Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.

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Kazuya Kitamura

Full Text Available 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.

Adult-type myogenesis of the frog Xenopus laevis specifically suppressed by notochord cells but promoted by spinal cord cells in vitro.

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Yamane, Hitomi; Ihara, Setsunosuke; Kuroda, Masaaki; Nishikawa, Akio

2011-08-01

Larval-to-adult myogenic conversion occurs in the dorsal muscle but not in the tail muscle during Xenopus laevis metamorphosis. To know the mechanism for tail-specific suppression of adult myogenesis, response character was compared between adult myogenic cells (Ad-cells) and larval tail myogenic cells (La-cells) to a Sonic hedgehog (Shh) inhibitor, notochord (Nc) cells, and spinal cord (SC) cells in vitro. Cyclopamine, an Shh inhibitor, suppressed the differentiation of cultured Ad (but not La) cells, suggesting the significance of Shh signaling in promoting adult myogenesis. To test the possibility that Shh-producing axial elements (notochord and spinal cord) regulate adult myogenesis, Ad-cells or La-cells were co-cultured with Nc or SC cells. The results showed that differentiation of Ad-cells were strongly inhibited by Nc cells but promoted by SC cells. If Ad-cells were "separately" co-cultured with Nc cells without direct cell-cell interactions, adult differentiation was not inhibited but rather promoted, suggesting that Nc cells have two roles, one is a short-range suppression and another is a long-range promotion for adult myogenesis. Immunohistochemical analysis showed both notochord and spinal cord express the N-terminal Shh fragment throughout metamorphosis. The "spinal cord-promotion" and long-range effect by Nc cells on adult myogenesis is thus involved in Shh signaling, while the signaling concerning the short-range "Nc suppression" will be determined by future studies. Interestingly, these effects, "Nc suppression" and "SC promotion" were not observed for La-cells. Situation where the spinal cord/notochord cross-sectional ratio is quite larger in tadpole trunk than in the tail seems to contribute to trunk-specific promotion and tail-specific suppression of adult myogenesis during Xenopus metamorphosis.

Electro-acupuncture promotes survival, differentiation of the bone marrow mesenchymal stem cells as well as functional recovery in the spinal cord-transected rats

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Ding, Ying; Yan, Qing; Ruan, Jing-Wen; Zhang, Yan-Qing; Li, Wen-Jie; Zhang, Yu-Jiao; Li, Yan; Dong, Hongxin; Zeng, Yuan-Shan

2009-01-01

Background Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools for treatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injured spinal cord still need to be improved. In the present study, we investigated whether Governor Vessel electro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs) survival and differentiation, axonal regeneration and finally, functional recovery in the transected spinal cord. Results The spinal cords of adult Sprague-Dawley (SD) rats were completely transected at T10, five experimental groups were performed: 1. sham operated control (Sham-control); 2. operated control (Op-control); 3. electro-acupuncture treatment (EA); 4. MSCs transplantation (MSCs); and 5. MSCs transplantation combined with electro-acupuncture (MSCs+EA). After 2-8 weeks of MSCs transplantation plus EA treatment, we found that the neurotrophin-3 (NT-3), cAMP level, the differentiation of MSCs, the 5-HT positive and CGRP positive nerve fibers in the lesion site and nearby tissue of injured spinal cord were significantly increased in the MSCs+EA group as compared to the group of the MSCs transplantation or the EA treated alone. Furthermore, behavioral test and spinal cord evoked potentials detection demonstrated a significantly functional recovery in the MSCs +EA group. Conclusion These results suggest that EA treatment may promote grafted MSCs survival and differentiation; MSCs transplantation combined with EA treatment could promote axonal regeneration and partial locomotor functional recovery in the transected spinal cord in rats and indicate a promising avenue of treatment of spinal cord injury. PMID:19374777

Small GTPase R-Ras participates in neural tube formation in zebrafish embryonic spinal cord.

