies that help prevent a reduction in exercise capacity whilst exercising in the heat have received considerable research interest over the past 3 decades, especially in the lead up to a relatively hot Olympic and Paralympic Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de Janeiro, could again present an environmental challenge for competing athletes. Despite the interest and vast array of research into cooling strategies for the able-bodied athlete, less is known regarding the application of these cooling strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic population. Individuals with a spinal cord injury (SCI) have a reduced afferent input to the thermoregulatory centre and a loss of both sweating capacity and vasomotor control below the level of the spinal cord lesion. The magnitude of this thermoregulatory impairment is proportional to the level of the lesion. For instance, individuals with high-level lesions (tetraplegia) are at a greater risk of heat illness than individuals with lower-level lesions (paraplegia) at a given exercise intensity. Therefore, cooling strategies may be highly beneficial in this population group, even in moderate ambient conditions (~21 °C). This review was undertaken to examine the scientific literature that addresses the application of cooling strategies in individuals with an SCI. Each method is discussed in regards to the practical issues associated with the method and the potential underlying mechanism. For instance, site-specific cooling would be more suitable for an athlete with an SCI than whole body water immersion, due to the practical difficulties of administering this method in this population group. From the studies reviewed, wearing an ice vest during intermittent sprint exercise has been shown to decrease thermal strain and improve performance. These garments have also been shown to be effective during exercise in the able-bodied. Drawing on additional findings from the able-bodied literature, the combination of methods used prior to and during exercise and/or during rest periods/half-time may increase the effectiveness of a strategy. However, due to the paucity of research involving athletes with an SCI, it is difficult to establish an optimal cooling strategy. Future studies are needed to ensure that research outcomes can be translated into meaningful performance enhancements by investigating cooling strategies under the constraints of actual competition. Cooling strategies that meet the demands of intermittent wheelchair sports need to be identified, with particular attention to the logistics of the sport. PMID:25119157

Griggs, Katy E; Price, Michael J; Goosey-Tolfrey, Victoria L

2015-01-01

49

National survey of spinal injuries in hockey players.  

PubMed

There has been an alarming increase in the number of spinal injuries in hockey players. Between 1976 and 1983, 42 were reported to the Committee on Prevention of Spinal Injuries due to Hockey. The median age of the injured players was 17 years. Of the 42 players 28 had spinal cord injuries, and 17 of them had complete paralysis below the vertebral level of the injury. Strikes from behind and collisions with the boards were common mechanisms of injury. Many of the players had suffered a burst fracture of the cervical spine following a blow to the top of the helmet when the neck was slightly flexed. The committee studied a number of possible etiologic factors and made several recommendations regarding prevention. League officials, coaches, players and equipment manufacturers can all play a role in prevention. PMID:6704840

Tator, C H; Edmonds, V E

1984-04-01

50

Reshaping the chromatin landscape after spinal cord injury  

PubMed Central

The pathophysiology underlying spinal cord injury is complex. Mechanistic understanding of the adaptive responses to injury is critical for targeted therapy aimed at reestablishing lost connections between proximal and distal neurons. After injury, cell-type specific gene transcription programs govern distinct cellular behaviors, and chromatin regulators play a central role in shaping the chromatin landscape to adjust transcriptional profiles in a context-dependent manner. In this review, we summarize recent progress on the pleiotropic roles of chromatin regulators in mediating the diverse adaptive behaviors of neurons and glial cells after spinal cord injury, and wherever possible, discuss the underlying mechanisms and genomic targets. We specifically draw attention to the perspective that takes into consideration the impact of epigenetic modulation on axon growth potential, together with its effect on wound-healing properties of glial cells. Epigenetic modulation of chromatin state represents an emerging therapeutic direction to promote neural repair and axon regeneration after spinal cord injury.

WONG, Jamie K.; ZOU, Hongyan

2014-01-01

51

Temporal modifications in bone following spinal cord injury in rats  

PubMed Central

Introduction The aim of this study was to investigate the temporal modifications in bone mass, bone biomechanical properties and bone morphology in spinal cord injured rats 2, 4 and 6 weeks after a transection. Material and methods Control animals were randomly distributed into four groups (n = 10 each group): control group (CG) – control animals sacrificed immediately after surgery; spinal cord-injured 2 weeks (2W) – spinal cord-injured animals sacrificed 2 weeks after surgery; spinal cord-injured 4 weeks (4W) – spinal cord-injured animals sacrificed 4 weeks after surgery; spinal cord-injured 6 weeks (6W) – spinal cord-injured animals sacrificed 6 weeks after surgery. Results Biomechanical properties of the right tibia were determined by a three-point bending test and injured animals showed a statistically significant decrease in maximal load compared to control animals. The right femur was used for densitometric analysis and bone mineral content of the animals sacrificed 4 and 6 weeks after surgery was significantly higher compared to the control animals and animals sacrificed 2 weeks after surgery. Histopathological and morphological analysis of tibiae revealed intense resorptive areas in the group 2 weeks after injury only. Conclusions The results of this study show that this rat model is a valuable tool to investigate bone remodeling processes specifically associated with SCI. Taken together, our results suggest that spinal cord injury induced bone loss within 2 weeks after injury in rats. PMID:23319988

Amorim, Beatriz Oliveira; Fernandes, Kelly Rosseti; Pereira, Rosa Maria; Renno, Ana Cláudia Muniz; Ribeiro, Daniel Araki

2012-01-01

52

Spinal Injury: Regeneration, Recovery, and a Possible New Approach  

SciTech Connect

Spinal injury is most frequent in young healthy men, desperate to walk. Most treatments have focused on regeneration of the injured axons, but no one has as yet achieved success with this approach. However, in the lamprey, a primitive fish with a spinal cord having all the critical features of the human spinal cored, spinal injury is followed by complete regeneration of injured axons. Additionally, the animal recovers the ability to swim, and in many, the swimming is normal. Unfortunately, in most others, it is highly abnormal. This talk will review evidence from the abnormal regeneration, why it bespeaks difficulties heretofore not considered, and suggest an alternate approach for the near future. In so doing, the speaker will introduce the normal function of the spinal cord, what happens in normal and abnormal regeneration, and the new techniques that employ methods from neuromorphic engineering, a synthesis of neuroscience and engineering to engineer smart devices.

Cohen, Avis (U of Maryland, Dept of Biology) [U of Maryland, Dept of Biology

2009-02-04

53

Chronic complications of spinal cord injury.  

PubMed

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

Sezer, Nebahat; Akku?, Selami; U?urlu, Fatma Gülçin

2015-01-18

54

Chronic complications of spinal cord injury  

PubMed Central

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

Sezer, Nebahat; Akku?, Selami; U?urlu, Fatma Gülçin

2015-01-01

55

Causes and control of spinal cord injury in automotive crashes  

Microsoft Academic Search

This paper provides a history of automotive safety and a review of biomedical research on human tolerance and occupant protection. It discusses current understandings of body kinematics and impact biomechanics that result in neck injury. Perspective is given on the linkage between mechanical forces that are the cause and physiologic disruptions that are the consequence of spinal cord injury. The

David C. Viano

1992-01-01

56

The Role of Hope in Spinal Cord Injury Rehabilitation.  

ERIC Educational Resources Information Center

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…

Heinemann, Allen; And Others

57

Trajectories of Resilience, Depression, and Anxiety Following Spinal Cord Injury  

Microsoft Academic Search

Purpose\\/Objective: To investigate longitudinal trajectories of depression and anxiety symptoms following spinal cord injury (SCI) as well as the predictors of those trajectories. Research Method\\/Design: A longitudinal study of 233 participants assessed at 4 time points: within 6 weeks, 3 months, 1 year, and 2 years from the point of injury. Data were analyzed using latent growth mixture modeling to

George A. Bonanno; Paul Kennedy; Isaac R. Galatzer-Levy; Peter Lude; Mangus L. Elfström

2012-01-01

58

Perspectives on the treatment of the longitudinal spinal cord injury.  

PubMed

The current technique for surgical treatment of the longitudinal spinal cord injury has proven to be successful for restoration of some motor function and alleviation of pain. This has been the first step in finding a cure for spinal cord injuries, but so far there are many obstacles still to be overcome. In this particular injury return of function from spinal cord surgery is only partial. Some of the main remaining problems are related to injury-induced neuronal death, direction and specificity of regeneration and muscle, and receptor disintegration from long time denervation. Currently this is a surgical procedure without any adjuvant treatments. In order to gain further functional improvement combinational therapies developed in basic science experiments are essential. PMID:21206763

Carlstedt, Thomas

2010-01-01

59

Risk Factors for Chest Illness in Chronic Spinal Cord Injury  

PubMed Central

Objective Chest illnesses commonly cause morbidity in persons with chronic spinal cord injury. Risk factors remain poorly characterized because previous studies have not accounted for factors other than spinal cord injury. Design Between 1994 and 2005, 403 participants completed a respiratory questionnaire and underwent spirometry. Participants were contacted at a median of 1.7 yrs [interquartile range: 1.3–2.5 yrs] apart over a mean (SD) of 5.1 ± 3.0 yrs and asked to report chest illnesses that had resulted in time off work, spent indoors, or in bed since prior contact. Results In 97 participants, there were 247 chest illnesses (0.12/person-year) with 54 hospitalizations (22%). Spinal cord injury level, completeness of injury, and duration of injury were not associated with illness risk. Adjusting for age and smoking history, any wheeze (relative risk = 1.92; 95% confidence interval: 1.19, 3.08), pneumonia or bronchitis since spinal cord injury (relative risk = 2.29; 95% confidence interval: 1.40, 3.75), and physician-diagnosed chronic obstructive pulmonary disease (relative risk = 2.17; 95% confidence interval: 1.08, 4.37) were associated with a greater risk of chest illness. Each percent-predicted decrease in forced expiratory volume in 1 sec was associated with a 1.2% increase in risk of chest illness (P = 0.030). Conclusions In chronic spinal cord injury, chest illness resulting in time spent away from usual activities was not related to the level or completeness of spinal cord injury but was related to reduced pulmonary function, wheeze, chronic obstructive pulmonary disease, a history of pneumonia and bronchitis, and smoking. PMID:20463565

Stolzmann, Kelly L.; Gagnon, David R.; Brown, Robert; Tun, Carlos G.; Garshick, Eric

2011-01-01

60

Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries  

PubMed Central

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

Straley, Karin S.; Po Foo, Cheryl Wong

2010-01-01

61

[Unilateral, paramedian spinal contusion after athletic injury with complete recovery].  

PubMed

The acute injury of the spinal column and the spinal cord asks for immediate diagnostic techniques and adequate therapeutical intensive care in order to secure the possibility of a maximum of neurologic recovery. An impact trauma of the spinal cord in sports accidents can cause an incomplete paraplegia. In some cases, morphologic lesions of the myelon cannot be detected. We present an exceptional and striking case of a 15-year old young woman who suffered from a contusio spinalis after high jump with the clinical signs of an incomplete, sensomotoric paraplegia which showed a strictly unilateral and paramedian border at the right side of her body for about two weeks. Additionally, the diagnostic possibilities of physical examination, magnetic resonance imaging, computed tomography and neurophysiologic diagnostic techniques in detecting spinal cord injuries are demonstrated. PMID:7778020

Ebert, B; Badke, A

1995-03-01

62

Rodent Models and Behavioral Outcomes of Cervical Spinal Cord Injury  

PubMed Central

Rodent spinal cord injury (SCI) models have been developed to examine functional and physiological deficits after spinal cord injury with the hope that these models will elucidate information about human SCI. Models are needed to examine possible treatments and to understand histopathology after SCI; however, they should be considered carefully and chosen based on the goals of the study being performed. Contusion, compression, transection, and other models exist and have the potential to reveal important information about SCI that may be related to human SCI and the outcomes of treatment and timing of intervention. PMID:25309824

Geissler, Sydney A.; Schmidt, Christine E.; Schallert, Timothy

2014-01-01

63

Life stress and psychologic adjustment following spinal cord injury.  

PubMed

Previous research on psychologic adjustment following spinal cord injury has not systematically investigated the impact of negative life events from contemporary perspectives. In order to examine the effects of life stress on adjustment, 53 spinal cord injured patients were assessed by the Symptom Checklist-90, Beck Depression Inventory, and a measure of life events. Patients who were experiencing higher subjective levels of life stress displayed more distress than those reporting lower levels of life stress. The findings were not mediated by the passage of time since injury. PMID:3592946

Frank, R G; Elliott, T R

1987-06-01

64

Nonfatal All-Terrain Vehicle-Related Injuries to Youths Living on Farms in the United States, 2001  

ERIC Educational Resources Information Center

Use of all-terrain vehicles (ATVs) in agriculture appears to be growing. Purpose: To provide estimates of ATV ownership and exposure on US farms and an overview of injuries to youths as a result of ATV use on the farm in 2001. Methods: Analysis of the National Institute for Occupational Safety and Health and US Department of Agriculture 2001…

Goldcamp, E. Michael; Myers, John; Hendricks, Kitty; Layne, Larry; Helmkamp, Jim

2006-01-01

65

Labour market outcomes for people with a spinal cord injury.  

PubMed

The consequences of spinal cord injury are profound and extend well beyond the immediate loss of mobility and sensation. Employment is a well-recognised rehabilitation goal. In this study, we examine the impact of a publicly funded "package" of services that is designed to enable people with a spinal cord injury to return to the workplace. Specifically, this package of services provided client directed assistance for assisting the recipient with the activities of daily living (e.g., bathing, food preparation, etc.). We combine primary data collection methods well developed in other scientific disciplines, but less frequently utilised within economics, with traditional econometric techniques, to present a novel approach to this methodological issue. The Spinal Injuries Survey Instrument was developed and administered using a matched sampling approach. Collected data included, labour market outcomes, exposure to the packages, as well as clinical and demographic covariates commonly identified by the spinal cord injury literature. Concern for endogeneity was addressed by collecting data on several variables that might serve as suitable instruments for the econometric work and measures of otherwise-unobserved sources of heterogeneity. For example, a psychological measure of "attributional style was adapted from the field of psychology in order to control for a potentially confounding source of latent individual heterogeneity, viz. "motivation". While our results find zero marginal effect of support packages on labour market outcomes, we find that training undertaken post-injury and age are both positively correlated with labour market participation. PMID:20605751

Rowell, David; Connelly, Luke

2010-07-01

66

Acute Leptin Treatment Enhances Functional Recovery after Spinal Cord Injury  

PubMed Central

Background Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury. Findings Based on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning. Conclusions Our data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent. PMID:22536415

Fernández-Martos, Carmen María; González, Pau; Rodriguez, Francisco Javier

2012-01-01

67

Cortical reorganization after spinal cord injury: always for good?  

PubMed

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

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

2014-12-26

68

Alternative, complementary, energy-based medicine for spinal cord injury  

Microsoft Academic Search

This paper provides an overview on various alternative, complementary, or energy-based therapies that expand the healing spectrum\\u000a of individuals with spinal cord injury (SCI). Not only do they have the capability to help a variety of secondary conditions,\\u000a they have the ability in some people, for certain injuries, to restore function, sometimes dramatically. After providing an\\u000a overall contextual rationale for

L. Johnston

69

Post traumatic stress disorder and spinal cord injuries  

Microsoft Academic Search

Post Traumatic Stress Disorder (PTSD) was first recognised by psychiatric international classification systems in 1980 and a wealth of research and treatment literature has developed since. This paper provides a review of PTSD and Spinal Cord Injuries. A brief history of the disorder is provided before descriptions of the defining characteristics, assessment and differential diagnoses. The paper provides an overview

Paul Kennedy; Jane Duff

2001-01-01

70

Substance Use by Persons with Recent Spinal Cord Injuries.  

ERIC Educational Resources Information Center

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…

Heinemann, Allen W.; And Others

71

Drinking Patterns, Drinking Expectancies, and Coping after Spinal Cord Injury.  

ERIC Educational Resources Information Center

Drinking patterns, alcohol expectancies, and coping strategies were assessed for 121 persons with recent spinal cord injuries during hospitalization, 3 months after surgery, and 12 months after surgery. Although the rate of heavy drinking decreased, preinjury problem drinkers still had the lowest rate of positive reappraisal, problem solving, and…

Heinemann, Allen W.; And Others

1994-01-01

72

Chronic cervical spinal cord injury and autonomic hyperreflexia in rats  

E-print Network

describethe preparation and characterization of a rat modelof chronic cervical spinal cord injury andautonomic hyperreflexia. Adult male Sprague-Dawley rats were chroni- cally instrumentedwith arterial, venous hypertensive responsesto amodestincreaseof urinary bladderpressure(O- 20mmHg)werestudied. Mean arterial

Schramm, Lawrence P.

73

Extinction and synesthesia in patients with spinal cord injuries  

Microsoft Academic Search

Extinction and synesthesia were studied in 50 patients with spinal cord injury with various levels and extents. Extinction was found in 20 (40 per cent) and synesthesia in 6 (12 per cent) of the 40 males and 10 females. No correlations were found between either of the two phenomena and parameters of patient's age, lesion's age, lesion's level and extent,

Ernest Bors

1979-01-01

74

Autonomic nervous system dysfunction after spinal cord injury.  

PubMed

The autonomic nervous system (ANS) plays a key role in the regulation of many physiologic processes, mediated by supraspinal control from centers in the central nervous system. The role of autonomic dysfunction in persons with spinal cord injuries is crucial to understand because many aspects of the altered physiology seen in these individuals are directly caused by ANS dysregulation. PMID:17543773

Garstang, Susan V; Miller-Smith, Stacey A

2007-05-01

75

Abdominal hollow viscus injuries are associated with spine and neurologic infections after penetrating spinal cord injuries.  

PubMed

Penetrating spinal cord injuries are rare but potentially devastating injuries that are associated with significant morbidity. The objective of this study was to assess the impact of abdominal hollow viscus injuries (HVIs) on neurologic and spinal infectious complications in patients sustaining penetrating spinal cord injuries. We performed a 13-year retrospective review of a Level I trauma center database. Variables analyzed included demographics, injury patterns and severity, spine operations, and outcomes. Spine and neurologic infections (SNIs) were defined as paraspinal or spinal abscess, osteomyelitis, and meningitis. Multivariate analysis was performed to identify factors associated with SNI. Of 137 patients, there were 126 males (92%) with a mean age of 27 ± 10 years. Eight patients (6%) underwent operative stabilization of their spine. Fifteen patients (11%) developed SNI. There was a higher incidence of SNI among patients with abdominal HVI compared with those without (eight [26%] vs six [6%], P < 0.001). On multivariate analysis, after controlling for injury severity, solid abdominal injury and HVI, vascular injury, and spine operation, abdominal HVIs were independently associated with an increased risk for SNI (odds ratio, 6.88; 95% confidence interval, 2.14 to 22.09; P = 0.001). Further studies are required to determine the optimal management strategy to prevent and successfully treat these infections. PMID:25264640

Schwed, Alexander C; Plurad, David S; Bricker, Scott; Neville, Angela; Bongard, Fred; Putnam, Brant; Kim, Dennis Y

2014-10-01

76

Prevalence and incidence of pressure sores in acute spinal cord injuries  

Microsoft Academic Search

The prevalence of pressure sores following acute spinal cord injury was determined on 549 patients who entered the Midwest Regional Spinal Cord Injury Care Centre from 1973 until June 1978- The compiled data was based upon system versus non-system entry, anatomical levels of injury, multiple site or single site location, complete or incomplete physiological injury, and the presence of pressure

Robert R Richardson; Paul R Meyer

1981-01-01

77

Endogenous Proliferation after Spinal Cord Injury in Animal Models  

PubMed Central

Spinal cord injury (SCI) results in motor and sensory deficits, the severity of which depends on the level and extent of the injury. Animal models for SCI research include transection, contusion, and compression mouse models. In this paper we will discuss the endogenous stem cell response to SCI in animal models. All SCI animal models experience a similar peak of cell proliferation three days after injury; however, each specific type of injury promotes a specific and distinct stem cell response. For example, the transection model results in a strong and localized initial increase of proliferation, while in contusion and compression models, the initial level of proliferation is lower but encompasses the entire rostrocaudal extent of the spinal cord. All injury types result in an increased ependymal proliferation, but only in contusion and compression models is there a significant level of proliferation in the lateral regions of the spinal cord. Finally, the fate of newly generated cells varies from a mainly oligodendrocyte fate in contusion and compression to a mostly astrocyte fate in the transection model. Here we will discuss the potential of endogenous stem/progenitor cell manipulation as a therapeutic tool to treat SCI. PMID:23316243

McDonough, Ashley; Martínez-Cerdeño, Verónica

2012-01-01

78

Spinal Cord Injury Without Radiological Abnormality in Adult Thoracic Spinal Trauma  

PubMed Central

Introduction: Spinal cord injury without radiological abnormality (SCIWORA) is a rare entity and usually involves the cervical spine. Thoracic spine involvement is very rare due to the stability provided by the rib cage. The mechanisms of injury and pathophysiology are still debatable. Case Presentation: We present a case of an adult male who had road traffic accident and presented with paraplegia. The initial radiological investigations carried out in the emergency department were reported to be normal, however, subsequent magnetic resonance imaging revealed spinal cord contusion without vertebral column disruption. The patient recovered partially with conservative treatment measures including bed rest and methylprednisolone. Conclusions: Spinal trauma patients presenting with neurological deficit but no radiological abnormality should be treated as a case of SCIWORA. PMID:25599065

Khatri, Kavin; Farooque, Kamran; Gupta, Ankit; Sharma, Vijay

2014-01-01

79

Advances in the management of spinal cord and spinal column injuries.  

PubMed

Spinal cord injury (SCI) is a significant public problem, with recent data suggesting that over 1 million people in the U.S.A. alone are affected by paralysis resulting from SCI. Recent advances in prehospital care have improved survival as well as reduced incidence and severity of SCI following spine trauma. Furthermore, increased understanding of the secondary mechanisms of injury following SCI has provided improvements in critical care and acute management in patients suffering from SCI, thus limiting morbidity following injury. In addition, improved technology and biomechanical understanding of the mechanisms of spine trauma have allowed further advances in available techniques for spinal decompression and stabilization. In this chapter we review the most recent data and salient literature regarding SCI and address current controversies, including the use of pharmacological adjuncts in the setting of acute SCI. We will also attempt to provide a reader with basic understanding of the classifications of SCI and spinal column injury. Finally, we review advances in spinal column stabilization including improvements in instrumented fusion and minimally invasive surgery. PMID:23098709

Taghva, Alexander; Hoh, Daniel J; Lauryssen, Carl L

2012-01-01

80

A novel porcine model of traumatic thoracic spinal cord injury.  

PubMed

Spinal cord injury (SCI) researchers have predominately utilized rodents and mice for in vivo SCI modeling and experimentation. From these small animal models have come many insights into the biology of SCI, and a growing number of novel treatments that promote behavioral recovery. It has, however, been difficult to demonstrate the efficacy of such treatments in human clinical trials. A large animal SCI model that is an intermediary between rodent and human SCI may be a valuable translational research resource for pre-clinically evaluating novel therapies, prior to embarking upon lengthy and expensive clinical trials. Here, we describe the development of such a large animal model. A thoracic spinal cord injury at T10/11 was induced in Yucatan miniature pigs (20-25?kg) using a weight drop device. Varying degrees of injury severity were induced by altering the height of the weight drop (5, 10, 20, 30, 40, and 50?cm). Behavioral recovery over 12 weeks was measured using a newly developed Porcine Thoracic Injury Behavior Scale (PTIBS). This scale distinguished locomotor recovery among animals of different injury severities, with strong intra-observer and inter-observer reliability. Histological analysis of the spinal cords 12 weeks post-injury revealed that animals with the more biomechanically severe injuries had less spared white matter and gray matter and less neurofilament immunoreactivity. Additionally, the PTIBS scores correlated strongly with the extent of tissue sparing through the epicenter of injury. This large animal model of SCI may represent a useful intermediary in the testing of novel pharmacological treatments and cell transplantation strategies. PMID:23316955

Lee, Jae H T; Jones, Claire F; Okon, Elena B; Anderson, Lisa; Tigchelaar, Seth; Kooner, Paul; Godbey, Tamara; Chua, Bev; Gray, Gordon; Hildebrandt, Rhonda; Cripton, Peter; Tetzlaff, Wolfram; Kwon, Brian K

2013-02-01

81

Effects of injury level and severity on direct costs of care for acute spinal cord injury.  

PubMed

New treatments are being investigated for spinal cord injury (SCI), and any improvement may result in incremental cost savings. The objective of this study was to determine the direct costs of care 2 years after an SCI, stratifying for completeness and level of injury. A retrospective database analysis was carried out using data from the Quebec Trauma Registry, the Quebec Medical Insurance Board, and the Quebec Automobile Insurance Corporation between 1997 and 2007. Excluding individuals sustaining moderate or severe traumatic brain injuries, 481 individuals who sustained an SCI from motor vehicle accidents were identified. Individuals were classified as complete and incomplete in the following categories: C1-C7, C8-T6, T7-L1, L2-S5. Using data from governmental public healthcare organizations makes this study comprehensive. For C1-C7 complete and incomplete spinal cord injuries, the first-year cost was $157?718 and $56?505, respectively (2009 Canadian dollars calculated per patient). Similar differences between complete and incomplete spinal cord injuries were seen for the other groups. Furthermore, for complete injuries, costs were higher for higher levels of injury during both the first and the second year after injury. For incomplete lesions, costs did not differ significantly between groups during the first or the second year. Incomplete spinal cord injuries result in lower healthcare costs compared with complete injuries across all groups during the first 2 years after injury. As less severe levels of injury result in measurably lower costs, the funds spent to reduce the severity or level of SCI could at least partially be recouped through healthcare savings. PMID:25192008

Radhakrishna, Mohan; Makriyianni, Ioli; Marcoux, Judith; Zhang, Xun

2014-12-01

82

Electrical stimulation modulates injury potentials in rats after spinal cord injury  

PubMed Central

An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around –70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx. PMID:25206563

Zhang, Guanghao; Huo, Xiaolin; Wang, Aihua; Wu, Changzhe; Zhang, Cheng; Bai, Jinzhu

2013-01-01

83

Gastrointestinal transit after spinal cord injury: effect of cisapride.  

PubMed

Heartburn, bloating, and abdominal discomfort are common problems in patients with spinal cord injury but, despite its clinical significance, little is known about the gastrointestinal effects of spinal transections. To address the potential gastrointestinal pathophysiology of spinal cord injury, we measured mouth-to-cecum transit time (MCTT) in seven subjects with paraplegia and seven with quadriplegia. Gastric emptying was studied in six subjects with quadriplegia. MCTT was significantly prolonged in patients with quadriplegia, an abnormality corrected by the administration of cisapride. Patients with paraplegia, in contrast to those with quadriplegia, have normal mouth-to-cecum transit time. In addition, patients with quadriplegia had neither a prolonged gastric emptying time nor a change in gastric emptying time, with cisapride. Changes in gastrointestinal transit after spinal cord injury and the improvement of mouth-to-cecum transit time in subjects with quadriplegia, but not in those with paraplegia, may be explained by an imbalance between parasympathetic and sympathetic outflows to the gastrointestinal tract in this group of subjects. PMID:1442685

Rajendran, S K; Reiser, J R; Bauman, W; Zhang, R L; Gordon, S K; Korsten, M A

1992-11-01

84

Male fertility and sexual function after spinal cord injury.  

PubMed

Spinal cord injury has an enormous impact upon the sexual relationship of a man and his partner. Erection may be partial or absent, orgasm altered or impossible, and fertility severely impaired. New understanding of the physiology of sexual function and improved treatment can enable most cord-injured men to achieve erections suitable for sexual satisfaction. Modern methods of sperm collection and fertility treatment mean that many can also be fathers. The best results are obtained by a team approach involving rehabilitation and reproductive medicine clinicians, nurses, spinal cord injury specialists and counselors with the cord-injured man and his partner. Erections can be achieved by drugs, such as sildenafil, that block phosphodiesterase 5, prolonging the action of nitric oxide with resultant smooth muscle relaxation. Intracavernosal prostaglandin E1 and mechanical systems, such as vacuum pumps and constriction rings, are also effective. Sexual gratification can be promoted in the context of an understanding relationship in which the cord-injured person can gain pleasure from pleasing his partner and also from his partner's exploration of erotogenic areas not affected by the spinal cord injury. An emphasis on the broader view of sexuality in relationships allows for a continuance and strengthening of bonds between the couple. Vibration ejaculation or electroejaculation can be used to collect semen. For a limited period in the acute phase, usually for about 6-12 days after injury, normal semen can be obtained by electroejaculation from some cord-injured men. With chronic spinal cord injury the semen is of variable quality. Some patients have necrospermia, which may be improved by regular ejaculation. Others have poor quality semen or spermatogenic disorders and, in this situation, in vitro fertilization techniques must be used to achieve parenthood. Trials of assisted ejaculation help individualize cost-effective management of the infertility. PMID:16198718

Brown, D J; Hill, S T; Baker, H W G

2006-01-01

85

Re-expression of Locomotor Function After Partial Spinal Cord Injury  

NSDL National Science Digital Library

After a complete spinal section, quadruped mammals (cats, rats, and mice) can generally regain hindlimb locomotion on a treadmill because the spinal cord below the lesion can express locomotion through a neural circuitry termed the central pattern generator (CPG). In this review, we propose that the spinal CPG also plays a crucial role in the locomotor recovery after incomplete spinal cord injury.

G. Barriere (Universite de Montreal)

2009-04-01

86

Assessment of Hyperactive Reflexes in Patients with Spinal Cord Injury  

PubMed Central

Hyperactive reflexes are commonly observed in patients with spinal cord injury (SCI) but there is a lack of convenient and quantitative characterizations. Patellar tendon reflexes were examined in nine SCI patients and ten healthy control subjects by tapping the tendon using a hand-held instrumented hammer at various knee flexion angles, and the tapping force, quadriceps EMG, and knee extension torque were measured to characterize patellar tendon reflexes quantitatively in terms of the tendon reflex gain (Gtr), contraction rate (Rc), and reflex loop time delay (td). It was found that there are significant increases in Gtr and Rc and decrease in td in patients with spinal cord injury as compared to the controls (P < 0.05). This study presented a convenient and quantitative method to evaluate reflex excitability and muscle contraction dynamics. With proper simplifications, it can potentially be used for quantitative diagnosis and outcome evaluations of hyperreflexia in clinical settings. PMID:25654084

Yang, Chung-Yong

2015-01-01

87

Spinal cord injury: a 25-year morbidity and mortality study.  

PubMed

The morbidity and mortality occurring during 25 years following spinal cord injury were analyzed. A cohort of 230 patients was selected from the Vietnam Head and Spinal Cord Injury Study Registry meeting the following criteria: (1) survival beyond triage (72 hours); (2) significant myelopathy; and (3) availability of medical records. The military and Veteran's Hospital medical records were compiled and reviewed. Additional death records were obtained from the Department of Veterans Affairs pension office. The major morbidity problems continue to be sepsis related to genitourinary and decubiti sequelae. Psychosocial maladjustment and substance abuse were prevalent and created heavy health care demand. The most frequent cause of death was sepsis. Suicide in the paraplegic group occurred at a rate exceeding by 10 times the frequency reported for uninjured peers. Survival after 5 years approached but never reached the rate established for uninjured peers. PMID:9038035

Rish, B L; Dilustro, J F; Salazar, A M; Schwab, K A; Brown, H R

1997-02-01

88

Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury  

PubMed Central

Spinal cord injury (SCI) is a serious disease of the center nervous system (CNS). It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET), magnetic resonance imaging (MRI), optical imaging (i.e., bioluminescence imaging (BLI)) gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI. PMID:24701583

Tian, Mei; Zhang, Hong

2014-01-01

89

Activity-dependent plasticity in spinal cord injury  

PubMed Central

The adult mammalian central nervous system (CNS) is capable of considerable plasticity, both in health and disease. After spinal neurotrauma, the degrees and extent of neuroplasticity and recovery depend on multiple factors, including the level and extent of injury, postinjury medical and surgical care, and rehabilitative interventions. Rehabilitation strategies focus less on repairing lost connections and more on influencing CNS plasticity for regaining function. Current evidence indicates that strategies for rehabilitation, including passive exercise, active exercise with some voluntary control, and use of neuroprostheses, can enhance sensorimotor recovery after spinal cord injury (SCI) by promoting adaptive structural and functional plasticity while mitigating maladaptive changes at multiple levels of the neuraxis. In this review, we will discuss CNS plasticity that occurs both spontaneously after SCI and in response to rehabilitative therapies. PMID:18566941

Lynskey, James V.; Belanger, Adam; Jung, Ranu

2008-01-01

90

Spinal Cord Injury—Past, Present, and Future  

PubMed Central

Summary: This special report traces the path of spinal cord injury (SCI) from ancient times through the present and provides an optimistic overview of promising clinical trials and avenues of basic research. The spinal cord injuries of Lord Admiral Sir Horatio Nelson, President James A. Garfield, and General George Patton provide an interesting perspective on the evolution of the standard of care for SCI. The author details the contributions of a wide spectrum of professionals in the United States, Europe, and Australia, as well as the roles of various government and professional organizations, legislation, and overall advances in surgery, anesthesia, trauma care, imaging, pharmacology, and infection control, in the advancement of care for the individual with SCI. PMID:17591221

Donovan, William H

2007-01-01

91

Return of spinal reflex after spinal cord surgery for brachial plexus avulsion injury.  

PubMed

Motor but not sensory function has been described after spinal cord surgery in patients with brachial plexus avulsion injury. In the featured case, motor-related nerve roots as well as sensory spinal nerves distal to the dorsal root ganglion were reconnected to neurons in the ventral and dorsal horns of the spinal cord by implanting nerve grafts. Peripheral and sensory functions were assessed 10 years after an accident and subsequent spinal cord surgery. The biceps stretch reflex could be elicited, and electrophysiological testing demonstrated a Hoffman reflex, or Hreflex, in the biceps muscle when the musculocutaneous nerve was stimulated. Functional MR imaging demonstrated sensory motor cortex activities on active as well as passive elbow flexion. Quantitative sensory testing and contact heat evoked potential stimulation did not detect any cutaneous sensory function, however. To the best of the authors' knowledge, this case represents the first time that spinal cord surgery could restore not only motor function but also proprioception completing a spinal reflex arch. PMID:21838504

Carlstedt, Thomas; Misra, V Peter; Papadaki, Anastasia; McRobbie, Donald; Anand, Praveen

2012-02-01

92

Low-level laser therapy for spinal cord injury in rats: effects of polarization  

E-print Network

The effects of laser polarization on the efficacy of near-infrared low-level laser therapy for spinal cord injury (SCI) are presented. Rat spinal cords were injured with a weight-drop device, and the lesion sites were ...

Ando, Takahiro

93

Review Article Hypothermia for spinal cord injury  

Microsoft Academic Search

BACKGROUND CONTEXT: Interest in systemic and local hypothermia extends back over many decades, and both have been investigated as potential neuroprotective interventions in a number of clinical settings, including traumatic brain injury, stroke, cardiac arrest, and both intracranial and thoracoabdominal aortic aneurysm surgery. The recent use of systemic hypothermia in an injured National Football League football player has focused a

Brian K. Kwon; Cody Mann; Hong Moon Sohn; Alan S. Hilibrand; Frank M. Phillips; Jeffrey C. Wang; Michael G. Fehlings; Heather Pavilion

94

Development and Treatments of Inflammatory Cells and Cytokines in Spinal Cord Ischemia-Reperfusion Injury  

PubMed Central

During aortic surgery, interruption of spinal cord blood flow might cause spinal cord ischemia-reperfusion injury (IRI). The incidence of spinal cord IRI after aortic surgery is up to 28%, and patients with spinal cord IRI might suffer from postoperative paraplegia or paraparesis. Spinal cord IRI includes two phases. The immediate spinal cord injury is related to acute ischemia. And the delayed spinal cord injury involves both ischemic cellular death and reperfusion injury. Inflammation is a subsequent event of spinal cord ischemia and possibly a major contributor to spinal cord IRI. However, the development of inflammatory mediators is incompletely demonstrated. And treatments available for inflammation in spinal cord IRI are insufficient. Improved understanding about spinal cord IRI and the development of inflammatory cells and cytokines in this process will provide novel therapeutic strategies for spinal cord IRI. Inflammatory cytokines (e.g., TNF-? and IL-1) may play an important role in spinal cord IRI. For treatment of several intractable autoimmune diseases (e.g., rheumatoid arthritis), where inflammatory cytokines are involved in disease progression, anti-inflammatory cytokine antagonist is now available. Hence, there is great potential of anti-inflammatory cytokine antagonist for therapeutic use of spinal cord IRI. We here review the mediators and several possibilities of treatment in spinal cord IRI. PMID:23956505

Zhu, Ping; Li, Jia-xin; Fujino, Masayuki; Zhuang, Jian; Li, Xiao-Kang

2013-01-01

95

Prevention of spinal cord injury: an elementary education approach.  

PubMed

Spinal cord injury (SCI) results in permanent paralysis and most often happens to teenagers and young adults. High risk behaviors are most often the cause; therefore these injuries are often preventable. In response to a gap in existing prevention programs, an elementary age SCI prevention program was developed, designed for implementation by teachers. Evaluation was carried out via a quasi-experimental pre-post comparison group design. Experimental students demonstrated significantly improved knowledge of SCI and its prevention. Similar changes in self-reported safety belt use were not noted. Development of the curriculum, related grant activities, and plans for national dissemination are described. PMID:1744808

Richards, J S; Hendricks, C; Roberts, M

1991-10-01

96

Association of Antidepressant Medication Therapy With Inpatient Rehabilitation Outcomes for Stroke, Traumatic Brain Injury, or Traumatic Spinal Cord Injury  

Microsoft Academic Search

Weeks DL, Greer CL, Bray BS, Schwartz CR, White JR Jr. Association of antidepressant medication therapy with inpatient rehabilitation outcomes for stroke, traumatic brain injury, or traumatic spinal cord injury.

Christopher L. Greer; Brenda S. Bray; Catrina R. Schwartz; John R. White

2011-01-01

97

Sympathetic influence on biomechanical skin properties after spinal cord injury  

Microsoft Academic Search

Study design:Case–control study.Objectives:To investigate changes of biomechanical skin properties and their relationship with paralysis following spinal cord injury (SCI).Setting:South Korea.Methods:A total of 48 male subjects with chronic SCI and 48 age-matched healthy controls were enrolled into this study. The C4 shoulder group and L2 thigh group were prescribed by two measured anatomical regions that represented the C4 and L2 American

J W Park; C H Seo; S H Han; Y G Lee

2011-01-01

98

Spinal cord injury in Italy: A multicenter retrospective study  

Microsoft Academic Search

Celani MG, Spizzichino L, Ricci S, Zampolini M, Franceschini M, Retrospective Study Group on SCI. Spinal cord injury in Italy: a multicenter retrospective study. Arch Phys Med Rehabil 2001;82:589-96. Objective: To investigate certain factors influencing the length of stay (LOS) in a rehabilitation center, the incidence of pressure ulcers, and the neurologic improvement of patients with traumatic (T\\/SCI) and nontraumatic

M. Grazia Celani; Lorenzo Spizzichino; Stefano Ricci; Mauro Zampolini; Marco Franceschini

2001-01-01

99

Magnetic resonance imaging of acute spinal cord injury  

Microsoft Academic Search

Magnetic resonance imaging of acute spinal cord injury is described. The traumatized cord segment was clearly shown as a hyperintensity in a T2-weighted image whereas it appeared as an isointensity in a moderately T1-weighted image. This different sensitivity may result from parenchymal hemorrhagic tissue and edematous changes due to direct trauma. Hyperintense tissue was also seen in the retro-pharyngeal and-tracheal

S. Kadoya; T. Nakamura; S. Kobayashi; I. Yamamoto

1987-01-01

100

Emerging Concepts in Myeloid Cell Biology after Spinal Cord Injury  

Microsoft Academic Search

Summary  Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte\\/macrophages.\\u000a Because these myeloid cells can positively and negatively affect survival of neurons and glia, they are among the most commonly\\u000a studied immune cells. However, the mechanisms that regulate myeloid cell activation and recruitment after SCI have not been\\u000a adequately defined. In general, the dynamics

Alicia L. Hawthorne; Phillip G. Popovich

2011-01-01

101

[Modern neurological treatment strategies for patients with spinal cord injury].  

PubMed

Modern treatment methods for neurogenic bladder dysfunction take into consideration the primacy of obtaining good bladder storage capacity by merely lowering the leak point pressure. The medical benefit for the patient is seen in the stability of renal function and the social advantage in achieving continence. The development of modern findings on the management of neuro-urological disorders in spinal cord injury as well as the underlying principles, indications, and benefits of the most frequently applied treatment approaches are described. PMID:22269993

Domurath, B; Kutzenberger, J

2012-02-01

102

Neuroprotective Effects of Sulforaphane after Contusive Spinal Cord Injury  

PubMed Central

Abstract Traumatic spinal cord injury (SCI) leads to oxidative stress, calcium mobilization, glutamate toxicity, the release of proinflammatory factors, and depletion of reduced glutathione (GSH) at the site of injury. Induction of the Keap1/Nrf2/ARE pathway can alleviate neurotoxicity by protecting against GSH depletion, oxidation, intracellular calcium overload, mitochondrial dysfunction, and excitotoxicity. Sulforaphane (SF), an isothiocyanate derived from broccoli, is a potent naturally-occurring inducer of the Keap1/Nrf2/ARE pathway, leading to upregulation of genes encoding cytoprotective proteins such as NAD(P)H: quinone oxidoreductase 1, and GSH-regulatory enzymes. Additionally, SF can attenuate inflammation by inhibiting the nuclear factor-?B (NF-?B) pathway, and the enzymatic activity of the proinflammatory cytokine macrophage inhibitory factor (MIF). Our study examined systemic administration of SF in a rat model of contusion SCI, in an effort to utilize its indirect antioxidant and anti-inflammatory properties to decrease secondary injury. Two doses of SF (10 or 50?mg/kg) were administered at 10?min and 72?h after contusion SCI. SF (50?mg/kg) treatment resulted in both acute and long-term beneficial effects, including upregulation of the phase 2 antioxidant response at the injury site, decreased mRNA levels of inflammatory cytokines (i.e., MMP-9) in the injured spinal cord, inactivation of urinary MIF tautomerase activity, enhanced hindlimb locomotor function, and an increased number of serotonergic axons caudal to the lesion site. These findings demonstrate that SF provides neuroprotective effects in the spinal cord after injury, and could be a candidate for therapy of SCI. PMID:22853439

Benedict, Andrea L.; Mountney, Andrea; Hurtado, Andres; Bryan, Kelley E.; Schnaar, Ronald L.; Dinkova-Kostova, Albena T.

2012-01-01

103

Decorin treatment of spinal cord injury  

PubMed Central

The scarring response after a penetrant central nervous system injury results from the interaction between invading leptominingeal/pericyte-derived fibroblasts and endogenous reactive astrocytes about the wound margin. Extracellular matrix and scar-derived axon growth inhibitory molecules fill the lesion site providing both a physical and chemical barrier to regenerating axons. Decorin, a small leucine-rich chondroitin-dermatan sulphate proteoglycan expressed by neurons and astrocytes in the central nervous system, is both anti-fibrotic and anti-inflammatory and attenuates the formation and partial dissolution of established and chronic scars. Here, we discuss the potential of using Decorin to antagonise scarring in the central nervous system. PMID:25374584

Esmaeili, Maryam; Berry, Martin; Logan, Ann; Ahmed, Zubair

2014-01-01

104

Traumatic spinal cord injury in Botswana: characteristics, aetiology and mortality.  

