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Therapy of spinal cord injury

Jakub Smolar, Souzan Salemi, Maya Horst, Tullio Sulser, Daniel Eberli
Conditions impairing bladder function in children and adults, such as myelomeningocele, posterior urethral valves, bladder exstrophy or spinal cord injury, often need urinary diversion or augmentation cystoplasty as when untreated they may cause severe bladder dysfunction and kidney failure. Currently, the gold standard therapy of end-stage bladder disease refractory to conservative management is enterocystoplasty, a surgical enlargement of the bladder with intestinal tissue. Despite providing functional improvement, enterocystoplasty is associated with significant long-term complications, such as recurrent urinary tract infections, metabolic abnormalities, stone formation, and malignancies...
September 2016: Transfusion Medicine and Hemotherapy
Suzanne E Geerlings
Urinary tract infection (UTI) is one of the most common bacterial infections, and the incidence in women is much higher than in men. The diagnosis of a UTI can be made based on a combination of symptoms and a positive urine analysis or culture. Most UTIs are uncomplicated UTIs, defined as cystitis in a woman who is not pregnant, is not immunocompromised, has no anatomical and functional abnormalities of the urogenital tract, and does not exhibit signs of tissue invasion and systemic infection. All UTIs that are not uncomplicated are considered to be complicated UTIs...
October 2016: Microbiology Spectrum
Jean-Jacques Wyndaele
The management of patients with neurogenic bladder has changed substantially over the past decades. Obtaining balanced lower urinary tract function has become possible in most patients, although, urological complications remain among the most serious complications these patients are likely to have and, even today, these can have a negative effect on quality of life. To this extent, patients with spinal cord injury (SCI) are likely to develop neurogenic bladder, and data are available on most aspects of neurogenic bladder in these patients...
October 25, 2016: Nature Reviews. Urology
Geeta Shroff, Dipin Thakur, Varun Dhingra, Deepak Singh Baroli, Deepanshu Khatri, Rahul Dev Gautam
BACKGROUND: The major complication faced by patients with chronic static spinal cord injury (SCI) is the loss of mobilization. With the aim to rehabilitate SCI patients, physiotherapy is performed worldwide. However, it only helps the patients to live with their disabilities. An interdisciplinary management involving human embryonic stem cell (hESC) therapy along with physiotherapy as a supportive therapy offers regenerative treatment of the patients with SCI. MAIN BODY: The present study focuses on the role of physiotherapy in the mobilization of patients with SCI (paraplegic 136; tetraplegics 90) undergoing hESC therapy...
December 2016: Clinical and Translational Medicine
David Reigada, Rosa María Navarro-Ruiz, Marcos Javier Caballero-López, Ángela Del Águila, Teresa Muñoz-Galdeano, Rodrigo M Maza, Manuel Nieto-Díaz
Reducing cell death during the secondary injury is a major priority in the development of a cure for traumatic spinal cord injury (SCI). One of the earliest processes that follow SCI is the excitotoxicity resulting from the massive release of excitotoxicity mediators, including ATP, which induce an excessive and/or prolonged activation of their receptors and a deregulation of the calcium homeostasis. Diadenosine tetraphosphate (Ap4A) is an endogenous purinergic agonist, present in both extracellular and intracellular fluids, with promising cytoprotective effects in different diseases including neurodegenerative processes...
October 19, 2016: Purinergic Signalling
Claudia Kathe, Thomas Haynes Hutson, Stephen Brendan McMahon, Lawrence David Falcon Moon
Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity...
