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The 2nd Step by Step International Spinal Cord Repair—Combining research Step by Step into multi-pronged approaches for spinal cord repair  [PDF]
Maria Teresa Moreno-Flores, Francois Ferón, Victor Arvanian, Armin Blesch, Armin Curt, David J. Fink, Marina Mata, Kinichi Nakashima, Xavier Navarro, Francisco Javier Rodríguez, Michal Schwartz, Mikael Svensson, Erik Sundstrom, Joan Romero, Filip Lim
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.67A2003
Abstract: On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting research including clinical trials which show promise for treatments for this devastating disorder. This meeting brought together clinicians, clinical scientists and molecular biologists from more than 10 countries to evaluate current knowledge on clinical, cellular, and biomolecular aspects of spinal cord injury. A major goal of the conference in advancing the translation of research data to the clinic was to promote multi-pronged approaches for therapy of this complex problem.
Schwann cells for spinal cord repair
Oudega, M.;Moon, L.D.F.;de Almeida Leme, R.J.;
Brazilian Journal of Medical and Biological Research , 2005, DOI: 10.1590/S0100-879X2005000600003
Abstract: the complex nature of spinal cord injury appears to demand a multifactorial repair strategy. one of the components that will likely be included is an implant that will fill the area of lost nervous tissue and provide a growth substrate for injured axons. here we will discuss the role of schwann cells (scs) in cell-based, surgical repair strategies of the injured adult spinal cord. we will review key studies that showed that intraspinal sc grafts limit injury-induced tissue loss and promote axonal regeneration and myelination, and that this response can be improved by adding neurotrophic factors or anti-inflammatory agents. these results will be compared with several other approaches to the repair of the spinal cord. a general concern with repair strategies is the limited functional recovery, which is in large part due to the failure of axons to grow across the scar tissue at the distal graft-spinal cord interface. consequently, new synaptic connections with spinal neurons involved in motor function are not formed. we will highlight repair approaches that did result in growth across the scar and discuss the necessity for more studies involving larger, clinically relevant types of injuries, addressing this specific issue. finally, this review will reflect on the prospect of scs for repair strategies in the clinic.
Schwann cells for spinal cord repair  [cached]
Oudega M.,Moon L.D.F.,de Almeida Leme R.J.
Brazilian Journal of Medical and Biological Research , 2005,
Abstract: The complex nature of spinal cord injury appears to demand a multifactorial repair strategy. One of the components that will likely be included is an implant that will fill the area of lost nervous tissue and provide a growth substrate for injured axons. Here we will discuss the role of Schwann cells (SCs) in cell-based, surgical repair strategies of the injured adult spinal cord. We will review key studies that showed that intraspinal SC grafts limit injury-induced tissue loss and promote axonal regeneration and myelination, and that this response can be improved by adding neurotrophic factors or anti-inflammatory agents. These results will be compared with several other approaches to the repair of the spinal cord. A general concern with repair strategies is the limited functional recovery, which is in large part due to the failure of axons to grow across the scar tissue at the distal graft-spinal cord interface. Consequently, new synaptic connections with spinal neurons involved in motor function are not formed. We will highlight repair approaches that did result in growth across the scar and discuss the necessity for more studies involving larger, clinically relevant types of injuries, addressing this specific issue. Finally, this review will reflect on the prospect of SCs for repair strategies in the clinic.