PubMed

Study design:Descriptive study with a cross-sectional design.Objectives:To describe the epidemiology of traumatic spinal cord injuries (TSCIs) in Botswana, with a specific focus on road traffic crashes (RTC).Setting:Main public referral hospital, Gaborone, Botswana.Method:Two samples were included. Sample one described the epidemiology and included patients admitted during a 2-year period with acute TSCI. Sample two included only patients with TSCI due to RTC.Results:Annual incidence was 13 per million population. Epidemiology of TSCI: 49 patients were included, 71% male, age ranging from 4 to 81 years, 80% ?45 years. Tetraplegia was more common than paraplegia (59/41%), and 39% had C1-C4 level of injury. The main cause of TSCI was RTC (68%), followed by assault (16%) and falls (10%). Mortality was 20%, where all, but one, had tetraplegia (18%). Median time from injury to spinal surgery was 12 days, with longer time for women, 16 days compared with 8 for men. Burst tire was the primary cause of RTC resulting in a TSCI, followed by hitting animals on the road. The majority had been passengers and 72% were involved in single crashes.Conclusion:The most common cause for TSCI was RTC, followed by assault. In-hospital mortality was high and the waiting period from the time of accident to spinal surgery was long, especially for women. The aetiology and high mortality of TSCI in Botswana indicate that improvements in roadway safety and medical care may decrease the TSCI incidence and mortality.Spinal Cord advance online publication, 25 November 2014; doi:10.1038/sc.2014.203. PMID:25420494

Löfvenmark, I; Norrbrink, C; Nilsson-Wikmar, L; Hultling, C; Chakandinakira, S; Hasselberg, M

2014-11-25

105

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

NASA Astrophysics Data System (ADS)

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.

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

2009-02-01

106

Role of Melatonin in Traumatic Brain Injury and Spinal Cord Injury  

PubMed Central

Brain and spinal cord are implicated in incidences of two of the most severe injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a devastating neurological deficit involving primary and secondary injury cascades. The primary and secondary mechanisms include complex consequences of activation of proinflammatory cytokines, cerebral edema, upregulation of NF-??, disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury (SCI) includes primary and secondary injury cascades. Primary injury leads to secondary injury in which generation of free radicals and oxidative or nitrative damage play an important pathophysiological role. The indoleamine melatonin is a hormone secreted or synthesized by pineal gland in the brain which helps to regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory properties. It has a special characteristic of crossing BBB. Melatonin has neuroprotective role in the injured part of the CNS after TBI and SCI. A number of studies have successfully shown its therapeutic value as a neuroprotective agent in the treatment of neurodegenerative diseases. Here in this review we have compiled the literature supporting consequences of CNS injuries, TBI and SCI, and the protective role of melatonin in it. PMID:25587567

Naseem, Mehar; Parvez, Suhel

2014-01-01

107

Restoring function after spinal cord injury: towards clinical translation of experimental strategies.  

PubMed

Spinal cord injury is currently incurable and treatment is limited to minimising secondary complications and maximising residual function by rehabilitation. Improved understanding of the pathophysiology of spinal cord injury and the factors that prevent nerve and tissue repair has fuelled a move towards more ambitious experimental treatments aimed at promoting neuroprotection, axonal regeneration, and neuroplasticity. By necessity, these new options are more invasive. However, in view of recent advances in spinal cord injury research and demand from patients, clinicians, and the scientific community to push promising experimental treatments to the clinic, momentum and optimism exist for the translation of candidate experimental treatments to clinical spinal cord injury. The ability to rescue, reactivate, and rewire spinal systems to restore function after spinal cord injury might soon be within reach. PMID:25453463

Ramer, Leanne M; Ramer, Matt S; Bradbury, Elizabeth J

2014-12-01

108

Gastric dysreflexia after acute experimental spinal cord injury in rats  

PubMed Central

Gastric reflexes are mediated mainly by vago-vagal reflex circuits in the caudal medulla. Despite the fact that brainstem vago-vagal circuitry remains intact after spinal cord injury (SCI), patients with SCI at the cervical level most often present gastric stasis with an increased risk of reflux and aspiration of gastric contents. Using a miniature strain gauge sutured to the gastric surface; we tested gastric motility and reflexive gastric relaxation following oesophageal distension (oesophageal-gastric relaxation reflex) in animals 3 days after a severe spinal contusion at either the third or ninth thoracic spinal segment (acute T3- or T9 SCI, respectively). Both basal gastric motility and the oesophageal-gastric relaxation reflex were significantly diminished in animals with T3 SCI. Conversely, both basal gastric motility and the oesophageal-gastric relaxation reflex were not significantly reduced in T9 SCI animals compared to controls. The reduced gastric motility and oesophageal-gastric reflex in T3 SCI rats was not ameliorated by celiac sympathectomy. Our results show that gastric stasis following acute SCI is independent of altered spinal sympathetic input to the stomach caudal to the lesion. Our data suggest that SCI may alter the sensitivity of vagal reflex function, perhaps by interrupting ascending spinosolitary input to brainstem vagal nuclei. PMID:19126185

Tong, M.; Holmes, G. M.

2009-01-01

109

Fibronectin Inhibits Chronic Pain Development after Spinal Cord Injury  

PubMed Central

Abstract Chronic pain following spinal cord injury (SCI) is a highly prevalent clinical condition that is difficult to treat. Using both von Frey filaments and radiant infrared heat to assess mechanical allodynia and thermal hyperalgesia, respectively, we have demonstrated that a one-time injection of fibronectin (50??g/mL) into the spinal dorsal column (1??L/min each injection for a total of 5??L) immediately after SCI inhibits the development of mechanical allodynia (but not thermal hyperalgesia) over an 8-month observation period following spinal cord dorsal column crush (DCC). DCC will only induce mechanical Allodynia, but not thermal hyperalgesia or overt motor deficits. By applying various fibronectin fragments as well as competitive inhibitors, these effects were shown to be dependent on the connecting segment-1 (CS-1) motif of fibronectin. Furthermore, we found that acute fibronectin treatment diminished inflammation and blood–spinal cord barrier permeability, which in turn leads to enhanced fiber sparing and sprouting. In particular, the reduction of serotonin (5-HT) in the superficial dorsal horn, an important descending brainstem system in the modulation of pain, was blocked with fibronectin treatment. We conclude that treatment of SCI with fibronectin preserves sensory regulation and prevents the development of chronic allodynia, providing a potential therapeutic intervention to treat chronic pain following SCI. PMID:22022865

Lee, Yu-Shang; Lin, Vernon W.; Silver, Jerry

2012-01-01

110

Modulating inflammatory cell responses to spinal cord injury: all in good time.  

PubMed

Spinal cord injury can have a range of debilitating effects, permanently impacting a patient's quality of life. Initially thought to be an immune privileged site, the spinal cord is able to mount a timely and well organized inflammatory response to injury. Intricate immune cell interactions are triggered, typically consisting of a staggered multiphasic immune cell response, which can become deregulated if left unchecked. Although several immunomodulatory compounds have yielded success in experimental rodent spinal cord injury models, their translation to human clinical studies needs further consideration. Because temporal differences between rodent and human inflammatory responses to spinal cord injury do exist, drug delivery timing will be a crucial component in recovery from spinal cord injury. Given too early, immunomodulatory therapies may impede beneficial inflammatory reactions to the injured spinal cord or even miss the opportunity to dampen delayed harmful autoimmune processes. Therefore, this review aims to summarize the temporal inflammatory response to spinal cord injury, as well as detailing specific immune cell functions. By clearly defining the chronological order of inflammatory events after trauma, immunomodulatory drug delivery timing can be better optimized. Further, we compare spinal cord injury-induced inflammatory responses in rodent and human studies, enabling clinicians to consider these differences when initiating clinical trials. Improved understanding of the cellular immune response after spinal cord injury would enhance the efficacy of immunomodulatory agents, enabling combined therapies to be considered. PMID:24934600

Bowes, Amy L; Yip, Ping K

2014-11-01

111

The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury  

Microsoft Academic Search

Substantial residual neurological function may persist after spinal cord injury (SCI) with survival of as few as 5–10% of the original number of axons. A detailed understanding of the relationships among the severity of injury, the number and origin of surviving axons at the injury site, and the extent of neurological recovery after SCI is of importance in understanding the

Michael G. Fehlings; Charles H. Tator

1995-01-01

112

Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury  

PubMed Central

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

Aloe, Luigi; Bianchi, Patrizia; De Bellis, Alberto; Soligo, Marzia; Rocco, Maria Luisa

2014-01-01

113

Effects of Spinal Cord Injury on Semen Parameters  

PubMed Central

Objective/Background: Neurogenic reproductive dysfunction in men with spinal cord injury (SCI) is common and the result of a combination of impotence, ejaculatory failure, and abnormal semen characteristics. It is well established that the semen quality of men with SCI is poor and that changes are seen as early as 2 weeks after injury. The distinguishing characters of poor quality are abnormal sperm motility and viability. In the majority of the men with SCI, the sperm count is not abnormal. We elaborate on the effects of the SCI on semen parameters that may contribute to poor motility and poor viability. Methods: Review. Design: PubMed and MEDLINE databases were searched using the following key words: spinal cord injuries, fertility, sexual dysfunction, and spermatogenesis. All literature was reviewed by the team of authors according to the various stages of sperm development and transport in the male reproductive cycle. Findings: The cause of asthenozoospermia appears to be multifactorial. Conclusion: Current literature does not support the preeminence of a single factor relating to neurogenic reproductive dysfunction in men with SCI. After SCI, there is ample evidence of disturbance of sperm production, maturation and storage, and transport due to an abnormal neuroendocrine milieu. Semen quality seems to be primarily affected by changes to the seminal plasma constituents, type of bladder management, and the neurogenic impairment to the ejaculatory function. Further focused and structured studies are required. PMID:18533408

Patki, Prasad; Woodhouse, Joe; Hamid, Rizwan; Craggs, Michael; Shah, Julian

2008-01-01

114

Spinal cord injury causes chronic liver pathology in rats.  

PubMed

Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1?, IL-1?, chemokine ligand-2, and tumor necrosis factor-? mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

Sauerbeck, Andrew D; Laws, J Lukas; Bandaru, Veera V R; Popovich, Phillip G; Haughey, Norman J; McTigue, Dana M

2015-02-01

115

A Structural Analysis of Health Outcomes After Spinal Cord Injury  

PubMed Central

Objective: To develop and validate a latent model of health outcomes among persons with spinal cord injury. Methods: Survey data were collected at a large specialty hospital in the southeastern USA from 1,388 adult participants with traumatic spinal cord injury of at least 1 year's duration. Multiple indicators of health outcomes were used, including general health ratings, days adversely affected by poor health and poor mental health, treatments and hospitalizations, depressive symptoms, symptoms of illness or infection (eg, sweats, chills, fever), and multiple individual conditions (eg, pressure ulcers, subsequent injuries, fractures, contractures). Results: We performed exploratory factor analysis on half of the sample and confirmatory factor analysis on the other. A 6-factor solution was the best overall solution, because there was an excellent fit with the exploratory factor analysis (root mean square error of approximation ?=? 0.042) and acceptable fit with the confirmatory factor analysis (root mean square error of approximation ?=? 0.065). Four of the factors were types of secondary conditions, including symptoms of illness or infection, orthopedic conditions, pressure ulcers, and subsequent injuries. The 2 remaining factors reflected global health and treatment. Gender, race-ethnicity, age, injury severity, and years of education were all significantly related to at least 1 factor dimension, indicating variations in health outcomes related to these characteristics. Conclusion: Identification of the 6 factors represents an improvement over the utilization of multiple individual indicators, because composite scores generated from multiple individual indicators provide more informative and stable outcome scores than utilization of single indicators. PMID:20397441

Krause, James S; Reed, Karla S; McArdle, John J

2010-01-01

116

Spinal Cord Injury: Scenario in an Indian State.  

PubMed

Study design:Prospective observational study.Objectives:To find out the epidemiology and demographic factors associated with patients of traumatic spinal cord injury (SCI).Setting:Sawai Man Singh Medical College and Hospital, Jaipur, India.Methods:Consecutive SCI cases admitted from January 2000 to December 2008 were evaluated on a preformed proforma for demographic factors, epidemiological data and neurological status.Results:In 2716 cases of SCI, 1400 were cervical and 1316 thoracolumbar, with male to female ratio of 4.2:1 and 71% in the age group of 20-49 years. Around 79% patients were from rural background. About 23.3% were farmers while 22.9% were laborers. Among the causes of injury, 53% patients had a fall from height and 28% suffered from road traffic accidents. Fall of heavy object over head and back (10.7%), fall with heavy object over head (3.0%) and fall following electric shock (4.0%) were uncommon causes. Complete paralysis was found in 20.5% cervical and 23.3% in thoracic injuries. Extremity and rib fractures (10.6%) and head injuries (7.2%) were common associated injuries. About 55% cases were initially attended at non-specialized centers. Proper bladder and bowel management in early phase was lacking.Conclusion:Epidemiological factors of SCI in Indian scenario are different from western countries with major cause being fall. The low socio-economic status and younger age group had a major financial, social and psychological impact as majority of the patients were the primary earning members of the family. Therefore, measures should be taken to reduce the incidence of SCI.Spinal Cord advance online publication, 16 September 2014; doi:10.1038/sc.2014.153. PMID:25224599

Mathur, N; Jain, S; Kumar, N; Srivastava, A; Purohit, N; Patni, A

2014-09-16

117

Dermatological problems following spinal cord injury in Korean patients.  

PubMed

Objective To identify dermatological conditions following spinal cord injury (SCI) and analyze these conditions in relation to various characteristics of SCI. Design Retrospective chart review. Setting National Health Insurance Corporation Ilsan Hospital of Korea, Rehabilitation Center, Spinal Cord Unit. Participants Patients treated for SCI who were referred to dermatology for dermatological problems, 2000-2012. Results Of the 1408 SCI patients treated at the spinal cord unit, 253 patients with SCI were identified to have been referred to dermatology for skin problems and a total of 335 dermatological conditions were diagnosed. The most common dermatological finding was infectious (n = 123, 36.7%) followed by eczematous lesions (n = 109, 32.5%). Among the infectious lesions, fungal infection (n = 76, 61.8%) was the most common, followed by bacterial (n = 27, 21.9%) lesions. Seborrheic dermatitis (n = 59, 64.1%) was the most frequent eczematous lesion. Ingrown toenail occurred more frequently in tetraplegics whereas vascular skin lesions occurred more commonly in patients with paraplegia (P < 0.05). Xerotic dermatitis showed a higher occurrence within 12 months of injury rather than thereafter (P < 0.05). Of these, 72.4% of the infectious and 94.7% of the fungal skin lesions manifested below the neurological level of injury (NLI; P < 0.001) and 61.5% of the eczematous lesions and 94.9% of seborrheic dermatitis cases occurred above the NLI (P < 0.001). There was no significant difference in dermatological diagnoses between patients with neurologically complete and incomplete SCI. Conclusion The most common dermatological condition in patients with SCI among those referred to dermatology was fungal infection, followed by seborrheic dermatitis. Although dermatological problems after SCI are not critical in SCI outcome, they negatively affect the quality of life. Patients and caregivers should be educated about appropriate skin care and routine dermatological examinations. PMID:24090454

Han, Zee-A; Choi, Ja Young; Ko, Young Jin

2013-10-24

118

Resection of Glial Scar Following Spinal Cord Injury  

PubMed Central

While many studies have focused on modulating the immune response and enhancing axonal regeneration after spinal cord injury (SCI), there is limited work being performed on evaluating the role of glial scar in SCI. We sought to evaluate the effects of glial scar resection in contusion models and dorsal hemisection models of SCI. At one week postinjury, 2mm of glial scar was excised from specimens in one of the two groups from each injury model. Functional outcome was measured weekly using the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale along with histologic evaluation of spinal cord tracts to determine axonal regeneration. Within the dorsal hemisection model, there was no significant difference in recovery for animals that underwent glial scar excision versus animals that did not have scar excision (p=0.61). Animals subjected to the contusion model, however, demonstrated lower BBB scores in the glial resection group during the earlier postoperative periods (<4 weeks; p<0.05). Histological analysis revealed no axons within the glial resection contusion model, and moderate axonal growth within the nonresection contusion group and both hemisection groups (p>0.05 for differences among the three groups). While glial scar may serve to stabilize the preserved axonal tracts and thereby permit modest recovery in a contusion model of SCI, it may be of less importance with a dorsal hemisection model. These experiments highlight that basic biologic processes following SCI may vary tremendously based on the injury mechanism and that the role of glial scar in spinal cord regeneration must be elucidated. PMID:19062171

Rasouli, Alexandre; Bhatia, Nitin; Dinh, Paul; Cahill, Kim; Suryadevara, Sourabh; Gupta, Ranjan

2008-01-01

119

Quality Assessment of Spinal Cord Injury Patient Education Resources.  

PubMed

Study Design. Analysis of spinal cord injury patient education resources.Objective. To assess the quality of online patient education materials written about spinal cord injury.Summary of Background Data. The use of online materials by healthcare consumers to access medical information presents unique challenges. Most Americans have access to the Internet and frequently turn to it as a first-line resource.Methods. The quality of online patient education materials was evaluated via a readability analysis. Materials provided by the National Institute of Neurological Disorders and Stroke (NINDS); Centers for Disease Control (CDC); American Association of Neurological Surgeons (AANS); National Spinal Cord Injury Association (NSCIA); Mayo Clinic (Mayo); Department of Veterans Affairs (VA); Kessler Institute for Rehabilitation (Kessler); American Academy of Neurology (AAN); Paralyzed Veterans of America (PVA); and the Shepherd Center (SC) were assessed using the Flesch Reading Ease and Flesch-Kincaid Grade Level evaluations with Microsoft Office Word software. Unnecessary formatting was removed and the readability was evaluated with the Spelling and Grammar function.Results. A total of 104 sections from 10 different websites were analyzed. Overall, the average values of the Flesch-Kincaid Grade Level (11.9) and Flesch Reading Ease (40.2) indicated that most Americans would not be able to fully comprehend this material.Conclusion. Results indicate that the language used on materials provided by the aforementioned sites is perhaps too advanced for the average American to fully comprehend. The quality of these education resources may be improved via website revisions, which might be beneficial for improved patient utilization. PMID:24718059

Agarwal, Nitin; Hansberry, David R; Singh, Priyanka L; Heary, Robert F; Goldstein, Ira M

2014-04-01

120

Advances in stem cell therapy for spinal cord injury  

PubMed Central

Spinal cord injury (SCI) is a devastating condition producing great personal and societal costs and for which there is no effective treatment. Stem cell transplantation is a promising therapeutic strategy, though much preclinical and clinical research work remains. Here, we briefly describe SCI epidemiology, pathophysiology, and experimental and clinical stem cell strategies. Research in stem cell biology and cell reprogramming is rapidly advancing, with the hope of moving stem cell therapy closer to helping people with SCI. We examine issues important for clinical translation and provide a commentary on recent developments, including termination of the first human embryonic stem cell transplantation trial in human SCI. PMID:23114605

Mothe, Andrea J.; Tator, Charles H.

2012-01-01

121

Thoracic rat spinal cord contusion injury induces remote spinal gliogenesis but not neurogenesis or gliogenesis in the brain.  

PubMed

After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement. PMID:25050623

Franz, Steffen; Ciatipis, Mareva; Pfeifer, Kathrin; Kierdorf, Birthe; Sandner, Beatrice; Bogdahn, Ulrich; Blesch, Armin; Winner, Beate; Weidner, Norbert

2014-01-01

122

Training the Interdisciplinary Team in Sexuality Rehabilitation Following Spinal Cord Injury: A Needs Assessment  

Microsoft Academic Search

Historically, the management of sexuality issues in spinal cord injury rehabilitation has received scant attention as a staff training issue. This has occurred despite evidence in the literature identifying significant barriers to the provision of sexuality rehabilitation. This paper reports on a needs assessment conducted within an Australian spinal cord injury rehabilitation service to identify the training needs of staff

Susan Booth; Melissa Kendall; Patricia Fronek; Deborah Miller; Timothy Geraghty

2003-01-01

123

Bilateral extracorporeal shock wave lithotripsy in a spinal cord injury patient with a cardiac pacemaker  

Microsoft Academic Search

Objectives: To review the precautions to be observed before and during extracorporeal shock wave lithotripsy (ESWL) in spinal cord injury (SCI) patients with a cardiac pacemaker and the safety of bilateral ESWL performed on the same day.Design: A case report of bilateral ESWL in a SCI patient with a permanent cardiac pacemaker.Setting: The Regional Spinal Injuries Centre, Southport, the Lithotripsy

S Vaidyanathan; R Hirst; KF Parsons; G Singh; BM Soni; T Oo; A Zaidi; JWH Watt; P Sett

2001-01-01

124

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

125

Detrimental Effects of Uncontrollable Stimulation on Recovery After Spinal Cord Injury  

E-print Network

using a spinal contusion surgery on rats to simulate spinal cord injury, and uncontrollable shock to act as pain signals from peripheral injury. Although it is known that the brain is necessary for this destructive effect to occur, it is not known...

Hudson, Kara

2007-07-23

126

Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain  

Microsoft Academic Search

Several experimental models of peripheral neuropathy show that a significant upregulation of spinal dynorphin A and its precursor peptide, prodynorphin, is a common consequence of nerve injury. A genetically modified mouse strain lacking prodynorphin does not exhibit sustained neuropathic pain after nerve injury, supporting a pronociceptive role of elevated levels of spinal dynorphin. A null mutation of the ? isoform

L. R. GARDELL; M. IBRAHIM; R. WANG; Z. WANG; M. H. OSSIPOV; T. P. MALAN JR; F Porreca; J Lai

2004-01-01

127

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

PubMed Central

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

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

2012-01-01

128

Bilateral Cervical Contusion Spinal Cord Injury in Rats  

PubMed Central

There is increasing motivation to develop clinically relevant experimental models for cervical SCI in rodents and techniques to assess deficits in forelimb function. Here we describe a bilateral cervical contusion model in rats. Female Sprague-Dawley rats received mild or moderate cervical contusion injuries (using the Infinite Horizons device) at C5, C6, or C7/8. Forelimb motor function was assessed using a Grip Strength Meter (GSM); sensory function was assessed by the von Frey hair test; the integrity of the corticospinal tract (CST) was assessed by biotinylated dextran amine (BDA) tract tracing. Mild contusions caused primarily dorsal column (DC) and gray matter (GM) damage while moderate contusions produced additional damage to lateral and ventral tissue. Forelimb and hindlimb function was severely impaired immediately post-injury, but all rats regained the ability to use their hindlimbs for locomotion. Gripping ability was abolished immediately after injury but recovered partially, depending upon the spinal level and severity of the injury. Rats exhibited a loss of sensation in both fore- and hindlimbs that partially recovered, and did not exhibit allodynia. Tract tracing revealed that the main contingent of CST axons in the DC was completely interrupted in all but one animal whereas the dorsolateral CST (dlCST) was partially spared, and dlCST axons gave rise to axons that arborized in the GM caudal to the injury. Our data demonstrate that rats can survive significant bilateral cervical contusion injuries at or below C5 and that forepaw gripping function recovers after mild injuries even when the main component of CST axons in the dorsal column is completely interrupted. PMID:19559699

Anderson, Kim D.; Sharp, Kelli G.; Steward, Oswald

2009-01-01

129

Neuroprotective Effects of Methylprednisolone and Hypothermia after Experimental Spinal Cord Injury: A Histopathological and Stereological Study  

PubMed Central

Objective: Spinal cord injury is a common trauma among severe accidents in which the spinal cord has been severed; intravenous methylprednisolone and hypothermia are widely used in the treatment of traumatic spinal cord injuries. However, no common consensus has been reached on therapeutic approaches to prevent and reduce disability caused by spinal cord injuries. In this study, the efficacy of methylprednisolone and hypothermia treatments after experimental spinal cord injury made by dynamic weight-drop model in rabbits was investigated. Materials and Methods: This experiment consists of three groups: injured, methylprednisolone-treated and hypothermia-treated groups. The methylprednisolone-treated group received intravenous methylprednisolone (30 mg/kg/day) immediately after spinal cord injury for three days. In the hypothermia-treated group, cold isotonic saline (5°C) was infused via a cannula into the epidural space at a rate of 10 ml/min. The temperature of the tissue was allowed to reach 25ºC, and then isotonic saline solution was given at a rate of 5 ml/min for 3 hours. Saline was given to the injured group following spinal cord injury. After 1 week of experimental injury, mid-thoracic level tissue was removed from the spinal cord for histopathological evaluation and subsequent stereological analysis. Results: The volume of spinal cord segment, not only parenchyma of grey and white matter but also cavity, was estimated by the Cavalieri principle. Significant differences were seen between the injured group and methylprednisolone /hypothermia-treated groups in terms of the total volume cavity of spinal cord segment; cavity volume in the grey matter and cavity volume in the white matter. No significant differences were seen between methylprednisolone and hypothermia-treated groups in terms of the total volume cavity of spinal cord segment; cavity volume in the grey matter and cavity volume in the white matter. Conclusions: These results suggested that both methylprednisolone and hypothermia treatment are neuroprotective in preventing spinal cord tissue from tissue damage after experimental injury.

Unal, Bunyami; Kaplan, Suleyman; Odaci, Ersan; Aslan, Huseyin; Aksak, Selina; Unal, Deniz; Altunkaynak, B. Zuhal; Gundogdu, Cemal; Gokyar, Ahmet

2009-01-01

130

Brain-Derived Neurotrophic Factor Stimulates Hindlimb Stepping and Sprouting of Cholinergic Fibers after Spinal Cord Injury  

Microsoft Academic Search

Neurotrophic factors have been proposed as a therapeutic treatment for traumatic brain and spinal cord injury. The present study determined whether exogenous administration of one such factor, brain-derived neurotrophic factor (BDNF), could effect behavioral recovery and\\/or histopathological changes after spinal cord injury. Adult rats received a mild or moderate contusion injury or complete transection of the midthoracic spinal cord. Immediately

Lyn B. Jakeman; Ping Wei; Zhen Guan; Bradford T. Stokes

1998-01-01

131

Risk for Subsequent Injuries After Spinal Cord Injury: A 10-Year Longitudinal Analysis  

PubMed Central

Objectives To identify: (a) the annual incidence of subsequent injury and injury related hospitalizations among individuals with pre-existing spinal cord injury (SCI) and (b) risk and protective behaviors associated with differential risk of injury. Design Longitudinal, mailed survey. Participants were enrolled in 1997-1998, with a follow-up conducted 10 years later. Setting Data were collected from participants identified from a specialty hospital and analyzed at a medical university in the Southeastern United States. Participants There were 1386 participants during the baseline enrollment, 821 of whom also participated in the 10-year follow-up. Inclusion criteria were: (1) traumatic SCI with residual impairment A-D, (2) non-surgical onset, (3) age 18 years or older, and (4) a minimum of 12 months post-SCI. Interventions Main Outcome Measures Number of injuries severe enough to require treatment in a clinic, emergency department, or hospital in the 12 months prior to the survey, and number of injury related hospitalizations. Predictor variables included selected items from the Behavioral Risk Factor Surveillance System, the Zuckerman-Kuhlman Personality Questionnaire, and prescription medication usage. Results Over 23% of participants reported at least 1 injury within the past year, an increase from that reported 10 years earlier by the same participants (19%), and 7% reported at least 1 injury related hospitalization. Those who reported a subsequent injury during the preliminary baseline data collection were about twice as likely to report at least 1 injury 10 years later. Binge drinking, psychotropic prescription medication use, and several personality characteristics were also related to injuries and/or injury hospitalization. Conclusions Risk of injury continues to be a significant concern in the years and decades after SCI onset. Behavioral and personality factors hold the key to prevention. PMID:21044720

Krause, James S.

2011-01-01

132

Late-life spinal cord injury and aging with a long term injury: characteristics of two emerging populations.  

PubMed

Modern care of patients with spinal cord injury is leading to greater numbers of individuals surviving into old age and the emergence of a cohort that has sustained injury at an advanced age. The clinical characteristics of either group of patients has not been well characterized. Analyses from the Aging with a Long-Term Disability Research Program database, which is enriched by the presence of a high quality Spinal Cord Injury Service, revealed a population of 510 recently assessed individuals with a mean age of 50 years, ranging from 16 to 84 years. Twenty-three percent of the patients were at least 65 years of age. Spinal cord injuries were usually the result of automobile accidents in individuals injured younger than 50 years of age and falls in individuals injured when older than 50 years of age. Patients surviving late life injury are much more likely to have incomplete injuries predominantly affecting the cervical spine. A number of conditions were found to be more prevalent in older patients. These included carpal tunnel syndrome, chronic obstructive pulmonary disease, myocardial infarction, diabetes, kidney stones, pressure ulcers and hypertension. The development of diabetes, kidney stones and perhaps pressure ulcers was directly related to aging with SCI, but not just to aging alone. The better functional outcomes in late life spinal cord injury may be secondary to selective survival. The excess morbidity associated with late life spinal cord injury has significance for future planning of healthcare needs for the spinal cord injured patient. PMID:7552423

McGlinchey-Berroth, R; Morrow, L; Ahlquist, M; Sarkarati, M; Minaker, K L

1995-07-01

133

Autonomic Dysreflexia Causes Chronic Immune Suppression after Spinal Cord Injury  

PubMed Central

Autonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immune suppression are not known. Data presented herein indicate that AD causes immune suppression. Using in vivo telemetry, we show that AD develops spontaneously in SCI mice with the frequency of dysreflexic episodes increasing as a function of time postinjury. As the frequency of AD increases, there is a corresponding increase in splenic leucopenia and immune suppression. Experimental activation of spinal sympathetic reflexes in SCI mice (e.g., via colorectal distension) elicits AD and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. Reversal of postinjury immune suppression in SCI mice can be achieved by pharmacological inhibition of receptors for norepinephrine and glucocorticoids during the onset and progression of AD. In a human subject with C5 SCI, stimulating the micturition reflex caused AD with exaggerated catecholamine release and impaired immune function, thus confirming the relevance of the mouse data. These data implicate AD as a cause of secondary immune deficiency after SCI and reveal novel therapeutic targets for overcoming infectious complications that arise due to deficits in immune function. PMID:23926252

Zhang, Yi; Guan, Zhen; Reader, Brenda; Shawler, Todd; Mandrekar-Colucci, Shweta; Huang, Kun; Weil, Zachary; Bratasz, Anna; Wells, Jonathan; Powell, Nicole D.; Sheridan, John F.; Whitacre, Caroline C.; Rabchevsky, Alexander G.; Nash, Mark S.

2013-01-01

134

The Sur1-Trpm4 Channel in Spinal Cord Injury  

PubMed Central

Spinal cord injury (SCI) is a major unsolved challenge in medicine. Impact trauma to the spinal cord shears blood vessels, causing an immediate ‘primary hemorrhage’. During the hours following trauma, the region of hemorrhage enlarges progressively, with delayed or ‘secondary hemorrhage’ adding to the primary hemorrhage, and effectively doubling its volume. The process responsible for the secondary hemorrhage that results in early expansion of the hemorrhagic lesion is termed ‘progressive hemorrhagic necrosis’ (PHN). PHN is a dynamic process of auto destruction whose molecular underpinnings are only now beginning to be elucidated. PHN results from the delayed, progressive, catastrophic failure of the structural integrity of capillaries. The resulting ‘capillary fragmentation’ is a unique, pathognomonic feature of PHN. Recent work has implicated the Sur1-Trpm4 channel that is newly upregulated in penumbral microvessels as being required for the development of PHN. Targeting the Sur1-Trpm4 channel by gene deletion, gene suppression, or pharmacological inhibition of either of the two channel subunits, Sur1 or Trpm4, yields exactly the same effects histologically and functionally, and exactly the same unique, pathognomonic phenotype – the prevention of capillary fragmentation. The potential advantage of inhibiting Sur1-Trpm4 channels using glibenclamide is a highly promising strategy for ameliorating the devastating sequelae of spinal cord trauma in humans. PMID:24834370

Simard, J Marc; Woo, Seung Kyoon; Aarabi, Bizhan; Gerzanich, Volodymyr

2013-01-01

135

The Sur1-Trpm4 Channel in Spinal Cord Injury.  

PubMed

Spinal cord injury (SCI) is a major unsolved challenge in medicine. Impact trauma to the spinal cord shears blood vessels, causing an immediate 'primary hemorrhage'. During the hours following trauma, the region of hemorrhage enlarges progressively, with delayed or 'secondary hemorrhage' adding to the primary hemorrhage, and effectively doubling its volume. The process responsible for the secondary hemorrhage that results in early expansion of the hemorrhagic lesion is termed 'progressive hemorrhagic necrosis' (PHN). PHN is a dynamic process of auto destruction whose molecular underpinnings are only now beginning to be elucidated. PHN results from the delayed, progressive, catastrophic failure of the structural integrity of capillaries. The resulting 'capillary fragmentation' is a unique, pathognomonic feature of PHN. Recent work has implicated the Sur1-Trpm4 channel that is newly upregulated in penumbral microvessels as being required for the development of PHN. Targeting the Sur1-Trpm4 channel by gene deletion, gene suppression, or pharmacological inhibition of either of the two channel subunits, Sur1 or Trpm4, yields exactly the same effects histologically and functionally, and exactly the same unique, pathognomonic phenotype - the prevention of capillary fragmentation. The potential advantage of inhibiting Sur1-Trpm4 channels using glibenclamide is a highly promising strategy for ameliorating the devastating sequelae of spinal cord trauma in humans. PMID:24834370

Simard, J Marc; Woo, Seung Kyoon; Aarabi, Bizhan; Gerzanich, Volodymyr

2013-08-17

136

Sensory Stimulation Prior to Spinal Cord Injury Induces Post-Injury Dysesthesia in Mice  

PubMed Central

Abstract Chronic pain and dysesthesias are debilitating conditions that can arise following spinal cord injury (SCI). Research studies frequently employ rodent models of SCI to better understand the underlying mechanisms and develop better treatments for these phenomena. While evoked withdrawal tests can assess hypersensitivity in these SCI models, there is little consensus over how to evaluate spontaneous sensory abnormalities that are seen in clinical SCI subjects. Overgrooming (OG) and biting after peripheral nerve injury or spinal cord excitotoxic lesions are thought to be one behavioral demonstration of spontaneous neuropathic pain or dysesthesia. However, reports of OG after contusion SCI are largely anecdotal and conditions causing this response are poorly understood. The present study investigated whether repeated application of sensory stimuli to the trunk prior to mid-thoracic contusion SCI would induce OG after SCI in mice. One week prior to SCI or laminectomy, mice were subjected either to nociceptive and mechanical stimulation, mechanical stimulation only, the testing situation without stimulation, or no treatment. They were then examined for 14 days after surgery and the sizes and locations of OG sites were recorded on anatomical maps. Mice subjected to either stimulus paradigm showed increased OG compared with unstimulated or uninjured mice. Histological analysis showed no difference in spinal cord lesion size due to sensory stimulation, or between mice that overgroomed or did not overgroom. The relationship between prior stimulation and contusion injury in mice that display OG indicates a critical interaction that may underlie one facet of spontaneous neuropathic symptoms after SCI. PMID:20121420

Hoschouer, Emily L.; Finseth, Taylor; Flinn, Sharon; Basso, D. Michele

2010-01-01

137

Interleukin-33 treatment reduces secondary injury and improves functional recovery after contusion spinal cord injury.  

PubMed

Interleukin-33 (IL-33) is a member of the interleukin-1 cytokine family and highly expressed in the naïve mouse brain and spinal cord. Despite the fact that IL-33 is known to be inducible by various inflammatory stimuli, its cellular localization in the central nervous system and role in pathological conditions is controversial. Administration of recombinant IL-33 has been shown to attenuate experimental autoimmune encephalomyelitis progression in one study, yet contradictory reports also exist. Here we investigated for the first time the pattern of IL-33 expression in the contused mouse spinal cord and demonstrated that after spinal cord injury (SCI) IL-33 was up-regulated and exhibited a nuclear localization predominantly in astrocytes. Importantly, we found that treatment with recombinant IL-33 alleviated secondary damage by significantly decreasing tissue loss, demyelination and astrogliosis in the contused mouse spinal cord, resulting in dramatically improved functional recovery. We identified both central and peripheral mechanisms of IL-33 action. In spinal cord, IL-33 treatment reduced the expression of pro-inflammatory tumor necrosis factor-alpha and promoted the activation of anti-inflammatory arginase-1 positive M2 microglia/macrophages, which chronically persisted in the injured spinal cord for up to at least 42 days after the treatment. In addition, IL-33 treatment showed a tendency towards reduced T-cell infiltration into the spinal cord. In the periphery, IL-33 treatment induced a shift towards the Th2 type cytokine profile and reduced the percentage and absolute number of cytotoxic, tumor necrosis factor-alpha expressing CD4+ cells in the spleen. Additionally, IL-33 treatment increased expression of T-regulatory cell marker FoxP3 and reduced expression of M1 marker iNOS in the spleen. Taken together, these results provide the first evidence that IL-33 administration is beneficial after CNS trauma. Treatment with IL33 may offer a novel therapeutic strategy for patients with acute contusion SCI. PMID:25153903

Pomeshchik, Yuriy; Kidin, Iurii; Korhonen, Paula; Savchenko, Ekaterina; Jaronen, Merja; Lehtonen, Sarka; Wojciechowski, Sara; Kanninen, Katja; Koistinaho, Jari; Malm, Tarja

2015-02-01

138

Effectiveness of olfactory ensheathing cell transplantation for treatment of spinal cord injury.  

PubMed

The aim of this study was to determine the effectiveness and safety of transplantation of olfactory ensheathing cells for functional repair of the spinal cord. An olfactory bulb was obtained from a 4- to 5-month-old aborted fetus, and it was digested into single olfactory ensheathing cells and then cultured and purified for 1 to 2 weeks. Under general anesthesia, these single-cell suspensions of olfactory ensheathing cells were injected into the corresponding spinal injury site with 0.45-mm-diameter injections. The American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate spinal function. A total of 15 patients (12 men, 3 women; age range, 18-56 years; mean age, 40) were admitted for obsolete spinal injuries. Spinal functions of the 15 patients were observed and followed postoperatively for a period ranging from 2 weeks to 1 month. All the 15 patients exhibited improvements in spinal function, and the improvement tendencies continued. Twelve patients had obvious spinal function improvement, and three had slight improvement according to the ASIA scale, with an obvious difference between preoperation and postoperation measures (P < 0.05). No fevers, infections, functional deteriorations, or deaths were seen. Thus, transplantation of olfactory ensheathing cells promoted spinal and neurofunctional recovery in patients with malignant spinal injuries, and this therapeutic method was safe. PMID:24938704

Rao, Y J; Zhu, W X; Du, Z Q; Jia, C X; Du, T X; Zhao, Q A; Cao, X Y; Wang, Y J

2014-01-01

139

Thrombospondin-4 and excitatory synaptogenesis promote spinal sensitization after painful mechanical joint injury.  

PubMed

Facet joint injury induces persistent pain that may be maintained by structural plasticity in the spinal cord. Astrocyte-derived thrombospondins, especially thrombospondin-4 (TSP4), have been implicated in synaptogenesis and spinal sensitization in neuropathic pain, but the TSP4 response and its relationship to synaptic changes in the spinal cord have not been investigated for painful joint injury. This study investigates the role of TSP4 in the development and maintenance of persistent pain following injurious facet joint distraction in rats and tests the hypothesis that excitatory synaptogenesis contributes to such pain. Painful facet joint loading induces dorsal horn excitatory synaptogenesis along with decreased TSP4 in the DRG and increased astrocytic release of TSP4 in the spinal cord, all of which parallel the time course of sustained tactile allodynia. Blocking injury-induced spinal TSP4 expression with antisense oligonucleotides or reducing TSP4 activity at its neuronal receptor in the spinal cord with gabapentin treatment both attenuate the allodynia and dorsal horn synaptogenesis that develop after painful facet joint loading. Increased spinal TSP4 also facilitates the development of allodynia and spinal hyperexcitability, even after non-painful physiological loading of the facet joint. These results suggest that spinal TSP4 plays an important role in the development and maintenance of persistent joint-mediated pain by inducing excitatory synaptogenesis and facilitating the transduction of mechanical loading of the facet joint that leads to spinal hyperexcitability. PMID:25483397

Crosby, Nathan D; Zaucke, Frank; Kras, Jeffrey V; Dong, Ling; Luo, Z David; Winkelstein, Beth A

2015-02-01

140

Improved rat spinal cord injury model using spinal cord compression by percutaneous method  

PubMed Central

Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 µL (n = 18), 50 µL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 µL was used, but not after 50 µL was applied. In the 50 µL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo. PMID:23820159

Chung, Wook-Hun; Lee, Jae-Hoon; Chung, Dai-Jung; Yang, Wo-Jong; Lee, A-Jin; Choi, Chi-Bong; Chang, Hwa-Seok; Kim, Dae-Hyun; Chung, Hyo Jin; Suh, Hyun Jung; Hwang, Soo-Han; Han, Hoon; Do, Sun Hee

2013-01-01

141

Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury  

PubMed Central

Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2–4 × 106, into multiple sites in the injured area under the surgical microscope. The sympathetic skin response in patients was measured with an electromyography/evoked potential instrument 1 day before transplantation and 3–8 weeks after transtion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory ensheathing cell transplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing cell transplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury. PMID:25206606

Zheng, Zuncheng; Liu, Guifeng; Chen, Yuexia; Wei, Shugang

2013-01-01

142

Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injury  

PubMed Central

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

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

2014-01-01

143

The Impact of Morphine After a Spinal Cord Injury  

PubMed Central

Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment 1 showed that after spinal cord injury 20 mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20 mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury. PMID:17383022

Hook, Michelle A.; Liu, Grace T.; Washburn, Stephanie N.; Ferguson, Adam R.; Bopp, Anne C.; Huie, John R.; Grau, James W.

2007-01-01

144

Obstacles to community participation among youth with spinal cord injury  

PubMed Central

Objective Examine caregiver-report of obstacles to community participation for youth with spinal cord injury (SCI), and explore relationships between obstacles and child, caregiver, and community characteristics. Design Two hundred and one primary caregivers of youth with SCI ages 7–17 years were interviewed at three pediatric SCI centers within a single-hospital system. Caregivers answered an open-ended question assessing obstacles to youth participation. A mixed-methods approach was incorporated, where qualitative methods analyzed caregiver-reported obstacles, and exploratory multivariate analyses examined relationships between obstacles and demographic variables. Results Caregivers were primarily mothers (74%), married (69%), employed (54%), had college experience (67%), and lived in small towns (55%). Youths' mean age was 12.60 years at interview and 7.19 years at injury, 70% had paraplegia, and 55% had complete injuries. Analyses revealed that youth participation was limited by obstacles across six domains: community, disability-related, practical concerns, child-internal, social, and other. Child, caregiver, and community characteristics were related to overall report of obstacles, and report of community obstacles, disability-related obstacles, and practical concerns. Caregiver college experience and small town living predicted overall report of obstacles. Having a child injured at a younger age, caregiver college experience, and small town living predicted community obstacles. Having a child with an incomplete injury and recent medical complication predicted disability-related obstacles. Caregiver employment predicted practical concerns. Conclusion Youth from small towns, those injured younger, those with incomplete injuries, and those experiencing recent medical complications may need additional supports and resources to maximize participation. Clinicians should work with caregivers to identify and problem-solve obstacles to youth participation. PMID:22330113

Gorzkowski, Julie; Kelly, Erin H.; Klaas, Sara J.; Vogel, Lawrence C.