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Ohata, Shinya; Uga, Hideko; Okamoto, Hitoshi; Katada, Toshiaki

2018-06-27

Ras related (R-Ras), a small GTPase, is involved in the maintenance of apico-basal polarity in neuroepithelial cells of the zebrafish hindbrain, axonal collapse in cultured murine hippocampal neurons, and maturation of blood vessels in adult mice. However, the role of R-Ras in neural tube formation remains unknown. Using antisense morpholino oligonucleotides (AMOs), we found that in the spinal cord of zebrafish embryos, the lumen was formed bilaterally in rras morphants, whereas it was formed at the midline in control embryos. As AMO can cause off-target effects, we generated rras mutant zebrafish lines using CRISPR/Cas9 technology. Although these rras mutant embryos did not have a bilateral lumen in the spinal cord, the following findings suggest that the phenotype is unlikely due to an off-target effect of rras AMO: 1) The rras morphant phenotype was rescued by an injection of AMO-resistant rras mRNA, and 2) a bilaterally segregated spinal cord was not observed in rras mutant embryos injected with rras AMO. The results suggest that the function of other ras family genes may be redundant in rras mutants. Previous research reported a bilaterally formed lumen in the spinal cord of zebrafish embryos with a mutation in a planar cell polarity (PCP) gene, van gogh-like 2 (vangl2). In the present study, in cultured cells, R-Ras was co-immunoprecipitated with Vangl2 but not with another PCP regulator, Pricke1. Interestingly, the interaction between R-Ras and Vangl2 was stronger in guanine-nucleotide free point mutants of R-Ras than in wild-type or constitutively active (GTP-bound) forms of R-Ras. R-Ras may regulate neural tube formation in cooperation with Vangl2 in the developing zebrafish spinal cord. Copyright © 2018 Elsevier Inc. All rights reserved.

Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

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Xian-bin Kong

2017-01-01

Full Text Available Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compelling findings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels: (1 polyethylene glycol as an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury. (2 Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers. (3 Polyethylene glycol hydrogels have been used as supporting substrates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury

Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

Institute of Scientific and Technical Information of China (English)

Xian-bin Kong; Qiu-yan Tang; Xu-yi Chen; Yue Tu; Shi-zhong Sun; Zhong-lei Sun

2017-01-01

Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compellingfindings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels: (1) polyethylene glycol as an adjustable bio-molecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury. (2) Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers. (3) Polyethylene glycol hydrogels have been used as supporting sub-strates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury.

Electroacupuncture in the repair of spinal cord injury: inhibiting the Notch signaling pathway and promoting neural stem cell proliferation

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Xin Geng

2015-01-01

Full Text Available Electroacupuncture for the treatment of spinal cord injury has a good clinical curative effect, but the underlying mechanism is unclear. In our experiments, the spinal cord of adult Sprague-Dawley rats was clamped for 60 seconds. Dazhui (GV14 and Mingmen (GV4 acupoints of rats were subjected to electroacupuncture. Enzyme-linked immunosorbent assay revealed that the expression of serum inflammatory factors was apparently downregulated in rat models of spinal cord injury after electroacupuncture. Hematoxylin-eosin staining and immunohistochemistry results demonstrated that electroacupuncture contributed to the proliferation of neural stem cells in rat injured spinal cord, and suppressed their differentiation into astrocytes. Real-time quantitative PCR and western blot assays showed that electroacupuncture inhibited activation of the Notch signaling pathway induced by spinal cord injury. These findings indicate that electroacupuncture repaired the injured spinal cord by suppressing the Notch signaling pathway and promoting the proliferation of endogenous neural stem cells.