October 19, 2016: ELife
Saul Wilson, Kingsley O Abode-Iyamah, John W Miller, Chandan G Reddy, Sina Safayi, Douglas C Fredericks, Nicholas D Jeffery, Nicole A DeVries-Watson, Sara K Shivapour, Stephanus Viljoen, Brian D Dalm, Katherine N Gibson-Corley, Michael D Johnson, George T Gillies, Matthew A Howard
OBJECTIVE: To develop a large animal model of spinal cord injury (SCI), for use in translational studies of spinal cord stimulation (SCS) in the treatment of spasticity. We seek to establish thresholds for the SCS parameters associated with reduction of post-SCI spasticity in the pelvic limbs, with implications for patients. STUDY DESIGN: The weight-drop method was used to create a moderate SCI in adult sheep, leading to mild spasticity in the pelvic limbs. Electrodes for electromyography (EMG) and an epidural spinal cord stimulator were then implanted...
October 19, 2016: Journal of Spinal Cord Medicine
So Young Joo, Yoon Soo Cho, Sung-Rae Cho, Dohern Kym, Cheong Hoon Seo
PURPOSE: Pain Scrambler therapy is a patient-specific electrocutaneous nerve stimulation device. Burn pruritus is a common form of chronic and disabling neuropathic pain that is often difficult to treat effectively. Pruritus is mediated by histamines, which are effector molecules stored in mast cells and released locally during injury or inflammation. Burn pruritus may be accompanied by peripheral neuropathic pain, which may result from injury to sensory nerves that hampers conductance of neuronal messages along the large A and small C afferent fibers to the spinal cord...
October 15, 2016: Burns: Journal of the International Society for Burn Injuries
D Zbogar, J J Eng, W C Miller, A V Krassioukov, M C Verrier
STUDY DESIGN: Longitudinal observational study. OBJECTIVE: To quantify the amount of upper- and lower-extremity movement repetitions (that is, voluntary movements as part of a functional task or specific motion) occurring during inpatient spinal cord injury (SCI), physical (PT) and occupational therapy (OT), and examine changes over the inpatient rehabilitation stay. SETTING: Two stand-alone inpatient SCI rehabilitation centers. METHODS: Participants: A total of 103 patients were recruited through consecutive admissions to SCI rehabilitation...
October 18, 2016: Spinal Cord
Mohammad T Abu-Rub, Ben Newland, Michelle Naughton, Wenxin Wang, Siobhan McMahon, Abhay Pandit
Reactive astrocytosis and the subsequent glial scar is ubiquitous to injuries of the central nervous system, especially spinal cord injury (SCI) and primarily serves to protect against further damage, but is also a prominent inhibitor of regeneration. Manipulating the glial scar by targeting chondroitin sulphate proteoglycans (CSPGs) has been the focus of much study as a means to improve axon regeneration and subsequently functional recovery. In this study we investigate the ability of small interfering RNA (siRNA) delivered by a non-viral polymer vector to silence the rate-limiting enzyme involved in CSPG synthesis...
October 12, 2016: Neuroscience
Zhijian Cheng, Dale B Bosco, Li Sun, Xiaoming Chen, Yunsheng Xu, Wenjiao Tai, Ruth Didier, Jinhua Li, Jianqing Fan, Xijing He, Yi Ren
Spinal cord injury (SCI) causes functional impairment as a result of the initial injury followed by secondary injury mechanism. SCI provokes an inflammatory response that causes secondary tissue damage and neurodegeneration. While, the use of neural stem cell (NSC) engraftment to mitigate secondary injury has been of interest to many researchers, it still faces several limitations. As such, we investigated if NSC-conditioned media (NSC-M) possesses therapeutic potential for the treatment of SCI. It has been proposed that many of the beneficial effects attributed to stem cell therapies are due to secreted factors...
October 12, 2016: Cell Transplantation
Jacob Kjell, Lars Olson
A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors...
October 1, 2016: Disease Models & Mechanisms
Sara Bermudez, Guzal Khayrullina, Yujia Zhao, Kimberly R Byrnes
Spinal cord injury (SCI) results in both acute and chronic inflammation, as a result of activation of microglia, invasion of macrophages and activation of the NADPH oxidase (NOX) enzyme. The NOX enzyme is a primary source of reactive oxygen species (ROS) and is expressed by microglia and macrophages after SCI. These cells can assume either a pro- (M1) or anti-inflammatory (M2) polarization phenotype and contribute to tissue response to SCI. However, the contribution of NOX expression and ROS production to this polarization and vice versa is currently undefined...