2011-01-01

145

Assessment and Evaluation of Primary Prevention in Spinal Cord Injury  

PubMed Central

Although the incidence of spinal cord injury (SCI) is low, the consequences of this disabling condition are extremely significant for the individual, family, and the community. Sequelae occur in the physical, psychosocial, sexual, and financial arenas, making global prevention of SCI crucial. Understanding how to assess and evaluate primary prevention programs is an important competency for SCI professionals. Assessing a program’s success requires measuring processes, outcomes, and impact. Effective evaluation can lead future efforts for program design while ensuring accountability for the program itself. The intended impact of primary prevention programs for SCI is to decrease the number of individuals who sustain traumatic injury; many programs have process and outcome goals as well. An understanding of the basic types of evaluation, evaluation design, and the overall process of program evaluation is essential for ensuring that these programs are efficacious. All health care professionals have the opportunity to put prevention at the forefront of their practice. With the current paucity of available data, it is important that clinicians share their program design, their successes, and their failures so that all can benefit and future injury can be prevented. PMID:23678281

2013-01-01

146

Recognition and management of spinal cord injuries in sports and recreation.  

PubMed

Spinal injuries and spinal cord injuries in sports and recreation represent frequent and important causes of injury and disability. These injuries are virtually all preventable through strict adherence to the codes of conduct of the rules and regulations for sports and recreation and through an attitude of respect for one's own welfare and the welfare of the opponents or other participants. Adherence to guidelines for return to sport after injury can help to prevent worsening of deficits and the onset of new deficits. PMID:19084764

Tator, Charles H

2009-02-01

147

Exercise awareness and barriers after spinal cord injury.  

PubMed

Exercise is an essential element in managing several of the non-communicable diseases after spinal cord injury (SCI). Awareness of the importance of prescribing a customized exercise program that meets the goals of persons with SCI should be highly considered in the rehabilitation community. The barriers of implementing specific exercise program as well as the factors that may mask the outcomes of regular exercise regimen need to be continuously addressed as a part of patients' rehabilitation care. The focus of this editorial is to encourage the medical community to consider routine physical activity as one of the necessary vital signs that needs to be routinely checked in patients with SCI. Providing education tips, nutritional counseling and engaging in recreational programs may provide motivational route to the community of SCI. This may result in reinforcing active lifestyle in survivors with SCI as well as to reduce the impact of chronic life threatening medical disorders. PMID:25035817

Gorgey, Ashraf S

2014-07-18

148

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

PubMed Central

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

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

2012-01-01

149

Gap junction proteins and their role in spinal cord injury  

PubMed Central

Gap junctions are specialized intercellular communication channels that are formed by two hexameric connexin hemichannels, one provided by each of the two adjacent cells. Gap junctions and hemichannels play an important role in regulating cellular metabolism, signaling, and functions in both normal and pathological conditions. Following spinal cord injury (SCI), there is damage and disturbance to the neuronal elements of the spinal cord including severing of axon tracts and rapid cell death. The initial mechanical disruption is followed by multiple secondary cascades that cause further tissue loss and dysfunction. Recent studies have implicated connexin proteins as playing a critical role in the secondary phase of SCI by propagating death signals through extensive glial networks. In this review, we bring together past and current studies to outline the distribution, changes and roles of various connexins found in neurons and glial cells, before and in response to SCI. We discuss the contribution of pathologically activated connexin proteins, in particular connexin 43, to functional recovery and neuropathic pain, as well as providing an update on potential connexin specific pharmacological agents to treat SCI. PMID:25610368

Tonkin, Ryan S.; Mao, Yilin; O’Carroll, Simon J.; Nicholson, Louise F. B.; Green, Colin R.; Gorrie, Catherine A.; Moalem-Taylor, Gila

2015-01-01

150

Phrenic motoneuron discharge patterns following chronic cervical spinal cord injury  

PubMed Central

Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and triggers biochemical, as well as morphological, plasticity in relation to the phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to determine if chronic SCI induces fundamental changes in the recruitment profile and discharge patterns of PhMNs. Individual PhMN action potentials were recorded from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in uninjured controls. PhMNs were phenotypically classified as early (Early-I) or late inspiratory (Late-I), or silent according to discharge patterns. Following C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I burst parameters (e.g., spikes per breath, burst frequency and duration) were initially reduced but returned towards control values by 8 wks post-injury. In addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells burst tonically during hypocapnic inspiratory apnea. We also quantified the impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined, the C2Hx animals had greater inspiratory frequencies (breaths*min?1) and more substantial decreases in ipsilateral phrenic burst amplitude. We conclude that the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a persistent delay in burst onset, transient reductions in burst frequency, and the emergence of tonic burst patterns. The inspiratory frequency data suggest that plasticity in brainstem networks is likely to play an important role in phrenic motor output after cervical SCI. PMID:23954215

Lee, Kun-Ze; Dougherty, Brendan J.; Sandhu, Milapjit S.; Lane, Michael A.; Reier, Paul J.; Fuller, David D.

2013-01-01

151

Dual diagnoses: the person with a spinal cord injury and a concomitant brain injury.  

PubMed

Spinal cord injury (SCI) alone is a devastating event that often results in physical disability. When the SCI is combined with a brain injury, the degree of disability can be magnified and the patient's rehabilitation becomes further complicated. It is not unusual for the head injury to be overlooked or undetected during the emergent and acute phases of treatment. The brain injury may first appear when the client demonstrates an inability or resistance to carry out functional activities appropriate to his/her level of injury. Cognitive deficits can limit or complicate the client's ability to adapt to his/her physical limitations, learn compensatory skills, and achieve the maximal level of independence. These patients require a wide base of physical, psychological, educational, and medical support. Because they are at a high risk for developing complications, they will require lifelong interventions and involvement from an interdisciplinary team to provide a safety net. The following article examines the patient with dual diagnoses of SCI and brain injury. A comprehensive review of commonly encountered problematic scenarios and interventions is presented. PMID:14626031

Arzaga, Deborah; Shaw, Vance; Vasile, Ann T

2003-01-01

152

Axon regeneration and exercise-dependent plasticity after spinal cord injury  

PubMed Central

Current dogma is that meaningful recovery of function after spinal cord injury (SCI) likely will require a combination of therapeutic interventions comprised of regenerative/neuroprotective transplants, addition of neurotrophic factors, elimination of inhibitory molecules, functional sensorimotor training, and/or stimulation of paralyzed muscles or spinal circuits. We routinely use: (1) peripheral nerve grafts to support and direct axonal regeneration across an incomplete cervical or a complete thoracic transection injury, (2) matrix modulation with chondroitinase (ChABC) to facilitate axonal extension beyond the distal graft-spinal cord interface and (3) exercise, such as forced wheel walking, bicycling or step training on a treadmill. We (and others) have demonstrated an increase in spinal cord levels of endogenous neurotrophic factors with exercise, which may be useful in facilitating elongation and/or synaptic activity of regenerating axons and plasticity of spinal neurons below the level of injury PMID:23531013

Houlé, John D; Côté, Marie-Pascale

2013-01-01

153

Severe Spinal Cord Injury Causes Immediate Multi-cellular Dysfunction at the Chondro-Osseous Junction  

PubMed Central

Spinal cord injury is associated with rapid bone loss and arrested long bone growth due to mechanisms that are poorly understood. In this study, we sought to determine the effects of severe T10 contusion spinal cord injury on the sublesional bone microenvironment in adolescent rats. A severe lower thoracic (vertebral T10) spinal cord injury was generated by weight drop (10 g×50 mm). Severely injured and body weight-matched uninjured male Sprague–Dawley rats were studied. At 3 and 5 days post-injury, we performed histological analysis of the distal femoral metaphysis, TUNEL assay, immunohistochemistry, real-time PCR, and western blot analysis compared to uninjured controls. We observed severe hindlimb functional deficits typical of this model. We detected uncoupled remodeling with increased osteoclast activity in the absence of osteoblast activity. We detected osteoblast, osteocyte, and chondrocyte apoptosis with suppressed osteoblast and chondrocyte proliferation and growth plate arrest due to spinal cord injury. We also detected altered gene expression in both whole bone extracts and bone marrow monocytes following spinal cord injury. We conclude that spinal cord injury results in altered gene expression of key regulators of osteoblast and chondrocyte activity. This leads to premature cellular apoptosis, suppressed cellular proliferation, growth plate arrest, and uncoupled bone remodeling in sublesional bone with unopposed osteoclastic resorption. PMID:22368723

Xu, Yan; Solomon, Bethlehem; Boyle, Lara; Yoganathan, Subbiah; Stashenko, Philip; Battaglino, Ricardo A.

2011-01-01

154

Arrested development of the dorsal column following neonatal spinal cord injury in the opossum, Monodelphis domestica.  

PubMed

Developmental studies of spinal cord injury in which regrowth of axons occurs across the site of transection rarely distinguish between the recovery of motor-controlling pathways and that of ascending axons carrying sensory information. We describe the morphological changes that occur in the dorsal column (DC) of the grey short-tailed opossum, Monodelphis domestica, following spinal cord injury at two early developmental ages. The spinal cords of opossums that had had their mid-thoracic spinal cords completely transected at postnatal day 7 (P7) or P28 were analysed. Profiles of neurofilament immunoreactivity in transected cords showing DC development were differentially affected by the injury compared with the rest of the cord and cytoarchitecture was modified in an age- and site-dependent manner. The ability of DC neurites to grow across the site of transection was confirmed by injection of fluorescent tracer below the injury. P7 transected cords showed labelling in the DC above the site of original transection indicating that neurites of this sensory tract were able to span the injury. No growth of any neuronal processes was seen after P28 transection. Thus, DC is affected by spinal injury in a differential manner depending on the age at which the transection occurs. This age-differential response, together with other facets of remodelling that occur after neonatal spinal injury, might explain the locomotor adaptations and recovery observed in these animals. PMID:25487408

Wheaton, Benjamin J; Noor, Natassya M; Dziegielewska, Katarzyna M; Whish, Sophie; Saunders, Norman R

2014-12-01

155

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

ERIC Educational Resources Information Center

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

Chapin, Martha H.; Holbert, Donald

2009-01-01

156

Morbid obesity and spinal cord injury: a case study.  

PubMed

With obesity on the rise in the United States, most nurses will probably encounter the unique challenges that result from the pathophysiological changes in this population. The combination of morbid obesity and any other disease process or injury create complex medical management issues for caregivers during hospitalization and after discharge. Complications of spinal cord injury are intensified with obesity. Prevention and treatment of secondary complications require nursing practice to go above and beyond the standards of care. This paper clearly illustrates the nursing challenges by focusing on the experience of caring for a morbidly obese person who sustained a C5-6 spinal cord injury. Complications unique to this patient, as well as adjustments in care, will be discussed with a main focus on the acute rehabilitation phase. Ms. Z. is a 24-year-old female who worked as a home health aide. One cold winter day, as she was driving to a client's house, she lost control of her truck and struck another vehicle. The result of Ms. Z.'s accident was a C5-6 complete spinal cord injury (SCI), which would be complicated by her weight of more than 400 pounds. When the accident occurred, Ms. Z. was not wearing a seatbelt and had not worn one since age 12 because they did not fit. In fact, it is reported that obesity is associated with decreased seat belt use (Lichtenstein, Bolton & Wade, 1989). It took an hour to extricate Ms. Z. from the truck. She was then flown via Mayo One life support helicopter to our Type I Emergency Trauma Unit/Center. There she received methylprednisolone 4.8 gm i.v./1 hour followed by 22 cc/hr or 5.4 mg/kg over 23 hours. After medical personnel made assessments, they sent her to the operating room for cervical fusion. Ms. Z.'s obesity complicated positioning, X-ray, draping, and all facets of the operative procedure. Ms. Z. was in the intensive care unit (ICU) for six weeks, where she faced more complications that included: prolonged ventilator dependence; right upper lobe collapse; three episodes of asystole after being turned; a midback adipose fold wound; and urinary tract infections. Members of the rehabilitation team (physicians, nurses, physical therapists, occupational therapists, and a psychologist) became involved in her care at the beginning of her ICU stay. Early intervention by the rehabilitation team was essential to provide Ms. Z. with collaborative care and to eventually ensure an adequately prepared transition to the rehabilitation unit while maintaining continuity of care. Innovative planning for Ms. Z.'s transition to rehabilitation and mobilization included careful selection of beds, wheelchairs, and lifts to accommodate her weight and body size. PMID:9883184

Beck, L A

1998-03-01

157

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

PubMed Central

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

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

2013-01-01

158

Spinal injury in a U.S. Army light observation helicopter.  

PubMed

All accident reports involving U.S. Army OH-58 series helicopters were analyzed to determine vertical and horizontal velocity change at impact and the relationship of this kinematic data to the production of spinal injury. This analysis determined that spinal injury is related primarily to vertical velocity change at impact and is relatively independent of horizontal velocity change. The dramatic increase in the rate of spinal injury occurring just above the design sink speed of the aircraft landing gear (3.7 m/s) suggests that the fuselage and seat provide little additional impact attenuation capability above that of the gear alone. It is concluded that if this aircraft were modified to provide protection to the occupants for impacts up to 9.1 m/s (30 ft/s), approximately 80% of all spinal injury incurred in survivable accidents could be substantially mitigated. The incorporation of energy absorbing seats is recommended. PMID:6696693

Shanahan, D F; Mastroianni, G R

1984-01-01

159

W. M. Keck Center for Collaborative Neuroscience THE SPINAL CORD INJURY PROJECT  

E-print Network

W. M. Keck Center for Collaborative Neuroscience THE SPINAL CORD INJURY PROJECT WORKSHOP. ___ Refresher Course (for previous attendees), $425. Personal Information (Please print clearly) Title: __ Dr Neuroscience. __ Purchase Order #_________. Purchase Order Total $ __________ ___ is enclosed; ___ will follow

Chen, Kuang-Yu

160

U.S. Veterans Hospital, Jefferson Barracks, Spinal Cord Injury Unit and ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

U.S. Veterans Hospital, Jefferson Barracks, Spinal Cord Injury Unit and Tuberculosis Neuropsychiatric Building, VA Medical Center, Jefferson Barracks Division 1 Jefferson Barracks Drive, Saint Louis, Independent City, MO

161

Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury  

E-print Network

, and thereby reduce secondary damage and perhaps the development of chronic central pain. To test stimulation could result from peripheral injuries that accom- pany spinal trauma. Moreover, previous studies

Grau, James

162

Sexual activities, desire, and satisfaction in males pre- and post-spinal cord injury  

Microsoft Academic Search

Thirty-eight spinal cord injured (SCI) males (median age = 26) completed an 80-item multiple choice questionnaire (median 37 months postinjury) which assessed sexual functioning pre- and post-spinal cord injury in four areas: (i) sexual activities and preferences, (ii) sexual abilities, (iii) sexual desire, arousal, and satisfaction, and, (iv) sexual adjustment. Frequency of sexual activity decreased following SCI with a reduction

Craig J. Alexander; Marca L. Sipski; Thomas W. Findley

1993-01-01

163

Realization of an active book for multichannel intrathecal root stimulation in spinal cord injury — Preliminary results  

Microsoft Academic Search

After spinal cord injury, electrical stimulation of the roots inside the spinal column at the level of the cauda equina is a safe and effective way to regain some degree of control over lower body function, e.g. bladder and bowel management and leg movement. The success of current systems used for so-called intrathecal stimulation is limited by the low number

Martin Schuettler; Anne Vanhoestenberghe; Nooshin Saeidi; Xiao Liu; Joe Evans; Cindy Colinge; Andreas Demosthenous; Nick Donaldson

2011-01-01

164

Examining the effect of spinal cord injury on emotional awareness, expressivity and memory for emotional material  

Microsoft Academic Search

The prevailing view on the effects of spinal cord injury (SCI) on emotion is that it dampens emotional experience due to a loss of peripheral bodily feedback, with the higher the lesion on the spinal cord the greater the reduction in the intensity of emotional experience. This view persists despite many studies showing an absence of such an emotional impairment

D. K. Deady; N. T. North; D. Allan; M. J. Law Smith; R. E. OCarroll

2010-01-01

165

Neuroprotective effects of rosuvastatin against traumatic spinal cord injury in rats.  

PubMed

Rosuvastatin, which is a potent statin, has never been studied in traumatic spinal cord injury. The aim of this study was to investigate whether rosuvastatin treatment could protect the spinal cord after experimental spinal cord injury. Rats were randomized into the following five groups of eight animals each: control, sham, trauma, rosuvastatin, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumor necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analyzed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test.After traumatic spinal cord injury, increases in caspase-3 activity, tumor necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. In contrast, the superoxide dismutase levels were decreased. After the administration of rosuvastatin, decreases were observed in the tissue caspase-3 activity, tumor necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. In contrast, tissue superoxide dismutase levels were increased. Furthermore, rosuvastatin treatment showed improved results concerning the histopathological scores, the ultrastructural score and the functional tests. Biochemical, histopathological, ultrastructural analysis and functional tests revealed that rosuvastatin exhibits meaningful neuroprotective effects against spinal cord injury. PMID:25084223

Kahveci, Ramazan; Gökçe, Emre Cemal; Gürer, Bora; Gökçe, Aysun; Kisa, Uçler; Cemil, Duran Berker; Sargon, Mustafa Fevzi; Kahveci, Fatih Ozan; Aksoy, Nurkan; Erdo?an, Bülent

2014-10-15

166

Charcot Arthropathy of the Lumbosacral Spine Mimicking a Vertebral Tumor after Spinal Cord Injury  

PubMed Central

Charcot spinal arthropathy is a rare, progressive type of vertebral joint degeneration that occurs in the setting of any preexisting condition characterized by decreased afferent innervation to the extent that normal protective joint sensation in the vertebral column is impaired. The authors report on a case of Charcot arthropathy of the lower lumbar spine mimicking a spinal tumor following cervical cord injury. PMID:24527202

Son, Soo-Bum; Kim, Eun-Sang; Eoh, Whan

2013-01-01

167

Neural stem cell transplantation in experimental contusive model of spinal cord injury.  

PubMed

Spinal cord injury is a devastating clinical condition, characterized by a complex of neurological dysfunctions. Animal models of spinal cord injury can be used both to investigate the biological responses to injury and to test potential therapies. Contusion or compression injury delivered to the surgically exposed spinal cord are the most widely used models of the pathology. In this report the experimental contusion is performed by using the Infinite Horizon (IH) Impactor device, which allows the creation of a reproducible injury animal model through definition of specific injury parameters. Stem cell transplantation is commonly considered a potentially useful strategy for curing this debilitating condition. Numerous studies have evaluated the effects of transplanting a variety of stem cells. Here we demonstrate an adapted method for spinal cord injury followed by tail vein injection of cells in CD1 mice. In short, we provide procedures for: i) cell labeling with a vital tracer, ii) pre-operative care of mice, iii) execution of a contusive spinal cord injury, and iv) intravenous administration of post mortem neural precursors. This contusion model can be utilized to evaluate the efficacy and safety of stem cell transplantation in a regenerative medicine approach. PMID:25548937

Carelli, Stephana; Giallongo, Toniella; Gerace, Claudio; De Angelis, Anthea; Basso, Michele D; Di Giulio, Anna Maria; Gorio, Alfredo

2014-01-01

168

Supported treadmill ambulation training after spinal cord injury: A pilot study  

Microsoft Academic Search

Protas EJ, Holmes SA, Qureshy H, Johnson A, Lee D, Sherwood AM. Supported treadmill ambulation training after spinal cord injury: a pilot study. Arch Phys Med Rehabil 2001;82:825-31. Objectives: To conduct a pilot study of weight-supported ambulation training after incomplete spinal cord injury (SCI), and to assess its safety. Design: Quasiexperimental, repeated measures, single group. Setting: Veterans Affairs medical center.

Elizabeth J. Protas; S. Ann Holmes; Huma Qureshy; Andrew Johnson; Dongchul Lee; Arthur M. Sherwood

2001-01-01

169

Treatment of detrusor-sphincter dyssynergia by pudendal nerve block in patients with spinal cord injury  

Microsoft Academic Search

Tsai S-J, Lew HL, Date E, Bih L-I. Treatment of detrusor-sphincter dyssynergia by pudendal nerve block in patients with spinal cord injury. Arch Phys Med Rehabil 2002;83:714-7. Objective: To study the effects of pudendal nerve block with phenol on detrusor-sphincter dyssynergia in patients with spinal cord injury (SCI). Design: Before-after trial performed by using a consecutive sample. Setting: Rehabilitation hospital

Su-Ju Tsai; Henry L. Lew; Elaine Date; Liu-Ing Bih

2002-01-01

170

A correction procedure for the minnesota Multiphasic Personality Inventory—2 for persons with spinal cord injury  

Microsoft Academic Search

Barncord SB, Wanlass RL. A correction procedure for the Minnesota Multiphasic Personality Inventory—2 for persons with spinal cord injury. Arch Phys Med Rehabil 2000;81:1185-90. Objective: To develop a procedure that adjusts scoring of the Minnesota Multiphasic Personality Inventory—2 (MMPI-2) for the items related to spinal cord injury (SCI) that skew interpretations with this population, and to assess the accuracy of

Steven W. Barncord; Richard L. Wanlass

2000-01-01

171

Chair configuration and balance control in persons with spinal cord injury  

Microsoft Academic Search

Janssen-Potten YJM, Seelen HAM, Drukker J, Reulen JPH. Chair configuration and balance control in persons with spinal cord injury. Arch Phys Med Rehabil 2000;81:401-8. Objective: To study whether chair configuration influences sitting balance in persons with spinal cord injury (SCI). Design: Cross-sectional group study. Setting: Rehabilitation centers and hospital rehabilitation departments. Patients: Ten complete high thoracic SCI (level T2-T8) patients,

Yvonne J. M Janssen-Potten; Henk A. M Seelen; Jan Drukker; Jos P. H Reulen

2000-01-01

172

Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient: Case report.  

PubMed

Over the last decade, human cell transplantation and neural stem cell trials have examined the feasibility and safety of these potential therapies for treatment of a variety of neurological disorders. However, significant safety concerns have surrounded these trials due to the possibility of ectopic, uncontrolled cellular growth and tumor formation. The authors present the case of an 18-year-old woman who sustained a complete spinal cord injury at T10-11. Three years after injury, she remained paraplegic and underwent olfactory mucosal cell implantation at the site of injury. She developed back pain 8 years later, and imaging revealed an intramedullary spinal cord mass at the site of cell implantation, which required resection. Intraoperative findings revealed an expanded spinal cord with a multicystic mass containing large amounts of thick mucus-like material. Histological examination and immunohistochemical staining revealed that the mass was composed mostly of cysts lined by respiratory epithelium, submucosal glands with goblet cells, and intervening nerve twigs. This is the first report of a human spinal cord mass complicating spinal cord cell transplantation and neural stem cell therapy. Given the prolonged time to presentation, safety monitoring of all patients with cell transplantation and neural stem cell implantation should be maintained for many years. PMID:25002238

Dlouhy, Brian J; Awe, Olatilewa; Rao, Rajesh C; Kirby, Patricia A; Hitchon, Patrick W

2014-10-01

173

Licofelone modulates neuroinflammation and attenuates mechanical hypersensitivity in the chronic phase of spinal cord injury  

PubMed Central

Inflammation is a major factor shaping outcome during the early, acute phase of traumatic spinal cord injury (SCI). It is known that pro-inflammatory signaling within the injured spinal cord drives pathological alterations in neurosensory processing and shapes functional outcome early after injury. However, it is unclear whether inflammation persists into the chronic phase of injury or shapes sensory processing long after injury. In order to investigate these possibilities, we have performed biochemical and behavioral assessments 9 months after moderate thoracic spinal contusion injury in the rat. We have found that levels of the pro-inflammatory lipid mediators leukotriene B4 and prostaglandin E2 are elevated in the chronic spinal cord lesion site. Additionally, using metabolomic profiling, we have detected elevated levels of pro-oxidative and inflammatory metabolites, along with alterations in multiple biological pathways within the chronic lesion site. We found that 28-day treatment of chronically-injured rats with the dual COX/5-LOX inhibitor licofelone elevated levels of endogenous anti-oxidant and anti-inflammatory metabolites within the lesion site. Furthermore, licofelone treatment reduced hypersensitivity of hindpaws to mechanical, but not thermal, stimulation, indicating that mechanical sensitivity is modulated by pro-inflammatory signaling in the chronic phase of injury. Together, these findings provide novel evidence of inflammation and oxidative stress within spinal cord tissue far into the chronic phase of SCI, and demonstrate a role for inflammatory modulation of mechanical sensitivity in the chronic phase of injury. PMID:23303944

Dulin, Jennifer N.; Karoly, Edward D.; Wang, Ying; Strobel, Henry W.; Grill, Raymond J.

2013-01-01

174

CSF Proteomics of Secondary Phase Spinal Cord Injury in Human Subjects: Perturbed Molecular Pathways Post Injury  

PubMed Central

Recovery of sensory and motor functions following traumatic spinal cord injury (SCI) is dependent on injury severity. Here we identified 49 proteins from cerebrospinal fluid (CSF) of SCI patients, eight of which were differentially abundant among two severity groups of SCI. It was observed that the abundance profiles of these proteins change over a time period of days to months post SCI. Statistical analysis revealed that these proteins take part in several molecular pathways including DNA repair, protein phosphorylation, tRNA transcription, iron transport, mRNA metabolism, immune response and lipid and ATP catabolism. These pathways reflect a set of mechanisms that the system may adopt to cope up with the assault depending on the injury severity, thus leading to observed physiological responses. Apart from putting forward a picture of the molecular scenario at the injury site in a human study, this finding further delineates consequent pathways and molecules that may be altered by external intervention to restrict neural degeneration. PMID:25350754

Sengupta, Mohor Biplab; Basu, Mahashweta; Iswarari, Sourav; Mukhopadhyay, Kiran Kumar; Sardar, Krishna Pada; Acharyya, Biplab; Mohanty, Pradeep K.; Mukhopadhyay, Debashis

2014-01-01

175

Systemic effects induced by intralesional injection of ?-conotoxin MVIIC after spinal cord injury in rats  

PubMed Central

Background Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes. Results The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol. Conclusions These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue. PMID:24739121

2014-01-01

176

Adult spinal cord ependymal layer: a promising pool of quiescent stem cells to treat spinal cord injury  

PubMed Central

Spinal cord injury (SCI) is a major health burden and currently there is no effective medical intervention. Research performed over the last decade revealed that cells surrounding the central canal of the adult spinal cord and forming the ependymal layer acquire stem cell properties either in vitro or in response to injury. Following SCI activated ependymal cells generate progeny cells which migrate to the injury site but fail to produce the appropriate type of cells in sufficient number to limit the damage, rendering this physiological response mainly ineffective. Research is now focusing on the manipulation of ependymal cells to produce cells of the oligodendrocyte lineage which are primarily lost in such a situation leading to secondary neuronal degeneration. Thus, there is a need for a more focused approach to understand the molecular properties of adult ependymal cells in greater detail and develop effective strategies for guiding their response during SCI. PMID:24348422

Panayiotou, Elena; Malas, Stavros

2013-01-01

177

Minimizing Errors in Acute Traumatic Spinal Cord Injury Trials by Acknowledging the Heterogeneity of Spinal Cord Anatomy and Injury Severity: An Observational Canadian Cohort Analysis  

PubMed Central

Abstract Clinical trials of therapies for acute traumatic spinal cord injury (tSCI) have failed to convincingly demonstrate efficacy in improving neurologic function. Failing to acknowledge the heterogeneity of these injuries and under-appreciating the impact of the most important baseline prognostic variables likely contributes to this translational failure. Our hypothesis was that neurological level and severity of initial injury (measured by the American Spinal Injury Association Impairment Scale [AIS]) act jointly and are the major determinants of motor recovery. Our objective was to quantify the influence of these variables when considered together on early motor score recovery following acute tSCI. Eight hundred thirty-six participants from the Rick Hansen Spinal Cord Injury Registry were analyzed for motor score improvement from baseline to follow-up. In AIS A, B, and C patients, cervical and thoracic injuries displayed significantly different motor score recovery. AIS A patients with thoracic (T2-T10) and thoracolumbar (T11-L2) injuries had significantly different motor improvement. High (C1-C4) and low (C5-T1) cervical injuries demonstrated differences in upper extremity motor recovery in AIS B, C, and D. A hypothetical clinical trial example demonstrated the benefits of stratifying on neurological level and severity of injury. Clinically meaningful motor score recovery is predictably related to the neurological level of injury and the severity of the baseline neurological impairment. Stratifying clinical trial cohorts using a joint distribution of these two variables will enhance a study's chance of identifying a true treatment effect and minimize the risk of misattributed treatment effects. Clinical studies should stratify participants based on these factors and record the number of participants and their mean baseline motor scores for each category of this joint distribution as part of the reporting of participant characteristics. Improved clinical trial design is a high priority as new therapies and interventions for tSCI emerge. PMID:24811484

Noonan, Vanessa K.; Fallah, Nader; Fisher, Charles G.; Rivers, Carly S.; Ahn, Henry; Tsai, Eve C.; Linassi, A.G.; Christie, Sean D.; Attabib, Najmedden; Hurlbert, R. John; Fourney, Daryl R.; Johnson, Michael G.; Fehlings, Michael G.; Drew, Brian; Bailey, Christopher S.; Paquet, Jérôme; Parent, Stefan; Townson, Andrea; Ho, Chester; Craven, B.C.; Gagnon, Dany; Tsui, Deborah; Fox, Richard; Mac-Thiong, Jean-Marc; Kwon, Brian K.

2014-01-01

178

Incomplete Freund's adjuvant enhances locomotor performance following spinal cord injury.  

PubMed

Following spinal cord injury (SCI), the pathological sequelae which ensue through the secondary mechanisms of degeneration produce myelin deposits which are potent inhibitors of endogenous neuroregeneration. We have enhanced the immune-mediated response following a hemisection lesion by immunizing adult C57Bl/6 female mice against the inhibitor of neurite outgrowth Nogo-A(623-640) peptide. Moderate anti-Nogo-A(623-640) antibody titre levels were obtained by using Montanide as the adjuvant. However, this antibody response was not obtained using incomplete Freund's adjuvant (IFA). Significant benefit in locomotor performance was demonstrated only in animals which were vaccinated with IFA and not with Montanide. No further benefit could be demonstrated with the Nogo-A(623-640) peptide beyond that seen for adjuvant alone. These data imply that generating antibodies against Nogo-A(623-640) in vivo alone is not sufficient to enhance locomotor recovery and that subcutaneous injection of IFA prior to SCI can enhance locomotor performance. PMID:16324097

Azari, M F; Karnezis, T; Bernard, C C; Profyris, C; LeGrande, M R; Zang, D W; Cheema, S S; Petratos, S

2005-12-01

179

[Possibility of controlling orthostatic instability in spinal cord injuries].  

PubMed

Hemodynamics were studied in 10 patients with high (cervical) spinal cord injury in a change to a vertical position. They were fitted with special antioverexertion gear (AOG) consisting of an abdominal, two thigh, and two knee inflatable rubber cuffs in which pressure of +50 mm Hg was produced. Measurements were taken every minute of arterial pressure, volumetric rate of blood flow in the upper limb (by venous-occlusion plethysmography), cardiac output and stroke volume (by body integral rheography); peripheral resistance and vascular resistance were calculated from a formula. Change of the patient to a vertical position without the use of the AOG was attended by a sharp fall in arterial pressure, stroke volume, and peripheral resistance and by marked tachycardia. Orthostatic collapse developed in the third-fourth minute. The use of the AOG prevented such a fall in the hemodynamic parameters which stayed on a higher level, this made it possible for the patients to remain in an erect position for 10 minutes and longer. These of the AOG in recommended in the first stage of training patients with sharply pronounced orthostatic instability. PMID:6331694

Moiseev, V A

1984-01-01

180

Recent Advances in Pathophysiology and Treatment of Spinal Cord Injury  

NSDL National Science Digital Library

Thirty years ago, patients with spinal cord injury (SCI) and their families were told "nothing can be done" to improve function. Since the SCI patient population is reaching normal life expectancy through better health care, it has become an obviously worthwhile enterprise to devote considerable research effort to SCI. Targets for intervention in SCI toward improved function have been identified using basic research approaches and can be simplified into a list: 1) reduction of edema and free-radical production, 2) rescue of neural tissue at risk of dying in secondary processes such as abnormally high extracellular glutamate concentrations, 3) control of inflammation, 4) rescue of neuronal/glial populations at risk of continued apoptosis, 5) repair of demyelination and conduction deficits, 6) promotion of neurite growth through improved extracellular environment, 7) cell replacement therapies, 8) efforts to bridge the gap with transplantation approaches, 9) efforts to retrain and relearn motor tasks, 10) restoration of lost function by electrical stimulation, and 11) relief of chronic pain syndromes. Currently, over 70 clinical trials are in progress worldwide. Consequently, in this millennium, unlike in the last, no SCI patient will have to hear "nothing can be done."

Claire E. Hulsebosch (University of Texas Medical Branch Department of Anatomy and Neurosciences)

2002-12-01

181

Combination Drug Therapy for Pain following Chronic Spinal Cord Injury  

PubMed Central

A number of mechanisms have been elucidated that maintain neuropathic pain due to spinal cord injury (SCI). While target-based therapeutics are being developed based on elucidation of these mechanisms, treatment for neuropathic SCI pain has not been entirely satisfactory due in part to the significant convergence of neurological and inflammatory processes that maintain the neuropathic pain state. Thus, a combination drug treatment strategy, wherein several pain-related mechanism are simultaneously engaged, could be more efficacious than treatment against individual mechanisms alone. Also, by engaging several targets at once, it may be possible to reduce the doses of the individual drugs, thereby minimizing the potential for adverse side effects. Positive preclinical and clinical studies have demonstrated improved efficacy of combination drug treatment over single drug treatment in neuropathic pain of peripheral origin, and perhaps such combinations could be utilized for neuropathic SCI pain. At the same time, there are mechanisms that distinguish SCI from peripheral neuropathic pain, so novel combination therapies will be needed. PMID:22550581

Hama, Aldric; Sagen, Jacqueline

2012-01-01

182

Treatment of infertility in men with spinal cord injury.  

PubMed

Most men with spinal cord injury (SCI) are infertile. Erectile dysfunction, ejaculatory dysfunction and semen abnormalities contribute to the problem. Treatments for erectile dysfunction include phosphodiesterase type 5 inhibitors, intracavernous injections of alprostadil, penile prostheses, and vacuum constriction devices. In anejaculatory patients who wish to father children, semen retrieval is necessary. Penile vibratory stimulation is recommended as the first line of treatment. Patients who fail penile vibratory stimulation can be referred for electroejaculation. If this approach is not possible, prostate massage is an alternative. Surgical sperm retrieval should be considered as a last resort when other methods fail. Most men with SCI have a unique semen profile characterized by normal sperm count but abnormally low sperm motility. Scientific investigations indicate that accessory gland dysfunction and abnormal semen constituents contribute to the problem. Despite abnormalities, sperm from men with SCI can successfully induce pregnancy. In selected couples, the simple method of intravaginal insemination is a viable option. Another option is intrauterine insemination. The efficacy of intrauterine insemination increases as the total motile sperm count inseminated increases. In vitro fertilization and intracytoplasmic sperm injection are options in cases of extremely low total motile sperm count. Reproductive outcomes for SCI male factor infertility are similar to outcomes for general male factor infertility. PMID:20157304

Brackett, Nancy L; Lynne, Charles M; Ibrahim, Emad; Ohl, Dana A; Sønksen, Jens

2010-03-01

183

Trigemino-cervical reflex in spinal cord injury.  

PubMed

Abnormal enhancement of polysynaptic brainstem reflexes has been previously reported in patients with spinal cord injury (SCI). We aimed to investigate trigemino-cervical reflex (TCR) in SCI since it may reflect alterations in the connections of trigeminal proprioceptive system and cervical motoneurons. Consecutive 14 patients with SCI and 16 healthy subjects were included in this study. All patients were in the chronic phase. TCR was recorded over sternocleidomastoid (SCM) and splenius capitis (SC) muscles by stimulation of infraorbital nerve. We measured onset latency, amplitudes and durations of responses and compared between groups. We obtained stable responses over both muscles after one sided stimulation in healthy volunteers whereas probability of TCR was decreased in patients over both SCM (78.6% vs. 100%, p=0.050) and SC (71.4% vs. 100%, p=0.022). The absence of TCR was related to use of oral baclofen (?50mg/day). However, when present, responses of SCI group had higher amplitudes and were more persistent. We demonstrated that TCR probability was similar to healthy subjects in SCI patients who used no or low dose oral baclofen. But it had higher amplitudes and longer durations. It was not obtained in only two patients who used oral baclofen more than 50mg/day. PMID:25128217

Gündüz, Ay?egül; Uzun, Nurten; Örnek, Nurettin ?rem; Ünalan, Halil; Karamehmeto?lu, ?afak Sahir; K?z?ltan, Meral E

2014-09-19

184

Death Anxiety as a Predictor of Posttraumatic Stress Levels among Individuals with Spinal Cord Injuries  

ERIC Educational Resources Information Center

Because the onset of a spinal cord injury may involve a brush with death and because serious injury and disability can act as a reminder of death, death anxiety was examined as a predictor of posttraumatic stress levels among individuals with disabilities. This cross-sectional study used multiple regression and multivariate multiple regression to…

Martz, Erin

2004-01-01

185

Changes of intracellular free calcium following mechanical injury in a spinal cord slice preparation  

Microsoft Academic Search

Intracellular calcium ions are, in addition to free radicals, an important mediator of tissue destruction following traumatic injury to the spinal cord. In vivo measurements of calcium in the interstitial space and in the tissue suggest the occurrence of a posttraumatic shift of calcium from the extracellular to the intracellular compartment at the injury site. No information is, however, available

Luc Leybaert; Alex de Hemptinne

1996-01-01

186

Relationship of Personality and Locus of Control With Employment Outcomes among Participants with Spinal Cord Injury  

ERIC Educational Resources Information Center

We investigated relationships among personality, locus of control, and current post-injury employment status for 1,391 participants with spinal cord injury. Participants with higher internality locus-of-control scores and activity scores (personality) reported more favorable employment outcomes. Higher scores on chance and powerful others (locus…

Krause, James S.; Broderick, Lynne

2006-01-01

187

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

PubMed

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions. PMID:21915768

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

2012-04-01

188

Suppression of spinal connexin 43 expression attenuates mechanical hypersensitivity in rats after an L5 spinal nerve injury.  

PubMed

Activation of spinal astrocytes may contribute to neuropathic pain. Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. Yet, the role of spinal astroglial gap junctions in neuropathic pain is not fully understood. Since Cx43 is the connexin isoform expressed preferentially in astrocytes in the spinal cord, we used a small interfering RNA (siRNA) approach to examine whether suppression of spinal Cx43 expression inhibits mechanical hypersensitivity in rats after an L5 spinal nerve ligation (SNL). SNL rats were administered intrathecal Cx43 siRNA (3?g/15?l, twice/day) or an equal amount of mismatch siRNA (control) on days 14-17 post-SNL. Cx43 siRNA, but not mismatch siRNA, alleviated mechanical hypersensitivity in SNL rats. Furthermore, Western blot analysis showed that the pain inhibition induced by Cx43 siRNA correlated with downregulation of Cx43 expression, but not that of Cx36 (the neuronal gap junction protein) or glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) in the spinal cord of SNL rats. Western blot analysis and immunohistochemistry also showed that SNL increased GFAP expression, but decreased Cx43 expression, in spinal cord. Our results provide direct evidence that selective suppression of spinal Cx43 after nerve injury alleviates neuropathic mechanical hypersensitivity. These findings suggest that in the spinal cord, the enhanced function of astroglial gap junctions, especially those formed by Cx43, may be important to neuropathic pain in SNL rats. PMID:24631560

Xu, Qian; Cheong, Yong-Kwan; He, Shao-Qiu; Tiwari, Vinod; Liu, Jian; Wang, Yun; Raja, Srinivasa N; Li, Jinheng; Guan, Yun; Li, Weiyan

2014-04-30

189

The Asparaginyl Endopeptidase Legumain Is Essential for Functional Recovery after Spinal Cord Injury in Adult Zebrafish  

PubMed Central

Unlike mammals, adult zebrafish are capable of regenerating severed axons and regaining locomotor function after spinal cord injury. A key factor for this regenerative capacity is the innate ability of neurons to re-express growth-associated genes and regrow their axons after injury in a permissive environment. By microarray analysis, we have previously shown that the expression of legumain (also known as asparaginyl endopeptidase) is upregulated after complete transection of the spinal cord. In situ hybridization showed upregulation of legumain expression in neurons of regenerative nuclei during the phase of axon regrowth/sprouting after spinal cord injury. Upregulation of Legumain protein expression was confirmed by immunohistochemistry. Interestingly, upregulation of legumain expression was also observed in macrophages/microglia and neurons in the spinal cord caudal to the lesion site after injury. The role of legumain in locomotor function after spinal cord injury was tested by reducing Legumain expression by application of anti-sense morpholino oligonucleotides. Using two independent anti-sense morpholinos, locomotor recovery and axonal regrowth were impaired when compared with a standard control morpholino. We conclude that upregulation of legumain expression after spinal cord injury in the adult zebrafish is an essential component of the capacity of injured neurons to regrow their axons. Another feature contributing to functional recovery implicates upregulation of legumain expression in the spinal cord caudal to the injury site. In conclusion, we established for the first time a function for an unusual protease, the asparaginyl endopeptidase, in the nervous system. This study is also the first to demonstrate the importance of legumain for repair of an injured adult central nervous system of a spontaneously regenerating vertebrate and is expected to yield insights into its potential in nervous system regeneration in mammals. PMID:24747977

Ma, Liping; Shen, Yan-Qin; Khatri, Harsh P.; Schachner, Melitta

2014-01-01

190

The asparaginyl endopeptidase legumain is essential for functional recovery after spinal cord injury in adult zebrafish.  

PubMed

Unlike mammals, adult zebrafish are capable of regenerating severed axons and regaining locomotor function after spinal cord injury. A key factor for this regenerative capacity is the innate ability of neurons to re-express growth-associated genes and regrow their axons after injury in a permissive environment. By microarray analysis, we have previously shown that the expression of legumain (also known as asparaginyl endopeptidase) is upregulated after complete transection of the spinal cord. In situ hybridization showed upregulation of legumain expression in neurons of regenerative nuclei during the phase of axon regrowth/sprouting after spinal cord injury. Upregulation of Legumain protein expression was confirmed by immunohistochemistry. Interestingly, upregulation of legumain expression was also observed in macrophages/microglia and neurons in the spinal cord caudal to the lesion site after injury. The role of legumain in locomotor function after spinal cord injury was tested by reducing Legumain expression by application of anti-sense morpholino oligonucleotides. Using two independent anti-sense morpholinos, locomotor recovery and axonal regrowth were impaired when compared with a standard control morpholino. We conclude that upregulation of legumain expression after spinal cord injury in the adult zebrafish is an essential component of the capacity of injured neurons to regrow their axons. Another feature contributing to functional recovery implicates upregulation of legumain expression in the spinal cord caudal to the injury site. In conclusion, we established for the first time a function for an unusual protease, the asparaginyl endopeptidase, in the nervous system. This study is also the first to demonstrate the importance of legumain for repair of an injured adult central nervous system of a spontaneously regenerating vertebrate and is expected to yield insights into its potential in nervous system regeneration in mammals. PMID:24747977

Ma, Liping; Shen, Yan-Qin; Khatri, Harsh P; Schachner, Melitta

2014-01-01

191

Neurological outcome in a series of 58 patients operated for traumatic thoracolumbar spinal cord injuries  

PubMed Central

Background: Traumatic thoracolumbar spinal fractures represent approximately 65% of all traumatic spinal fractures and are frequently associated to permanent disability with significant social and economic impact. These injuries create severe physical limitations depending on neurological status, level of fracture, severity of injury, patient age and comorbidities. Predicting neurological improvement in patients with traumatic spinal cord injuries (SCIs) is very difficult because it is related to different preoperative prognostic factors. We evaluated the neurological improvement related to the preoperative neurological conditions and the anatomic level of spinal cord injury. Methods: From January 2004 to June 2010, we operated 207 patients for unstable thoracolumbar spinal fractures. We carried out a retrospective analysis of 69 patients with traumatic SCIs operated on by a posterior fixation performed within 24 hours from the trauma. The preoperative neurological conditions (ASIA grade), the type of the fracture, the anatomic level of spinal cord injury and the postoperative neurological improvement were evaluated for each patient. Results: The ASIA grade at admission (P = 0,0005), the fracture type according to the AO spine classification (P = 0,0002), and the anatomic location of the injury (P = 0,0213) represented predictive factors of neurological improvement at univariate analysis. The preoperative neurological status (P = 0,0491) and the fracture type (P = 0,049) confirmed a positive predictive value also in the multivariate analysis. Conclusions: Our study confirms that the preoperative neurological status, the fracture type and the anatomic location of the fracture are predictive factors of the neurological outcome in patients with spinal cord injury. PMID:25289154

Dobran, Mauro; Iacoangeli, Maurizio; Di Somma, Lucia Giovanna Maria; Di Rienzo, A.; Colasanti, Roberto; Nocchi, Niccolò; Alvaro, Lorenzo; Moriconi, Elisa; Nasi, Davide; Scerrati, Massimo

2014-01-01

192

Men's adjustment to spinal cord injury: the unique contributions of conformity to masculine gender norms.  