Structural and functional reorganization of propriospinal connections promotes functional recovery after spinal cord injury

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Linard Filli

2015-01-01

Full Text Available Axonal regeneration and fiber regrowth is limited in the adult central nervous system, but research over the last decades has revealed a high intrinsic capacity of brain and spinal cord circuits to adapt and reorganize after smaller injuries or denervation. Short-distance fiber growth and synaptic rewiring was found in cortex, brain stem and spinal cord and could be associated with restoration of sensorimotor functions that were impaired by the injury. Such processes of structural plasticity were initially observed in the corticospinal system following spinal cord injury or stroke, but recent studies showed an equally high potential for structural and functional reorganization in reticulospinal, rubrospinal or propriospinal projections. Here we review the lesion-induced plastic changes in the propriospinal pathways, and we argue that they represent a key mechanism triggering sensorimotor recovery upon incomplete spinal cord injury. The formation or strengthening of spinal detour pathways bypassing supraspinal commands around the lesion site to the denervated spinal cord were identified as prominent neural substrate inducing substantial motor recovery in different species from mice to primates. Indications for the existence of propriospinal bypasses were also found in humans after cortical stroke. It is mandatory for current research to dissect the biological mechanisms underlying spinal circuit remodeling and to investigate how these processes can be stimulated in an optimal way by therapeutic interventions (e.g., fiber-growth enhancing interventions, rehabilitation. This knowledge will clear the way for the development of novel strategies targeting the remarkable plastic potential of propriospinal circuits to maximize functional recovery after spinal cord injury.

Working mechanisms of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury

NARCIS (Netherlands)

Nooijen, Carla F. J.; Stam, Henk J.; Schoenmakers, Imte; Sluis, Tebbe; Post, Marcel; Twisk, Jos; van den Berg-Emons, Rita J. G.

OBJECTIVE: In order to unravel the working mechanisms that underlie the effectiveness of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury, the aim of this study was to assess the mediating effects of physical and psychosocial factors on the

Young People's Safety Beliefs after a Spinal Cord Injury Health Promotion and Awareness Presentation

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Watling, David P.; Bishara, Jason D.; Zeeman, Heidi

2018-01-01

Objective: Adolescence is presented as a vulnerable period for accidental injury, particularly spinal cord injury, given young people's propensity for risky behaviours. School-based health promotion initiatives provide opportunities for education about the risks associated with dangerous behaviours. In this study, we aimed to describe young…

Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism.

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Halder, Sebok K; Kant, Ravi; Milner, Richard

2018-05-01

Spinal cord injury (SCI) leads to rapid destruction of neuronal tissue, resulting in devastating motor and sensory deficits. This is exacerbated by damage to spinal cord blood vessels and loss of vascular integrity. Thus, approaches that protect existing blood vessels or stimulate the growth of new blood vessels might present a novel approach to minimize loss or promote regeneration of spinal cord tissue following SCI. In light of the remarkable power of chronic mild hypoxia (CMH) to stimulate vascular remodeling in the brain, the goal of this study was to examine how CMH (8% O 2 for up to 7 days) affects blood vessel remodeling in the spinal cord. We found that CMH promoted the following: (1) endothelial proliferation and increased vascularity as a result of angiogenesis and arteriogenesis, (2) increased vascular expression of the angiogenic extracellular matrix protein fibronectin as well as concomitant increases in endothelial expression of the fibronectin receptor α5β1 integrin, (3) strongly upregulated endothelial expression of the tight junction proteins claudin-5, ZO-1 and occludin and (4) astrocyte activation. Of note, the vascular remodeling changes induced by CMH were more extensive in white matter. Interestingly, hypoxic-induced vascular remodeling in spinal cord blood vessels was markedly attenuated in mice lacking endothelial α5 integrin expression (α5-EC-KO mice). Taken together, these studies demonstrate the considerable remodeling potential of spinal cord blood vessels and highlight an important angiogenic role for the α5β1 integrin in promoting endothelial proliferation. They also imply that stimulation of the α5β1 integrin or controlled use of mild hypoxia might provide new approaches for promoting angiogenesis and improving vascular integrity in spinal cord blood vessels.