October 8, 2016: Molecular and Cellular Neurosciences
Anne Tscherter, Martina Heidemann, Sonja Kleinlogel, Jürg Streit
Presently there exists no cure for spinal cord injury (SCI). However, transplantation of embryonic tissue into spinal cord (SC) lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated SC circuits...
2016: Frontiers in Cellular Neuroscience
Lauren N Russell, Kyle J Lampe
Millions of people suffer from damage or disease to the nervous system that results in a loss of myelin, such as through a spinal cord injury or multiple sclerosis. Diminished myelin levels lead to further cell death in which unmyelinated neurons die. In the central nervous system, a loss of myelin is especially detrimental because of its poor ability to regenerate. Cell therapies such as stem or precursor cell injection have been investigated as stem cells are able to grow and differentiate into the damaged cells; however, stem cell injection alone has been unsuccessful in many areas of neural regeneration...
2016: Cells, Tissues, Organs
Courtney M Dumont, Daniel J Margul, Lonnie D Shea
Tissue engineering strategies have shown promise in promoting healing and regeneration after spinal cord injury (SCI); however, these strategies are limited by inflammation and the immune response. Infiltration of cells of the innate and adaptive immune responses and the inflammation that follows cause secondary damage adjacent to the injury, increased scarring, and a potently inhibitory environment for the regeneration of damaged neurons. While the inflammation that ensues is typically associated with limited regeneration, the immune response is a crucial element in the closing of the blood-brain barrier, minimizing the spread of injury, and initiating healing...
2016: Cells, Tissues, Organs
Ying Wang, Hua Jia, Wen-Yuan Li, Li-Xin Guan, Lingxiao Deng, Yan-Cui Liu, Gui-Bo Liu
The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs)...
October 2016: Experimental and Therapeutic Medicine
Lucian Beer, Michael Mildner, Mariann Gyöngyösi, Hendrik Jan Ankersmit
For almost two decades, cell-based therapies have been tested in modern regenerative medicine to either replace or regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. These factors are called the cell secretome and include a variety of proteins, lipids, microRNAs, and extracellular vesicles, such as exosomes and microparticles. The stem cell secretome has most commonly been investigated in pre-clinical settings...
October 1, 2016: Apoptosis: An International Journal on Programmed Cell Death
Aurélie Rochefolle, Chloé Chazaud, Amandine Guinet-Lacoste, Sophie Jacquin-Courtois, Catherine Rioufol, Jacques Luaute, Gilles Rode, Emmanuelle Carré
OBJECTIVE: Patients with spinal cord injury suffer from urinary tract infection (UTI) repeatedly. An assessment of the professional practices in UTI has been set up since 2013. The aim of this study is to assess the impact of physician/pharmacist's collaboration on 3 quality indicators (QI) in UTI during 2014/2015. MATERIAL/PATIENTS AND METHODS: At the beginning of the treatment and then twice a week, pharmacists validate every antibiotic therapy. QI assess the conformity of the duration, the conformity of the dosage and the conformity to the susceptibility testing...
September 2016: Annals of Physical and Rehabilitation Medicine
Yann Le Déan, Benjamin Brissebrat, Evelyne Castel-Lacanal, Xavier De Boissezon, Philippe Marque
OBJECTIVE: Central neuropathic pain is common among neurological patients. Drug therapy has high pharmacoresistance and some GABAergic agents can be detrimental to the recovery process. Alternative therapies include neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and motor imagery techniques with mirror therapy. The objective of this study was to evaluate their effectiveness in clinical practice on central neuropathic pain. MATERIAL/PATIENTS AND METHODS: Thirty-two patients followed in the Physical Medicine and Rehabilitation department of Rangueil University Hospital were included...
September 2016: Annals of Physical and Rehabilitation Medicine
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