PubMed

Men constitute 82% of the approximately 250,000 people in the United States living with a spinal cord injury. Unfortunately, however, little is known about the impact of men's adherence to gender norms on their adjustment to such injuries. The present investigation examined the utility of masculine norms in explaining variance in depression beyond that accounted for by commonly identified predictors of men's adjustment following spinal cord injury. As hypothesized, results suggested that men's adherence to masculine norms accounted for unique variance in their depression scores beyond that contributed by social support, environmental barriers/access, and erectile functioning. Respondents who adhered to norms stressing the primacy of men's work demonstrated lower rates of depression, whereas those who conformed to norms for self-reliance demonstrated higher depression scores. The authors discuss future research directions and potential psychotherapeutic strategies for working with men with spinal cord injuries. PMID:19477753

Burns, Shaun Michael; Hough, Sigmund; Boyd, Briana L; Hill, Justin

2010-06-01

193

Minimum Information about a Spinal Cord Injury Experiment: A Proposed Reporting Standard for Spinal Cord Injury Experiments  

PubMed Central

Abstract The lack of reproducibility in many areas of experimental science has a number of causes, including a lack of transparency and precision in the description of experimental approaches. This has far-reaching consequences, including wasted resources and slowing of progress. Additionally, the large number of laboratories around the world publishing articles on a given topic make it difficult, if not impossible, for individual researchers to read all of the relevant literature. Consequently, centralized databases are needed to facilitate the generation of new hypotheses for testing. One strategy to improve transparency in experimental description, and to allow the development of frameworks for computer-readable knowledge repositories, is the adoption of uniform reporting standards, such as common data elements (data elements used in multiple clinical studies) and minimum information standards. This article describes a minimum information standard for spinal cord injury (SCI) experiments, its major elements, and the approaches used to develop it. Transparent reporting standards for experiments using animal models of human SCI aim to reduce inherent bias and increase experimental value. PMID:24870067

Ferguson, Adam R.; Popovich, Phillip G.; Xu, Xiao-Ming; Snow, Diane M.; Igarashi, Michihiro; Beattie, Christine E.; Bixby, John L.

2014-01-01

194

Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments.  

PubMed

The lack of reproducibility in many areas of experimental science has a number of causes, including a lack of transparency and precision in the description of experimental approaches. This has far-reaching consequences, including wasted resources and slowing of progress. Additionally, the large number of laboratories around the world publishing articles on a given topic make it difficult, if not impossible, for individual researchers to read all of the relevant literature. Consequently, centralized databases are needed to facilitate the generation of new hypotheses for testing. One strategy to improve transparency in experimental description, and to allow the development of frameworks for computer-readable knowledge repositories, is the adoption of uniform reporting standards, such as common data elements (data elements used in multiple clinical studies) and minimum information standards. This article describes a minimum information standard for spinal cord injury (SCI) experiments, its major elements, and the approaches used to develop it. Transparent reporting standards for experiments using animal models of human SCI aim to reduce inherent bias and increase experimental value. PMID:24870067

Lemmon, Vance P; Ferguson, Adam R; Popovich, Phillip G; Xu, Xiao-Ming; Snow, Diane M; Igarashi, Michihiro; Beattie, Christine E; Bixby, John L

2014-08-01

195

[Cervical spine injuries in stable lower cervical spine with spinal stenosis].  

PubMed

The aim of the study was to investigate the neurological outcome of spinal cord injuries in the traumatized cervical spine with a stenosis of the spinal medullary canal. From 1992 to 1999 we treated 145 spinal cord injuries and/or injuries with an unstable cervical spine, 138 were treated operatively, in 7 patients we found an injury of the spinal cord with a stable cervical spine and a stenosis of the spinal medullary canal. The radiological diagnostics consisted of anterioposterior X-rays of the cervical spine, an X-ray view of the dens axis and a stress roentgenogramm in extension and flection. An MRI was performed within the first 12 hours after the accident. The stenosis of the spinal medullary canal was evaluated by the quotient of the mid-sagittal diameter of the spinal medullary canal as well as the vertebral body (Torg-quotient) and ranged from 0.5 to 0.8. Pathological changed values were found in 4 patients within 2 segments and in 3 patients within 3 segments. In the T2-turbospin echo sequence hyperintense lesions of the spinal cord, accordingly to an edema were found in 6 patients. The neurological evaluation was performed according to the "Standard Neurological Classification of Spinal Cord Injuries". Treatment of these 7 patients was performed conservatively, consisting of NSAR as well as Methyl-Prednisolon according to the pattern of NASCIS-II and III. The follow-up was performed after 12 to 18 months. We evaluated the X-rays in anterioposterior and lateral view, stress roentgenogramms and neurological status. Radiological findings showed stable conditions of the cervical spine with block vertebras and increased osteophytes. The neurological outcome was evaluated according to the "Motor-Score" and showed an improvement from 8 to 63 points within 13 months in one case. In 6 cases, the average "Motor-Score" of 78 increased to 100 points within 2 to 5 months after injury. Most defunctionalization symptoms were found in the upper extremities. Disturbances in fine motor movement were unable to be examined with the "Motor-Score". We can conclude that spinal cord injuries in stable cervical spines with stenosis of the spinal medullary canal can be treated conservatively with a good outcome. A regression of the neurological deficiency can be expected within 2 to 5 months, but even after one year, deficiency regression is possible. PMID:11968545

Schweighofer, F; Stockenhuber, N; Bratschitsch, G; Raith, J

2002-02-01

196

Assessing limb apraxia in traumatic brain injury and spinal cord injury  

PubMed Central

People with traumatic brain injury (TBI) may demonstrate action planning disorders and limb apraxia. Many patients, who sustain a spinal cord injury (SCI), sustain a co-occurring TBI (11-29 percent of people with SCI) and therefore are at risk for limb apraxia. People with SCI and TBI (SCI/TBI) rely on powered assistive devices which amplify movement. Their ability to learn complex motor compensatory strategies, that is, limb praxis, is critical to function. We wished to identify methods of screening for apraxia in patients with SCI/TBI. We reviewed instruments available for limb praxis assessment, presenting information on psychometric development, patient groups tested, commercial/clinical availability, and appropriateness for administration to people with motor weakness. Our review revealed that insufficient normative information exists for apraxia assessment in populations comparable to SCI/TBI patients who are typically young adults at the time of injury. There are few apraxia assessment instruments which do not require a motor response. Non-motoric apraxia assessments would be optimal for patients with an underlying motor weakness. PMID:23277082

McKenna, Cristin; Thakur, Uma; Marcus, Bradley; Barrett, Anna Mariya

2013-01-01

197

Proprioceptive neuropathy affects normalization of the H-reflex by exercise after spinal cord injury  

PubMed Central

The H-reflex habituates at relatively low frequency (10 Hz) stimulation in the intact spinal cord, but loss of descending inhibition resulting from spinal cord transection reduces this habituation. There is a return towards a normal pattern of low-frequency habituation in the reflex activity with cycling exercise of the affected hind limbs. This implies that repetitive passive stretching of the muscles in spinalized animals and the accompanying stimulation of large (Group I and II) proprioceptive fibers has modulatory effects on spinal cord reflexes after injury. To test this hypothesis, we induced pyridoxine neurotoxicity that preferentially affects large dorsal root ganglia neurons in intact and spinalized rats. Pyridoxine or saline injections were given twice daily (IP) for 6 weeks and half of the spinalized animals were subjected to cycling exercise during that period. After 6 weeks, the tibial nerve was stimulated electrically and recordings of M and H waves were made from interosseous muscles of the hind paw. Results show that pyridoxine treatment completely eliminated the H-reflex in spinal intact animals. In contrast, transection paired with pyridoxine treatment resulted in a reduction of the frequency-dependent habituation of the H-reflex that was not affected by exercise. These results indicate that normal Group I and II afferent input is critical to achieve exercise-based reversal of hyper-reflexia of the H-reflex after spinal cord injury. PMID:19913536

Ollivier-Lanvin, Karen; Keeler, Benjamin E.; Siegfried, Rachel; Houlé, John D.; Lemay, Michel A.

2009-01-01

198

Intraspinal penetrating stab injury to the middle thoracic spinal cord with no neurologic deficit.  

PubMed

The annual incidence of traumatic spinal cord injury worldwide is estimated to be 35 patients per million. Nonmissile penetrating spinal injuries most commonly occur in the thoracic region, and the majority has neurologic deficits on admission. The management of patients who lack neurologic deficits is controversial due to the risk of neurologic status alteration intraoperatively. However, failure to intervene increases the risk of infection, delayed onset of neurologic deficits, and worsening functional outcome.A 17-year-old boy presented with an intradural T7-T8 knife penetration injury to the spinal cord with no neurologic deficit. Rapid surgical intervention was critical because the knife was lodged between the 2 hemispheres of the spinal cord. The patient was intubated in the lateral position, transferred to the prone position on a Jackson table, and underwent surgical decompression with laminectomy 1 level above and below the injury site, removal of the knife blade in the original path of trajectory, and repair of the dural tear with a collagen matrix. The patient sustained no neurologic sequelae from the penetrating knife injury. He was able to ambulate at discharge and had no complications. To our knowledge, this is the only report of a patient with intradural spinal cord penetration by a foreign object (knife blade) presenting with a normal neurologic preoperative examination that persisted throughout the course of postoperative care. PMID:22588426

Li, Xinning; Curry, Emily J; Blais, Micah; Ma, Richard; Sungarian, Arno S

2012-05-01

199

Sclerostin Inhibition Prevents Spinal Cord Injury Induced Cancellous Bone Loss.  

PubMed

Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt-signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl-Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl-Ab to that of testosterone-enanthate (TE), an agent that we have previously shown prevents SCI-induced bone loss. Fifty-five (n?=?11-19/group) skeletally-mature male Sprague-Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe (250 kilodyne) SCI, (C) 250 kilodyne SCI?+?TE (7.0mg/week, i.m.), or (D) 250 kilodyne SCI?+?Scl-Ab (25mg/kg, twice weekly, s.c.) for three weeks. Twenty-one days post-injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via µCT and histomorphometry) and distal femur (via µCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and plate-like trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl-Ab and TE both prevented SCI-induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI?+?Scl-Ab and SCI?+?TE animals, while only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population. © 2014 American Society for Bone and Mineral Research. PMID:25359699

Beggs, Luke A; Ye, Fan; Ghosh, Payal; Beck, Darren T; Conover, Christine F; Balaez, Alexander; Miller, Julie R; Phillips, Ean G; Zheng, Nigel; Williams, Alyssa A; Aguirre, J Ignacio; Wronski, Thomas J; Bose, Prodip K; Borst, Stephen E; Yarrow, Joshua F

2014-10-31

200

Development of a database for translational spinal cord injury research.  

PubMed

Efforts to understand spinal cord injury (SCI) and other complex neurotrauma disorders at the pre-clinical level have shown progress in recent years. However, successful translation of basic research into clinical practice has been slow, partly because of the large, heterogeneous data sets involved. In this sense, translational neurological research represents a "big data" problem. In an effort to expedite translation of pre-clinical knowledge into standards of patient care for SCI, we describe the development of a novel database for translational neurotrauma research known as Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI). We present demographics, descriptive statistics, and translational syndromic outcomes derived from our ongoing efforts to build a multi-center, multi-species pre-clinical database for SCI models. We leveraged archived surgical records, postoperative care logs, behavioral outcome measures, and histopathology from approximately 3000 mice, rats, and monkeys from pre-clinical SCI studies published between 1993 and 2013. The majority of animals in the database have measures collected for health monitoring, such as weight loss/gain, heart rate, blood pressure, postoperative monitoring of bladder function and drug/fluid administration, behavioral outcome measures of locomotion, and tissue sparing postmortem. Attempts to align these variables with currently accepted common data elements highlighted the need for more translational outcomes to be identified as clinical endpoints for therapeutic testing. Last, we use syndromic analysis to identify conserved biological mechanisms of recovery after cervical SCI between rats and monkeys that will allow for more-efficient testing of therapeutics that will need to be translated toward future clinical trials. PMID:25077610

Nielson, Jessica L; Guandique, Cristian F; Liu, Aiwen W; Burke, Darlene A; Lash, A Todd; Moseanko, Rod; Hawbecker, Stephanie; Strand, Sarah C; Zdunowski, Sharon; Irvine, Karen-Amanda; Brock, John H; Nout-Lomas, Yvette S; Gensel, John C; Anderson, Kim D; Segal, Mark R; Rosenzweig, Ephron S; Magnuson, David S K; Whittemore, Scott R; McTigue, Dana M; Popovich, Phillip G; Rabchevsky, Alexander G; Scheff, Stephen W; Steward, Oswald; Courtine, Grégoire; Edgerton, V Reggie; Tuszynski, Mark H; Beattie, Michael S; Bresnahan, Jacqueline C; Ferguson, Adam R

2014-11-01

201

Brown-Sequard syndrome associated with unusual spinal cord injury by a screwdriver stab wound  

PubMed Central

Introduction: Stab wounds resulting in spinal cord injuries are very rare. In direct central back stabbings, the layers of muscles and the spinal column tends to deflect blades, rarely causing injuries to the spinal cord. We report an unusual case of traumatic spinal cord injury by a screwdriver stab, presented as Brown-Séquard syndrome and discuss possible pitfalls on the surgical treatment. Case report: A 34 year-old man was brought to the emergency department after a group assault with a single screwdriver stab wound on the back. Neurological examination revealed an incomplete Brown-Sequard syndrome, with grade IV motor deficit on the left leg and contralateral hemihypoalgesia below T9 level. Radiological evaluation showed a retained 9 cm screwdriver that entered and trespassed the spinal canal at T6 level, reaching the posterior mediastinum with close relation to the thoracic aorta. Vascular injury could not be excluded. The joint decision between the neurosurgery and the vascular surgery teams was the surgical removal of the screwdriver under direct visualization. A left mini-thoracotomy was performed. Simultaneously, a careful dissection was done and screwdriver was firmly pulled back on the opposite path of entry under direct visualization of the aorta. The neurological deficit was maintained immediately after the surgical procedure. Follow-up visit after 1 year showed minor motor deficit and good healing. Conclusions: It is important to consider all aspects of secondary injury on the surgical planning of penetrating spinal cord injury. The secondary injury can be minimized with multidisciplinary planning of the surgical procedure. PMID:24482724

Beer-Furlan, André Luiz; Paiva, Wellingson Silva; Tavares, Wagner Malagó; de Andrade, Almir Ferreira; Teixeira, Manoel Jacobsen

2014-01-01

202

Posterior circulation infarction in patients with traumatic cervical spinal cord injury and its relationship to vertebral artery injury.  

PubMed

Study design:Prospective study.Objective:To ascertain the prevalence of posterior circulation stroke in traumatic chronic spinal cord injured (SCI) patients and associated traumatic vertebral artery injuries (VAI).Methods:All adult patients with cervical SCI and American Spinal Injury Association Impairment Scale (AIS) grade A or B referred for follow-up magnetic resonance imaging of their spinal cord were invited to take part in the study between January 2010 and December 2012 at the National Spinal Injury Centre. Two additional sequences were added to the existing imaging protocol to evaluate the brain and vertebral arteries.Results:Ninety-eight patients were recruited. All imaging were analysed independently by three consultant radiologists. Posterior circulation infarcts were noted in seven (7%) patients. Significant VAI was noted in 13 patients (13%) with 10 occlusions and 3 with high-grade stenosis. However, only one patient had co-existent posterior circulation infarct and significant VAI.Conclusion:There is an increased prevalence of posterior circulation infarction in SCI patients. The relationship with associated traumatic VAI requires further investigation.Spinal Cord advance online publication, 2 September 2014; doi:10.1038/sc.2014.145. PMID:25179661

de Heredia, L L; Belci, M; Briley, D; Hughes, R J; McNeillis, B; Meagher, T M; Yanny, S; McKean, D

2014-09-01

203

Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury induced neuropathic pain states  

PubMed Central

Spinal cord injury (SCI) commonly results in the development of neuropathic pain, which can dramatically impair the quality of life for SCI patients. SCI induced neuropathic pain can be manifested as both tactile allodynia (a painful sensation to a non-noxious stimulus) and or hyperalgesia (an enhanced sensation to a painful stimulus). The mechanisms underlying these pain states are poorly understood. Clinical studies have shown that gabapentin, a drug that binds to the voltage gated calcium channel alpha-2-delta-1 subunit (Cav?2?-1) proteins is effective in the management of SCI induced neuropathic pain. Accordingly, we hypothesized that tactile allodynia post SCI is mediated by an upregulation of Cav?2?-1 in dorsal spinal cord (DSC). To test this hypothesis, we examined if SCI-induced dysregulation of spinal Cav?2?-1 plays a contributory role in below-level allodynia development in a rat spinal T9 contusion injury model. We found that Cav?2?-1 expression levels were significantly increased in L4-6 dorsal, but not ventral, spinal cord of SCI rats that correlated with tactile allodynia development in the hindpaw plantar surface. Furthermore, both intrathecal gabapentin treatment and blocking SCI induced Cav?2?-1 protein upregulation by intrathecal Cav?2?-1 antisense oligodeoxynucleotides could reverse tactile allodynia in SCI rats. These findings support that SCI induced Cav?2?-1 upregulation in spinal dorsal horn is a key component in mediating below-level neuropathic pain development and selectively targeting this pathway may provide effective pain relief for SCI patients. PMID:21239111

Boroujerdi, Amin; Zeng, Jun; Sharp, Kelli; Kim, Donghyun; Steward, Oswald; Luo, Z. David

2011-01-01

204

Temporospatial expression of fibulin-1 after acute spinal cord injury in rats.  

PubMed

Objective Fibulin-1 is a matricellular protein that plays important roles in motility inhibition in a variety of cells and blocks the proliferation of cultured neural stem cells. The biological function of fibulin-1 in the spinal cord has not been fully elucidated. Methods To clarify the expressions and possible functions of fibulin-1 in spinal cord injury (SCI), we performed an acute spinal cord contusion injury model in adult rats. Our work studied the temporospatial expression patterns of fibulin-1. Results Western blot analysis revealed that fibulin-1 levels significantly increased 5 days after spinal cord contusion. Immunohistochemistry confirmed an increased number of fibulin-1 immunopositive cells about 2 mm from the lesion site. Moreover, double immunofluorescence labeling suggested that these changes were especially prominent in neurons and microglia. Conclusion These findings suggest that fibulin-1 may be involved in neuronal apoptosis and microglial activation after SCI. PMID:24969770

Xu, Guanhua; Cui, Ying; Wang, Lingling; Zhang, Jinlong; Shen, Aiguo; Li, Weidong; Bao, Guofeng; Sun, Yuyu; Cui, Zhiming

2014-06-26

205

Regulation of nitric oxide generation by up-regulated arginase I in rat spinal cord injury  

PubMed Central

Recently, arginase is suggested to regulate nitric oxide production by competing with nitric oxide synthase for the same substrate, L-arginine, in experimental asthma. We investigated the role of arginase and its relationship to nitric oxide production after spinal cord injury. Rats were subjected to laminectomy and complete transection of their spinal cords (injury group) or laminectomy only (sham group). In the injury group, arginase I was increased in the macrophages at the transection edge, and the peak was observed 48 h after spinal cord injury. However, nitric oxide production decreased significantly in the injury group despite increased nitric oxide synthase2 mRNA expression compared with the sham group. We also demonstrated the reduction in L-arginine concentrations, which was inversely associated with changes in arginase activity. Therefore, arginase appeared to regulate nitric oxide production by consuming L-arginine. The regulation of arginase activity and L-arginine levels may improve nitroxidative stress and reduce tissue damage in spinal cord injury. PMID:22798716

Imagama, Takashi; Ogino, Keiki; Takemoto, Kei; Kato, Yoshihiko; Kataoka, Hideo; Suzuki, Hidenori; Ran, Zhang; Setiawan, Heri; Fujikura, Yoshihisa; Taguchi, Toshihiko

2012-01-01

206

Polysialic Acid Glycomimetic Promotes Functional Recovery and Plasticity After Spinal Cord Injury in Mice  

PubMed Central

Regeneration after injury of the central nervous system is poor due to the abundance of molecules inhibiting axonal growth. Here we pursued to promote regeneration after thoracic spinal cord injury in young adult C57BL/6J mice using peptides which functionally mimic polysialic acid (PSA) and human natural killer cell-1 (HNK-1) glycan, carbohydrate epitopes known to promote neurite outgrowth in vitro. Subdural infusions were performed with an osmotic pump, over 2 weeks. When applied immediately after injury, the PSA mimetic and the combination of PSA and HNK-1 mimetics, but not the HNK-1 mimetic alone, improved functional recovery as assessed by locomotor rating and video-based motion analysis over a 6-week observation period. Better outcome in PSA mimetic-treated mice was associated with higher, as compared with control mice, numbers of cholinergic and glutamatergic terminals and monaminergic axons in the lumbar spinal cord, and better axonal myelination proximal to the injury site. In contrast to immediate post-traumatic application, the PSA mimetic treatment was ineffective when initiated 3 weeks after spinal cord injury. Our data suggest that PSA mimetic peptides can be efficient therapeutic tools improving, by augmenting plasticity, functional recovery when applied during the acute phase of spinal cord injury. PMID:19826404

Mehanna, Ali; Jakovcevski, Igor; Acar, Ay?e; Xiao, Meifang; Loers, Gabriele; Rougon, Geneviève; Irintchev, Andrey; Schachner, Melitta

2009-01-01

207

Pure traumatic upper cervical disc herniation causing spinal cord injury: a case report and review of literature  

PubMed Central

Abstract: One third of all spinal injuries involve cervical vertebrae, and the impact of injury to the cervical spinal cord is profound and requires systemic treatment. The role and timing of surgical decompression after an acute spinal cord injury (SCI) remains one of the most controversial topics pertaining to spinal surgery. Lack of controlled, prospective, multicenter clinical studies has contributed to confusion in optimal treatment methods for patients with injuries of the cervical spinal cord. Clinically, the question of whether surgical decompression improves motor recovery following SCI remains surrounded by controversy. Case: Two cases with a 32-year-old man who developed right -sided Brown-Séquard Syndrome Following a motor to car accident with the large right paramedian C3–C4 disc herniation, and ipsilateral spinal cord compression and a 30-year-old man with the syndrome of acute central cervical spinal cord injury with motor impairment involving only upper extremities due to central C2–C3 disc herniation following a pedestrian accident are reported. Discectomy and anterior cervical fusion with the polyetheretherketone (PEEK) cage were performed. A complete motor deficit recovery and a marked sensitive deficit improvement were obtained. The need for and timing of surgical decompression in post traumatic spinal cord injury is controversial. Surgery may expedite neurological recovery in some patients and may provide additional neurological recovery when clinical improvement has plateaued or worsened. In our patient a complete motor deficit recovery was observed. Keywords: Cervical, Disc herniation, Spinal cord injury

Sharifi, Guive; Mosavi, Seyed Ali; Shafieezad, Misagh; Asgari Nosari, Massoud

2012-01-01

208

Effects of methylprednisolone and dextromethorphan on lipid peroxidation in an experimental model of spinal cord injury  

Microsoft Academic Search

.   \\u000a Objective. This study examines the effects of agents purported to improve recovery following spinal cord trauma, methylprednisolone\\u000a sodium succinate, dextromethorphan, and the combination of both, on the post-traumatic alterations of membrane lipid metabolism.\\u000a Methods. After sparing ten rats for a control group (G1) and performing T3–T6 laminectomies in 150 rats, spinal cord injuries were\\u000a accomplished in 120 of 150

Cahide Topsakal; Fatih S. Erol; Faik M. Ozveren; Nejat Yilmaz; Nevin Ilhan

2002-01-01

209

Segmental spinal root avulsion in the adult rat: a model to study avulsion injury pain.  

PubMed

Road traffic accidents are the most common cause of avulsion injury, in which spinal roots are torn from the spinal cord. Patients suffer from a loss of sensorimotor function, intractable spontaneous pain, and border-zone hypersensitivity. The neuropathic pains are particularly difficult to treat because the lack of a well-established animal model of avulsion injury prevents identifying the underlying mechanisms and hinders the development of efficacious drugs. This article describes a hindlimb model of avulsion injury in adult rats where the L5 dorsal and ventral spinal root are unilaterally avulsed (spinal root avulsion [SRA]), leaving the adjacent L4 spinal root intact. SRA produced a significant ipsilateral hypersensitivity to mechanical and thermal stimulation by 5 days compared with sham-operated or naïve rats. This hypersensitivity is maintained for up to 60 days. No autotomy was observed and locomotor deficits were minimal. The hypersensitivity to peripheral stimuli could be temporarily ameliorated by administration of amitriptyline and carbamazepine, drugs that are currently prescribed to avulsion patients. Histological assessment of the L4 ganglion cells revealed no significant alterations in calcitonin gene-related peptide (CGRP), IB4, transient receptor potential cation channel subfamily V member 1 (TrpV1), or N52 staining across groups. Immunohistochemistry of the spinal cord revealed a localized glial response, phagocyte infiltration, and neuronal loss within the ipsilateral avulsed segment. A comparable response from glia and phagocytes was also found in the intact L4 spinal cord, supporting the role for central mechanisms within the L4-5 spinal cord in contributing to the generation of the pain-related behavior. The SRA model provides a platform to investigate possible new pharmacological treatments for avulsion injuries. PMID:22934818

Chew, Daniel J; Murrell, Karen; Carlstedt, Thomas; Shortland, Peter J

2013-02-01

210

Applications of diffusion-weighted MRI in thoracic spinal cord injury without radiographic abnormality  

Microsoft Academic Search

Diffusion-weighted MRI (DWI) has been proposed as a method to evaluate the integrity of white matter tracts in the spinal\\u000a cord. The integrity of the spinal cord reflects the exact stage of traumatic injury. The purpose of this study was to evaluate\\u000a the diagnostic value of DWI in SCIWORA in the thoracic spine. A total of five patients with thoracic

Huiyong Shen; Yong Tang; Lin Huang; Rui Yang; Yanfeng Wu; Peng Wang; Yupeng Shi; Xiaoyu He; Hu Liu; Jichao Ye

2007-01-01

211

Suicide bombing as an unusual cause of spinal cord injury: a case series from Pakistan  

Microsoft Academic Search

Study design:Descriptive case series.Objectives:Describe the unusual etiology and pattern of spinal cord injury due to terrorist suicide bombings in Pakistan.Settings:Spinal Rehabilitation Unit, Armed Forces Institute of Rehabilitation Medicine, Rawalpindi, Pakistan.Methods:Hundreds of suicide attacks on civil and military forces have occurred over the last 6 years in Pakistan. These have resulted in thousands of death and many more injured. Six victims

F A Rathore; A Ayub; S Farooq; P W New

2011-01-01

212

Role of Matrix Metalloproteinases and Therapeutic Benefits of Their Inhibition in Spinal Cord Injury  

Microsoft Academic Search

Summary  This review will focus on matrix metalloproteinases (MMPs) and their inhibitors in the context of spinal cord injury (SCI).\\u000a MMPs have a specific cellular and temporal pattern of expression in the injured spinal cord. Here we consider their diverse\\u000a functions in the acutely injured cord and during wound healing. Excessive activity of MMPs, and in particular gelatinase B\\u000a (MMP-9), in

Haoqian Zhang; Mayland Chang; Christopher N. Hansen; D. Michele Basso; Linda J. Noble-Haeusslein

2011-01-01

213

Spinal cord injury – there is not just one way of treating it  

PubMed Central

In the last century, research in the field of spinal cord trauma has brought insightful knowledge which has led to a detailed understanding of mechanisms that are involved in injury- and recovery-related processes. The quest for a cure for the yet generally incurable condition as well as the exponential rise in gained information has brought about the development of numerous treatment approaches while at the same time the abundance of data has become quite unmanageable. Owing to an enormous amount of preclinical therapeutic approaches, this report highlights important trends rather than specific treatment strategies. We focus on current advances in the treatment of spinal cord injury and want to further draw attention to arising problems in spinal cord injury (SCI) research and discuss possible solutions. PMID:25343041

Estrada, Veronica

2014-01-01

214

MicroRNAs as potential therapeutics for treating spinal cord injury  

PubMed Central

MicroRNAs are a class of recently discovered, small non-coding RNAs that have been shown to play essential roles in a vast majority of biological processes. Very little is known about the role of microRNAs during spinal cord injury. This review summarizes the changes in expression levels of microRNAs after spinal cord injury. These aberrant changes suggest that microRNAs play an important role in inflammation, oxidative stress, apoptosis, glial scar formation and axonal regeneration. Given their small size and specificity of action, microRNAs could be potential therapeutics for treating spinal cord injury in the future. There are rapidly developing techniques for manipulating microRNA levels in animals; we review different chemical modification and delivery strategies. These may provide platforms for designing efficient microRNA delivery protocols for use in the clinic.

Yan, Hualin; Hong, Peiwei; Jiang, Mei; Li, Hedong

2012-01-01

215

Motoneuron Intrinsic Properties, but Not Their Receptive Fields, Recover in Chronic Spinal Injury  

PubMed Central

Proper movement execution relies on precise input processing by spinal motoneurons (MNs). Spinal MNs are activated by limb joint rotations. Typically, their movement-related receptive fields (MRRFs) are sharply focused and joint-specific. After acute spinal transection MRRFs become wide, but their manifestation is not apparent, as intrinsic excitability, primarily resulting from the loss of persistent inward currents (PICs), dramatically decreases. PICs undergo a remarkable recovery with time after injury. Here we investigate whether MRRFs undergo a recovery that parallels that of the PIC. Using the chronic spinal cat in acute terminal decerebrate preparations, we found that MRRFs remain expanded 1 month after spinal transaction, whereas PICs recovered to >80% of their preinjury amplitudes. These recovered PICs substantially amplified the expanded inputs underlying the MRRFs. As a result, we show that single joint rotations lead to the activation of muscles across the entire limb. These results provide a potential mechanism for the propagation of spasms throughout the limb. PMID:24285887

Kajtaz, Elma; Cain, Charlette M.; Heckman, C.J.

2013-01-01

216

The process of confrontation with disability in patients with spinal cord injury  

PubMed Central

BACKGROUND: Spinal injury can establish severe psychological outcomes for the patient and his/her family which requires high adjustment. Health system staff would be able to play their roles well in caring these patients provided with knowing what steps spinal injured people should pass to handle their disability and also what assistance they need in what stages from what sources. This study aimed to explain the process of confrontation with disability in spinal cord injured patients. METHODS: This was a qualitative study with grounded theory approach which was performed in Strauss and Corbin proposed method on twenty people with spinal cord injury who had past at least three months from their spinal injury. Sampling was done in purposive and theoretical method, and analysis of the results was also performed during constant comparative process. RESULTS: Central concept in the data was support which was associated with other concepts and affected them. The patients, with the help of internal and external support could overcome their main problem that was disability feeling and dependency on others and find a new definition for the self, and ultimately achieve the sense of independence and autonomy. CONCLUSIONS: Knowing the process of confrontation with disability along with better understanding of spinal cord injured people would help health system staff to actualize and support their potentials much better through strengthening internal resources and providing appropriate supportive services of each individual. PMID:22069411

Ahmadzadeh, Gholamhossein; Kouchaki, Anahita; Malekian, Azadeh; Aminorro’aya, Mahin; Boroujeni, Ali Zargham

2010-01-01

217

Activity-Dependent Increase in Neurotrophic Factors Is Associated with an Enhanced Modulation of Spinal Reflexes after Spinal Cord Injury  

PubMed Central

Abstract Activity-based therapies such as passive bicycling and step-training on a treadmill contribute to motor recovery after spinal cord injury (SCI), leading to a greater number of steps performed, improved gait kinematics, recovery of phase-dependent modulation of spinal reflexes, and prevention of decrease in muscle mass. Both tasks consist of alternating movements that rhythmically stretch and shorten hindlimb muscles. However, the paralyzed hindlimbs are passively moved by a motorized apparatus during bike-training, whereas locomotor movements during step-training are generated by spinal networks triggered by afferent feedback. Our objective was to compare the task-dependent effect of bike- and step-training after SCI on physiological measures of spinal cord plasticity in relation to changes in levels of neurotrophic factors. Thirty adult female Sprague-Dawley rats underwent complete spinal transection at a low thoracic level (T12). The rats were assigned to one of three groups: bike-training, step-training, or no training. The exercise regimen consisted of 15?min/d, 5 days/week, for 4 weeks, beginning 5 days after SCI. During a terminal experiment, H-reflexes were recorded from interosseus foot muscles following stimulation of the tibial nerve at 0.3, 5, or 10?Hz. The animals were sacrificed and the spinal cords were harvested for Western blot analysis of the expression of neurotrophic factors in the lumbar spinal cord. We provide evidence that bike- and step-training significantly increase the levels of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4 in the lumbar enlargement of SCI rats, whereas only step-training increased glial cell-derived neurotrophic factor (GDNF) levels. An increase in neurotrophic factor protein levels that positively correlated with the recovery of H-reflex frequency-dependent depression suggests a role for neurotrophic factors in reflex normalization. PMID:21083432

Côté, Marie-Pascale; Azzam, Gregory A.; Lemay, Michel A.; Zhukareva, Victoria

2011-01-01

218

Current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury using polymer scaffolds  

Microsoft Academic Search

This review highlights current tissue engineering and novel therapeutic approaches to axonal regeneration following spinal cord injury. The concept of developing 3-dimensional polymer scaffolds for placement into a spinal cord transection model has recently been more extensively explored as a solution for restoring neurologic function after injury. Given the patient morbidity associated with respiratory compromise, the discrete tracts in the

Nicolas N. Madigan; Siobhan McMahon; Timothy O’Brien; Michael J. Yaszemski; Anthony J. Windebank

2009-01-01

219

Endogenous Neural Progenitor Cells as Therapeutic Target After Spinal Cord Injury  

NSDL National Science Digital Library

Growing knowledge about the role of neural progenitor cells supports the hope that stem cell-based therapeutic approaches aimed at restoring function in the lesioned central nervous system can be established. Possible therapies for promoting recovery after spinal cord injury include stimulating the formation of neurons and glial cells by endogenous progenitor cells. This article reviews the current knowledge about the nature of adult progenitor cells in the intact and injured spinal cord and summarizes possibilities and limitations of cellular replacement strategies based on manipulations of endogenous spinal cord progenitor cells and their environment.

Franz-Josef Obermair (University of Zurich Neuromorphology)

2008-10-18

220

Managing Inflammation after Spinal Cord Injury through Manipulation of Macrophage Function  

PubMed Central

Spinal cord injury (SCI) triggers inflammation with activation of innate immune responses that contribute to secondary injury including oligodendrocyte apoptosis, demyelination, axonal degeneration, and neuronal death. Macrophage activation, accumulation, and persistent inflammation occur in SCI. Macrophages are heterogeneous cells with extensive functional plasticity and have the capacity to switch phenotypes by factors present in the inflammatory microenvironment of the injured spinal cord. This review will discuss the role of different polarized macrophages and the potential effect of macrophage-based therapies for SCI. PMID:24288627

Ren, Yi; Young, Wise

2013-01-01

221

A Review on Response of Immune System in Spinal Cord Injury and Therapeutic Agents useful in Treatment.  

PubMed

Every year more than 12,000 people in US alone suffer from spinal cord injury. However, complete recovery of physical function is difficult due to multiple factors involved in disease progression. Currently available therapeutic regimens do not address all the factors concerned with the disease progression. The present review focuses mainly on the role of immune cells in progression of spinal cord injury and the drugs that target these immune cells. Literature search shows that inflammatory reactions and subsequent reactions that follow direct injury to spinal cord are sometimes responsible for the severity of the disease. Therefore, for design of proper treatment regimen a deep understanding in this area is required. Understanding the pathophysiology will help in creating delivery system that can target multiple factors involved in progression of spinal cord injury. A combination of various treatment strategies is required to reduce the disability in patients with spinal cord injury. PMID:25374028

Kasinathan, Narayanan; Vanathi, Meenashi B; Subrahmanyam, Volety M; Rao, Josyula V

2015-01-01

222

Brain vs. Spinal Cord A Directed Case Study in CNS Injury  

NSDL National Science Digital Library

In this case study, students read about the injuries sustained by a young man hurt in a serious diving accident. To solve the case, they must determine the type of central nervous system injury described using their knowledge of the differences between symptoms and signs of brain and spinal cord injury. The case was developed for upper-level neuroscience courses and rehabilitation courses that cover the neuroanatomy of the central nervous system and the symptoms of different types of central nervous system injury.

Patrick R. Field

2001-01-01

223

Protection of rat spinal cord against contusion injury by new prostaglandin derivatives.  

PubMed

Two prostaglandin oligomeric compounds, an acid-form compound and an ester-form compound, were synthesized from alprostadil (prostaglandin E1). They were found to provide significant protection to the rat spinal cord against contusion injury. After laminectomy at the T-11 segment of the spinal cord, a weight drop (10 g x 5 cm) caused a "dynamic" injury. The degree of recovery was estimated by several neurologic deficit indices; the Tarlov score, inclined plane test and hot plate test. In the control group (no drug), animals were still paralyzed 4 weeks after injury (Tarlov score 1 to 2). By administering these prostaglandin oligomers, either pre-injury (30 min before injury; one dose of 6 mg/kg i.p.) or post-injury (3 doses, each of 6 mg/kg i.p. at 30 min, 6 h, and 12 h after injury), the Tarlov scores recovered to 3.5 to 4.5 by 4 weeks, and animals were able to either support body weight or to walk with a slight deficit. Although both acid- and ester-forms of the compound demonstrated efficacy, the ester-form provided greater protection to the spinal cord. Other neurologic deficit indices also supported these observations. PMID:2730694

Ohnishi, S T; Barr, J K; Katagi, C; Katsuoka, M

1989-02-01

224

Daily intermittent hypoxia enhances walking after chronic spinal cord injury  

PubMed Central

Objectives: To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI). Methods: Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349). Results: dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1–6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9–6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5–171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1–173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3–134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6–173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3–206.6 m, p < 0.001). Conclusions: dAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI. Classification of evidence: This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI. PMID:24285617

Hayes, Heather B.; Jayaraman, Arun; Herrmann, Megan; Mitchell, Gordon S.; Rymer, William Z.

2014-01-01

225

New perspectives on improving upper extremity function after spinal cord injury.  

PubMed

Injury to the cervical spinal cord adversely affects arm and hand function to varying degrees depending on the level and severity of injury. These impairments typically result in reduced independence in the performance of activities of daily living and limit participation in recreational activities. There is evidence to suggest individuals with incomplete spinal cord injury may benefit from intensive rehabilitation interventions aimed at improving hand and arm function. Massed practice (repetitive activity-based training) and somatosensory stimulation (prolonged peripheral nerve electrical stimulation at submotor threshold intensity) are 2 interventions that have been shown to improve strength and function in individuals with stroke, presumably by changing cortical excitability. These techniques, however, had not previously been investigated in individuals with spinal cord injury (SCI). In this article the stroke and SCI literature supporting the use of massed practice and somatosensory stimulation as a potential rehabilitative tool to promote recovery of function in individuals with incomplete cervical spinal cord injury (SCI) is reviewed. Recently published research using these novel techniques in which a combination of massed practice and somatosensory stimulation resulted in increased pinch grip strength and upper extremity function in individuals with incomplete cervical SCI when compared to subjects participating in massed practice alone is presented. PMID:16398948

Beekhuizen, Kristina S

2005-09-01

226

A typology of alcohol use patterns among persons with recent traumatic brain injury or spinal cord injury: Implications for treatment matching  

Microsoft Academic Search

Turner AP, Bombardier CH, Rimmele CT. A typology of alcohol use patterns among persons with recent traumatic brain injury or spinal cord injury: implications for treatment matching. Arch Phys Med Rehabil 2003;84:358-64. Objective: To describe empirically valid and clinically meaningful types of alcohol use among persons with recent traumatic brain or spinal cord injury. Design: Cross-sectional cohort survey. Setting: Acute

Aaron P. Turner; Charles H. Bombardier; Carl T. Rimmele

2003-01-01

227

Possible mechanisms for observed pathophysiological variability in experimental spinal cord injury by the method of Allen.  

PubMed

Experimental spinal cord injuries were induced in dogs by dropping calibrated weights through a vented tube onto a small impounder resting on the surgically exposed cord. The motion of the impounder and the drop-mass were recorded by high-speed photography and the resulting data were compared to those obtained from a computer simulation of the dynamics of the injury mechanism. It is concluded that this method of induced spinal cord injuries may yield markedly different degrees of cord compression depending upon the parameters of the animal material and apparatus even when the gm-cm of impact energy is maintained at a constant value. Some approaches to standardization of this injury model are suggested. PMID:1255233

Koozekanani, S H; Vise, W M; Hashemi, R M; McGhee, R B

1976-04-01

228

Epidemiology of traumatic spinal cord injury in Asia: A systematic review  

PubMed Central

Study design A systematic review. Background The number of traumatic spinal cord injury (TSCI) reports grows annually, especially in China and Korea. The epidemiological characteristics of TSCI in Asia differ from those in other countries. Thus, we compiled epidemiological factors from Asia to compare with those from other countries. Method We searched articles published in any language between January 1980 to December 2011 using the terms “spinal cord injury”, “traumatic spinal cord injury”, “epidemiology”, and “Asia”. The articles were reviewed for information regarding TSCI incidence, total cases, case criteria, case source, causes of injury, male/female ratio, mean age, prospective or retrospective, neurological level of injury, extent of injury, and America Spinal Injury Association Impairment Scale (AIS)/grade. Results Epidemiological data were extracted from 39 reports in the published literature that met the inclusion criteria. Only two studies reported prevalence rates. Incidence rates ranged from 12.06 to 61.6 per million. The average age ranged from 26.8 to 56.6 years old. Men were at higher risk than women. Motor vehicle collisions (MVCs) and falls were the main causes of TSCI. However, several countries reported war wounds as the major cause. The neurological level and extent of injury were mixed, and most patients were categorized as AIS/Frankel grade A. Conclusion TSCI is an important public health problem and a major cause of paralysis. We must understand the epidemiology to implement appropriate preventative measures. Asian epidemiology is different from that in other regions, so intervention measures must be established according to population-specific characteristics. PMID:22925749

Ning, Guang-Zhi; Wu, Qiang; Li, Yu-Lin; Feng, Shi-Qing

2012-01-01

229

Long-term medical complications after traumatic spinal cord injury: A regional model systems analysis  

Microsoft Academic Search

Objective: To analyze the incidence, risk factors, and trends of long-term secondary medical complications in individuals with traumatic spinal cord injury.Design: Data were reviewed from the National SCI Statistical Center on annual evaluations performed at 1, 2, 5, 10, 15, and 20 years after injury on patients injured between 1973 and 1998.Setting: Multicenter Regional SCI Model Systems.Main Outcome Measures: Secondary

William O. McKinley; Amie B. Jackson; Diana D. Cardenas; Michael J. De Vivo

1999-01-01

230

Increased synapsin expression and neurite sprouting in lamprey brain after spinal cord injury.  