Potential of Olfactory Ensheathing Cells from Different Sources for Spinal Cord Repair  [PDF]
Anne Mayeur, Célia Duclos, Axel Honoré, Maxime Gauberti, Laurent Drouot, Jean-Claude do Rego, Nicolas Bon-Mardion, Laetitia Jean, Eric Vérin, Evelyne Emery, Sighild Lemarchant, Denis Vivien, Olivier Boyer, Jean-Paul Marie, Nicolas Guérout
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062860
Abstract: Spinal cord injury (SCI) induces a permanent disability in patients. To this day no curative treatment can be proposed to restore lost functions. Therefore, extensive experimental studies have been conducted to induce recovery after SCI. One of the most promising therapies is based on the use of olfactory ensheathing cells (OECs). OECs can be obtained from either the olfactory bulbs (OB-OECs) or from olfactory mucosa (OM-OECs), involving a less invasive approach for autotransplantation. However the vast majority of experimental transplantations have been focusing on OB-OECs although the OM represents a more accessible source of OECs. Importantly, the ability of OM-OECs in comparison to OB-OECs to induce spinal cord recovery in the same lesion paradigm has never been described. We here present data using a multiparametric approach, based on electrophysiological, behavioral, histological and magnetic resonance imaging experiments on the repair potential of OB-OECs and OM-OECs from either primary or purified cultures after a severe model of SCI. Our data demonstrate that transplantation of OECs obtained from OB or OM induces electrophysiological and functional recovery, reduces astrocyte reactivity and glial scar formation and improves axonal regrowth. We also show that the purification step is essential for OM-OECs while not required for OB-OECs. Altogether, our study strongly indicates that transplantation of OECs from OM represents the best benefit/risk ratio according to the safety of access of OM and the results induced by transplantations of OM-OECs. Indeed, purified OM-OECs in addition to induce recovery can integrate and survive up to 60 days into the spinal cord. Therefore, our results provide strong support for these cells as a viable therapy for SCI.
Age-Dependent Modulation of Cortical Transcriptomes in Spinal Cord Injury and Repair  [PDF]
Anne Jaerve, Fabian Kruse, Katharina Malik, Hans-Peter Hartung, Hans Werner Müller
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049812
Abstract: Both injury and aging of the central nervous system reportedly produce profound changes in gene expression. Therefore, aging may interfere with the success of therapeutic interventions which were tailored for young patients. Using genome-scale transcriptional profiling, we identified distinct age-dependent expression profiles in rat sensorimotor cortex during acute, subacute and chronic phases of spinal cord injury (SCI). Aging affects the cortical transcriptomes triggered by transection of the corticospinal tract as there was only a small overlap between the significantly lesion-regulated genes in both age groups. Over-representation analysis of the lesion-regulated genes revealed that, in addition to biological processes in common, such as lipid metabolism, others, such as activation of complement cascade, were specific for aged animals. When a recently developed treatment to suppress fibrotic scarring (anti-scarring treatment AST) was applied to the injured spinal cord of aged (22 months) and young (2 months) rats, we found that the cortical gene expression in old rats was modulated to resemble regeneration-associated profiles of young animals including the up-regulation of known repair promoting growth and transcription factors at 35 dpo. In combination with recent immunohistochemical findings demonstrating regenerative axon growth upon AST in aged animals, the present investigation on the level of gene expression strongly supports the feasibility of a successful AST therapy in elderly patients.
Reliability of daily step activity monitoring in adults with incomplete spinal cord injury  [PDF]
Saori Ishikawa, MS, ATC, CSCS,Sandy L. Stevens, PhD,Minsoo Kang, PhD,Don W. Morgan, PhD
Journal of Rehabilitation Research and Development , 2011,
Abstract: We determined the number of days of step activity monitoring required to establish stable measures of walking activity in adults with incomplete spinal cord injury (iSCI). Eleven individuals with iSCI (mean age 49 +/– 14 years) wore a StepWatch Activity Monitor during waking hours for 7 consecutive days. We used generalizability theory to identify sources of variance in daily step counts and determine the minimum number of days necessary to obtain a reliability coefficient (G-coefficient) greater than or equal to 0.80. Average daily step activity (DSA) was 1,281 +/– 1,594 steps. Participants and days accounted for 70.9% and 1.3% of total variance in DSA, respectively, while unidentifiable error accounted for 27.8% of the total variance in DSA. A minimum of 2 days was required to achieve a G-coefficient greater than or equal to 0.80. An acceptably stable measure of walking activity in adults with iSCI can be obtained by averaging step count values from any 2-day period in a week. Results from this investigation should be useful in evaluating the effect of activity-based programs designed to enhance locomotor function in persons with iSCI.
Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair
Dallo, Jo?o Gabriel Martins;Reichert, Bernardo Vergara;Vallad?o Júnior, José Benedito Ramos;Silva, Camila;Luca, Bianca Aparecida de;Levy, Beatriz de Freitas Azevedo;Chadi, Gerson;
Acta Cirurgica Brasileira , 2007, DOI: 10.1590/S0102-86502007000600013
Abstract: purpose: reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. schwann cells (sc), a peripheral glia, also react after nerve lesion favoring wound/repair, fiber outgrowth and neuronal regeneration. we investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. methods: injections of a cultured sc suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. local injection of phosphate buffered saline (pbs) served as control. one week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantified by means of quantitative image analysis. results: in the ipsilateral ventral horn, slight astroglial activations were seen after pbs or sc injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. moreover, sc suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. conclusion: spinal cord astrocytes react according to repair processes of axotomized nerve, which may influence the functional outcome. the event should be considered during the neurosurgery strategies.
Spinal Cord Ischemia after Endovascular Repair of Infrarenal Abdominal Aortic Aneurysm: A Rare Complication
George N. Kouvelos,Nektario Papa,Christos Nassis,Nikolaos Xiropotamos,George Papadopoulos,Miltiadis I. Matsagkas
Case Reports in Medicine , 2011, DOI: 10.1155/2011/954572
Abstract: Neurologic deficit secondary to spinal cord ischemia after elective infrarenal, endovascular aneurysm repair (EVAR), consists a rare and rather disastrous complication. The etiology of such neurologic complication seems to be multifactorial, making this event unpredictable and foremost unpreventable. We report a case of paraparesis and bladder dysfunction that occurred immediately after the EVAR procedure. Prompt management by conservative or invasive methods seems to be important for the reversal of the neurologic deficit and the optimization of patient's outcome.
Review of Thoracic Endovascular Aneurysm Repair (TEVAR), Spinal Cord Ischemia (SCI), Cerebrospinal Fluid (CSF) Drainage and Blood Pressure (BP) Augmentation  [PDF]
R. Englund
Surgical Science (SS) , 2017, DOI: 10.4236/ss.2017.82009
Abstract: The object of this review is to examine the role of TEVAR in causing SCI. The anatomy and physiology of blood flow to the spinal cord is examined. The role of auto regulation of blood flow within the spinal cord is also examined. This review examines the reported results from the scientific literature of the effect of thoracic aortic aneurysm repair on spinal cord blood flow. In the light of the-se findings several conclusions can reasonably be reached. These conclusions are that the development of SCI can reasonably be predicted based on complexity and extent of the TEVAR procedure performed and BP augmentation and CSF drainage can significantly reduce the impact of SCI.
Effects of Combinatorial Treatment with Pituitary Adenylate Cyclase Activating Peptide and Human Mesenchymal Stem Cells on Spinal Cord Tissue Repair  [PDF]
Kuan-Min Fang,Jen-Kun Chen,Shih-Chieh Hung,Mei-Chun Chen,Yi-Ting Wu,Tsung-Jung Wu,Hsin-I Lin,Chia-Hua Chen,Henrich Cheng,Chung-Shi Yang,Shun-Fen Tzeng
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015299
Abstract: The aim of this study is to understand if human mesenchymal stem cells (hMSCs) and neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) have synergistic protective effect that promotes functional recovery in rats with severe spinal cord injury (SCI). To evaluate the effect of delayed combinatorial therapy of PACAP and hMSCs on spinal cord tissue repair, we used the immortalized hMSCs that retain their potential of neuronal differentiation under the stimulation of neurogenic factors and possess the properties for the production of several growth factors beneficial for neural cell survival. The results indicated that delayed treatment with PACAP and hMSCs at day 7 post SCI increased the remaining neuronal fibers in the injured spinal cord, leading to better locomotor functional recovery in SCI rats when compared to treatment only with PACAP or hMSCs. Western blotting also showed that the levels of antioxidant enzymes, Mn-superoxide dismutase (MnSOD) and peroxiredoxin-1/6 (Prx-1 and Prx-6), were increased at the lesion center 1 week after the delayed treatment with the combinatorial therapy when compared to that observed in the vehicle-treated control. Furthermore, in vitro studies showed that co-culture with hMSCs in the presence of PACAP not only increased a subpopulation of microglia expressing galectin-3, but also enhanced the ability of astrocytes to uptake extracellular glutamate. In summary, our in vivo and in vitro studies reveal that delayed transplantation of hMSCs combined with PACAP provides trophic molecules to promote neuronal cell survival, which also foster beneficial microenvironment for endogenous glia to increase their neuroprotective effect on the repair of injured spinal cord tissue.
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