PubMed

Spinal cord injury induces structural plasticity throughout the mammalian nervous system, including distant locations in the brain. Several types of injury-induced plasticity have been identified, such as neurite sprouting, axon regeneration, and synaptic remodeling. However, the molecular mechanisms involved in injury-induced plasticity are unclear as is the extent to which injury-induced plasticity in brain is conserved across vertebrate lineages. Due to its robust roles in neurite outgrowth and synapse formation during developmental processes, we examined synapsin for its potential involvement in injury-induced plasticity. We used lamprey, a vertebrate that undergoes robust anatomical plasticity and functional recovery after spinal cord injury. At 3 and 11 weeks after spinal cord transection, synapsin I mRNA was upregulated >2-fold in lamprey brain, as assayed by semi-quantitative RT-PCR. Other synaptic vesicle-associated genes remained unchanged. In situ hybridization revealed that synapsin I mRNA was increased globally throughout the lamprey brain. Immunolabeling for synapsin I protein revealed a significant increase in both the intensity and density of synapsin I-positive structures in lamprey hindbrain at 11 weeks post-transection, relative to controls. Moreover, the number of structures immunolabeled for phospho-synapsin (serine 9) increased after injury, suggestive of neurite sprouting. Indeed, at the ultrastructural level, there was an increase in neurite density at 11 weeks post-transection. Taken together, these data show that neurite sprouting in the brain is an evolutionarily conserved response to a distant spinal cord injury and suggest that synapsin and its phosphorylation at serine 9 play key roles in the sprouting mechanism. PMID:21316361

Lau, Billy Y B; Foldes, Andrea E; Alieva, Naila O; Oliphint, Paul A; Busch, David J; Morgan, Jennifer R

2011-04-01

231

Psychological Well-Being After Spinal Cord Injury: Perception of Loss and Meaning Making  

Microsoft Academic Search

Objective: This study examined the influence of medical injury severity, perceived loss of physical functioning (conceptualized as physical resource loss), and global meaning making on psychological well-being among 79 veterans living with a spinal cord injury. Measures: Structured interviews were completed to assess perceived loss of physical abilities using the Conservation of Resources—Evaluation and SF-36 Health Survey, global meaning making

Terri A. deRoon-Cassini; Ed de St. Aubin; Abbey Valvano; James Hastings; Patricia Horn

2009-01-01

232

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury  

Microsoft Academic Search

Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes\\u000a a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Methylprednisolone (MP), by reducing\\u000a edema and protecting the cell membrane against peroxidation, is the only pharmacological agent with a proven clinically beneficial\\u000a effect on SCI. Melatonin,

Suleyman R. Cayli; Ayhan Kocak; Ugur Yilmaz; Ayhan Tekiner; Mine Erbil; Cetin Ozturk; Kadir Batcioglu; Saim Yologlu

2004-01-01

233

Therapeutic Strategy for Acute Spinal Cord Contusion Injury: Cell Elimination Combined with Microsurgical Intervention  

PubMed Central

Background No cure is available for human spinal cord injury. Cell elimination by localized radiation therapy that is timed within 2–3 weeks postinjury can facilitate repair of structure and function in transected rat spinal cord. In pilot studies in contusion spinal cord injury, a model similar to crush/fracture injury in human, we did not observe the expected beneficial effects of radiation therapy. Long forgotten data show that in contusion/crush injury, fluid accumulation from hemorrhage is critical. Alfred Reginald Allen observed that the most devastating sequelae in contusive injury are secondary to fluid accumulation which could be alleviated by surgical intervention, midline slits (myelotomy) at the lesion site. Methods and Findings Here, we tested whether release of fluid buildup by microsurgery (partial myelotomy) would affect the structural outcome of radiation therapy in the severely contused rat spinal cord. Surgical intervention alone significantly enhanced tissue and functional preservation in the contused cord, thus confirming Allen's observations. Combining partial myelotomy with radiation therapy that is specifically timed postinjury elicited substantial beneficial therapeutic outcome; it led to significant increase in tissue repair/preservation compared with the group that received surgical intervention only, as determined by histology and in vivo MRI. Altogether, the combined treatments led to a 1.8 fold increase in tissue repair/preservation as compared with the contused group. Conclusions The data suggest that a clinical protocol could be developed to treat acute human spinal cord injury through conventional clinical procedures, a combination of microsurgical manipulation and radiation therapy. These also suggest it is imperative to first prevent the secondary damage caused by fluid accumulation for a cure to be possible. PMID:17637827

Kalderon, Nurit; Muruganandham, Manickam; Koutcher, Jason A.; Potuzak, Melissa

2007-01-01

234

Blood-Spinal Cord Barrier Permeability in Experimental Spinal Cord Injury: Dynamic Contrast-Enhanced Magnetic Resonance Imaging  

PubMed Central

Following the primary traumatic injury, spinal cord tissue undergoes a series of pathobiological changes, including compromised blood-spinal cord-barrier (BSCB) integrity. These vascular changes occur over both time and space. In an experimental model of spinal cord injury (SCI), longitudinal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)studies were performed up to 56 days post-SCI to quantify spatial and temporal changes in the BSCB permeability in tissue that did not show any visible enhancement on the post-contrast MRI(non-enhancing tissue). DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. These studies demonstrate gradual restoration of BSCB with post-SCI time. But, based on DCE-MRI, and confirmed by immunohistochemistry, the BSCB remained compromised even at 56 days post-SCI. In addition, open-field locomotion was evaluated using the 21 point Basso-Beattie-Bresnahan scale. A significant correlation between decreased BSCB permeability and improved locomotor recovery was observed. PMID:19023867

Cohen, David M.; Patel, Chirag B.; Ahobila-Vajjula, Pallavi; Sundberg, Laura M.; Chacko, Tessy; Liu, Shi-Jie; Narayana, Ponnada A.

2009-01-01

235

NO mediates microglial response to acute spinal cord injury under ATP control in vivo.  

PubMed

To understand the pathomechanisms of spinal cord injuries will be a prerequisite to develop efficient therapies. By investigating acute lesions of spinal cord white matter in anesthetized mice with fluorescently labeled microglia and axons using in vivo two-photon laser-scanning microscopy (2P-LSM), we identified the messenger nitric oxide (NO) as a modulator of injury-activated microglia. Local tissue damages evoked by high-power laser pulses provoked an immediate attraction of microglial processes. Spinal superfusion with NO synthase and guanylate cyclase inhibitors blocked these extensions. Furthermore, local injection of the NO-donor spermine NONOate (SPNO) or the NO-dependent second messenger cGMP induced efficient migration of microglial cells toward the injection site. High-tissue levels of NO, achieved by uniform superfusion with SPNO and mimicking extended tissue damage, resulted in a fast conversion of the microglial shape from ramified to ameboid indicating cellular activation. When the spinal white matter was preconditioned by increased, ambient ATP (known as a microglial chemoattractant) levels, the attraction of microglial processes to local NO release was augmented, whereas it was abolished at low levels of tissue ATP. Because both signaling molecules, NO and ATP, mediate acute microglial reactions, coordinated pharmacological targeting of NO and purinergic pathways will be an effective mean to influence the innate immune processes after spinal cord injury. PMID:20468054

Dibaj, Payam; Nadrigny, Fabien; Steffens, Heinz; Scheller, Anja; Hirrlinger, Johannes; Schomburg, Eike D; Neusch, Clemens; Kirchhoff, Frank

2010-07-01

236

Intraspinal sprouting of unmyelinated pelvic afferents after complete spinal cord injury is correlated with autonomic dysreflexia induced by visceral pain  

Microsoft Academic Search

Autonomic dysreflexia is a potentially life-threatening hypertensive syndrome following high thoracic (T) spinal cord injury (SCI). It is commonly triggered by noxious pelvic stimuli below the injury site that correlates with increased sprouting of primary afferent C-fibers into the lumbosacral (L\\/S) spinal cord. We have recently demonstrated that injury-induced plasticity of (L\\/S) propriospinal neurons, which relay pelvic visceral sensations to

S. Hou; H. Duale; A. G. Rabchevsky

2009-01-01

237

Participation in Organized Sports Is Positively Associated with Employment in Adults with Spinal Cord Injury  

PubMed Central

Objective The aim of this study was to determine the association between participation in organized sports programs and employment in adults with chronic spinal cord injury. Design This is a cross-sectional study of 149 adults with chronic spinal cord injury. Motor level and completeness of injury were confirmed by physical examination. Information related to demographics, employment, level of education, body mass index, duration of injury, participation in individually planned exercise, and participation in organized sports was obtained using a standardized questionnaire. Multivariable logistic regression analyses were used to assess factors associated with employment. Results In univariate analyses, employment was associated with younger age (P = 0.001) and a higher level of education (P = 0.01), whereas obesity decreased the likelihood of employment (P = 0.04). Participation in organized sports approached significance (P = 0.06). In the multivariable analysis and after adjusting for age, education, and body mass index, participation in organized sports was significantly associated with employment (odds ratio, 2.4; P = 0.04). Sex, duration of injury, wheelchair use, and participation in individually planned exercise were not significantly associated with employment (P = 0.16–0.94). Conclusions In the adults with chronic spinal cord injury, participation in organized sports was positively associated with employment. Further studies are necessary to determine the causative nature of this association and how various factors related to sports participation may contribute. PMID:23478458

Blauwet, Cheri; Sudhakar, Supreetha; Doherty, Ashley L.; Garshick, Eric; Zafonte, Ross; Morse, Leslie R.

2014-01-01

238

Development of a Rat Model of Graded Contusive Spinal Cord Injury Using a Pneumatic Impact Device  

PubMed Central

An animal model of spinal cord trauma is essential for understanding the injury mechanisms, cord regeneration, and to aid the development of new therapeutic modalities. This study focused on the development of a graded experimental contusion model for spinal cord injury (SCI) using a pneumatic impact device made in Korea. A contusive injury was made to the dorsal aspect of the cord. Three trauma groups were defined according to the impact velocity (IV). A control group (n=6), received laminectomy only. Group 1 (n=10), 2 (n=10), and 3 (n=10) had IVs of 1.5 m/sec, 2.0 m/sec, and 3.5 m/sec respectively. Functional assessments were made up to the 14th day after injury. The cord was removed at the 14th post-injury day and prepared for histopathologic examination. Significant behavioral and histopathological abnormalities were found in control and each trauma group. All trauma groups showed severe functional impairment immediately after injury but following different rates of functional recovery (Fig. 5). As the impact velocity and impulse increased, the depth of contusive lesion revealed to be profound the results show that the rat model reproduces spinal cord lesions consistently, has a distinctive value in assessing the effects of impact energy. PMID:15308850

Yeo, Sang Jun; Park, Seung Won; Kim, Young Baeg; Min, Byung Kook; Kwon, Jeong Taik; Suk, Jong Sik

2004-01-01

239

Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury  

PubMed Central

OBJECTIVES: Prevention of the development of paraplegia during the repair of the damage caused by descending thoracic and thoracoabdominal aneurysms remains an important issue. Therefore, we investigated the protective effect of atorvastatin on ischemia-induced spinal cord injury in a rabbit model. METHOD: Thirty-two rabbits were divided into the following four equally sized groups: group I (control), group II (ischemia-reperfusion), group III (atorvastatin treatment) and group IV (atorvastatin withdrawal). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs of each animal was evaluated according to the Tarlov score. Spinal cord and blood samples were obtained for histopathological and biochemical analyses. RESULTS: All of the rabbits in group II exhibited severe neurological deficits. Atorvastatin treatment (groups III and IV) significantly reduced the level of motor dysfunction. No significant differences were observed between the motor function scores of groups III and IV at the evaluated time points. Light microscopic examination of spinal cord tissue samples obtained at the 72nd hour of reperfusion indicated greater tissue preservation in groups III and IV than in group II. CONCLUSION: This study demonstrates the considerable neuroprotective effect of atorvastatin on the neurological, biochemical and histopathological status of rabbits with ischemia-induced spinal cord injury. Moreover, the acute withdrawal of atorvastatin therapy following the induction of spinal cord ischemia did not increase the neuronal damage in this rabbit model.

Nazli, Yunus; Colak, Necmettin; Alpay, Mehmet Fatih; Uysal, Sema; Uzunlar, Ali Kemal; Cakir, Omer

2015-01-01

240

Prevention of deep tissue injury through muscle contractions induced by intermittent electrical stimulation after spinal cord injury in pigs  

PubMed Central

Deep tissue injury (DTI) is a severe medical complication that commonly affects those with spinal cord injury. It is caused by prolonged external loading of the muscles, entrapping them between a bony prominence and the support surface. The entrapment causes excessive mechanical deformation and increases in interstitial pressure, leading to muscle breakdown deep around the bony prominences. We proposed the use of intermittent electrical stimulation (IES) as a novel prophylactic method for the prevention of DTI. In this study, we assessed the long-term effectiveness of this technique in pigs that had received a partial spinal cord injury that paralyzed one hindlimb. The pigs recovered for 2 wk postsurgery, and subsequently, their paralyzed limbs were loaded to 25% of their body weights 4 h/day for 4 consecutive days each week for 1 mo. One group of pigs (n = 3) received IES during the loading, whereas another group (n = 3) did not. DTI was quantified using magnetic resonance imaging (MRI) and postmortem histology. In the group that did not receive IES, MRI assessments revealed signs of tissue damage in 48% of the volume of the loaded muscle. In the group that did receive IES, only 8% of the loaded muscle volume showed signs of tissue damage. Similar findings were found through postmortem histology. This study demonstrates, for the first time, that IES may be an effective technique for preventing the formation of DTI in loaded muscles after spinal cord injury. PMID:23172030

Solis, Leandro R.; Twist, Elizabeth; Seres, Peter; Thompson, Richard B.

2013-01-01

241

Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury  

PubMed Central

Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury. PMID:25657742

Li, Zhi; Zhao, Wei; Liu, Wei; Zhou, Ye; Jia, Jingqiao; Yang, Lifeng

2014-01-01

242

Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation.  

PubMed

Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4-/- mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI. PMID:25652774

Nagai, Jun; Kitamura, Yoshiteru; Owada, Kazuki; Yamashita, Naoya; Takei, Kohtaro; Goshima, Yoshio; Ohshima, Toshio

2015-01-01

243

Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation  

PubMed Central

Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4?/? mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI. PMID:25652774

Nagai, Jun; Kitamura, Yoshiteru; Owada, Kazuki; Yamashita, Naoya; Takei, Kohtaro; Goshima, Yoshio; Ohshima, Toshio

2015-01-01

244

Sildenafil effects on sexual and cardiovascular responses in women with spinal cord injury  

Microsoft Academic Search

Objectives. Sexual dysfunction is common in women with spinal cord injuries (SCIs) and other neurologic conditions. Sildenafil has previously been shown to be safe and effective in the treatment of erectile dysfunction due to SCI. This study is the first to evaluate the sexual and cardiovascular effects of sildenafil in women with SCIs in a controlled, laboratory setting.Methods. Nineteen premenopausal

Marca L Sipski; Raymond C Rosen; Craig J Alexander; Robert M Hamer

2000-01-01

245

Quantification of deficits in lateral paw positioning after spinal cord injury in dogs  

PubMed Central

Background Previous analysis of the behavioural effects of spinal cord injury has focussed on coordination in the sagittal plane of movement between joints, limb girdle pairs or thoracic and pelvic limb pairs. In this study we extend the functional analysis of the consequences of clinical thoracolumbar spinal cord injury in dogs to quantify the well-recognised deficits in lateral stability during locomotion. Dogs have a high centre of mass thereby facilitating recognition of lateral instability. Results We confirm that errors in lateral positioning of the pelvic limb paws can be quantified and that there is a highly significant difference in variability of foot placement between normal and spinal cord injured dogs. In this study there was no detectable difference in lateral paw positioning variability between complete and incomplete injuries, but it appears that intergirdle limb coordination and appropriate lateral paw placement recover independently from one another. Conclusion Analysis of lateral paw position in the dog provides an additional tier of analysis of outcome after spinal cord injury that will be of great value in interpreting the effects of putative therapeutic interventions. PMID:19032742

Hamilton, Lindsay; Franklin, Robin JM; Jeffery, Nicholas D

2008-01-01

246

The Use of Functional Electrical Stimulation to Improve Function in People with Spinal Cord Injury  

Microsoft Academic Search

1. Clinical Bottom Line: Currently there is no evidence to support the notion that in people with spinal cord injury, the use of FES as a physical therapy intervention results in improved functional outcomes. All of the articles we critically analyzed had significant threats to internal validity preventing us from generalizing the results to our clinical scenarios. Higher quality research

April R. Baker; Candace M. Callison

2007-01-01

247

Sprouting of axonal collaterals after spinal cord injury is prevented by delayed axonal degeneration.  

PubMed

After an incomplete spinal cord injury (SCI), partial recovery of locomotion is accomplished with time. Previous studies have established a functional link between extension of axon collaterals from spared spinal tracts and locomotor recovery after SCI, but the tissular signals triggering collateral sprouting have not been identified. Here, we investigated whether axonal degeneration after SCI contributes to the sprouting of collaterals from axons spared after injury. To this end, we evaluated collateral sprouting from BDA-labeled uninjured corticospinal axons after spinal cord hemisection (SCI(H)) in wild type (WT) mouse and Wld(S) mouse strains, which shows a significant delay in Wallerian degeneration after injury. After SCI(H), spared fibers of WT mice extend collateral sprouts to both intact and denervated sides of the spinal cord distant from the injury site. On the contrary, in the Wld(S) mice collateral sprouting from spared fibers was greatly reduced after SCI(H). Consistent with a role for collateral sprouting in functional recovery after SCI, locomotor recovery after SCI(H) was impaired in Wld(S) mice compared to WT animals. In conclusion, our results identify axonal degeneration as one of the triggers for collateral sprouting from the contralesional uninjured fibers after an SCI(H). These results open the path for identifying molecular signals associated with tissular changes after SCI that promotes collateral sprouting and functional recovery. PMID:25079366

Collyer, E; Catenaccio, A; Lemaitre, D; Diaz, P; Valenzuela, V; Bronfman, F; Court, F A

2014-11-01

248

Increased calpain content and progressive degradation of neurofilament protein in spinal cord injury  

Microsoft Academic Search

Spinal cord injury was induced in rat by weight drop. The extent of degradation of neurofilament proteins in the lesion following trauma was examined and served as a measure of calpain activity. Calpain was identified in the samples by myelin mealpain antibody and the content was estimated from the immunoblot. There was progressive degradation of both 68 kDa and 200

Naren L. Banik; Denise C. Matzelle; Gloria Gantt-Wilford; Anne Osborne; Edward L. Hogan

1997-01-01

249

Shoulder Pain in Cases of Spinal Injury: Influence of the Position of the Wheelchair Seat  

ERIC Educational Resources Information Center

The objective of this study was to determine the relationship between shoulder pain and the position of the seat of a wheelchair relative to the ground and to determine the relationship between shoulder pain and structural damage. A transversal study of a patient cohort of 140 patients with grade A and B spinal cord injuries below the T1 vertebra,…

Giner-Pascual, Manuel; Alcanyis-Alberola, Modesto; Millan Gonzalez, Luis; Aguilar-Rodriguez, Marta; Querol, Felipe

2011-01-01

250

Reversal of Peripheral Nerve Injury-induced Hypersensitivity in the Postpartum Period: Role of Spinal Oxytocin  

PubMed Central

Background Physical injury, including surgery, can result in chronic pain; yet chronic pain following childbirth, including cesarean delivery in women, is rare. The mechanisms involved in this protection by pregnancy or delivery have not been explored. Methods We examined the effect of pregnancy and delivery on hypersensitivity to mechanical stimuli of the rat hindpaw induced by peripheral nerve injury (spinal nerve ligation) and after intrathecal oxytocin, atosiban and naloxone. Additionally, oxytocin concentration in lumbar spinal cerebrospinal fluid was determined. Results Spinal nerve ligation performed at mid-pregnancy resulted in similar hypersensitivity to nonpregnant controls, but hypersensitivity partially resolved beginning after delivery. Removal of pups after delivery prevented this partial resolution. Cerebrospinal fluid concentrations of oxytocin were greater in normal postpartum rats prior to weaning. To examine the effect of injury at the time of delivery rather than during pregnancy, spinal nerve ligation was performed within 24 h of delivery. This resulted in acute hypersensitivity that partially resolved over the next 2–3 weeks. Weaning of pups resulted only in a temporary return of hypersensitivity. Intrathecal oxytocin effectively reversed the hypersensitivity following separation of the pups. Postpartum resolution of hypersensitivity was transiently abolished by intrathecal injection of the oxytocin receptor antagonist, atosiban. Conclusions These results suggest that the postpartum period rather than pregnancy protects against chronic hypersensitivity from peripheral nerve injury and that this protection may reflect sustained oxytocin signaling in the central nervous system during this period. PMID:23249932

Gutierrez, Silvia; Liu, Baogang; Hayashida, Ken-ichiro; Houle, Timothy T.; Eisenach, James C.

2012-01-01

251

Adjustment to Spinal Cord Injury: A Comprehensive Follow-Up Study.  

ERIC Educational Resources Information Center

This document reports a comprehensive followup study to describe postservice life status of former vocational rehabilitation clients and to develop an empirical index of postservice adjustment to spinal cord injury. Significant findings, conclusions, and implications are found at the beginning. The introduction section summarizes followup studies…

Cook, Daniel; And Others

252

Prevention Practice Differences Among Persons With Spinal Cord Injuries Who Rarely Versus Frequently Sustain Pressure Ulcers  

ERIC Educational Resources Information Center

Pressure ulcers are common among people with spinal cord injury (SCI) and not only are costly to treat but also affect the quality of life of those affected by them. Despite a plethora of literature on prevention, there are few wellness studies focusing on the practices of people who do not develop pressure ulcers. This preliminary study sought to…

Jones, Michael L.; Marini, Irmo; Slate, John R.

2005-01-01

253

Detection of Abnormal Muscle Activations during Walking Following Spinal Cord Injury (SCI)  

ERIC Educational Resources Information Center

In order to identify optimal rehabilitation strategies for spinal cord injury (SCI) participants, assessment of impaired walking is required to detect, monitor and quantify movement disorders. In the proposed assessment, ten healthy and seven SCI participants were recruited to perform an over-ground walking test at slow walking speeds. SCI…

Wang, Ping; Low, K. H.; McGregor, Alison H.; Tow, Adela

2013-01-01

254

The Effectiveness of a Sexuality Training Program for the Interdisciplinary Spinal Cord Injury Rehabilitation Team  

Microsoft Academic Search

While there is evidence to support consideration of client sexuality needs in the provision of rehabilitation services to people with spinal cord injury (SCI), the interdisciplinary team rarely receives training in this area. The current study aimed to examine the effectiveness of a consumer-driven sexuality training program in improving staff knowledge, comfort (general and personal) and attitudes. Using a local

Patricia Fronek; Susan Booth; Melissa Kendall; Deborah Miller; Timothy Geraghty

2005-01-01

255

Oxidative phosphorylated neurofilament protein M protects spinal cord against ischemia/reperfusion injury  

PubMed Central

Previous studies have shown that neurofilament protein M expression is upregulated in the early stage of spinal cord ischemia/reperfusion injury, indicating that this protein may play a role in the injury process. In the present study, we compared protein expression in spinal cord tissue of rabbits after 25 minutes of ischemia followed by 0, 12, 24, or 48 hours of reperfusion with that of sham operated rabbits, using proteomic two-dimensional gel electrophoresis and mass spectrometry. In addition, the nerve repair-related neurofilament protein M with the unregulated expression was detected with immunohistochemistry and western blot analysis. Two-dimensional gel electrophoresis and mass spectrometry showed that, compared with the sham group, upregulation of protein expression was most significant in the spinal cords of rabbits that had undergone ischemia and 24 hours of reperfusion. Immunohistochemical analysis revealed that neurofilament protein M was located in the membrane and cytoplasm of neuronal soma and axons at each time point after injury. Western blot analysis showed that neurofilament protein M expression increased with reperfusion time until it peaked at 24 hours and returned to baseline level after 48 hours. Furthermore, neurofilament protein M is phosphorylated under oxidative stress, and expression changes were parallel for the phosphorylated and non-phosphorylated forms. Neurofilament protein M plays an important role in spinal cord ischemia/reperfusion injury, and its functions are achieved through oxidative phosphorylation. PMID:25374588

Wang, Haitao; Pan, Su; Yang, Xiaoyu; Zhu, Benqing; Wang, Dalin

2014-01-01

256

A profile of psychosexual functioning in males following spinal cord injury  

Microsoft Academic Search

The psychosexual functioning of 47 men with spinal cord injury was studied using the Derogatis Sexual Functioning Inventory (DSFI). Subjects with paraplegia did not differ significantly from subjects with quadriplegia on any of the scales of the DSFI. Subject groups were then aggregated, and the means across DSFI scales were compared to the means of the non-disabled DSFI normative group.

Allen J. Romeo; Richard Wanlass; Silverio Arenas

1993-01-01

257

Immune depression syndrome following human spinal cord injury (SCI): a pilot study.  

PubMed

Experimental spinal cord injury (SCI) has been identified to trigger a systemic, neurogenic immune depression syndrome. Here, we have analyzed fluctuations of immune cell populations following human SCI by FACS analysis. In humans, a rapid and drastic decrease of CD14+ monocytes (<50% of control level), CD3+ T-lymphocytes (<20%, P<0.0001) and CD19+ B-lymphocytes (<30%, P=0.0009) and MHC class II (HLA-DR)+ cells (<30%, P<0.0001) is evident within 24 h after spinal cord injury reaching minimum levels within the first week. CD15+ granulocytes were the only leukocyte subpopulation not decreasing after SCI. A contributing, worsening effect of high dose methylprednisolone cannot be excluded with this pilot study. We demonstrate that spinal cord injury is associated with an early onset of immune suppression and secondary immune deficiency syndrome (SCI-IDS). Identification of patients suffering spinal cord injury as immune compromised is a clinically relevant, yet widely underappreciated finding. PMID:18790013

Riegger, T; Conrad, S; Schluesener, H J; Kaps, H-P; Badke, A; Baron, C; Gerstein, J; Dietz, K; Abdizahdeh, M; Schwab, J M

2009-02-01

258

THE EFFECTS OF EXERCISE TRAINING ON CARDIOVASCULAR REGULATION IN INDIVIUALS WITH SPINAL CORD INJURY  

Microsoft Academic Search

Introduction. Individuals with spinal cord injury (SCI) are prone to severe cardiovascular dysfunction and an increased risk of mortality from various cardiovascular diseases. The underlying mechanisms responsible for the increased cardiovascular risk are not precisely understood, however, the reduced activity levels that accompany SCI certainly contribute. Unfortunately, muscular paralysis (partial or complete) limits the exercise options for individuals with SCI

DAVID DITOR

2003-01-01

259

Disability and Self-Help: A Case Study of the Spinal Injuries Association.  

ERIC Educational Resources Information Center

The important role of the self-help approach in helping persons deal with medical, emotional, and practical effects of a sudden disability is considered in a discussion of the work of the Spinal Injuries Association in Britain. Services that can be provided and controlled by disabled persons are described. (Author/CB)

Oliver, Mike; Hasler, Frances

1987-01-01

260

4-AMINOPYRIDINE DERIVATIVES ENHANCE IMPULSE CONDUCTION IN GUINEA-PIG SPINAL CORD FOLLOWING TRAUMATIC INJURY  

E-print Network

trauma. Previous studies have indicated increased activity of potassium channels as a contributor the myelin sheath. Consequently, myelin damage, a well-documented secondary injury subsequent to spinal cord trauma (Blight, 1983a, 1985) will likely unmask these otherwise silent channels leading to conduction

Shi, Riyi

261

Attenuating the Endoplasmic Reticulum Stress Response Improves Functional Recovery After Spinal Cord Injury  

E-print Network

; ER-stress; locomoter activity; oligodendrocyte; spinal cord injury; white-matter sparing ABSTRACT that in neurons, the UPR appeared at 6 and 24-h post-SCI. In contrast, in oligodendrocytes and astroglia, UPR CHOP was among the UPR markers upregulated in neurons and oligodendrocytes, but not in astrocytes

Harkema, Susan

262

Activity-Based Restorative Therapies: Concepts and Applications in Spinal Cord Injury-Related Neurorehabilitation  

ERIC Educational Resources Information Center

Physical rehabilitation following spinal cord injury-related paralysis has traditionally focused on teaching compensatory techniques, thus enabling the individual to achieve day-to-day function despite significant neurological deficits. But the concept of an irreparable central nervous system (CNS) is slowly being replaced with evidence related to…

Sadowsky, Cristina L.; McDonald, John W.

2009-01-01

263

Cognitive Training Program for Youths/Young Adults Having a Spinal Cord Injury.  

ERIC Educational Resources Information Center

The pilot study determined the effectiveness of a cognitive skills training program on both the vocational retraining of five young adults with traumatic spinal cord injuries and learning difficulties and the adaptation process to an altered lifestyle required by permanent paralysis. After a 40-hour Instrumental Enrichment (IE) program, Ss showed…

Stirling, Gloria; And Others

264

Glycyrrhizin reduces secondary inflammatory process after spinal cord compression injury in mice.  

PubMed

Glycyrrhizin, a major active constituent of liquorice root (Glycyrrhiza glabra), has a free radical scavenging property, and its effects were evaluated on an animal model of spinal cord injury (SCI) induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling staining, Bax, and Bcl-2 expression). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS, and poly(adenosine diphosphate-ribose) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB. In contrast, the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) formation, (3) iNOS expression, (4) nuclear factor-kappaB activation, and (5) apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling, Bax, and Bcl-2) was markedly reduced in spinal cord tissue obtained from mice treated with glycyrrhizin extract (10 mg/kg, i.p., 30 min before and 1 and 6 h after SCI). In a separate set of experiments, we have clearly demonstrated that glycyrrhizin extract treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with glycyrrhizin extract reduces the development of inflammation and tissue injury events associated with spinal cord trauma. PMID:18665052

Genovese, Tiziana; Menegazzi, Marta; Mazzon, Emanuela; Crisafulli, Concetta; Di Paola, Rosanna; Dal Bosco, Martina; Zou, Zhenzhen; Suzuki, Hisanori; Cuzzocrea, Salvatore

2009-04-01

265

Myelotomy reduces spinal cord edema and inhibits aquaporin-4 and aquaporin-9 expression in rats with spinal cord injury.  

PubMed

Objective:Spinal cord edema contributes to the pathophysiological mechanisms underlying spinal cord injury (SCI) and is associated with functional recovery after SCI. Early myelotomy may be a promising surgical intervention for reducing SCI-induced edema. However, it remains unclear whether myelotomy can reduce SCI-induced edema. In addition, aquaporin-4 (AQP4) and aquaporin-9 (AQP9) have important roles in the regulation of water homeostasis. Here, we aimed to determine the effects of myelotomy on AQP4 and AQP9 expression and spinal cord edema in a rat model of moderate SCI.Methods:Rats were randomly assigned to three groups: the sham control group (n=22) receiving laminectomy alone; the contusion group (n=44) receiving laminectomy plus contusion; and the myelotomy group (n=44) receiving laminectomy plus contusion followed by myelotomy at 24?h. Functional recovery was estimated by the open-field and inclined plane tests. Spinal cord edema was determined by measuring the water content. The expression of AQP4 and AQP9 was determined by western blot.Results:Compared with the contusion group, myelotomy significantly improved the Basso, Beattie and Bresnahan scores in the open-field test and resulted in a higher mean angle value in the incline plane test. Myelotomy significantly reduced SCI-induced edema at 4 and 6 days after SCI, which was accompanied by downregulation of AQP4 and AQP9 expression.Conclusion:Myelotomy improves locomotor function, reduces edema in rats with SCI and is associated with decreased expression of AQP4 and AQP9.Spinal Cord advance online publication, 2 December 2014; doi:10.1038/sc.2014.209. PMID:25448191

Hu, A-M; Li, J-J; Sun, W; Yang, D-G; Yang, M-L; Du, L-J; Gu, R; Gao, F; Li, J; Chu, H-Y; Zhang, X; Gao, L-J

2014-12-01

266

Repertoire of microglial and macrophage responses after spinal cord injury  

Microsoft Academic Search

Macrophages from the peripheral circulation and those derived from resident microglia are among the main effector cells of the inflammatory response that follows spinal cord trauma. There has been considerable debate in the field as to whether the inflammatory response is good or bad for tissue protection and repair. Recent studies on macrophage polarization in non-neural tissues have shed much

Antje Kroner; Samuel David

2011-01-01

267

Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview  

PubMed Central

Structural discontinuity in the spinal cord after injury results in a disruption in the impulse conduction resulting in loss of various bodily functions depending upon the level of injury. This article presents a summary of the scientific research employing electrical stimulation as a means for anatomical or functional recovery for patients suffering from spinal cord injury. Electrical stimulation in the form of functional electrical stimulation (FES) can help facilitate and improve upper/lower limb mobility along with other body functions lost due to injury e.g. respiratory, sexual, bladder or bowel functions by applying a controlled electrical stimulus to generate contractions and functional movement in the paralysed muscles. The available rehabilitative techniques based on FES technology and various Food and Drug Administration, USA approved neuroprosthetic devices that are in use are discussed. The second part of the article summarises the experimental work done in the past 2 decades to study the effects of weakly applied direct current fields in promoting regeneration of neurites towards the cathode and the new emerging technique of oscillating field stimulation which has shown to promote bidirectional regeneration in the injured nerve fibres. The present article is not intended to be an exhaustive review but rather a summary aiming to highlight these two applications of electrical stimulation and the degree of anatomical/functional recovery associated with these in the field of spinal cord injury research. PMID:18677518

Hayek, Ray

2008-01-01

268

Perivascular Fibroblasts Form the Fibrotic Scar after Contusive Spinal Cord Injury  

PubMed Central

Injury to the CNS leads to formation of scar tissue, which is important in sealing the lesion and inhibiting axon regeneration. The fibrotic scar that comprises a dense extracellular matrix is thought to originate from meningeal cells surrounding the CNS. However, using transgenic mice, we demonstrate that perivascular collagen1?1 cells are the main source of the cellular composition of the fibrotic scar after contusive spinal cord injury in which the dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, and antigenic profiling, we identify collagen1?1 cells as perivascular fibroblasts that are distinct from pericytes. Our results identify collagen1?1 cells as a novel source of the fibrotic scar after spinal cord injury and shift the focus from the meninges to the vasculature during scar formation. PMID:23966707

Soderblom, Cynthia; Luo, Xueting; Blumenthal, Ezra; Bray, Eric; Lyapichev, Kirill; Ramos, Jose; Krishnan, Vidhya; Lai-Hsu, Catherine; Park, Kevin K.; Tsoulfas, Pantelis

2013-01-01

269

Research advances in the application of methylprednisolone in the treatment of acute spinal cord injury.  

PubMed

Acute spinal cord injury(ASCI),mainly caused by traffic accidents and fall injuries,is a catastrophic event that can profoundly affect the trajectory of a patient's life. Debate continues over the medical management of ASCI,in particular the usefulness,dosage,and potential risks of methylprednisolone(MP). Although the results of American National Acute Spinal Cord Injury Study 2 and 3 trials led to the wide adoption of a high-dose MP regimen for ASCI patients,the reliabilities of their study methods and data were still questionable. Based on the currently available literature,we conclude that high-dose MP is no longer a recommended therapy for ASCI;however,due to the lack of effective treatment,it remains a useful option for this condition. PMID:25556746

Kong, Xiang-Yi; Gao, Jun; Yang, Yi; Li, Yong-Ning; Ma, Wen-Bin; Xing, Bing; Wang, Ren-Zhi

2014-12-30

270

An overview of tissue engineering approaches for management of spinal cord injuries  

PubMed Central

Severe spinal cord injury (SCI) leads to devastating neurological deficits and disabilities, which necessitates spending a great deal of health budget for psychological and healthcare problems of these patients and their relatives. This justifies the cost of research into the new modalities for treatment of spinal cord injuries, even in developing countries. Apart from surgical management and nerve grafting, several other approaches have been adopted for management of this condition including pharmacologic and gene therapy, cell therapy, and use of different cell-free or cell-seeded bioscaffolds. In current paper, the recent developments for therapeutic delivery of stem and non-stem cells to the site of injury, and application of cell-free and cell-seeded natural and synthetic scaffolds have been reviewed. PMID:17501987

Samadikuchaksaraei, Ali

2007-01-01

271

Impact of spinal cord injury on sexuality: Broad-based clinical practice intervention and practical application  

PubMed Central

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

Hess, Marika J.; Hough, Sigmund

2012-01-01

272

Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury.  

PubMed

Injury to the CNS leads to formation of scar tissue, which is important in sealing the lesion and inhibiting axon regeneration. The fibrotic scar that comprises a dense extracellular matrix is thought to originate from meningeal cells surrounding the CNS. However, using transgenic mice, we demonstrate that perivascular collagen1?1 cells are the main source of the cellular composition of the fibrotic scar after contusive spinal cord injury in which the dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, and antigenic profiling, we identify collagen1?1 cells as perivascular fibroblasts that are distinct from pericytes. Our results identify collagen1?1 cells as a novel source of the fibrotic scar after spinal cord injury and shift the focus from the meninges to the vasculature during scar formation. PMID:23966707

Soderblom, Cynthia; Luo, Xueting; Blumenthal, Ezra; Bray, Eric; Lyapichev, Kirill; Ramos, Jose; Krishnan, Vidhya; Lai-Hsu, Catherine; Park, Kevin K; Tsoulfas, Pantelis; Lee, Jae K

2013-08-21

273

Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats  

PubMed Central

Hyperbaric oxygen therapy (HBOT) protects brain tissue from inflammatory injury by suppressing mitochondrial apoptotic pathways. However, its neuroprotective mechanism via anti-apoptosis in spinal cord injury (SCI) is still unclear. In our study, Male Sprague-Dawley rats were randomly divided into three groups: sham-operated (SH), SCI model, and SCI + HBOT. Rats in each group were randomly divided into four sub-groups in a time-dependent manner (1 day, 3 days, 7 days and 14 days after surgery). Expression of adaptor molecule apoptosis-associated speck-like protein (ASC) and caspase-3 was evaluated at the indicated time after injury. Our data showed that HBOT downregulated expression of ASC in SCI rats at the mRNA and protein levels. HBOT mitigated caspase-3 release in injured spinal cord tissue. We conclude that HBOT prevents inflammation apoptosis after SCI, likely through suppression of ASC and caspase-3.

Long, Ying; Liang, Fang; Gao, Chunjin; Li, Zhuo; Yang, Jing

2014-01-01

274

Diffusion tensor imaging as a predictor of locomotor function after experimental spinal cord injury and recovery.  

PubMed

Traumatic spinal cord injury (SCI) causes long-term disability with limited functional recovery linked to the extent of axonal connectivity. Quantitative diffusion tensor imaging (DTI) of axonal integrity has been suggested as a potential biomarker for prognostic and therapeutic evaluation after trauma, but its correlation with functional outcomes has not been clearly defined. To examine this application, female Sprague-Dawley rats underwent midthoracic laminectomy followed by traumatic spinal cord contusion of differing severities or laminectomy without contusion. Locomotor scores and hindlimb kinematic data were collected for 4 weeks post-injury. Ex vivo DTI was then performed to assess axonal integrity using tractography and fractional anisotropy (FA), a numerical measure of relative white matter integrity, at the injury epicenter and at specific intervals rostral and caudal to the injury site. Immunohistochemistry for tissue sparing was also performed. Statistical correlation between imaging data and functional performance was assessed as the primary outcome. All injured animals showed some recovery of locomotor function, while hindlimb kinematics revealed graded deficits consistent with injury severity. Standard T2 magnetic resonance sequences illustrated conventional spinal cord morphology adjacent to contusions while corresponding FA maps indicated graded white matter pathology within these adjacent regions. Positive correlations between locomotor (Basso, Beattie, and Bresnahan score and gait kinematics) and imaging (FA values) parameters were also observed within these adjacent regions, most strongly within caudal segments beyond the lesion. Evaluation of axonal injury by DTI provides a mechanism for functional recovery assessment in a rodent SCI model. These findings suggest that focused DTI analysis of caudal spinal cord should be studied in human cases in relationship to motor outcome to augment outcome biomarkers for clinical cases. PMID:24779685

Kelley, Brian J; Harel, Noam Y; Kim, Chang-Yeon; Papademetris, Xenophon; Coman, Daniel; Wang, Xingxing; Hasan, Omar; Kaufman, Adam; Globinsky, Ronen; Staib, Lawrence H; Cafferty, William B J; Hyder, Fahmeed; Strittmatter, Stephen M

2014-08-01

275

Changes of Functional Outcomes According to the Degree of Completeness of Spinal Cord Injury  

PubMed Central

Objective To evaluate whether an initial complete impairment of spinal cord injury (SCI) contributes to the functional outcome prediction, we analyzed the relationship between the degree of complete impairment according to the American Spinal Injury Association impairment scale (AIS), the posterior tibial nerve somatosensory evoked potential (PTSEP) and the changes of functional indices. Methods Sixty subjects with SCI were studied who received rehabilitative management for over 2 months. The degree of completeness on basis of the initial AIS and PTSEP were evaluated at the beginning of rehabilitation. Following treatment, several functional indices, such as walking index for spinal cord injury version II (WISCI II), spinal cord independence measure version III (SCIM III), Berg Balance Scale (BBS), and Modified Barthel Index (MBI), were evaluated until the index score reached a plateau value. Results The recovery efficiency of WISCI and BBS revealed a statistically significant difference between complete and incomplete impairments of initial AIS and PTSEP. The SCIM and MBI based analysis did not reveal any significant differences in terms of the degree of AIS and PTSEP completeness. Conclusion AIS and PTSEP were highly effective to evaluate the prognosis in post-acute phase SCI patients. BBS and WISCI might be better parameters than other functional indices for activities of daily living to predict the recovery of the walking ability in post-acute SCI. PMID:25024956

Kim, Hyo Sang; Jeong, Hyung Jun

2014-01-01

276

Effect of Robotic-Assisted Gait Training in Patients With Incomplete Spinal Cord Injury  

PubMed Central

Objective To determine the effect of robotic-assisted gait training (RAGT) compared to conventional overground training. Methods Sixty patients with motor incomplete spinal cord injury (SCI) were included in a prospective, randomized clinical trial by comparing RAGT to conventional overground training. The RAGT group received RAGT three sessions per week at duration of 40 minutes with regular physiotherapy in 4 weeks. The conventional group underwent regular physiotherapy twice a day, 5 times a week. Main outcomes were lower extremity motor score of American Spinal Injury Association impairment scale (LEMS), ambulatory motor index (AMI), Spinal Cord Independence Measure III mobility section (SCIM3-M), and walking index for spinal cord injury version II (WISCI-II) scale. Results At the end of rehabilitation, both groups showed significant improvement in LEMS, AMI, SCIM3-M, and WISCI-II. Based on WISCI-II, statistically significant improvement was observed in the RAGT group. For the remaining variables, no difference was found. Conclusion RAGT combined with conventional physiotherapy could yield more improvement in ambulatory function than conventional therapy alone. RAGT should be considered as one additional tool to provide neuromuscular reeducation in patient with incomplete SCI. PMID:25566469

Shin, Ji Cheol; Kim, Ji Yong; Park, Han Kyul

2014-01-01

277

Chondroitinase ABC plus bone marrow mesenchymal stem cells for repair of spinal cord injury?  

PubMed Central

As chondroitinase ABC can improve the hostile microenvironment and cell transplantation is proven to be effective after spinal cord injury, we hypothesized that their combination would be a more effective treatment option. At 5 days after T8 spinal cord crush injury, rats were injected with bone marrow mesenchymal stem cell suspension or chondroitinase ABC 1 mm from the edge of spinal cord damage zone. Chondroitinase ABC was first injected, and bone marrow mesenchymal stem cell suspension was injected on the next day in the combination group. At 14 days, the mean Basso, Beattie and Bresnahan score of the rats in the combination group was higher than other groups. Hematoxylin-eosin staining showed that the necrotic area was significantly reduced in the combination group compared with other groups. Glial fibrillary acidic protein-chondroitin sulfate proteoglycan double staining showed that the damage zone of astrocytic scars was significantly reduced without the cavity in the combination group. Glial fibrillary acidic protein/growth associated protein-43 double immunostaining revealed that positive fibers traversed the damage zone in the combination group. These results suggest that the combination of chondroitinase ABC and bone marrow mesenchymal stem cell transplantation contributes to the repair of spinal cord injury. PMID:25206389

Zhang, Chun; He, Xijing; Li, Haopeng; Wang, Guoyu

2013-01-01

278

A novel vertebral stabilization method for producing contusive spinal cord injury.  

PubMed

Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing reliable cervical SCI is difficult due to lack of satisfactory methods of vertebral stabilization. The conventional method to stabilize the spine is to suspend the rostral and caudal cervical spine via clamps attached to cervical spinous processes.  However, this method of stabilization fails to prevent tissue yielding during the contusion as the cervical spinal processes are too short to be effectively secured by the clamps (Figure 1).  Here we introduce a new method to completely stabilize the cervical vertebra at the same level of the impact injury.  This method effectively minimizes movement of the spinal column at the site of impact, which greatly improves the production of consistent SCIs.  We provide visual description of the equipment (Figure 2-4), methods, and a step-by-step protocol for the stabilization of the cervical 5 vertebra (C5) of adult rats, to perform laminectomy (Figure 5) and produce a contusive SCI thereafter.  Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS impactor device, this vertebral stabilization technique can be applied to other regions of the spinal cord, or be adapted to other SCI devices.  Improving spinal cord exposure and fixation through vertebral stabilization may be valuable for producing consistent and reliable injuries to the spinal cord.  This vertebral stabilization method can also be used for stereotactic injections of cells and tracers, and for imaging using two-photon microscopy in various neurobiological studies. PMID:25590284

Walker, Melissa J; Walker, Chandler L; Zhang, Y Ping; Shields, Lisa B E; Shields, Christopher B; Xu, Xiao-Ming

2015-01-01

279

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

PubMed

Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury. PMID:25490396

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

2014-01-01

280

Intralimb coordination as a sensitive indicator of motor-control impairment after spinal cord injury  

PubMed Central

Background: Recovery of walking function after neurotrauma, e.g., after spinal cord injury, is routinely captured using standardized walking outcome measures of time and distance. However, these measures do not provide information on possible underlying mechanisms of recovery, nor do they tell anything about the quality of gait. Subjects with an incomplete spinal cord injury are a very heterogeneous group of people with a wide range of functional impairments. A stratification of these subjects would allow increasing sensitivity for hypothesis testing and a more targeted treatment strategy. Methods: The gait of incomplete spinal cord injured subjects was compared to healthy control subjects by analyzing kinematic data obtained by a 3-D motion capture system. Hip–knee angle-angle plots (cyclograms) informed on the qualitative aspect of gait and the intralimb coordination. Features of the cyclogram, e.g., shape of the cyclogram, cycle-to-cycle consistency and its modulation due to changes in walking speed were discerned and used to stratify spinal cord injured subjects. Results: Spinal cord injured subjects were unable to modulate their cyclogram configuration when increasing speed from slow to preferred. Their gait quality remained clearly aberrant and showed even higher deviations from normal when walking at preferred speed. Qualitative categorization of spinal cord injured subjects based on their intralimb coordination was complemented by quantitative measures of cyclogram shape comparison. Discussion: Spinal cord injured subjects showed distinct distortions of intralimb coordination as well as limited modulation to changes in walking speed. The specific changes of the cyclograms revealed complementary insight in the disturbance of lower-limb control in addition to measures of time and distance and may be a useful tool for patient categorization and stratification prior to clinical trial inclusion. PMID:24672464

Awai, Lea; Curt, Armin

2014-01-01

281

Activity-Based Therapies To Promote Forelimb Use after a Cervical Spinal Cord Injury  

PubMed Central

Abstract Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard housing alone or enriched environments with daily training. A subset of animals received rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments/daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways. PMID:19317604

Dai, Haining; MacArthur, Linda; McAtee, Marietta; Hockenbury, Nicole; Tidwell, J. Lille; McHugh, Brian; Mansfield, Kevin; Finn, Tom; Hamers, Frank P.T.

2009-01-01

282

Spinal Cord Injury Reduces the Efficacy of Pseudorabies Virus Labeling of Sympathetic Preganglionic Neurons  

PubMed Central

The retrograde transynaptic tracer pseudorabies virus (PRV) is used as a marker for synaptic connectivity in the spinal cord. Using PRV we sought to document putative synaptic plasticity below a high thoracic (T) spinal cord transection. This lesion has been linked to the development of a number of debilitating conditions including autonomic dysreflexia. Two weeks after injury, complete T4-transected and/or T4-hemisected and sham rats were injected with PRV-expressing enhanced green fluorescent protein (EGFP) or monomeric red fluorescent protein (mRFP1) into the kidneys. We expected greater PRV labeling after injury due to plasticity of spinal circuitry but 96 hours post-PRV-EGFP inoculation, we found fewer EGFP+ cells in the thoracolumbar gray matter of T4-transected compared to sham rats (p < 0.01); Western blot analysis corroborated decreased EGFP protein levels (p < 0.01). Moreover, viral glycoproteins that are critical for cell adsorption and entry were also reduced in the thoracolumbar spinal cord of injured versus sham rats (p < 0.01). PRV labeling of sympathetic postganglionic neurons in the celiac ganglia innervating the kidneys was also significantly reduced in injured versus sham rats (p < 0.01). By contrast, the numbers and distribution of FluoroGold-labeled (intraperitoneal injection) sympathetic preganglionic neurons throughout the sampled regions appeared similar in injured and sham rats. These results question whether spinal cord injury exclusively retards PRV expression and/or transport or whether this injury broadly affects host cell-viral interactions. PMID:19151624

Duale, Hanad; Hou, Shaoping; Derbenev, Andrei V.; Smith, Bret N.; Rabchevsky, Alexander G.

2009-01-01

283

Spinal autofluorescent flavoprotein imaging in a rat model of nerve injury-induced pain and the effect of spinal cord stimulation.  

PubMed

Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level. PMID:25279562

Jongen, Joost L M; Smits, Helwin; Pederzani, Tiziana; Bechakra, Malik; Hossaini, Mehdi; Koekkoek, Sebastiaan K; Huygen, Frank J P M; De Zeeuw, Chris I; Holstege, Jan C; Joosten, Elbert A J

2014-01-01

284

Changes in Locomotor Muscle Activity After Treadmill Training in Subjects With Incomplete Spinal Cord Injury  

PubMed Central

Intensive treadmill training after incomplete spinal cord injury can improve functional walking abilities. To determine the changes in muscle activation patterns that are associated with improvements in walking, we measured the electromyography (EMG) of leg muscles in 17 individuals with incomplete spinal cord injury during similar walking conditions both before and after training. Specific differences were observed between subjects that eventually gained functional improvements in overground walking (responders), compared with subjects where treadmill training was ineffective (nonresponders). Although both groups developed a more regular and less clonic EMG pattern on the treadmill, it was only the tibialis anterior and hamstring muscles in the responders that displayed increases in EMG activation. Likewise, only the responders demonstrated decreases in burst duration and cocontraction of proximal (hamstrings and quadriceps) muscle activity. Surprisingly, the proximal muscle activity in the responders, unlike nonresponders, was three- to fourfold greater than that in uninjured control subjects walking at similar speeds and level of body weight support, suggesting that the ability to modify muscle activation patterns after injury may predict the ability of subjects to further compensate in response to motor training. In summary, increases in the amount and decreases in the duration of EMG activity of specific muscles are associated with functional recovery of walking skills after treadmill training in subjects that are able to modify muscle activity patterns following incomplete spinal cord injury. PMID:19073799

Gorassini, Monica A.; Norton, Jonathan A.; Nevett-Duchcherer, Jennifer; Roy, Francois D.; Yang, Jaynie F.

2009-01-01

285

Changes in locomotor muscle activity after treadmill training in subjects with incomplete spinal cord injury.  

PubMed

Intensive treadmill training after incomplete spinal cord injury can improve functional walking abilities. To determine the changes in muscle activation patterns that are associated with improvements in walking, we measured the electromyography (EMG) of leg muscles in 17 individuals with incomplete spinal cord injury during similar walking conditions both before and after training. Specific differences were observed between subjects that eventually gained functional improvements in overground walking (responders), compared with subjects where treadmill training was ineffective (nonresponders). Although both groups developed a more regular and less clonic EMG pattern on the treadmill, it was only the tibialis anterior and hamstring muscles in the responders that displayed increases in EMG activation. Likewise, only the responders demonstrated decreases in burst duration and cocontraction of proximal (hamstrings and quadriceps) muscle activity. Surprisingly, the proximal muscle activity in the responders, unlike nonresponders, was three- to fourfold greater than that in uninjured control subjects walking at similar speeds and level of body weight support, suggesting that the ability to modify muscle activation patterns after injury may predict the ability of subjects to further compensate in response to motor training. In summary, increases in the amount and decreases in the duration of EMG activity of specific muscles are associated with functional recovery of walking skills after treadmill training in subjects that are able to modify muscle activity patterns following incomplete spinal cord injury. PMID:19073799

Gorassini, Monica A; Norton, Jonathan A; Nevett-Duchcherer, Jennifer; Roy, Francois D; Yang, Jaynie F

2009-02-01

286

Viability-Dependent Promoting Action of Adult Neural Precursors in Spinal Cord Injury  

PubMed Central

The aim of the study was the assessment of the effects of adult neural stem cell (NSC) transplantation in a mouse model of spinal cord injury (SCI). The contusion injury was performed by means of the Infinite Horizon Device to allow the generation of reproducible traumatic lesion to the cord. We administered green fluorescent-labeled (GFP-)NSCs either by intravenous (i.v.) injection or by direct transplantation into the spinal cord (intraspinal route).We report that NSCs significantly improved recovery of hind limb function and greatly attenuated secondary degeneration. The i.v. route of NSC administration yielded better recovery than the intraspinal route of administration. About 2% of total i.v.-administered NSCs homed to the spinal cord injury site, and survived almost undifferentiated; thus the positive effect of NSC treatment cannot be ascribed to damaged tissue substitution. The NSCs homing to the injury site triggered, within 48 h, a large increase of the expression of neurotrophic factors and chemokines. One wk after transplantation, exogenous GFP-NSCs still retained their proliferation potential and produced neurospheres when recovered from the lesion site and cultured in vitro. At a later time, GFP-NSC were phagocytated by macrophages. We suggest that the process of triggering the recovery of function might be strongly related to the viability of GFP-NSC, still capable ex vivo of producing neurospheres, and their ability to modify the lesion environment in a positive fashion. PMID:18654659

Bottai, Daniele; Madaschi, Laura; Di Giulio, Anna M; Gorio, Alfredo

2008-01-01

287

An in vitro spinal cord injury model to screen neuroregenerative materials.  

PubMed

Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, safety, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofibre meshes (±poly-lysine + laminin coating) within injury sites using a lightweight construct. Patterns of nanotopography induced outgrowth/alignment of astrocytes and neurons in the in vitro model were strikingly similar to that induced by comparable materials in related studies in vivo. This highlights the value of our model in providing biologically-relevant readouts of the regeneration-promoting capacity of synthetic bridges within the complex environment of spinal cord lesions. Our approach can serve as a prototype to develop versatile bio-screening systems to identify materials/combinatorial strategies for regenerative medicine, whilst reducing live animal experimentation. PMID:24484676

Weightman, Alan P; Pickard, Mark R; Yang, Ying; Chari, Divya M

2014-04-01

288

Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury  

PubMed Central

Abstract Prior work has shown that a high dose (20?mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24?h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. Subjects were treated with one of three doses (0, 30, or 90??g) of intrathecal morphine 24?h after a moderate contusion injury. The 90-?g dose produced significant analgesia when subjects were exposed to noxious stimuli (thermal and incremented shock) below the level of injury. Yet, despite analgesic efficacy, intrathecal morphine significantly attenuated the recovery of locomotor function and increased lesion size rostral to the injury site. A single dose of 30 or 90??g of intrathecal morphine also decreased weight gain, and more than doubled the incidence of mortality and autophagia when compared to vehicle-treated controls. Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord. PMID:19388818

Moreno, Georgina; Woller, Sarah; Puga, Denise; Hoy, Kevin; Balden, Robyn; Grau, James W.

2009-01-01

289

Function of microglia and macrophages in secondary damage after spinal cord injury  

PubMed Central

Spinal cord injury (SCI) is a devastating type of neurological trauma with limited therapeutic opportunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary injury mechanisms, the inflammatory response is the major contributor and results in expansion of the lesion and further loss of neurologic function. Meanwhile, the inflammation directly and indirectly dominates the outcomes of SCI, including not only pain and motor dysfunction, but also preventingneuronal regeneration. Microglia and macrophages play very important roles in secondary injury. Microglia reside in spinal parenchyma and survey the microenvironment through the signals of injury or infection. Macrophages are derived from monocytes recruited to injured sites from the peripheral circulation. Activated resident microglia and monocyte-derived macrophages induce and magnify immune and inflammatory responses not only by means of their secretory moleculesand phagocytosis, but also through their influence on astrocytes, oligodendrocytes and demyelination. In this review, we focus on the roles of microglia and macrophages in secondary injury and how they contribute to the sequelae of SCI. PMID:25422640

Zhou, Xiang; He, Xijing; Ren, Yi

2014-01-01

290

Quality of Life Among Veterans With Chronic Spinal Cord Injury and Related Variables  

PubMed Central

Background: In recent decades, the incidence of spinal cord injuries has increased. In a systemic review on epidemiology of traumatic spinal cord injury in developing countries reported 25.5/million cases per year. Objectives: To assess the quality of life (QOL) of the veterans among Iran-Iraq war with chronic spinal cord injuries (SCI) and to evaluate long-term impressions of SCI on their quality of life. Patients and Methods: Fifty-two veterans, all male, with chronic spinal cord injury from Iran-Iraq war (1980-1988) were interviewed and examined. The mean age of veterans at the time of interview was 49.3 years (38 to 80 years). Veterans were assessed by using a 36-item short-form (SF-36), hospital anxiety and depression scale (HADS) and the Barthel index. The presence or absence of pressure sores and spasticity were documented as well. Results: The mean age of veterans at the time of study was 49.3 years. Pearson's correlation test showed that depression and anxiety have a reverse association with mental component summary (MCS) scale and physical component summary (PCS) scale scores, respectively. Regression analysis showed a negative effect of depression and pressure sore on PCS. Moreover, no association was found between the duration of injury and age with quality of life. Conclusions: Lower QOL was found among veterans with chronic SCI. More researches on health-related quality of life (HRQOL) are needed to give us a better understanding of changes in life of patients with SCI and the ways to improve them. PMID:25147777

Ebrahimzadeh, Mohammad Hosein; Soltani-Moghaddas, Seyed Hosein; Birjandinejad, Ali; Omidi-Kashani, Farzad; Bozorgnia, Shahram

2014-01-01

291

Curcumin improves the integrity of blood-spinal cord barrier after compressive spinal cord injury in rats.  

PubMed

Previous studies have shown that curcumin (Cur) can produce potent neuroprotective effects against damage due to spinal cord injury (SCI). However, whether Cur can preserve the function of the blood-spinal cord barrier (BSCB) is unclear. The present study was performed to investigate the mechanism underlying BSCB permeability changes, which were induced by treatment with Cur (75, 150, and 300mg/kg, i.p.) after compressive SCI in rats. BSCB permeability was evaluated by Evans blue leakage. Motor recovery of rats with SCI was assessed using the Basso, Beattie, and Bresnahan scoring system every day until the 21st days post-injury. The protein levels of heme oxygenase-1 (HO-1), tight junction protein, and inflammatory factors were analyzed by western blots. The expression of the inflammatory factors tumor necrosis factor-? (TNF-?) and nuclear factor-kappaB (NF-?B) mRNA was determined with reverse transcription-polymerase chain reactions. Treatment with Cur (150 and 300mg/kg) significantly reduced Evans blue leakage into the spinal cord tissue at 24h after SCI. Cur (150mg/kg) significantly increased HO-1 protein expression. The levels of TNF-? and NF-?B mRNA and protein greatly increased at 24h after SCI, and this increase was significantly attenuated by Cur treatment. ZO-1 and occludin expression was upregulated by Cur (150mg/kg) treatment after SCI, and this effect was blocked by the HO-1 inhibitor zinc protoporphyrin. Long-term effects of Cur on motor recovery after SCI were observed. Our results indicated that Cur can improve motor function after SCI, which could correlate with improvements in BSCB integrity. PMID:25129208

Yu, De-Shui; Cao, Yang; Mei, Xi-Fan; Wang, Yan-Feng; Fan, Zhong-Kai; Wang, Yan-Song; Lv, Gang

2014-11-15

292

Predicting Quality of Life Five Years Following Medical Discharge for a Traumatically-Acquired Spinal Cord Injury  

E-print Network

This dissertation presents the prediction of quality of life (QoL), composed of by life satisfaction and self-perceived health status, across 5 years post a spinal cord injury (SCI) hospital discharge. Predictor variables of functional independence...

Erosa, Norma

2012-10-19

293

Spinal nerve root injuries in brachial plexus lesions: basic science and clinical application of new surgical strategies. A review.  

PubMed

This paper reviews studies aimed at developing novel surgical means to correct functional deficits after spinal nerve root injuries in brachial plexus lesions. In a long series of animal experiments it has been possible to demonstrate re-established connectivity between severed roots and the damaged spinal cord segment. This encouraging functional recovery by a new surgical strategy of managing ventral root avulsion injuries prompted clinical application, with restoration of activity. PMID:7658961

Carlstedt, T P

1995-01-01

294

An exploratory study of pressure ulcers after spinal cord injury: Relationship to protective behaviors and risk factors  

Microsoft Academic Search

Krause JS, Vines CL, Farley TL, Sniezek J, Coker J. An exploratory study of pressure ulcers after spinal cord injury: relationship to protective behaviors and risk factors. Arch Phys Med Rehabil 2001;82:107-13. Objectives: To identify protective behaviors and risk factors associated with the development of pressure ulcers (PUs) after spinal cord injury (SCI). Design: A cross-sectional study to evaluate the

J. Stuart Krause; Cheryl L. Vines; Thomas L. Farley; Joseph Sniezek; Jennifer Coker

2001-01-01

295

Medical rehabilitation length of stay and outcomes for persons with traumatic spinal cord injury—1990–1997  

Microsoft Academic Search

Objectives: To describe changes in acute and rehabilitation length of stay (LOS) for persons with traumatic spinal cord injury (SCI), describe predictors of LOS, and explore year-1 anniversary medical and social outcomes.Design: Longitudinal, exploratory study of patients with SCI.Setting: Eighteen Model Spinal Cord Injury Centers across the United States.Sample: A total of 3,904 persons discharged from the Model Systems between

Elizabeth A. Eastwood; Kristofer J. Hagglund; Kristjan T. Ragnarsson; Wayne A. Gordon; Ralph J. Marino

1999-01-01

296

Long-distance growth and connectivity of neural stem cells after severe spinal cord injury.  

PubMed

Neural stem cells (NSCs) expressing GFP were embedded into fibrin matrices containing growth factor cocktails and grafted to sites of severe spinal cord injury. Grafted cells differentiated into multiple cellular phenotypes, including neurons, which extended large numbers of axons over remarkable distances. Extending axons formed abundant synapses with host cells. Axonal growth was partially dependent on mammalian target of rapamycin (mTOR), but not Nogo signaling. Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery. Two human stem cell lines (566RSC and HUES7) embedded in growth-factor-containing fibrin exhibited similar growth, and 566RSC cells supported functional recovery. Thus, properties intrinsic to early-stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth, resulting in formation of new relay circuits that significantly improve function. These therapeutic properties extend across stem cell sources and species. PMID:22980985

Lu, Paul; Wang, Yaozhi; Graham, Lori; McHale, Karla; Gao, Mingyong; Wu, Di; Brock, John; Blesch, Armin; Rosenzweig, Ephron S; Havton, Leif A; Zheng, Binhai; Conner, James M; Marsala, Martin; Tuszynski, Mark H

2012-09-14

297

Cyclic AMP promotes axon regeneration, lesion repair and neuronal survival in lampreys after spinal cord injury.  

PubMed

Axon regeneration after spinal cord injury in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Increasing the levels of the second messenger cyclic adenosine monophosphate (cAMP) after spinal cord injury enhances axon regeneration across a wide variety of species, making it an excellent candidate molecule that has therapeutic potential. However, several important aspects of the cellular and molecular mechanisms by which cAMP enhances axon regeneration are still unclear, such as how cAMP affects axon growth patterns, the molecular components within growing axon tips, the lesion scar, and neuronal survival. To address these points, we took advantage of the large, identified reticulospinal (RS) neurons in lamprey, a vertebrate that exhibits robust axon regeneration after a complete spinal cord transection. Application of a cAMP analog, db-cAMP, at the time of spinal cord transection increased the number of axons that regenerated across the lesion site. Db-cAMP also promoted axons to regenerate in straighter paths, prevented abnormal axonal growth patterns, increased the levels of synaptotagmin within axon tips, and increased the number of axotomized neurons that survived after spinal cord injury, thereby increasing the pool of neurons available for regeneration. There was also a transient increase in the number of microglia/macrophages and improved repair of the lesion site. Taken together, these data reveal several new features of the cellular and molecular mechanisms underlying cAMP-mediated enhancement of axon regeneration, further emphasizing the positive roles for this conserved pathway. PMID:24041988

Lau, Billy Y B; Fogerson, Stephanie M; Walsh, Rylie B; Morgan, Jennifer R

2013-12-01

298

Spinal Expression of Hippo Signaling Components YAP and TAZ Following Peripheral Nerve Injury in Rats  

PubMed Central

Previous studies have shown that the morphology and number of cells in the spinal cord dorsal horn could change following peripheral nerve injury and that the Hippo signaling pathway plays an important role in cell growth, proliferation, apoptosis, and dendritic remolding. In the present study, we examined whether the expression of YAP and TAZ, two critical components regulated by Hippo signaling, in the spinal cord dorsal horn would be altered by chronic constriction sciatic nerve injury (CCI). We found that 1) YAP was mainly expressed on CGRP- and IB4-immunoreactive primary afferent nerve terminals without noticeable expression on glial cells, whereas TAZ was mainly expressed on spinal cord second order neurons as well as microglia; 2) upregulation of YAP and TAZ expression followed two distinct temporal patterns after CCI, such that the highest expression of YAP and TAZ was on day 14 and day 1 after CCI, respectively; 3) there were also unique topographic patterns of YAP and TAZ distribution in the spinal cord dorsal horn consistent with their distinctive association with primary afferents and second order neurons; 4) changes in the YAP expression were selectively induced by CCI but not CFA-induced hindpaw inflammation; and 5) the number of nuclear profiles of TAZ expression was significantly increased after CCI, indicating translocation of TAZ from the cytoplasma to nucleus. These findings indicate that peripheral nerve injury induced time-dependent and region-specific changes in the spinal YAP and TAZ expression. A role for Hippo signaling in synaptic and structural plasticity is discussed in relation to the cellular mechanism of neuropathic pain. PMID:23998984

Li, Na; Lim, Grewo; Chen, Lucy; McCabe, Michael F.; Kim, Hyangin; Zhang, Shuzhuo; Mao, Jianren

2013-01-01

299

Changes in axonal physiology and morphology after chronic compressive injury of the rat thoracic spinal cord.  

PubMed

The spinal cord is rarely transected after spinal cord injury. Dysfunction of surviving axons, which traverse the site of spinal cord injury, appears to contribute to post-traumatic neurological deficits, although the underlying mechanisms remain unclear. The subpial rim frequently contains thinly myelinated axons which appear to conduct signals abnormally, although it is uncertain whether this truly reflects maladaptive alterations in conduction properties of injured axons during the chronic phase of spinal cord injury or whether this is merely the result of the selective survival of a subpopulation of axons. In the present study, we examined the changes in axonal conduction properties after chronic clip compression injury of the rat thoracic spinal cord, using the sucrose gap technique and quantitatively examined changes in the morphological and ultrastructural features of injured axonal fibers in order to clarify these issues. Chronically injured dorsal columns had a markedly reduced compound action potential amplitude (8.3% of control) and exhibited significantly reduced excitability. Other dysfunctional conduction properties of injured axons included a slower population conduction velocity, a longer refractory period and a greater degree of high-frequency conduction block at 200 Hz. Light microscopic and ultrastructural analysis showed numerous axons with abnormally thin myelin sheaths as well as unmyelinated axons in the injured spinal cord. The ventral column showed a reduced median axonal diameter and the lateral and dorsal columns showed increased median diameters, with evidence of abnormally large swollen axons. Plots of axonal diameter versus myelination ratio showed that post-injury, dorsal column axons of all diameters had thinner myelin sheaths. Noninjured dorsal column axons had a median myelination ratio (1.56) which was within the optimal range (1.43-1.67) for axonal conduction, whereas injured dorsal column axons had a median myelination ratio (1.33) below the optimal value. These data suggest that maladaptive alterations occur postinjury to myelin sheath thickness which reduce the efficiency of axonal signal transmission.In conclusion, chronically injured dorsal column axons show physiological evidence of dysfunction and morphological changes in axonal diameter and reduced myelination ratio. These maladaptive alterations to injured axons, including decrease in myelin thickness and the appearance of axonal swellings, contribute to the decreased excitability of chronically injured axons. These results further clarify the mechanisms underlying neurological dysfunction after chronic neurotrauma and have significant implications regarding approaches to augment neural repair and regeneration. PMID:11311546

Nashmi, R; Fehlings, M G

2001-01-01

300

Thinking through every step: how people with spinal cord injuries relearn to walk.  

PubMed

In this article we explore how people with incomplete spinal cord injury (iSCI) create meaning out of their changing bodies as they undergo a therapeutic intervention called locomotor training (LT). Therapeutic interventions like LT are used to promote the recovery of walking ability among individuals with iSCI. The chronological nature of this study--interviews at three points throughout the 12-week intervention--enhances understanding of the recovering self after spinal cord injury. Drawing on a constructivist theoretical framework, we organize data according to three narrative frames. Participants interpreted LT as (a) a physical change that was meaningful because of its social significance, (b) a coping strategy for dealing with the uncertainty of long-term recovery, and (c) a moral strategy to reconstitute the self. We offer findings that lay the conceptual groundwork for generating new knowledge about what is important to people with iSCI as they relearn how to walk. PMID:23774628

Jordan, Meggan M; Berkowitz, Dana; Hannold, Elizabeth; Velozo, Craig A; Behrman, Andrea L

2013-08-01

301

Bowel care for individuals with spinal cord injury: comparison of four approaches.  

PubMed

The efficacies of four bowel care regimens (bisacodyl suppositories, glycerin suppositories, mineral oil enemas and docusate sodium mini-enemas) were compared in seven subjects with traumatic spinal cord injury. Efficacy was assessed in terms of colonic transit time, bowel evacuation time and subjective responses to a questionnaire. Both docusate sodium mini-enemas and mineral oil enemas decreased total and left-sided colonic transit time. However, docusate sodium mini-enemas were superior to mineral oil enemas in terms of the decrease in bowel evacuation time and symptom reduction. Results in this small group of subjects suggest that docusate sodium mini-enemas may have advantages in the management of bowel evacuation in individuals with spinal cord injury. PMID:9541883

Amir, I; Sharma, R; Bauman, W A; Korsten, M A

1998-01-01

302

Lumbosacral evoked potentials and vesicourethral function in patients with chronic suprasacral spinal cord injury.  

PubMed Central

Persistent detrusor acontractility despite normal somatic reflex activity in some patients with high spinal cord injury is an enigma. Previous work has suggested disordered integration of afferent activity in sacral roots or the sacral spinal cord. Forty male patients with chronic stable suprasacral cord lesions were studied by filling and voiding videocystometrography, and recording lumbosacral evoked potentials from posterior tibial nerve stimulation. Only five of 15 patients with decreased detrusor contractility had abnormal lumbosacral evoked potentials. Similar abnormalities were found in four of 11 patients with efficient hyperreflexic bladders. The finding of normal lumbosacral evoked potentials in the majority of patients with suprasacral cord injuries and decreased detrusor contractility supports the argument that the pathophysiology of this specific form of neurogenic bladder dysfunction is multifactorial. PMID:2283530

Lucas, M G; Thomas, D G

1990-01-01

303

Assessing pain intensity following spinal cord injury: should rating scales measure 'overall' or 'maximal' values?  

PubMed

Rating scales (RSs) are important for the assessment of pain intensity (PI) following a spinal cord injury (SCI). Using a Graphic Rating Scale, this pilot study measured an 'overall' level of PI repeated about every 2?h over 1 day and compared it with maximal PI scores reported previously. Patients were categorized into severity groups according to the overall Graphic Rating Scale score at initial assessment (T0). Eight men and six women (mean age 53.1; range 28-75) participated. Comparison of the overall PI scores and their changes over time with the maximal PI scores reported previously showed loss of patients in the severe group and less pronounced PI changes over time. Rating scales used in spinal cord injury services should measure maximal pain experienced 'right now' to eliminate potential averaging out of pain over time, which might allow physicians to assist patients in understanding their pain and begin their adjustment. PMID:25419691

Frank, Andrew O; Spyridonis, Fotios; Ghinea, Gheorghita

2014-11-21

304

Donald Munro Lecture. Spinal cord injury--past, present, and future.  

PubMed

This special report traces the path of spinal cord injury (SCI) from ancient times through the present and provides an optimistic overview of promising clinical trials and avenues of basic research. The spinal cord injuries of Lord Admiral Sir Horatio Nelson, President James A. Garfield, and General George Patton provide an interesting perspective on the evolution of the standard of care for SCI. The author details the contributions of a wide spectrum of professionals in the United States, Europe, and Australia, as well as the roles of various government and professional organizations, legislation, and overall advances in surgery, anesthesia, trauma care, imaging, pharmacology, and infection control, in the advancement of care for the individual with SCI. PMID:17591221

Donovan, William H

2007-01-01

305

Spinal cord injury rehabilitation. 4. Individual experience, personal adaptation, and social perspectives.  

PubMed

This learner-directed module highlights contemporary perspectives on personal success in the adjustment and adaptation of patients with spinal cord injury (SCI). It is the fourth in a series of five modules within the chapter on spinal cord injury rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This module explores models of the multisystem effects on a person after SCI, disablement, theories of adjustment, patient autonomy, quality of life, community experience, adaptations enhancing sexuality, and minimization of pain after SCI. Perspectives of the patient's experience in disablement, interdisciplinary person-centered rehabilitation, and success of the individual in chosen life roles are emphasized. The module is designed to update SCI issues reviewed in past syllabi. PMID:9084370

Stiens, S A; Bergman, S B; Formal, C S

1997-03-01

306

Comprehensive management of pressure ulcers in spinal cord injury: Current concepts and future trends  

PubMed Central

Pressure ulcers in spinal cord injury represent a challenging problem for patients, their caregivers, and their physicians. They often lead to recurrent hospitalizations, multiple surgeries, and potentially devastating complications. They present a significant cost to the healthcare system, they require a multidisciplinary team approach to manage well, and outcomes directly depend on patients' education, prevention, and compliance with conservative and surgical protocols. With so many factors involved in the successful treatment of pressure ulcers, an update on their comprehensive management in spinal cord injury is warranted. Current concepts of local wound care, surgical options, as well as future trends from the latest wound healing research are reviewed to aid medical professionals in treating patients with this difficult problem. PMID:24090179

Kruger, Erwin A.; Pires, Marilyn; Ngann, Yvette; Sterling, Michelle; Rubayi, Salah

2013-01-01

307

Regulation of IL-10 by Chondroitinase ABC Promotes a Distinct Immune Response following Spinal Cord Injury  

PubMed Central

Chondroitinase ABC (ChABC) has striking effects on promoting neuronal plasticity after spinal cord injury (SCI), but little is known about its involvement in other pathological mechanisms. Recent work showed that ChABC might also modulate the immune response by promoting M2 macrophage polarization. Here we investigate in detail the immunoregulatory effects of ChABC after SCI in rats. Initially, we examined the expression profile of 16 M1/M2 macrophage polarization markers at 3 h and 7 d postinjury. ChABC treatment had a clear effect on the immune signature after SCI. More specifically, ChABC increased the expression of the anti-inflammatory cytokine IL-10, accompanied by a reduction in the proinflammatory cytokine IL-12B in injured spinal tissue. These effects were associated with a distinct, IL-10-mediated anti-inflammatory response in ChABC-treated spinal cords. Mechanistically, we show that IL-10 expression is driven by tissue injury and macrophage infiltration, while the p38 MAPK is the central regulator of IL-10 expression in vivo. These findings provide novel insights into the effects of ChABC in the injured spinal cord and explain its immunoregulatory activity. PMID:25471580

Iberl, Michaela; Vinsland, Elin; Bartus, Katalin

2014-01-01

308

Neuronal release and successful astrocyte uptake of aminoacidergic neurotransmitters after spinal cord injury in lampreys.  

PubMed

In contrast to mammals, the spinal cord of lampreys spontaneously recovers from a complete spinal cord injury (SCI). Understanding the differences between lampreys and mammals in their response to SCI could provide valuable information to propose new therapies. Unique properties of the astrocytes of lampreys probably contribute to the success of spinal cord regeneration. The main aim of our study was to investigate, in the sea lamprey, the release of aminoacidergic neurotransmitters and the subsequent astrocyte uptake of these neurotransmitters during the first week following a complete SCI by detecting glutamate, GABA, glycine, Hu and cytokeratin immunoreactivities. This is the first time that aminoacidergic neurotransmitter release from neurons and the subsequent astrocytic response after SCI are analysed by immunocytochemistry in any vertebrate. Spinal injury caused the immediate loss of glutamate, GABA and glycine immunoreactivities in neurons close to the lesion site (except for the cerebrospinal fluid-contacting GABA cells). Only after SCI, astrocytes showed glutamate, GABA and glycine immunoreactivity. Treatment with an inhibitor of glutamate transporters (DL-TBOA) showed that neuronal glutamate was actively transported into astrocytes after SCI. Moreover, after SCI, a massive accumulation of inhibitory neurotransmitters around some reticulospinal axons was observed. Presence of GABA accumulation significantly correlated with a higher survival ability of these neurons. Our data show that, in contrast to mammals, astrocytes of lampreys have a high capacity to actively uptake glutamate after SCI. GABA may play a protective role that could explain the higher regenerative and survival ability of specific descending neurons of lampreys. PMID:24733772

Fernández-López, Blanca; Valle-Maroto, Silvia María; Barreiro-Iglesias, Antón; Rodicio, María Celina

2014-08-01

309

Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face  

PubMed Central

Over the past 20 years, tremendous advances have been made in the field of spinal cord injury research. Yet, consumed with individual pieces of the puzzle, we have failed as a community to grasp the magnitude of the sum of our findings. Our current knowledge should allow us to improve the lives of patients suffering from spinal cord injury. Advances in multiple areas have provided tools for pursuing effective combination of strategies for recovering stepping and standing after a severe spinal cord injury. Muscle physiology research has provided insight into how to maintain functional muscle properties after a spinal cord injury. Understanding the role of the spinal networks in processing sensory information that is important for the generation of motor functions has focused research on developing treatments that sharpen the sensitivity of the locomotor circuitry and that carefully manage the presentation of proprioceptive and cutaneous stimuli to favor recovery. Pharmacological facilitation or inhibition of neurotransmitter systems, spinal cord stimulation, and rehabilitative motor training, which all function by modulating the physiological state of the spinal circuitry, have emerged as promising approaches. Early technological developments, such as robotic training systems and high-density electrode arrays for stimulating the spinal cord, can significantly enhance the precision and minimize the invasiveness of treatment after an injury. Strategies that seek out the complementary effects of combination treatments and that efficiently integrate relevant technical advances in bioengineering represent an untapped potential and are likely to have an immediate impact. Herein, we review key findings in each of these areas of research and present a unified vision for moving forward. Much work remains, but we already have the capability, and more importantly, the responsibility, to help spinal cord injury patients now. PMID:19660669

Fong, Andy J.; Roy, Roland R.; Ichiyama, Ronaldo M.; Lavrov, Igor; Courtine, Grégoire; Gerasimenko, Yury; Tai, Y.C.; Burdick, Joel; Edgerton, V. Reggie

2010-01-01

310

Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face.  

PubMed

Over the past 20 years, tremendous advances have been made in the field of spinal cord injury research. Yet, consumed with individual pieces of the puzzle, we have failed as a community to grasp the magnitude of the sum of our findings. Our current knowledge should allow us to improve the lives of patients suffering from spinal cord injury. Advances in multiple areas have provided tools for pursuing effective combination of strategies for recovering stepping and standing after a severe spinal cord injury. Muscle physiology research has provided insight into how to maintain functional muscle properties after a spinal cord injury. Understanding the role of the spinal networks in processing sensory information that is important for the generation of motor functions has focused research on developing treatments that sharpen the sensitivity of the locomotor circuitry and that carefully manage the presentation of proprioceptive and cutaneous stimuli to favor recovery. Pharmacological facilitation or inhibition of neurotransmitter systems, spinal cord stimulation, and rehabilitative motor training, which all function by modulating the physiological state of the spinal circuitry, have emerged as promising approaches. Early technological developments, such as robotic training systems and high-density electrode arrays for stimulating the spinal cord, can significantly enhance the precision and minimize the invasiveness of treatment after an injury. Strategies that seek out the complementary effects of combination treatments and that efficiently integrate relevant technical advances in bioengineering represent an untapped potential and are likely to have an immediate impact. Herein, we review key findings in each of these areas of research and present a unified vision for moving forward. Much work remains, but we already have the capability, and more importantly, the responsibility, to help spinal cord injury patients now. PMID:19660669

Fong, Andy J; Roy, Roland R; Ichiyama, Ronaldo M; Lavrov, Igor; Courtine, Grégoire; Gerasimenko, Yury; Tai, Y C; Burdick, Joel; Edgerton, V Reggie

2009-01-01

311

Physiologic parameters associated with sexual arousal in women with incomplete spinal cord injuries  

Microsoft Academic Search

Objective: To compare the physiologic sexual responses of women with incomplete spinal cord injuries (SCIs) with and without preservation of the ability to perceive T11-L2 pinprick sensation.Design: Controlled laboratory-based analysis of responses to varying combinations of audiovisual erotic stimulation, manual genital stimulation, and performance of a distracting task coupled with manual genital stimulation.Setting: The sexual physiology laboratory at our freestanding

Marca L. Sipski; Craig J. Alexander; Raymond C. Rosen

1997-01-01

312

Physiological parameters associated with psychogenic sexual arousal in women with complete spinal cord injuries  

Microsoft Academic Search

Objective: To compare the physiological sexual responses of women with complete spinal cord injuries (SCIs) with those of able-bodied women. Design: Controlled laboratory-based analysis of responses to audiovisual erotic and audiovisual erotic combined with manual stimulation. Setting: The sexual physiology laboratory at our freestanding rehabilitation hospital. Participants: A volunteer sample of 13 women with complete SCIs above T6 along with

Marca L. Sipski; Craig J. Alexander; Raymond C. Rosen

1995-01-01

313

Predifferentiated GABAergic Neural Precursor Transplants for Alleviation of Dysesthetic Central Pain Following Excitotoxic Spinal Cord Injury  

PubMed Central

Intraspinal quisqualic acid (QUIS) injury induce (i) mechanical and thermal hyperalgesia, (ii) progressive self-injurious overgrooming of the affected dermatome. The latter is thought to resemble painful dysesthesia observed in spinal cord injury (SCI) patients. We have reported previously loss of endogenous GABA immunoreactive (IR) cells in the superficial dorsal horn of QUIS rats 2 weeks post injury. Further histological evaluation showed that GABA-, glycine-, and synaptic vesicular transporter VIAAT-IR persisted but were substantially decreased in the injured spinal cord. In this study, partially differentiated GABA-IR embryonic neural precursor cells (NPCs) were transplanted into the spinal cord of QUIS rats to reverse overgrooming by replenishing lost inhibitory circuitry. Rat E14 NPCs were predifferentiated in 0.1?ng/ml FGF-2 for 4?h prior to transplantation. In vitro immunocytochemistry of transplant cohort showed large population of GABA-IR NPCs that double labeled with nestin but few colocalized with NeuN, indicating partial maturation. Two weeks following QUIS lesion at T12-L1, and following the onset of overgrooming, NPCs were transplanted into the QUIS lesion sites; bovine adrenal fibroblast cells were used as control. Overgrooming was reduced in >55.5% of NPC grafted animals, with inverse relationship between the number of surviving GABA-IR cells and the size of overgrooming. Fibroblast-control animals showed a progressive worsening of overgrooming. At 3 weeks post-transplantation, numerous GABA-, nestin-, and GFAP-IR cells were present in the lesion site. Surviving grafted GABA-IR NPCs were NeuN+ and GFAP?. These results indicate that partially differentiated NPCs survive and differentiate in vivo into neuronal cells following transplantation into an injured spinal cord. GABA-IR NPC transplants can restore lost dorsal horn inhibitory signaling and are useful in alleviating central pain following SCI. PMID:22754531

Lee, Jeung Woon; Jergova, Stanislava; Furmanski, Orion; Gajavelli, Shyam; Sagen, Jacqueline

2012-01-01

314

The effect of level of spinal cord injury on shoulder joint kinetics during manual wheelchair propulsion  

Microsoft Academic Search

Objective. The effects of spinal cord injury level on shoulder kinetics during manual wheelchair propulsion were studied.Design. Single session data collection in a laboratory environment.Methods. Male subjects were divided into four groups: low level paraplegia (n=17), high level paraplegia (n=19), C7 tetraplegia (C7, n=16) and C6 tetraplegia (C6, n=17). Measurements were recorded using a six-camera VICON motion analysis system, a

Kornelia Kulig; Craig J Newsam; Sara J Mulroy; Sreesha Rao; JoAnne K Gronley; Ernest L Bontrager; Jacquelin Perry

2001-01-01

315

Selective Alpha Adrenergic Antagonist Reduces Severity of Transient Hypertension during Sexual Stimulation after Spinal Cord Injury.  

PubMed

Abstract On a daily basis, the majority of those with high-level spinal cord injury have autonomic dysreflexia, which describes a life-threatening episode of transient extreme hypertension (i.e., as high as 300?mm Hg) as many as 90% of people living with this condition. Unfortunately, ejaculation is a major initiating factor for autonomic dysreflexia, which discourages sexual activity. In order to obtain a sperm specimen, or for initial assessment of fertility, penile vibrostimulation is clinically performed. Nifedipine, a selective calcium channel blocker, is the most commonly prescribed pharmaceutical for a priori management of autonomic dysreflexia secondary to ejaculation or other causes; however, it is limited because of its potential exacerbation of low resting pressure, which also affects this population. The present study examined the effect of a short-acting selective ?1 antagonist (prazosin) on autonomic dysreflexia severity using a randomized placebo trial during medically supervised penile vibrostimulation in six males with cervical spinal cord injury. Beat-by-beat blood pressure and heart rate were recorded throughout penile vibrostimulation during placebo and prazosin-treated days. The increase in systolic blood pressure was mitigated during vibrostimulation in subjects administered prazosin as compared with those administered placebo (+140±19?mm Hg vs. +96±14 mmHg; p<0.05). On average, the peak in systolic blood pressure was 46?mm Hg lower during penile vibrostimulation when patients were administered prazosin (p<0.05), whereas resting blood pressure was not affected. Prazosin appears to be effective at reducing the severity of autonomic dysreflexia during sexual stimulation in patients with spinal cord injury, without exacerbating resting hypotension in high-level spinal cord injury. PMID:25093677

Phillips, Aaron A; Elliott, Stacy L; Zheng, Mei M Z; Krassioukov, Andrei V

2014-08-01

316

Effects of motor imagery training after chronic, complete spinal cord injury  

Microsoft Academic Search

Abnormalities in brain motor system function are present following spinal cord injury (SCI) and could reduce effectiveness\\u000a of restorative interventions. Motor imagery training, which can improve motor behavior and modulate brain function, might\\u000a address this concern but has not been examined in subjects with SCI. Ten subjects with SCI and complete tetra-\\/paraplegia\\u000a plus ten healthy controls underwent assessment before and

Steven C. Cramer; Elizabeth L. R. Orr; Michael J. Cohen; Michael G. Lacourse

2007-01-01

317

Locomotor Dysfunction and Pain: The Scylla and Charybdis of Fiber Sprouting After Spinal Cord Injury  

Microsoft Academic Search

Injury to the spinal cord (SCI) can produce a constellation of problems including chronic pain, autonomic dysreflexia, and\\u000a motor dysfunction. Neuroplasticity in the form of fiber sprouting or the lack thereof is an important phenomenon that can\\u000a contribute to the deleterious effects of SCI. Aberrant sprouting of primary afferent fibers and synaptogenesis within incorrect\\u000a dorsal horn laminae leads to the

Ronald Deumens; Elbert A. J. Joosten; Stephen G. Waxman; Bryan C. Hains

2008-01-01

318

Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury  

PubMed Central

Although studies have suggested a role for the complement system in the pathophysiology of spinal cord injury (SCI), that role remains poorly defined. Additionally, the relative contribution of individual complement pathways in SCI is unknown. Our initial studies revealed that systemic complement activation was strongly influenced by genetic background and gender. Thus, to investigate the role of the classical complement pathway in contusion-induced SCI, male C1q knockout (KO) and wildtype (WT) mice on a complement sufficient background (BUB) received a mild-moderate T9 contusion injury with the Infinite Horizon (IH) impactor. BUB C1q KO mice exhibited greater locomotor recovery in comparison to BUB WT mice (p < 0.05). Improved recovery observed in BUB C1q KO mice was also associated with decreased threshold for withdrawal from a mild stimulus using von Frey filament testing. Surprisingly, quantification of microglia/macrophages (F4/80) by FACS analysis showed that BUB C1q KO mice exhibited a significantly greater percentage of macrophages in the spinal cord compared to BUB WT mice 3 days post injury (p < 0.05). However, this increased macrophage response appeared to be transient as stereological assessment of spinal cord tissue obtained 28 days post injury revealed no difference in F4/80 positive cells between groups. Stereological assessment of spinal cord tissue showed that BUB C1q KO mice had reduced lesion volume and an increase in tissue sparing in comparison to BUB WT mice (p < 0.05). Taken together, these data suggest that initiation of the classical complement pathway via C1q is detrimental to recovery after SCI. PMID:19091977

Galvan, Manuel D.; Luchetti, Sabina; Burgos, Adrian M.; Nguyen, Hal X.; Hooshmand, Mitra J.; Anderson, Aileen J.; Hamers, Frank P.T.

2009-01-01

319

ICF Core Sets for individuals with spinal cord injury in the long-term context  

Microsoft Academic Search

Study design:A formal decision-making and consensus process integrating evidence gathered from preparatory studies was followed.Objectives:The objective of the study was to report on the results of the consensus process to develop the first version of a Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set, and a Brief ICF Core Set for individuals with spinal cord injury (SCI)

A Cieza; I Kirchberger; F Biering-Sørensen; M Baumberger; S Charlifue; M W Post; R Campbell; A Kovindha; H Ring; A Sinnott; N Kostanjsek; G Stucki

2010-01-01

320

ICF Core Sets for individuals with spinal cord injury in the early post-acute context  

Microsoft Academic Search

Study design:A formal decision-making and consensus process integrating evidence gathered from preparatory studies was followed.Objectives:The aim of this study was to report on the results of the consensus process to develop the first version of a Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set and a Brief ICF Core Set for individuals with spinal cord injury (SCI)

I Kirchberger; A Cieza; F Biering-Sørensen; M Baumberger; S Charlifue; M W Post; R Campbell; A Kovindha; H Ring; A Sinnott; N Kostanjsek; G Stucki

2010-01-01

321

Spatiotemporal profile and essential role of RBM3 expression after spinal cord injury in adult rats.  

PubMed

Hypoxia and other adverse conditions are usually encountered by rapidly growing cells. The RNA-binding motif protein 3 (RBM3) is induced by low temperature and hypoxia. However, its expression and function in spinal cord injury are still unclear. To investigate the certain expression and biological function in the central nervous system, we performed an acute spinal cord contusion injury (SCI) model in adult rats. Western blot analysis indicated a striking expression upregulation of RBM3 after spinal cord injury (SCI). Double immunofluorescence staining prompted that RBM3 immunoreactivity was found in astrocytes and neurons. Interestingly, RBM3 expression was increased predominantly in astrocytes. Furthermore, colocalization of RBM3 with proliferating cell nuclear antigen (PCNA) was detected in astrocytes. To further understand whether RBM3 plays a role in astrocyte proliferation, we applied lipopolysaccharide (LPS) to induce astrocyte proliferation in vitro. Western blot analysis demonstrated that RBM3 expression was positively correlated with PCNA expression following LPS stimulation. Immunofluorescence analysis showed that the expression of RBM3 was also changed following the stimulation of astrocytes with LPS, which was parallel with the data in vivo. Additionally, knocking RBM3 down with small interfering RNA (siRNA) demonstrated that RBM3 might play a significant role in the proliferation of astrocytes treated by hypoxia in vitro. These results suggest that RBM3 may be involved in the proliferation of astrocytes after SCI. To summarize, we firstly uncover the temporal and spatial expression changes of RBM3 in spinal cord injury. Our data suggest that RBM3 might be implicated in central nervous system pathophysiology after SCI. PMID:24668366

Cui, Zhiming; Zhang, Jinlong; Bao, Guofeng; Xu, Guanhua; Sun, Yuyu; Wang, Lingling; Chen, Jiajia; Jin, Huricha; Liu, Jian; Yang, Longfei; Feng, Guijuan; Li, Weidong

2014-10-01

322

Glossopharyngeal pistoning for lung insufflation in patients with cervical spinal cord injury  

Microsoft Academic Search

Study design:A prospective cohort study.Objectives:To evaluate whether patients with cervical spinal cord injury (CSCI) are able to learn the technique of glossopharyngeal pistoning (breathing) for lung insufflation (GI) and if learned, to evaluate the effects of GI on pulmonary function and chest expansion after 8 weeks.Setting:Karolinska University Hospital, Stockholm, Sweden.Methods:Twenty-five patients with CSCI (21 men, four women) with a mean

M Nygren-Bonnier; K Wahman; P Lindholm; A Markström; N Westgren; B Klefbeck

2009-01-01

323

Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury  

PubMed Central

Dysfunction and death of spinal cord neurons are critical determinants of neurological deficits in various pathological conditions, including multiple sclerosis (MS) and spinal cord injury. Yet, the molecular mechanisms underlying neuronal/axonal damage remain undefined. Our previous studies raised the possibility that a decrease in the levels of plasma membrane calcium ATPase isoform 2 (PMCA2), a major pump extruding calcium from neurons, promotes neuronal pathology in the spinal cord during experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and after spinal cord trauma. However, the causal relationship between alterations in PMCA2 levels and neuronal injury was not well established. We now report that inhibition of PMCA activity in purified spinal cord neuronal cultures delays calcium clearance, increases the number of nonphosphorylated neurofilament H (SMI-32) immunoreactive cells, and induces swelling and beading of SMI-32-positive neurites. These changes are followed by activation of caspase-3 and neuronal loss. Importantly, the number of spinal cord motor neurons is significantly decreased in PMCA2-deficient mice and the deafwaddler2J, a mouse with a functionally null mutation in the PMCA2 gene. Our findings suggest that a reduction in PMCA2 level or activity leading to delays in calcium clearance may cause neuronal damage and loss in the spinal cord. PMID:15576480

Kurnellas, Michael P.; Nicot, Arnaud; Shull, Gary E.; Elkabes, Stella

2010-01-01

324

Does diffusion tensor data reflect pathological changes in the spinal cord with chronic injury  

PubMed Central

Magnetic resonance diffusion tensor imaging has been shown to quantitatively measure the early pathological changes in chronic cervical spondylotic myelopathy. In this study, a novel spongy polyurethane material was implanted in the rat C3–5 epidural space to establish a rat model of chronic cervical spondylotic myelopathy. Diffusion tensor data were used to predict pathological changes. Results revealed that the fractional anisotropy value gradually decreased at 4, 24, and 72 hours and 1 week after injury in rat spinal cord, showing a time-dependent manner. Average diffusion coefficient increased at 72 hours and 1 week after implantation. Hematoxylin-eosin staining and Luxol-fast-blue staining exhibited that the number of neurons in the anterior horn of the spinal cord gray matter and the nerve fiber density of the white matter gradually reduced with prolonged compression time. Neuronal loss was most significant at 1 week after injury. Results verified that the fractional anisotropy value and average diffusion coefficient reflected the degree of pathological change in the site of compression in rat models at various time points after chronic spinal cord compression injury, which potentially has a reference value in the early diagnosis of chronic cervical spondylotic myelopathy. PMID:25206660

Lin, Erjian; Long, Houqing; Li, Guangsheng; Lei, Wanlong

2013-01-01

325

Screening for proteinuria in ‘at-risk’ patients with spinal cord injuries: lessons learnt from failure  

PubMed Central

Spinal cord injury patients may develop proteinuria as a result of glomerulosclerosis due to urosepsis, hydronephrosis, vesicoureteric reflux, and renal calculi. Proteinuria in turn contributes to progression of kidney disease. We report one paraplegic and two tetraplegic patients, who developed recurrent urine infections, urinary calculi, and hydronephrosis. These patients required several urological procedures (nephrostomy, cystoscopy and ureteric stenting, ureteroscopy and lithotripsy, extracorporeal shock wave lithotripsy). These patients had not received antimuscarinic drugs nor had they undergone video-urodynamics. Proteinuria was detected only at a late stage, as testing for proteinuria was not performed during follow-up visits. Urine electrophoresis showed no monoclonal bands in any; Serum glomerular basement membrane antibody screen was negative. Serum neutrophil cytoplasmic antibodies screen by fluorescence was negative. All patients were prescribed Ramipril 2.5 mg daily and there was no further deterioration of renal function. Spinal cord injury patients, who did not receive antimuscarinic drugs to reduce intravesical pressure, are at high risk for developing reflux nephropathy. When such patients develop glomerulosclerosis due to recurrent urosepsis, renal calculi, or hydronephrosis, risk of proteinuria is increased further. Take home message: (1) Screening for proteinuria should be performed regularly in the ‘at-risk’ patients. (2) In the absence of other renal diseases causing proteinuria, spinal cord injury patients with significant proteinuria may be prescribed angiotensin-converting enzyme inhibitor or angiotensin-II receptor antagonist to slow progression of chronic renal disease and reduce the risk of cardiovascular mortality. PMID:24955116

2014-01-01

326

What are the people's attitudes toward spinal cord injury victims (from common to elite)  

PubMed Central

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

Hosseinigolafshani, Zahra; Abedi, Heidarali; Ahmadi, Fazlolah

2014-01-01

327

Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury.  

PubMed

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene. PMID:25420034

Gaudin, Alice; Yemisci, Müge; Eroglu, Hakan; Lepetre-Mouelhi, Sinda; Turkoglu, Omer Faruk; Dönmez-Demir, Buket; Caban, Seçil; Sargon, Mustafa Fevzi; Garcia-Argote, Sébastien; Pieters, Grégory; Loreau, Olivier; Rousseau, Bernard; Tagit, Oya; Hildebrandt, Niko; Le Dantec, Yannick; Mougin, Julie; Valetti, Sabrina; Chacun, Hélène; Nicolas, Valérie; Desmaële, Didier; Andrieux, Karine; Capan, Yilmaz; Dalkara, Turgay; Couvreur, Patrick

2014-11-24

328

Mesenchymal Stem Cells as an Alternative for Schwann Cells in Rat Spinal Cord Injury  

PubMed Central

Background: Spinal cord has a limited capacity to repair; therefore, medical interventions are necessary for treatment of injuries. Transplantation of Schwann cells has shown a great promising result for spinal cord injury (SCI). However, harvesting Schwann cell has been limited due to donor morbidity and limited expansion capacity. Furthermore, accessible sources such as bone marrow stem cells have drawn attentions to themselves. Therefore, this study was designed to evaluate the effect of bone marrow-derived Schwann cell on functional recovery in adult rats after injury. Methods: Mesenchymal stem cells were cultured from adult rats’ bone marrow and induced into Schwann cells in vitro. Differentiation was confirmed by immunocytochemistry and RT-PCR. Next, Schwann cells were seeded into collagen scaffolds and engrafted in 3 mm lateral hemisection defects. For 8 weeks, motor and sensory improvements were assessed by open field locomotor scale, narrow beam, and tail flick tests. Afterwards, lesioned spinal cord was evaluated by conventional histology and immunohistochemistry. Results: In vitro observations showed that differentiated cells had Schwann cell morphology and markers. In this study, we had four groups (n = 10 each): laminectomy, control, scaffold and scaffold + Schwann cells. Locomotor and sensory scores of cell grafted group were significantly better than control and scaffold groups. In histology, axonal regeneration and remyelination were better than control and scaffold groups. Conclusion: This study demonstrates that bone marrow-derived Schwann cells can be considered as a cell source for Schwann cells in SCI treatment. PMID:23748888

Zaminy, Arash; Shokrgozar, Mohammad Ali; Sadeghi, Yousef; Noroozian, Mohsen; Heidari, Mohammad Hassan; Piryaei, Abbas

2013-01-01

329

Neural Substrates for the Motivational Regulation of Motor Recovery after Spinal-Cord Injury  

PubMed Central

It is believed that depression impedes and motivation enhances functional recovery after neuronal damage such as spinal-cord injury and stroke. However, the neuronal substrate underlying such psychological effects on functional recovery remains unclear. A longitudinal study of brain activation in the non-human primate model of partial spinal-cord injury using positron emission tomography (PET) revealed a contribution of the primary motor cortex (M1) to the recovery of finger dexterity through the rehabilitative training. Here, we show that activity of the ventral striatum, including the nucleus accumbens (NAc), which plays a critical role in processing of motivation, increased and its functional connectivity with M1 emerged and was progressively strengthened during the recovery. In addition, functional connectivities among M1, the ventral striatum and other structures belonging to neural circuits for processing motivation, such as the orbitofrontal cortex, anterior cingulate cortex and pedunculopontine tegmental nucleus were also strengthened during the recovery. These results give clues to the neuronal substrate for motivational regulation of motor learning required for functional recovery after spinal-cord injury. PMID:21969864

Nishimura, Yukio; Onoe, Hirotaka; Onoe, Kayo; Morichika, Yosuke; Tsukada, Hideo; Isa, Tadashi

2011-01-01

330

VEGF and FGF-2 delivery from spinal cord bridges to enhance angiogenesis following injury  

PubMed Central

The host response to spinal cord injury can lead to an ischemic environment that can induce cell death and limits cell transplantation approaches to promote spinal cord regeneration. Spinal cord bridges that provide a localized and sustained release of VEGF and FGF-2 were investigated for their ability to promote angiogenesis and nerve growth within the injury. Bridges were fabricated by fusion of poly(lactide-co-glycolide) microspheres using a gas foaming/particulate leaching technique, and proteins were incorporated by encapsulation into the microspheres and/or mixing with the microspheres before foaming. Compared to the mixing method, encapsulation reduced the losses during leaching and had a slower protein release, while VEGF was released more rapidly than FGF-2. In vivo implantation of bridges loaded with VEGF enhanced the levels of VEGF within the injury at one week, and bridges releasing VEGF and FGF-2 increased the infiltration of endothelial cells and the formation of blood vessel at 6 weeks post implantation. Additionally, substantial neurofilament staining was observed within the bridge; however, no significant difference was observed between bridges with or without protein. Bridges releasing angiogenic factors may provide an approach to overcome an ischemic environment that limits regeneration and cell transplantation based approaches. PMID:21630429

De Laporte, Laura; des Rieux, Anne; Tuinstra, Hannah M.; Zelivyanskaya, Marina L.; De Clerck, Nora M.; Postnov, Andrei A.; Préat, Véronique; Shea, Lonnie D.

2011-01-01

331

Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury  

NASA Astrophysics Data System (ADS)

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.

Gaudin, Alice; Yemisci, Müge; Eroglu, Hakan; Lepetre-Mouelhi, Sinda; Turkoglu, Omer Faruk; Dönmez-Demir, Buket; Caban, Seçil; Sargon, Mustafa Fevzi; Garcia-Argote, Sébastien; Pieters, Grégory; Loreau, Olivier; Rousseau, Bernard; Tagit, Oya; Hildebrandt, Niko; Le Dantec, Yannick; Mougin, Julie; Valetti, Sabrina; Chacun, Hélène; Nicolas, Valérie; Desmaële, Didier; Andrieux, Karine; Capan, Yilmaz; Dalkara, Turgay; Couvreur, Patrick

2014-12-01

332

Sympathetic skin response in incomplete spinal cord injury with urinary incontinence  

PubMed Central

Objectives: Sympathetic skin response (SSR) is a test for evaluation of the sympathetic sweat gland pathways, and it has been used to study the central sympathetic pathways in spinal cord injury (SCI). This study aimed to assess the autonomic pathways according to normal or abnormal SSR in urinary incontinence patients due to incomplete spinal cord injury. Materials and Methods: Suprapubic, palmar, and plantar SSR to the peripheral nerve electrical stimulation were recorded in 16 urinary incontinence patients with incomplete spinal cord injury at various neurological levels and in 30 healthy control subjects. Results: All the recordings of SSR from the incomplete SCI patients with urinary incontinence as compared with their counterparts in the control group showed significantly reduced amplitudes with more prominent reduction in the suprapubic area recording site (P value < 0.0004). SSR with significantly prolonged latencies were recorded from palm and plantar areas in response to suprapubic area and tibial N stimuli, respectively (P value < 0.02). In this study, a significantly higher stimulus intensity (P value < 0.01) was needed to elicit SSR in the cases compared with the control group. Conclusion: This study showed abnormal SSR in urinary incontinence patients due to incomplete SCI. In addition, for the first time we have described recording of abnormal SSR from the suprapubic area as another way to show bladder sympathetic system involvement. PMID:23956572

Emad, Reza; Zafarghasempour, Mohsen; Roshanzamir, Sharareh

2013-01-01

333

Inosine Enhances Axon Sprouting and Motor Recovery after Spinal Cord Injury  

PubMed Central

Although corticospinal tract axons cannot regenerate long distances after spinal cord injury, they are able to sprout collateral branches rostral to an injury site that can help form compensatory circuits in cases of incomplete lesions. We show here that inosine enhances the formation of compensatory circuits after a dorsal hemisection of the thoracic spinal cord in mature rats and improves coordinated limb use. Inosine is a naturally occurring metabolite of adenosine that crosses the cell membrane and, in neurons, activates Mst3b, a protein kinase that is part of a signal transduction pathway that regulates axon outgrowth. Compared to saline-treated controls, rats with dorsal hemisections that were treated with inosine showed three times as many synaptic contacts between corticospinal tract collaterals and long propriospinal interneurons that project from the cervical cord to the lumbar level. Inosine-treated rats also showed stronger serotonergic reinnervation of the lumbar cord than saline-treated controls, and performed well above controls in both open-field testing and a horizontal ladder rung-walking test. Inosine was equally effective whether delivered intracranially or intravenously, and has been shown to be safe for other indications in humans. Thus, inosine might be a useful therapeutic for improving outcome after spinal cord injury. PMID:24312612

Kim, Daniel; Zai, Laila; Liang, Peng; Schaffling, Colleen; Ahlborn, David; Benowitz, Larry I.

2013-01-01

334

Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat.  

PubMed

Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNF?, IL-4, IL-1?, IL-2, IL-6 and IL-12 and increased the levels of MIP-1? and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application. PMID:24968269

Urdzíková, Lucia Machová; R?ži?ka, Ji?í; LaBagnara, Michael; Kárová, Kristýna; Kubinová, Šárka; Jiráková, Klára; Murali, Raj; Syková, Eva; Jhanwar-Uniyal, Meena; Jendelová, Pavla

2014-01-01

335

Assertiveness, social support, and psychological adjustment following spinal cord injury  

Microsoft Academic Search

Summary-Tested predictions that assertiveness and social support would be significantly predictive of psychological adjustment. Furthermore, it was anticipated that assertiveness and certain types of social relationships would differentially interact to predict adjustment, since positive and negative effects of both variables have been noted in prior research. Trained raters interviewed 156 persons receiving either in-patient or out-patient care for cord injuries

TIMOTHY R. ELLIOTT; STEPHEN M. HERRICK; ANNE M. PATTI; THOMAS E. WITTY; FRANK J. GODSHALL; MICHAEL SPRUELL

1991-01-01

336

Selective Corticospinal Tract Injury in the Rat Induces Primary Afferent Fiber Sprouting in the Spinal Cord and Hyperreflexia  

PubMed Central

The corticospinal tract (CST) has dense contralateral and sparse ipsilateral spinal cord projections that converge with proprioceptive afferents on common spinal targets. Previous studies in adult rats indicate that the loss of dense contralateral spinal CST connections after unilateral pyramidal tract section (PTX), which models CST loss after stroke or spinal cord injury, leads to outgrowth from the spared side into the affected, ipsilateral, spinal cord. The reaction of proprioceptive afferents after this CST injury, however, is not known. Knowledge of proprioceptive afferent responses after loss of the CST could inform mechanisms of maladaptive plasticity in spinal sensorimotor circuits after injury. Here we hypothesize that the loss of the contralateral CST results in a reactive increase in muscle afferents from the impaired limb and enhancement of their physiological actions within the cervical spinal cord. We found that ten days after PTX, proprioceptive afferents sprout into cervical gray matter regions denervated by the loss of CST terminations. Further, VGlut1 positive boutons, indicative of group 1A afferent terminals, increased on motoneurons. PTX also produced an increase in microglial density within the gray matter regions where CST terminations were lost. These anatomical changes were paralleled by reduction in frequency-dependent depression of the H-reflex, suggesting hyperreflexia. Our data demonstrate for the first time that selective CST injury induces maladaptive afferent fiber plasticity remote from the lesion. Our findings suggest a novel structural reaction of proprioceptive afferents to the loss of CST terminations and provide insight into mechanisms underlying spasticity. PMID:22973013

Tan, Andrew M.; Chakrabarty, Samit; Kimura, Hiroki; Martin, John H.

2012-01-01

337

Neuroprotective Effects of N-Acetyl-Cysteine and Acetyl-L-Carnitine after Spinal Cord Injury in Adult Rats  

PubMed Central

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 microglial reaction was significantly attenuated. The results indicate a therapeutic potential for NAC and ALC in the early treatment of traumatic spinal cord injury. PMID:22815926

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

2012-01-01

338

The Relationship of Chronological Age, Age at Injury, and Duration of Injury to Employment Status in Individuals with Spinal Cord Injury  

Microsoft Academic Search

Employment status following spinal cord injury (SCI) has important implications for financial and psychosocial well-being.\\u000a Several age-related variables—in particular chronological age, duration of SCI, and age at SCI onset—have been identified\\u000a as being associated with employment among individuals with SCI. Cross-sectional investigations of this topic are complicated\\u000a by methodological and statistical issues associated with aging and disability. The purpose of

Adam T. Hirsh; Ivan R. Molton; Kurt L. Johnson; Charles H. Bombardier; Mark P. Jensen

2009-01-01

339

Nanoparticulate strategies for the five R's of traumatic spinal cord injury intervention: restriction, repair, regeneration, restoration and reorganization.  

PubMed

Nanomedicinal approaches for spinal cord injury (SCI) intervention encompasses the use of nanoscale materials and devices that prevent primary to secondary injury transition and improvement in the anatomical, physiological and functional outcomes of SCI. This review provides an incursion into the advances in nanoparticle-based neurotherapeutics for SCI and focuses on neuroactive-loaded nanoparticles for localized delivery of therapeutic factors to the severed spinal cord, targeted or nontargeted systemic drug delivery and nanoenclatherated neuroscaffolds. Special emphasis has been placed on the use of metal nanoparticles and functionalized structures as 'drug-free' interventions in SCI. Despite the immense advancements in nanoscience, nanointerventions still pose key challenges that need to be resolved in SCI. Several combinatorial strategies are proposed for the reconstruction of spinal architecture via restriction of the secondary injury cascade, reparation of the tethered neural architecture, regeneration of axons, restoration of biochemical functions and reorganization of the topographical and cortical networks of the spinal cord. PMID:24552564

Kumar, Pradeep; Choonara, Yahya E; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

2014-02-01

340

The impact of mild traumatic brain injury on cognitive functioning following co-occurring spinal cord injury.  

PubMed

Meta-analytic studies have shown that mild traumatic brain injury (MTBI) has relatively negligible effects on cognitive functioning at 90 or more days post-injury. Few studies have prospectively examined the effects of MTBI in acute physical trauma populations. This prospective, cohort study compared the cognitive performance of persons who sustained a spinal cord injury (SCI) and a co-occurring MTBI (N = 53) to persons who sustained an SCI alone (N = 64) between 26 and 76 days (mean = 46) post-injury. The presence of MTBI was determined based on acute medical record review using a standardized algorithm. Primary outcome measures were seven neuropsychological tests that evaluated visual, verbal, and working memory, perceptual reasoning, and processing speed that controlled for potential upper extremity impairment. Persons who sustained SCI with or without MTBI had lower than expected performance across all neuropsychological tests, on average about 1 SD below the mean. Analysis of covariance indicated that persons with MTBI did not evidence greater impairment on any neuropsychological test. The aggregated effect size (Cohen's d) was -0.16. The strongest predictors of neuropsychological test scores were education, race, history of learning problems, and days from injury to rehabilitation admission. MTBI did not predict performance on any neuropsychological test. These findings are consistent with other controlled studies that indicate a single MTBI has negligible long-term impacts on cognition. PMID:24055885

Macciocchi, Stephen N; Seel, Ronald T; Thompson, Nicole

2013-11-01

341

Complications in Patients With Spinal Cord Injuries Sustained in an Earthquake in Northern Pakistan  

PubMed Central

Background: Spinal cord injury (SCI) is a devastating trauma suffered by many of the victims of an earthquake that struck Northern Pakistan on October 8, 2005. It rendered approximately 600 patients paraplegic, which is the highest number ever reported in any disaster. This study was conducted to evaluate the risk of complications. Methods: The cross-sectional retrospective study covering a 2-month period was conducted on 194 patients admitted to the surgical/neurosurgical wards of Rawalpindi Medical College and allied hospitals (Holy Family Hospital, Rawalpindi General Hospital, and District Headquarter Hospital) and Melody Relief and Rehabilitation Center, Islamabad. Results: The male-to-female ratio was approximately 1:3 (n = 50 [26%] and n = 144 [74%], respectively). The majority (78% [n = 151]) were 16 to 39 years of age; 62% (n = 120) had lumbar-level injuries, 25% (n = 48) had thoracic-level injuries, 9% (n = 18) had thoracolumbar-level injuries, and a few had cervical- or sacral-level injuries. Forty-six percent (n = 90) had American Spinal Injury Association type A injuries; 4% (n = 8) were graded B, 11% (n = 21) were graded C, 9% (n = 18) were graded D, and 14% (n = 27) were graded E. Twenty percent (n =39) developed pressure ulcers, of which 38% (n = 15) had grade 1, 36% (n = 14) had grade 2, 23% (n = 9) had grade 3, and 3% (n = 1) had grade 4. All patients developed urinary tract infections; 15% (n = 30) had bowel complaints; 2% (n = 3) developed deep-vein thrombosis (1 died of pulmonary embolism); and 0.05% (n = 1) developed wound infection. Conclusion: Awareness of potential complications in patients with paraplegia is essential to care planning in the disaster setting. The priorities include skin, bowel, and bladder care and provision of prophylactic heparin. SCI post-disaster care requires comprehensive long-term planning. PMID:17853661

Tauqir, Syeda Fizza; Mirza, Shirin; Gul, Shahzad; Ghaffar, Hirra; Zafar, Asif

2007-01-01

342

Cardiovascular control, autonomic function, and elite endurance performance in spinal cord injury.  

PubMed

We aimed to determine the relationship between level of injury, completeness of injury, resting as well as exercise hemodynamics, and endurance performance in athletes with spinal cord injury (SCI). Twenty-three elite male paracycling athletes (C3-T8) were assessed for neurological level/completeness of injury, autonomic completeness of injury, resting cardiovascular function, and time to complete a 17.3-km World Championship time-trial test. A subset were also fitted with heart rate (HR) monitors and their cycles were fitted with a global positioning systems device (n?=?15). Thoracic SCI exhibited higher seated systolic blood pressure along with superior time-trial performance compared with cervical SCI (all P?injury, the four athletes with cervical autonomic incomplete SCI exhibited a faster time-trial time and a higher average speed compared with cervical autonomic complete SCI (all P?injury and the consequent ability of the cardiovascular system to respond to exercise appear to be a critical determinant of endurance performance in elite athletes with cervical SCI. PMID:25175825

West, C R; Gee, C M; Voss, C; Hubli, M; Currie, K D; Schmid, J; Krassioukov, A V

2014-08-31

343

Optimizing Speech Production in the Ventilator-Assisted Individual Following Cervical Spinal Cord Injury: A Preliminary Investigation  

ERIC Educational Resources Information Center

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…

MacBean, Naomi; Ward, Elizabeth; Murdoch, Bruce; Cahill, Louise; Solley, Maura; Geraghty, Timothy; Hukins, Craig

2009-01-01

344

Minocycline Treatment Reduces Delayed Oligodendrocyte Death, Attenuates Axonal Dieback, and Improves Functional Outcome after Spinal Cord Injury  

Microsoft Academic Search

Minocycline has been demonstrated to be neuroprotective after spinal cord injury (SCI). However, the cellular consequences of minocy- cline treatment on the secondary injury response are poorly understood. We examined the ability of minocycline to reduce oligodendro- cyte apoptosis, microglial\\/macrophage activation, corticospinal tract (CST) dieback, and lesion size and to improve functional outcome after SCI. Adult rats were subjected to

D. P. Stirling; Kourosh Khodarahmi; Jie Liu; Lowell T. Mcphail; Christopher B. Mcbride; John D. Steeves; Matt S. Ramer; Wolfram Tetzlaff

2004-01-01

345

Descriptions of Community by People with Spinal Cord Injuries: Concepts to Inform Community Integration and Community Rehabilitation  

ERIC Educational Resources Information Center

Effective measurement and optimization of re-entry into the community after injury depends on a degree of understanding of how those injured persons actually perceive their community. In light of the limited research about foundational concepts regarding community integration after spinal cord injury, this study investigated how a large number of…

Kuipers, Pim; Kendall, Melissa B.; Amsters, Delena; Pershouse, Kiley; Schuurs, Sarita

2011-01-01

346

Delayed anti-nogo-a antibody application after spinal cord injury shows progressive loss of responsiveness.  

PubMed

Blocking the function of the myelin protein Nogo-A or its signaling pathway is a promising method to overcome an important neurite growth inhibitory factor of the adult central nervous system (CNS), and to enhance axonal regeneration and plasticity after brain or spinal cord injuries. Several studies have shown increased axonal regeneration and enhanced compensatory sprouting, along with substantially improved functional recovery after treatment with anti-Nogo-A antibodies, Nogo-receptor antagonists, or inhibition of the downstream mediator RhoA/ROCK in adult rodents. Proof-of-concept studies in spinal cord-injured macaque monkeys with anti-Nogo-A antibodies have replicated these findings; recently, clinical trials in spinal cord-injured patients have begun. However, the optimal time window for successful Nogo-A function blocking treatments has not yet been determined. We studied the effect of acute as well as 1- or 2-weeks delayed intrathecal anti-Nogo-A antibody infusions on the regeneration of corticospinal tract (CST) axons and the recovery of motor function after large but anatomically incomplete thoracic spinal cord injuries in adult rats. We found that lesioned CST fibers regenerated over several millimeters after acute or 1-week-delayed treatments, but not when the antibody treatment was started with a delay of 2 weeks. Swimming and narrow beam crossing recovered well in rats treated acutely or with a 1-week delay with anti-Nogo-A antibodies, but not in the 2-week-delayed group. These results show that the time frame for treatment of spinal cord lesions with anti-Nogo-A antibodies is restricted to less than 2 weeks in adult rodents. PMID:21815784

Gonzenbach, Roman R; Zoerner, Bjoern; Schnell, Lisa; Weinmann, Oliver; Mir, Anis K; Schwab, Martin E

2012-02-10

347

Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury  

PubMed Central

Spinal cord injuries (SCIs) in humans1,2 and experimental animals3–6 are often associated with varying degrees of spontaneous functional recovery during the first months after injury. Such recovery is widely attributed to axons spared from injury that descend from the brain and bypass incomplete lesions, but its mechanisms are uncertain. To investigate the neural basis of spontaneous recovery, we used kinematic, physiological and anatomical analyses to evaluate mice with various combinations of spatially and temporally separated lateral hemisections with or without the excitotoxic ablation of intrinsic spinal cord neurons. We show that propriospinal relay connections that bypass one or more injury sites are able to mediate spontaneous functional recovery and supraspinal control of stepping, even when there has been essentially total and irreversible interruption of long descending supraspinal pathways in mice. Our findings show that pronounced functional recovery can occur after severe SCI without the maintenance or regeneration of direct projections from the brain past the lesion and can be mediated by the reorganization of descending and propriospinal connections4,7–9. Targeting interventions toward augmenting the remodeling of relay connections may provide new therapeutic strategies to bypass lesions and restore function after SCI and in other conditions such as stroke and multiple sclerosis. PMID:18157143

Courtine, Gregoire; Song, Bingbing; Roy, Roland R; Zhong, Hui; Herrmann, Julia E; Ao, Yan; Qi, Jingwei; Edgerton, V Reggie; Sofroniew, Michael V

2010-01-01

348

Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain  

PubMed Central

Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggests that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. PMID:20732348

Hama, Aldric T.; Plum, Ann Woodhouse; Sagen, Jacqueline

2010-01-01

349

Complications and urologic risks of neurogenic bladder in veterans with traumatic spinal cord injury.  

PubMed

Objectives:This observational study aimed to determine the types of urological lesion encountered in veterans with traumatic spinal cord injury (SCI) with neurogenic bladder (NGB), and the usage of bladder management programs to deal with NGB.Setting:NGB (detrusor muscle and urethral sphincter dysfunction with loss of bladder sensation to void) is common in daily practice; however, information on types of urological lesions encountered in these veterans with NGB and how best to manage their NGB is limited.Methods:We retrospectively reviewed the electronic charts of veterans with SCI enrolled in our program and regularly followed in our SCI clinic. Demographic data collected included: age, gender, ethnicity and age, level, severity and cause of spinal injury. Also noted was presence of NGB, episodes of urinary tract infection (UTI), bladder program followed and urological lesions found on renal nuclear scans, renal ultrasounds and cystoscopies.Results:Of the 161 veterans with SCI, symptoms of NGB was present in 133 (82.6%). Veterans with NGB had more severe spinal injury and more frequent UTI (P<0.05). Renal atrophy and hydronephrosis were the most common urological lesions seen in patients with UTI. Clean intermittent catheterization (CIC) was the most frequently used bladder program resulting in less frequent occurrence of UTI.Conclusion:Renal atrophy and hydronephrosis were the most common urological lesions encountered in veterans with NGB especially in those with UTI. CIC was the most frequently used bladder management program with the least risk for UTI.Spinal Cord advance online publication, 18 November 2014; doi:10.1038/sc.2014.205. PMID:25403501

Rabadi, M H; Aston, C

2014-11-18

350

The Effects of Dexmedetomidine on Ischemia Reperfusion Injury in Patients Undergoing Arthroscopy Under Spinal Anesthesia  

PubMed Central

Objective: Ischemia and reperfusion injury due to tourniquet application during arthroscopy is a well known problem. This study aimed to compare the effects of dexmedetomidine and ketamine on hemodynamic and respiratory variables and on total anti-oxidant status (TAS), total oxidant status (TOS) and malondialdehyde (MDA) as markers of ischemia-reperfusion injury. Materials and Methods: This study was approved by a local ethics committee. The study was performed on patients undergoing arthroscopic operation under spinal anesthesia. Thirty patients were randomized into two groups: Group D (dexmedetomidine; n=15) and Group K (Ketamine; n=15). Spinal anesthesia at the L2–4 level was achieved using a 25G spinal needle with hyperbaric bupivacaine at a dose of 12–15 mg in all patients. In Group D, patients were sedated with dexmedetomidine at a dose of 0.3–0.5 ?g/kg/h, while Group K received ketamine at a dose of 1–1.5 mg/kg/h. Hemodynamic parameters, oxygen saturation, Ramsey sedation scale (RSS), and TAS, TOS, and MDA levels were recorded. Results: Demographic parameters, TAS, TOS and MDA levels were similar between groups. In Group K, the TOS levels after tourniquet removal were significantly lower than at baseline and during the use of the tourniquet. Preoperative hemodynamic and respiratory variables were similar in both groups. Blood pressure values were decreased compared to baseline but these decreases were not statistically significant. Conclusion: In patients undergoing arthroscopy under spinal anesthesia, dexmedetomidine had effects similar to ketamine, led to insignificant alterations in hemodynamic and respiratory variables during surgery and had comparable effects on ischemia-reperfusion injury. Thus, we think that dexmedetomidine can be a safe alternative to ketamine as an intraoperative sedative.

Koruk, Senem; Mizrak, Ayse; Kaya, Recai; Ugur, Berna; Cebesoy, Oguz; Celik, Ahmet; Oner, Unsal

2010-01-01

351

Molecular mechanism of Jmjd3-mediated interleukin-6 gene regulation in endothelial cells underlying spinal cord injury.  

PubMed

The inflammatory response contributes substantially to secondary injury cascades after spinal cord injury, with both neurotoxic and protective effects. However, epigenetic regulations of inflammatory genes following spinal cord injury have yet to be characterized thoroughly. In this study, we found that histone H3K27me3 demethylase Jmjd3 expression is acutely up-regulated in blood vessels of the injured spinal cord. We also observed up-regulation of Jmjd3 gene expression in bEnd.3 endothelial cells that were subjected to oxygen-glucose deprivation/reperfusion injury. When Jmjd3 was depleted by siRNA, oxygen-glucose deprivation/reperfusion injury-induced up-regulation of IL-6 was significantly inhibited. In addition, Jmjd3 associated with NF-?B (p65/p50) and CCAAT-enhancer-binding protein ? at the IL-6 gene promoter. The recruitment of Jmjd3 coincided with decreased levels of tri-methylated H3K27 as well as increased levels of mono-methylated H3K27 at the IL-6 gene promoter. Furthermore, Jmjd3 depletion did not result in significant changes of methylation level of H3K27 at the IL-6 gene promoter. Collectively, our findings imply that Jmjd3-mediated H3K27me3 demethylation is crucial for IL-6 gene activation in endothelial cells, and this molecular event may regulate acute inflammatory response and integrity of the blood-spinal cord barrier following spinal cord injury. PMID:22578249

Lee, Kwanghyun; Na, Wonho; Lee, Jee Youn; Na, Jungtae; Cho, Heejung; Wu, Hongjin; Yune, Tae Young; Kim, Won-Sun; Ju, Bong-Gun

2012-07-01

352

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

PubMed Central

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. PMID:25374587

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

2014-01-01

353

Microsurgical anatomy of lumbosacral nerve rootlets for highly selective rhizotomy in chronic spinal cord injury.  

PubMed

It is known that selective sacral roots rhizotomy is effective for relieving the neurogenic bladder associated with spinal cord injury. The goal of this study is to review the surgical anatomy of the lumbosacral nerve rootlets and to provide some morphological bases for highly selective sacral roots rhizotomy. Spinal cord dissections were performed on five cadavers under surgical microscope. At each spinal cord segment, we recorded the number, diameter and length of the rootlets, subbundles and bundles from the L1 to S2 spinal segments, and the length of the dorsal/ventral root entry zone. Peripheral nervous system myelin was examined by immunohistochemistry. We found: (1) the ventral or the dorsal root of the lumbosacral segment of the spinal cord was divided into one to three nerve bundles and each bundle was subdivided into one to three subbundles. Each subbundle further gave out two to three rootlets connected with the spinal cord; (2) there were no significant differences in the number of rootlets within the L1 to S2 segments, but the size of rootlets and the length of nerve roots varied (P < 0.05); and (3) the more myelinated fibers a rootlet contained, the larger transection area it had. The area of peripheral nervous system myelin positive cells and the total area of rootlets were correlated (P < 0.001). Thus, during highly selective sacral roots rhizotomy, the ventral and dorsal roots can be divided into several bundles of rootlets, and we could initially distinct the rootlets by their diameters. PMID:21089050

Zhou, Mou-Wang; Wang, Wen-Ting; Huang, Hong-Shi; Zhu, Gen-Ying; Chen, Ya-Ping; Zhou, Chang-Man

2010-12-01

354

Single Collateral Reconstructions Reveal Distinct Phases of Corticospinal Remodeling after Spinal Cord Injury  

PubMed Central

Background Injuries to the spinal cord often result in severe functional deficits that, in case of incomplete injuries, can be partially compensated by axonal remodeling. The corticospinal tract (CST), for example, responds to a thoracic transection with the formation of an intraspinal detour circuit. The key step for the formation of the detour circuit is the sprouting of new CST collaterals in the cervical spinal cord that contact local interneurons. How individual collaterals are formed and refined over time is incompletely understood. Methodology/Principal Findings We traced the hindlimb corticospinal tract at different timepoints after lesion to show that cervical collateral formation is initiated in the first 10 days. These collaterals can then persist for at least 24 weeks. Interestingly, both major and minor CST components contribute to the formation of persistent CST collaterals. We then developed an approach to label single CST collaterals based on viral gene transfer of the Cre recombinase to a small number of cortical projection neurons in Thy1-STP-YFP or Thy1-Brainbow mice. Reconstruction and analysis of single collaterals for up to 12 weeks after lesion revealed that CST remodeling evolves in 3 phases. Collateral growth is initiated in the first 10 days after lesion. Between 10 days and 3–4 weeks after lesion elongated and highly branched collaterals form in the gray matter, the complexity of which depends on the CST component they originate from. Finally, between 3–4 weeks and 12 weeks after lesion the size of CST collaterals remains largely unchanged, while the pattern of their contacts onto interneurons matures. Conclusions/Significance This study provides a comprehensive anatomical analysis of CST reorganization after injury and reveals that CST remodeling occurs in distinct phases. Our results and techniques should facilitate future efforts to unravel the mechanisms that govern CST remodeling and to promote functional recovery after spinal cord injury. PMID:22291960

Kerschensteiner, Martin; Bareyre, Florence M.

2012-01-01

355

Nerve transfers for elbow and finger extension reconstruction in midcervical spinal cord injuries.  

PubMed

OBJECT The objective of this study was to report the results of elbow, thumb, and finger extension reconstruction via nerve transfer in midcervical spinal cord injuries. METHODS Thirteen upper limbs from 7 patients with tetraplegia, with an average age of 26 years, were operated on an average of 7 months after a spinal cord injury. The posterior division of the axillary nerve was used to reinnervate the triceps long and upper medial head motor branches in 9 upper limbs. Both the posterior division and the branch to the middle deltoid were used in 2 upper limbs, and the anterior division of the axillary nerve in the final 2 limbs. For thumb and finger extension reconstruction, the nerve to the supinator was transferred to the posterior interosseous nerve. RESULTS In 22 of the 27 recipient nerves, a peripheral type of palsy with muscle denervation was identified. At an average of 19 months follow-up, elbow strength scored M4 in 11 upper limbs and M3 in 2, according to the British Medical Research Council scale. Thumb extension scored M4 in 8 upper limbs and scored M3 in 4. Finger extension scored M4 in 12 hands. No donor-site deficits were reported or observed. CONCLUSIONS Nerve transfers are effective at restoring elbow, thumb, and finger extension in patients with a midcervical spinal cord injury, which occurs in the majority of patients with a peripheral type of palsy with muscle denervation in their upper limbs. Efforts should be made to perform operations in these patients within 12 months of injury. PMID:25343189

Bertelli, Jayme Augusto; Ghizoni, Marcos Flávio

2015-01-01

356

Human Hepatocyte Growth Factor Promotes Functional Recovery in Primates after Spinal Cord Injury  

PubMed Central

Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI. PMID:22140459

Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun-ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

2011-01-01

357

Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.  

PubMed

Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI. PMID:22140459

Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun-Ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

2011-01-01

358

Mesenchymal stem cells in the treatment of spinal cord injuries: A review.  

PubMed

With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. Recent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI. PMID:24772239

Dasari, Venkata Ramesh; Veeravalli, Krishna Kumar; Dinh, Dzung H

2014-04-26

359

The impact of discrete modes of spinal cord injury on bladder muscle contractility  

PubMed Central

Background Prior studies have compared the effect of spinal cord injury elicited using distinct approaches on motor and visceral function. However, the impact of such discrete modes of injury specifically on bladder muscle contractility has not been explored in detail. The goal of this study is to compare the impact of complete spinal cord transection versus clip compression at thoracic vertebra eight (T8) on bladder muscle contractility. Methods Rats underwent no treatment (Control), laminectomy (Sham, SH); complete extradural transection (TX); or cord compression with an aneurysm clip (CX). Bladders and spinal cords were harvested at 6 wk for contractility studies or histological analysis. Results Detrusor strips from TX and CX rats showed higher spontaneous activity than those from SH rats. Furthermore, the duration of the neurally-mediated contractile response was longer in TX and CX rats compared to controls and showed attenuated relaxation. No significant differences were observed between muscle strips from SH, TX or CX rats in response to KCl, ATP or phenylephrine. However, tissues from TX and CX rats showed a higher sensitivity to carbachol compared to that from SH animals. Conclusions Complete SCI in rats either by cord transection or compression elicits qualitatively similar changes in bladder muscle contractility. Whereas cord transection is arguably easier to perform experimentally, cord compression better models the situation observed clinically, such that each approach has clear advantages and limitations. PMID:23668225

2013-01-01

360

ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury.  

PubMed

Apolipoprotein E (apoE), a plasma protein responsible for transporting lipid and cholesterol, modulates responses of the central nervous system to injury. Small peptides derived from the receptor-binding region of apoE can simulate some important bioactivities of apoE holoprotein and offer neuroprotection against brain injury. We tested whether COG1410, an apoE-mimetic peptide, provides protection in a rat model of spinal cord injury (SCI). Traumatic injury was created at T8 by a cortical impact device. Injured rats were randomized to four treatment groups: vehicle, 0.15, 0.3, or 0.6 mg/kg COG1410; sham surgery rats received vehicle. Basso, Beattie, Bresnahan neurological score was evaluated prior to injury and at 1, 3, 7, and 14 days after injury. Histological changes were evaluated at 14 days. All injured rats lost body weight during the first week following injury. Body weight recovery was significantly improved in rats treated with COG1410. Mechanical impact resulted in severe motor deficit, and most animals had a BBB score of 0-1 at 24 hours postinjury. COG1410-treated rats showed significantly improved functional recovery and ameliorated motor deficit at 14 days postinjury. Histological analysis showed that COG1410 groups had a significantly reduced lesion size at the site of injury, a larger preserved luxol fast blue-stained area, and more visible neurons in the surrounding area of injury. Microglial activation was also significantly suppressed. These findings indicate that this apoE mimetic effectively improved neurological and histological outcome following SCI in rats, and the effect was associated with inhibition of microglial activation. PMID:24633884

Wang, Ruihua; Hong, Jun; Lu, Miaomiao; Neil, Jessica E; Vitek, Michael P; Liu, Xiaozhi; Warner, David S; Li, Fengqiao; Sheng, Huaxin

2014-07-01

361

Phase-Dependent Modulation of Percutaneously Elicited Multisegmental Muscle Responses After Spinal Cord Injury  

PubMed Central

Phase-dependent modulation of monosynaptic reflexes has been reported for several muscles of the lower limb of uninjured rats and humans. To assess whether this step-phase-dependent modulation can be mediated at the level of the human spinal cord, we compared the modulation of responses evoked simultaneously in multiple motor pools in clinically complete spinal cord injury (SCI) compared with noninjured (NI) individuals. We induced multisegmental responses of the soleus, medial gastrocnemius, tibialis anterior, medial hamstring, and vastus lateralis muscles in response to percutaneous spinal cord stimulation over the Th11–Th12 vertebrae during standing and stepping on a treadmill. Individuals with SCI stepped on a treadmill with partial body-weight support and manual assistance of leg movements. The NI group demonstrated phase-dependent modulation of evoked potentials in all recorded muscles with the modulation of the response amplitude corresponding with changes in EMG amplitude in the same muscle. The SCI group demonstrated more variation in the pattern of modulation across the step cycle and same individuals in the SCI group could display responses with a magnitude as great as that of modulation observed in the NI group. The relationship between modulation and EMG activity during the step cycle varied from noncorrelated to highly correlated patterns. These findings demonstrate that the human lumbosacral spinal cord can phase-dependently modulate motor neuron excitability in the absence of functional supraspinal influence, although with much less consistency than that in NI individuals. PMID:20357075

Dy, Christine J.; Gerasimenko, Yury P.; Edgerton, V. Reggie; Dyhre-Poulsen, Poul; Courtine, Grégoire

2010-01-01

362

Chronic Electrical Stimulation of the Intact Corticospinal System After Unilateral Injury Restores Skilled Locomotor Control and Promotes Spinal Axon Outgrowth  

PubMed Central

Injury to the brain or spinal cord usually preserves some corticospinal (CS) connections. These residual circuits sprout spontaneously and in response to activity-based treatments. We hypothesized that augmenting activity in spared CS circuits would restore the skilled motor control lost after injury and augment outgrowth of CS terminations in the spinal cord. After selective injury of one half of the CS tract (CST) in the rat, we applied 10 days of electrical stimulation to the forelimb area of motor cortex of the spared half and tested motor performance for 30 days. Rats with injury and CST stimulation showed substantial improvements in skilled paw placement while walking over a horizontal ladder. By the end of the testing period, the walking errors of the previously impaired forelimb in rats with injury and stimulation returned to baseline, while the errors remained elevated in rats with injury only. Whereas the time to perform the task returned to normal in all animals, the pattern of errors returned to normal only in the stimulated group. Electrical stimulation also caused robust outgrowth of CST axon terminations in the ipsilateral spinal cord, the side of impairment, compared with rats with injury only. The outgrowth was directed to the normal gray matter territory of ipsilateral CST axon terminations. Thus, stimulation of spared CS circuits induced substantial axon outgrowth to the largely denervated side of the spinal cord and restored normal motor control in the previously impaired limbs. PMID:20702720

Carmel, Jason B.; Berrol, Lauren J.; Brus-Ramer, Marcel; Martin, John H.

2010-01-01

363

Nerve Injury Increases GluA2-Lacking AMPA Receptor Prevalence in Spinal Cords: Functional Significance and Signaling Mechanisms  

PubMed Central

The glutamate ?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are critically involved in the excitatory synaptic transmission, and blocking AMPARs at the spinal level reverses neuropathic pain. However, little is known about changes in the composition of synaptic AMPARs in the spinal dorsal horn after peripheral nerve injury. AMPARs lacking the GluA2 subunit are permeable to Ca2+, and their currents show unique inward rectification. We found that AMPAR-mediated excitatory postsynaptic currents (AMPAR-EPSCs) of spinal dorsal horn neurons exhibited a linear current-voltage relationship in control rats, whereas AMPAR-EPSCs of dorsal horn neurons displayed inward rectification in rats with spinal nerve injury. In nerve-injured rats, compared with control rats, the GluA2 protein level was significantly less in the plasma membrane but was greater in the cytosolic vesicle fraction in the dorsal spinal cord. However, the GluA1 protein levels in these fractions did not differ significantly between nerve-injured and control rats. Blocking N-methyl-d-aspartate receptors (NMDARs) abolished inward rectification of AMPAR-EPSCs of dorsal horn neurons in nerve-injured rats. Furthermore, inhibition of calpain or calcineurin, but not protein kinase C, completely blocked nerve injury–induced inward rectification of AMPAR-EPSCs of dorsal horn neurons. In addition, blocking GluA2-lacking AMPARs at the spinal cord level reduced nerve injury–induced pain hypersensitivity. Our study suggests that nerve injury increases GluA2 internalization and the prevalence of GluA2-lacking AMPARs in the spinal dorsal horn to maintain chronic neuropathic pain. Increased prevalence of spinal GluA2-lacking AMPARs in neuropathic pain is mediated by NMDARs and subsequent stimulation of calpain and calcineurin signaling. PMID:24030012

Chen, Shao-Rui; Zhou, Hong-Yi; Byun, Hee Sun

2013-01-01

364

Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice.  

PubMed

The activation of a complement system can aggravate the secondary injury after spinal cord injury (SCI). However, it was reported recently that the activation of a complement could have both a secondary injury and a neuroprotective effect, in which C5a is the most important factor, but there is no direct evidence for this dual effect of C5a after SCI. In order to investigate the potential neuroprotective effect of C5a after SCI, in this study ectogenic C5a was injected intraperitoneally before/after SCI in vivo, or administrated to mechanically injured neurones in vitro; following this, neurone apoptosis, neurite outgrowth, axonal regeneration and functional recovery were investigated. The in-vivo experiments indicated that, following treatment with C5a 24 h before or immediately after injury, locomotor function was impaired significantly. However, when treatment with C5a took place 24 h after injury, locomotor function improved significantly. In-vitro experiments indicated that a certain concentration of C5a (50-100 nM) could inhibit caspase-3-mediated neurone apoptosis by binding to its receptor CD88, and that it could even promote the neurite outgrowth of uninjured neurones. In conclusion, delayed post-injury administration of C5a within a certain concentration could exert its neuroprotective effect through inhibiting caspase-3-mediated neurone apoptosis and promoting neurite outgrowth of uninjured neurones as well. These data suggest that C5a may have opposite functions in a time- and concentration-dependent manner after SCI. The dual roles of C5a have to be taken into account when measures are taken to inhibit complement activation in order to promote regeneration after SCI. PMID:23855891

Guo, Q; Cheng, J; Zhang, J; Su, B; Bian, C; Lin, S; Zhong, C

2013-11-01

365

Reduction of pathological and behavioral deficits following spinal cord contusion injury with the selective cyclooxygenase-2 inhibitor NS-398.  

PubMed

Spinal cord injury (SCI) results in loss of locomotor function and development of abnormal chronic pain syndromes (mechanical allodynia, thermal hyperalgesia). Following injury, secondary mechanisms including release of excitatory amino acids, inflammation and lipid peroxidation damage neural cells through release of cytotoxic free radicals. We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2), an inducible inflammatory mediator, would decrease tissue damage and subsequently reduce locomotor deficits and development of chronic central pain syndromes after injury. Fifteen minutes prior to receiving T13 spinal segment spinal cord contusion injury, 200-225-g male Sprague-Dawley rats received either vehicle (0.5 ml 1:1 v/v DMSO/saline, i.p., n = 20) or the selective COX-2 inhibitor NS-398 (5 mg/kg in DMSO/saline v/v, i.p., n = 20). Locomotor function via the BBB scale, and nociceptive behaviors measured by paw withdrawals to von Frey filaments and radiant heat stimuli were tested for 4 weeks postinjury. Histological examination and volumetric analysis of spinal cord tissue were performed concomitantly. Spinally contused animals receiving NS-398 demonstrated significantly (p < 0.05) reduced locomotor alteration and reductions in both fore- and hindlimb mechanical allodynia and thermal hyperalgesia when compared to vehicle controls. Histological examination of spinal segments at the lesion segment demonstrated reduced lesion extent and increased viable tissue when compared to vehicle controls. Prostaglandin E2 levels were significantly lowered in NS-398-treated but not vehicle-treated animals 12 h after injury. These results support the role of COX-2 in reducing pathological and behavioral deficits after spinal cord injury. PMID:11336442

Hains, B C; Yucra, J A; Hulsebosch, C E

2001-04-01

366

Management of unstable thoracolumbar spinal injuries by posterior short segment spinal fixation  

Microsoft Academic Search

Fifty patients with thoracolumbar fractures were treated operatively between July 2000 and December 2001. The average age\\u000a of the patients was 33.6 years (range: 20–50 years), 36 were males and 14 were females and the follow-up averaged 59 months\\u000a (range: 49–68 months). A fall from a height, usually a tree, was the most common cause of injury. Twenty six patients had\\u000a unstable burst fractures

Mohammad F. Butt; Munir Farooq; Bashir Mir; Ahmad Shabir Dhar; Anwar Hussain; Mohammad Mumtaz

2007-01-01

367

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

PubMed Central

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

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

2013-01-01

368

The SCI Info Pages - A free Spinal Cord Injury Resource Site  

NSDL National Science Digital Library

Originating from one individualâÂÂs personal interest in the spinal cord and everything associated with it, this Web site, created and regularly updated by M. Ginop, a quadriplegic, is a non-profit, non-commercial site designed for those who suffer directly or indirectly from spinal cord injuries or diseases of the spine. Well crafted and easily navigable, the site contains helpful information such as books, pamphlets, and publication resources; links to online disability communities; a listing, by state, of hospitals and rehabilitation facilities; a research section on treatments and cures; and information on wheelchair set up (manual and power). Additionally, the site has a health issues section that provides information on bladder and bowel management, skin management and much more. On the whole, this is definitely a quality "one stop site for all SCI information!"

2007-04-14

369

Tissue engineering is a promising method for the repair of spinal cord injuries (Review)  

PubMed Central

Spinal cord injury (SCI) may lead to a devastating and permanent loss of neurological function, which may place a great economic burden on the family of the patient and society. Methods for reducing the death of neuronal cells, inhibiting immune and inflammatory reactions, and promoting the growth of axons in order to build up synapses with the target cells are the focus of current research. Target cells are located in the damaged spinal cord which create a connect with the scaffold. As tissue engineering technology is developed for use in a variety of different areas, particularly the biomedical field, a clear understanding of the mechanisms of tissue engineering is important. This review establishes how this technology may be used in basic experiments with regard to SCI and considers its potential future clinical use. PMID:24520240

JI, WENCHEN; HU, SHOUYE; ZHOU, JIAO; WANG, GANG; WANG, KUNZHENG; ZHANG, YUELIN

2014-01-01

370

Lessons for spinal cord injury rehabilitation taken from adult developmental psychology: 2011 Essie Morgan Lecture  

PubMed Central

Background/objective Developmental phases affect how individuals cope with and challenge threats to self-concept, health and functioning. Understanding prominent models of adult psychological development can help spinal cord injury/disease (SCI/D) rehabilitation professionals facilitate positive change and growth. Design Author's theoretical model informed by literature review and personal experience. Setting Veterans administration (VA) medical center interdisciplinary outpatient clinic providing primary and specialty care to veterans with spinal cord injuries and disorders. Conclusion Threats to life expectations, health, well-being, identity, and other aspects of self create crises that can result in psychopathology or psychological growth. SCI/D can present multiple threats across the lifespan. For example, self-image, ability to perform various activities, ability to feel attractive, and even life itself may be challenged by SCI/D or its complications. Threats may be perceived at the time of injury or onset of symptoms. Also, as the injured body declines further over time, complications can cause significant temporary or permanent functional decline. Individuals interpret each of these threats in the context of current developmental needs. How people cope is influenced by developmental factors and personality traits. An integrated model of adult psychological development based on the works of Erikson, Gutmann, and Baltes is related to the literature on coping with SCI/D. This model provides insights that interdisciplinary rehabilitation teams may use to facilitate personal growth, optimal functioning, and physical health as adults with SCI negotiate normal developmental challenges throughout their lifetimes. PMID:22507022

Rose, Jon

2012-01-01

371

A New Role for RPTP{sigma} in Spinal Cord Injury: Signaling Chondroitin Sulfate Proteoglycan Inhibition  

NSDL National Science Digital Library

It has been known for more than two decades that chondroitin sulfate proteoglycans (CSPGs) inhibit axonal growth and regeneration. In the adult nervous system, CSPGs are enriched in perineuronal nets, and their abundance is increased in reactive astrocytes following injury to brain or spinal cord. Degradation of chondroitin sulfate (CS) sugar moieties by the local infusion of the bacterial enzyme chondroitinase ABC (ChaseABC) enhances experience-dependent neuronal plasticity in the adult visual cortex and results in substantially improved behavioral outcomes after spinal cord injury (SCI). Although the positive effects of ChaseABC treatment on neuronal plasticity have been known for some time, the underlying mechanisms remained enigmatic. The receptor protein tyrosine phosphatase sigma (RPTPσ) has now been identified as a receptor for inhibitory CSPGs. Similarly to ChaseABC treatment, functional ablation of Ptprs, the gene encoding RPTPσ, promotes neurite outgrowth in the presence of CSPGs in vitro and enhances axonal growth into CSPG-rich scar tissue following SCI in vivo. The discovery of neuronal RPTPσ as a receptor for inhibitory CSPGs not only provides important mechanistic clues about CSPG function, but also identifies a potential new target for enhancing axonal growth and plasticity after nervous system injury.

Yuntao Duan (University of Michigan School of Medicine;Department of Cell and Developmental Biology and Department of Neurology REV); Roman J. Giger (University of Michigan School of Medicine;Department of Cell and Developmental Biology and Department of Neurology REV)

2010-02-23

372

De novo expression of Trpm4 initiates secondary hemorrhage in spinal cord injury  

PubMed Central

The role of transient receptor potential M4 (Trpm4), an unusual member of the Trp family of ion channels, is poorly understood. Using rodent models of spinal cord injury, we studied involvement of Trpm4 in the progressive expansion of secondary hemorrhage associated with capillary fragmentation, the most destructive mechanism of secondary injury in the central nervous system. Trpm4 mRNA and protein were abundantly upregulated in capillaries preceding their fragmentation and formation of petechial hemorrhages. Trpm4 expression in vitro rendered COS-7 cells highly susceptible to oncotic swelling and oncotic death following ATP depletion. After spinal cord injury, in vivo gene suppression in rats treated with Trpm4 antisense or in Trpm4?/? mice preserved capillary structural integrity, eliminated secondary hemorrhage, yielded a threefold to fivefold reduction in lesion volume and produced a substantial improvement in neurological function. To our knowledge, this is the first example of a Trp channel that must undergo de novo expression for manifestation of central nervous system pathology. PMID:19169264

Gerzanich, Volodymyr; Woo, S Kyoon; Vennekens, Rudi; Tsymbalyuk, Orest; Ivanova, Svetlana; Ivanov, Alexander; Geng, Zhihua; Chen, Zheng; Nilius, Bernd; Flockerzi, Veit; Freichel, Marc; Simard, J Marc

2009-01-01

373

Spatiotemporal pattern of RNA-binding motif protein 3 expression after spinal cord injury in rats.  

PubMed

RNA-binding motif protein 3 (RBM3) belongs to a very small group of cold inducible proteins with anti-apoptotic and proliferative functions. To elucidate the expression and possible function of RBM3 in central nervous system (CNS) lesion and repair, we performed a spinal cord injury (SCI) model in adult rats. Western blot analysis revealed that RBM3 level significantly increased at 1 day after damage, and then declined during the following days. Immunohistochemistry further confirmed that RBM3 immunoactivity was expressed at low levels in gray and white matters in normal condition and increased at 1 day after SCI. Besides, double immunofluorescence staining showed RBM3 was primarily expressed in the neurons and a few of astrocytes in the normal group. While after injury, the expression of RBM3 increased both in neurons and astrocytes at 1 day. We also examined the expression profiles of proliferating cell nuclear antigen (PCNA) and active caspase-3 in injured spinal cords by western blot. Importantly, double immunofluorescence staining revealed that cell proliferation evaluated by PCNA appeared in many RBM3-expressing cells and rare caspase-3 was observed in RBM3-expressing cells at 1 day after injury. Our data suggested that RBM3 might play important roles in CNS pathophysiology after SCI. PMID:24570111

Zhao, Wei; Xu, Dawei; Cai, Gang; Zhu, Xinhui; Qian, Ming; Liu, Wei; Cui, Zhiming

2014-05-01

374

Relationships between physiological responses and presyncope symptoms during tilting up in patients with spinal cord injury.  

PubMed

This study attempted to use the eyesight range to quantify presyncope symptoms (PS), assess the relation between angle of head-up tilt, severity of injury on the American Spinal Injury Association (ASIA) scale, and PS on physiological signals, and determine the notable signals that represent PS in spinal cord injury (SCI) patients. Thirty-eight quadriplegic SCI subjects were recruited, in which the mean blood pressure (MBP), oxygen saturation (SpO(2)), heart rate (HR), and the low-frequency/high-frequency (LF/HF) ratio of the HR variability were measured during tilting up of the head. The SpO(2) and LF/HF differed significantly with the level of PS. These findings of the studied variables suggest that SpO(2) and LF/HF are the physiological signals that are most sensitive to detect in PS, and could be used for the optimal biofeedback design of tilt-table training systems aimed at overcoming posture hypotension in SCI patients. PMID:18449589

Liu, David S; Chang, Walter H; Wong, Alice M K; Chen, Shih-Ching; Lin, Kang-Ping; Lai, Chien-Hung

2008-07-01

375

Meglumine cyclic adenylate improves neurological function following acute spinal cord injury in rats.  

PubMed

Elevation of intracellular cyclic adenosine monophosphate (cAMP) levels facilitates recovery following spinal injury by suppressing secondary pathology and promoting axonal regeneration. However, this treatment strategy is limited by lack of effective and tolerable clinical agents. The present study examined the effects of meglumine cyclic adenylate (MCA) on neurological recovery, cAMP concentration, adenylate cyclase 3 (AC3) activity and phosphodiesterase 4D (PDE4D) activity during early stage acute spinal cord injury (SCI) in rats. A total of 48 Sprague?Dawley rats were randomly assigned to groups A, B or C, each consisting of 16 animals. SCI was induced by Allen's method using a 7 g x 3 cm extradural weight?drop impact on spinal cord segment T11. A total of 30 min following SCI, group A received a single 30 mg/kg?bw i.p. dose of methylprednisolone, group B received 2 mg/kg?bw i.p. MCA daily for seven days and group C were administered an equal volume of normal saline. Seven days following SCI, the spinal cord samples from eight rats per group were obtained to measure the cAMP concentration, and the activities of AC3 and PDE4D. The remaining eight rats per group were used for behavioral assessments using the inclined plane stability test and Gale scale for up to six weeks post?SCI. The drug?treated groups A and B had higher cAMP concentrations and AC3 activities but lower PDE4D activities at the lesion sites, as well as superior behavioral scores post?SCI compared with the vehicle?treated group C (P<0.05). Furthermore, cAMP was higher in group B than in group A (P<0.05). It was concluded that MCA may serve as an effective SCI treatment by activating AC3 and suppressing PDE4D. PMID:24970286

Liao, Jingwu; Xie, Jingming; Lin, Daqiang; Lu, Ning; Guo, Limin; Li, Weiqiang; Pu, Bo; Yang, Yang; Yang, Zhenlong; Zhang, Ying; Song, Yueming

2014-09-01

376

Macrophages in spinal cord injury: Phenotypic and functional change from exposure to myelin debris.  

PubMed

Macrophage activation and persistent inflammation contribute to the pathological process of spinal cord injury (SCI). It was reported that M2 macrophages were induced at 3-7 days after SCI but M2 markers were reduced or eliminated after 1 week. By contrast, M1 macrophage response is rapidly induced and then maintained at injured spinal cord. However, factors that modulate macrophage phenotype and function are poorly understood. We developed a model to distinguish bone-marrow derived macrophages (BMDMs) from residential microglia and explored how BMDMs change their phenotype and functions in response to the lesion-related factors in injured spinal cord. Infiltrating BMDMs expressing higher Mac-2 and lower CX3CR1 migrate to the epicenter of injury, while microglia expressing lower Mac-2 but higher CX3CR1 distribute to the edges of lesion. Myelin debris at the lesion site switches BMDMs from M2 phenotype towards M1-like phenotype. Myelin debris activates ATP-binding cassette transporter A1 (ABCA1) for cholesterol efflux in response to myelin debris loading in vitro. However, this homeostatic mechanism in injured site is overwhelmed, leading to the development of foamy macrophages and lipid plaque in the lesion site. The persistence of these cells indicates a pro-inflammatory environment, associated with enhanced neurotoxicity and impaired wound healing. These foamy macrophages have poor capacity to phagocytose apoptotic neutrophils resulting in uningested neutrophils releasing their toxic contents and further tissue damage. In conclusion, these data demonstrate for the first time that myelin debris generated in injured spinal cord modulates macrophage activation. Lipid accumulation following macrophage phenotype switch contributes to SCI pathology. GLIA 2015;63:635-651. PMID:25452166

Wang, Xi; Cao, Kai; Sun, Xin; Chen, Yongxiong; Duan, Zhaoxia; Sun, Li; Guo, Lei; Bai, Paul; Sun, Dongming; Fan, Jianqing; He, Xijing; Young, Wise; Ren, Yi

2015-04-01

377

Flexor reflex decreases during sympathetic stimulation in chronic human spinal cord injury.  

PubMed

A better understanding of autonomic influence on motor reflex pathways in spinal cord injury is important to the clinical management of autonomic dysreflexia and spasticity in spinal cord injured patients. The purpose of this study was to examine the modulation of flexor reflex windup during episodes of induced sympathetic activity in chronic human spinal cord injury (SCI). We simultaneously measured peripheral vascular conductance and the windup of the flexor reflex in response to conditioning stimuli of electrocutaneous stimulation to the opposite leg and bladder percussion. Flexor reflexes were quantified using torque measurements of the response to a noxious electrical stimulus applied to the skin of the medial arch of the foot. Both bladder percussion and skin conditioning stimuli produced a reduction (43-67%) in the ankle and hip flexor torques (p<0.05) of the flexor reflex. This reduction was accompanied by a simultaneous reduction in vascular conductance, measured using venous plethysmography, with a time course that matched the flexor reflex depression. While there was an overall attenuation of the flexor reflex, windup of the flexor reflex to repeated stimuli was maintained during periods of increased sympathetic activity. This paradoxical depression of flexor reflexes and minimal effect on windup is consistent with inhibition of afferent feedback within the superficial dorsal horn. The results of this study bring attention to the possible interaction of motor and sympathetic reflexes in SCI above and below the T5 spinal level, and have implications for clinicians in spasticity management and for researchers investigating motor reflexes post SCI. PMID:19615998

Garrison, M Kevin; Schmit, Brian D

2009-10-01

378

High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury  

NASA Astrophysics Data System (ADS)

A major hurdle for regeneration after spinal cord injury (SCI) is the ability of axons to penetrate and grow through the scar tissue. After SCI, inflammatory cells, astrocytes and meningeal cells all play a role in developing the glial scar. In addition, degradation of native high molecular weight (MW) hyaluronic acid (HA), a component of the extracellular matrix, has been shown to induce activation and proliferation of astrocytes. However, it is not known if the degradation of native HA actually enhances glial scar formation. We hypothesize that the presence of high MW HA (HA with limited degradation) after SCI will decrease glial scarring. Here, we demonstrate that high MW HA decreases cell proliferation and reduces chondroitin sulfate proteoglycan (CSPG) production in cultured neonatal and adult astrocytes. In addition, stiffness-matched high MW HA hydrogels crosslinked to resist degradation were implanted in a rat model of spinal dorsal hemisection injury. The numbers of immune cells (macrophages and microglia) detected at the lesion site in animals with HA hydrogel implants were significantly reduced at acute time points (one, three and ten days post-injury). Lesioned animals with HA implants also exhibited significantly lower CSPG expression at ten days post-injury. At nine weeks post-injury, animals with HA hydrogel implants exhibited a significantly decreased astrocytic response, but did not have significantly altered CSPG expression. Combined, these data suggest that high MW HA, when stabilized against degradation, mitigates astrocyte activation in vitro and in vivo. The presence of HA implants was also associated with a significant decrease in CSPG deposition at ten days after SCI. Therefore, HA-based hydrogel systems hold great potential for minimizing undesired scarring as part of future repair strategies after SCI.

Khaing, Zin Z.; Milman, Brian D.; Vanscoy, Jennifer E.; Seidlits, Stephanie K.; Grill, Raymond J.; Schmidt, Christine E.

2011-08-01

379

Characterization of a Graded Cervical Hemicontusion Spinal Cord Injury Model in Adult Male Rats  

PubMed Central

Abstract Most experimental models of spinal cord injury (SCI) in rodents induce damage in the thoracic cord and subsequently examine hindlimb function as an indicator of recovery. In these models, functional recovery is most attributable to white-matter preservation and is less influenced by grey-matter sparing. In contrast, most clinical cases of SCI occur at the lower cervical levels, a region in which both grey-matter and white-matter sparing contribute to functional motor recovery. Thus experimental cervical SCI models are beginning to be developed and used to assess protective and pharmacological interventions following SCI. The objective of this study was to characterize a model of graded cervical hemicontusion SCI with regard to several histological and behavioral outcome measures, including novel forelimb behavioral tasks. Using a commercially available rodent spinal cord impactor, adult male rats received hemicontusion SCI at vertebral level C5 at 100, 200, or 300?kdyn force, to produce mild, moderate, or severe injury severities. Tests of skilled and unskilled forelimb and locomotor function were employed to assess functional recovery, and spinal cord tissue was collected to assess lesion severity. Deficits in skilled and unskilled forelimb function and locomotion relating to injury severity were observed, as well as decreases in neuronal numbers, white-matter area, and white-matter gliosis. Significant correlations were observed between behavioral and histological data. Taken together, these data suggest that the forelimb functional and locomotor assessments employed here are sensitive enough to measure functional changes, and that this hemicontusion model can be used to evaluate potential protective and regenerative therapeutic strategies. PMID:21087156

Dunham, Kelly A.; Siriphorn, Akkradate; Chompoopong, Supin

2010-01-01

380

Chronic oligodendrogenesis and remyelination after spinal cord injury in mice and rats.  

PubMed

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 PDGFR?-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

Hesp, Zoe C; Goldstein, Evan A; Miranda, Carlos J; Kaspar, Brain K; McTigue, Dana M

2015-01-21

381

Acute Delivery of EphA4-Fc Improves Functional Recovery after Contusive Spinal Cord Injury in Rats  

PubMed Central

Abstract Blocking the action of inhibitory molecules at sites of central nervous system injury has been proposed as a strategy to promote axonal regeneration and functional recovery. We have previously shown that genetic deletion or competitive antagonism of EphA4 receptor activity promotes axonal regeneration and functional recovery in a mouse model of lateral hemisection spinal cord injury. Here we have assessed the effect of blocking EphA4 activation using the competitive antagonist EphA4-Fc in a rat model of thoracic contusive spinal cord injury. Using a ledged tapered balance beam and open-field testing, we observed significant improvements in recovery of locomotor function after EphA4-Fc treatment. Consistent with functional improvement, using high-resolution ex vivo magnetic resonance imaging at 16.4T, we found that rats treated with EphA4-Fc had a significantly increased cross-sectional area of the dorsal funiculus caudal to the injury epicenter compared with controls. Our findings indicate that EphA4-Fc promotes functional recovery following contusive spinal cord injury and provides further support for the therapeutic benefit of treatment with the competitive antagonist in acute cases of spinal cord injury. PMID:23557244

Spanevello, Mark Damien; Tajouri, Sophie Ines; Mirciov, Cornel; Kurniawan, Nyoman; Pearse, Martin John; Fabri, Louis Jerry; Owczarek, Catherine Mary; Hardy, Matthew Philip; Bradford, Rebecca Anne; Ramunno, Melanie Louise; Turnley, Ann Maree; Ruitenberg, Marc Jan

2013-01-01

382

In Vivo Longitudinal MRI and Behavioral Studies in Experimental Spinal Cord Injury  

PubMed Central

Abstract Comprehensive in vivo longitudinal studies that include multi-modal magnetic resonance imaging (MRI) and a battery of behavioral assays to assess functional outcome were performed at multiple time points up to 56 days post-traumatic spinal cord injury (SCI) in rodents. The MRI studies included high-resolution structural imaging for lesion volumetry, and diffusion tensor imaging (DTI) for probing the white matter integrity. The behavioral assays included open-field locomotion, grid walking, inclined plane, computerized activity box performance, and von Frey filament tests. Additionally, end-point histology was assessed for correlation with both the MRI and behavioral data. The temporal patterns of the lesions were documented on structural MRI. DTI studies showed significant changes in white matter that is proximal to the injury epicenter and persisted to day 56. White matter in regions up to 1?cm away from the injury epicenter that appeared normal on conventional MRI also exhibited changes that were indicative of tissue damage, suggesting that DTI is a more sensitive measure of the evolving injury. Correlations between DTI and histology after SCI could not be firmly established, suggesting that injury causes complex pathological changes in multiple tissue components that affect the DTI measures. Histological evidence confirmed a significant decrease in myelin and oligodendrocyte presence 56 days post-SCI. Multiple assays to evaluate aspects of functional recovery correlated with histology and DTI measures, suggesting that damage to specific white matter tracts can be assessed and tracked longitudinally after SCI. PMID:20649481

Sundberg, Laura M.; Herrera, Juan J.

2010-01-01

383

Psychological Stress as a Modulator of Functional Recovery Following Spinal Cord Injury  

PubMed Central

There is strong evidence indicating that the social environment triggers changes to the psychological stress response and glucocorticoid receptor function. Considerable literature links the subsequent changes in stress resiliency to physical health. Here, converging evidence for the modulatory role of chronic psychological stress in the recovery process following spinal cord injury (SCI) is presented. Despite the considerable advances in SCI research, we are still unable to identify the causes of variability in patients’ recovery following injury. We propose that individuals’ past and present life experiences (in the form of stress exposure) may significantly modulate patients’ outcome post-SCI. We propose a theoretical model to explain the negative impact of chronic psychological stress on physical and psychological recovery. The stress experienced in life prior to SCI and also as a result of the traumatic injury, could compromise glucocorticoid receptor sensitivity and function, and contribute to high levels of inflammation and apoptosis post-SCI, decreasing the tissue remaining at the injury site and undermining recovery of function. Both stress-induced glucocorticoid resistance and stress-induced epigenetic changes to the glucocorticoid receptor can modulate the nuclear factor-kappa B regulated inflammatory pathways and the Bcl-2 regulated apoptosis pathways. This model not only contributes to the theoretical understanding of the recovery process following injury, but also provides concrete testable hypotheses for future studies. PMID:24782818

Maldonado Bouchard, Sioui; Hook, Michelle A.

2014-01-01

384

Factors That Influence Employment After Spinal Cord Injury in South Korea  

PubMed Central

Objective To investigate employment status after spinal cord injury (SCI) and identify personal, family, and injury characteristics those affect their employment in South Korea. Methods Participants were 334 community-dwelling persons 20-64 years of age who had sustained SCI for more than one year. Investigators visited each participant's home to carry out the survey. Bivariate and binary logistic regression analyses were performed to identify personal, family, and injury characteristics that influenced employment after SCI. Results Employment rate decreased significantly from 82.5% to 27.5% after SCI. Logistic regression showed that the probability of employment was higher in men than women, and in individuals older than 45 years at the time of injury than those aged 31-45 years of age. Moreover, employment was higher in individuals injured for longer than 20 years than those injured for 1-5 years and in individuals with incomplete tetraplegia than those with complete paraplegia. Employment was lower in individuals with SCI caused by industrial accidents than those injured in non-industrial accidents. Conclusion Injury characteristics are the most important predictors of employment in persons with SCI. For persons with lower employment rate, individualized vocational rehabilitation and employment-support systems are required. PMID:24639924

Kang, Eun-Na; Shin, Hyung-Ik

2014-01-01

385

Chemokines as Possible Targets in Modulation of the Secondary Damage After Acute Spinal Cord Injury: A Review  

Microsoft Academic Search

In spite of many promising experimental studies, an effective treatment dramatically eliminating the secondary damage after\\u000a spinal cord injury (SCI) is still missing. Since clinical data on the therapeutical effect after methylprednisolone treatment\\u000a are not conclusive, new therapeutical modalities targeting specific components of secondary spinal cord damage needs to be\\u000a developed. It is known that immune cells are recruited to

Peter Gál; Petra Krav?uková; Michal Mokrý; Darina Kluchová

2009-01-01

386

Treatment of spinal cord injury: A review of engineering using neural and mesenchymal stem cells.  

PubMed

Over time, various treatment modalities for spinal cord injury have been trialed, including pharmacological and nonpharmacological methods. Among these, replacement of the injured neural and paraneural tissues via cellular transplantation of neural and mesenchymal stem cells has been the most attractive. Extensive experimental studies have been done to identify the safety and effectiveness of this transplantation in animal and human models. Herein, we review the literature for studies conducted, with a focus on the human-related studies, recruitment, isolation, and transplantation, of these multipotent stem cells, and associated outcomes. Clin. Anat. 28:37-44, 2015. © 2014 Wiley Periodicals, Inc. PMID:25156268

Mortazavi, Martin M; Harmon, Olivia A; Adeeb, Nimer; Deep, Aman; Tubbs, R Shane

2015-01-01

387

A longitudinal Raman microspectroscopic study of osteoporosis induced by spinal cord injury  

Microsoft Academic Search

Introduction  A longitudinal study was established to investigate bone compositional information in spinal cord injury (SCI) rat model.\\u000a \\u000a \\u000a \\u000a Methods  Raman spectroscopy was applied to detect the distal femur and humeri of SCI, sham-operated (SO), and age-matched control (CON)\\u000a male Sprague-Dawley (SD) rats at first, second, third, and fifth weeks after surgery. One-way ANOVA and Tukey’s HSD post hoc\\u000a multiple comparison tests were

J. Shen; L. Fan; J. Yang; A. G. Shen; J. M. Hu

2010-01-01

388

The volatile anesthetic methoxyflurane protects motoneurons against excitotoxicity in an in vitro model of rat spinal cord injury.  

PubMed

Neuroprotection of the spinal cord during the early phase of injury is an important goal to determine a favorable outcome by prevention of delayed pathological events, including excitotoxicity, which otherwise extend the primary damage and amplify the often irreversible loss of motor function. While intensive care and neurosurgical intervention are important treatments, effective neuroprotection requires further experimental studies focused to target vulnerable neurons, particularly motoneurons. The present investigation examined whether the volatile general anesthetic methoxyflurane might protect spinal locomotor networks from kainate-evoked excitotoxicity using an in vitro rat spinal cord preparation as a model. The protocols involved 1h excitotoxic stimulation on day 1 followed by electrophysiological and immunohistochemical testing on day 2. A single administration of methoxyflurane applied together with kainate (1h), or 30 or even 60min later prevented any depression of spinal reflexes, loss of motoneuron excitability, and histological damage. Methoxyflurane per se temporarily decreased synaptic transmission and motoneuron excitability, effects readily reversible on washout. Spinal locomotor activity recorded as alternating electrical discharges from lumbar motor pools was fully preserved on the second day after application of methoxyflurane together with (or after) kainate. These data suggest that a volatile general anesthetic could provide strong electrophysiological and histological neuroprotection that enabled expression of locomotor network activity 1day after the excitotoxic challenge. It is hypothesized that the benefits of early neurosurgery for acute spinal cord injury (SCI) might be enhanced if, in addition to injury decompression and stabilization, the protective role of general anesthesia is exploited. PMID:25446348

Shabbir, A; Bianchetti, E; Nistri, A

2015-01-29

389

Chronic neuropathic pain management in spinal cord injury patients. What is the efficacy of pharmacological treatments with a general mode of  

E-print Network

Title Chronic neuropathic pain management in spinal cord injury patients. What is the efficacy of patients with spinal cord injury (SCI) pain remains challenging despite new available drugs. Such treatment shoud always be viewed in the context of global pain management in these patients. To date few clinical

Paris-Sud XI, Université de

390

Rapid Upregulation of Caspase3 in Rat Spinal Cord after Injury: mRNA, Protein, and Cellular Localization Correlates with Apoptotic Cell Death  

Microsoft Academic Search

Although the precise mechanisms explaining loss of, and failure to regain, function after spinal cord injury are unknown, there is increasing interest in the role of “secondary cell death.” One prevalent theme in cell loss in other regions of the CNS involves apoptosis executed by the intracellular caspase proteases. A recent study demonstrated that spinal cord injury rapidly increased the

Bruce A. Citron; Paul M. Arnold; Cyril Sebastian; Fan Qin; Sundaravalli Malladi; Syed Ameenuddin; Mary E. Landis; Barry W. Festoff

2000-01-01

391

Neural precursor cell transplantation enhances functional recovery and reduces astrogliosis in bilateral compressive/contusive cervical spinal cord injury.  

PubMed

Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion-compression spinal cord injury. Bilateral C6-level clip contusion-compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain-derived NPCs, vehicle, or sham operation. Long-term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft-derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP-positive and chondroitin sulfate proteoglycan-positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell-treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation. PMID:25107585

Wilcox, Jared T; Satkunendrarajah, Kajana; Zuccato, Jeffrey A; Nassiri, Farshad; Fehlings, Michael G

2014-10-01

392

Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery.  

PubMed

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. Recently there has been increasing interest in cervical spinal cord injury models because the majority of spinal cord injuries are at cervical levels. Here we examined spontaneous functional recovery of adult rats with either laminectomy or lateral hemisection of the cervical spinal cord at C3-C4. Behavioral tests were carried out, including the forelimb locomotor scale (FLS), a postural instability test (PIT), a pasta-handling test that has been used to assess forepaw digit function and latency to eat, forelimb use during vertical-lateral wall exploration in a cylindrical enclosure, and vibrissae-elicited forel