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

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Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

Cell transplantation for the treatment of spinal cord injury - bone marrow stromal cells and choroid plexus epithelial cells

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Chizuka Ide

2016-01-01

Full Text Available Transplantation of bone marrow stromal cells (BMSCs enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI. BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate. The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.

Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

International Nuclear Information System (INIS)

Zhang, Fenxi; Hong, Yan; Liang, Wenmei; Ren, Tongming; Jing, Suhua; Lin, Juntang

2012-01-01

Highlights: ► Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). ► Presence of SCs dramatically increased proliferation and migration of UCMSCs. ► Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of “nurse” cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neural stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.

Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

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Zhang, Fenxi, E-mail: fxzhang0824@gmail.com [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Hong, Yan; Liang, Wenmei [Department of Histology and Embryology, Guiyang Medical University, Guizhou 550004, People' s Republic of China (China); Ren, Tongming [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Jing, Suhua [ICU Center, The Third Hospital of Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Lin, Juntang [Stem Cell Center, Xinxiang Medical University, Henan 453003, People' s Republic of China (China)

2012-10-12

Highlights: Black-Right-Pointing-Pointer Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). Black-Right-Pointing-Pointer Presence of SCs dramatically increased proliferation and migration of UCMSCs. Black-Right-Pointing-Pointer Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of 'nurse' cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neural stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.

Cu(II) promotes amyloid pore formation

International Nuclear Information System (INIS)

Zhang, Hangyu; Rochet, Jean-Christophe; Stanciu, Lia A.

2015-01-01

The aggregation of α-synuclein is associated with dopamine neuron death in Parkinson's disease. There is controversy in the field over the question of which species of the aggregates, fibrils or protofibrils, are toxic. Moreover, compelling evidence suggested the exposure to heavy metals to be a risk of PD. Nevertheless, the mechanism of metal ions in promoting PD remains unclear. In this research, we investigated the structural basis of Cu(II) induced aggregation of α-synuclein. Using transmission electron microscopy experiments, Cu(II) was found to promote in vitro aggregation of α-synuclein by facilitating annular protofibril formation rather than fibril formation. Furthermore, neuroprotective baicalein disaggregated annular protofibrils accompanied by considerable decrease of β-sheet content. These results strongly support the hypothesis that annular protofibrils are the toxic species, rather than fibrils, thereby inspiring us to search novel therapeutic strategies for the suppression of the toxic annular protofibril formation. - Highlights: • Cu(II) promoted the annular protofibril formation of α-synuclein in vitro. • Cu(II) postponed the in vitro fibrillization of α-synuclein. • Neuroprotective baicalein disaggregated annular protofibrils

Cu(II) promotes amyloid pore formation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Hangyu, E-mail: hangyuz@uw.edu [Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907 (United States); Rochet, Jean-Christophe [Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907 (United States); Stanciu, Lia A. [Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907 (United States); School of Materials Engineering, Purdue University, West Lafayette, IN 47907 (United States)

2015-08-14

The aggregation of α-synuclein is associated with dopamine neuron death in Parkinson's disease. There is controversy in the field over the question of which species of the aggregates, fibrils or protofibrils, are toxic. Moreover, compelling evidence suggested the exposure to heavy metals to be a risk of PD. Nevertheless, the mechanism of metal ions in promoting PD remains unclear. In this research, we investigated the structural basis of Cu(II) induced aggregation of α-synuclein. Using transmission electron microscopy experiments, Cu(II) was found to promote in vitro aggregation of α-synuclein by facilitating annular protofibril formation rather than fibril formation. Furthermore, neuroprotective baicalein disaggregated annular protofibrils accompanied by considerable decrease of β-sheet content. These results strongly support the hypothesis that annular protofibrils are the toxic species, rather than fibrils, thereby inspiring us to search novel therapeutic strategies for the suppression of the toxic annular protofibril formation. - Highlights: • Cu(II) promoted the annular protofibril formation of α-synuclein in vitro. • Cu(II) postponed the in vitro fibrillization of α-synuclein. • Neuroprotective baicalein disaggregated annular protofibrils.

Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture

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Cho, Yun Kyung; Kim, Gunha; Park, Serah; Sim, Ju Hee; Won, You Jin [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hwang, Chang Ho [Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, 290-3 Jeonha-dong, Dong-gu, Ulsan 682-714 (Korea, Republic of); Yoo, Jong Yoon, E-mail: jyyoo@amc.seoul.kr [Department of Rehabilitation Medicine, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Hong, Hea Nam, E-mail: hnhong@amc.seoul.kr [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of)

2012-01-13

Highlights: Black-Right-Pointing-Pointer Lysolecithin-induced demyelination elevated EpoR expression in OPCs. Black-Right-Pointing-Pointer In association with elevated EpoR, EPO increased OPCs proliferation. Black-Right-Pointing-Pointer EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. Black-Right-Pointing-Pointer EPO promoted myelin repair following lysolecithin-induced demyelination. -- Abstract: Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to a limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.

Re-theorising mobility and the formation of culture and language among the Corded Ware Culture in Europe

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Kristiansen, Kristian; Allentoft, Morten E.; Frei, Karin M.

2017-01-01

North European Neolithic cultures. The original herding economy of the Yamnaya migrants gradually gave way to new practices of crop cultivation, which led to the adoption of new words for those crops. The result of this hybridisation process was the formation of a new material culture, the Corded Ware......Recent genetic, isotopic and linguistic research has dramatically changed our understanding of how the Corded Ware Culture in Europe was formed. Here the authors explain it in terms of local adaptations and interactions between migrant Yamnaya people from the Pontic-Caspian steppe and indigenous...... Culture, and of a new dialect, Proto-Germanic. Despite a degree of hostility between expanding Corded Ware groups and indigenous Neolithic groups, stable isotope data suggest that exogamy provided a mechanism facilitating their integration. This article should be read in conjunction with that by Heyd...

Trehalose Polyphleates, External Cell Wall Lipids in Mycobacterium abscessus, Are Associated with the Formation of Clumps with Cording Morphology, Which Have Been Associated with Virulence

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Marta Llorens-Fons

2017-07-01

Full Text Available Mycobacterium abscessus is a reemerging pathogen that causes pulmonary diseases similar to tuberculosis, which is caused by Mycobacterium tuberculosis. When grown in agar medium, M. abscessus strains generate rough (R or smooth colonies (S. R morphotypes are more virulent than S morphotypes. In searching for the virulence factors responsible for this difference, R morphotypes have been found to form large aggregates (clumps that, after being phagocytozed, result in macrophage death. Furthermore, the aggregates released to the extracellular space by damaged macrophages grow, forming unphagocytosable structures that resemble cords. In contrast, bacilli of the S morphotype, which do not form aggregates, do not damage macrophages after phagocytosis and do not form cords. Cording has also been related to the virulence of M. tuberculosis. In this species, the presence of mycolic acids and surface-exposed cell wall lipids has been correlated with the formation of cords. The objective of this work was to study the roles of the surface-exposed cell wall lipids and mycolic acids in the formation of cords in M. abscessus. A comparative study of the pattern and structure of mycolic acids was performed on R (cording and S (non-cording morphotypes derived from the same parent strains, and no differences were observed between morphotypes. Furthermore, cords formed by R morphotypes were disrupted with petroleum ether (PE, and the extracted lipids were analyzed by thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry. Substantial amounts of trehalose polyphleates (TPP were recovered as major lipids from PE extracts, and images obtained by transmission electron microscopy suggested that these lipids are localized to the external surfaces of cords and R bacilli. The structure of M. abscessus TPP was revealed to be similar to those previously described in Mycobacterium smegmatis. Although the exact role of TPP is unknown, our

Local injection of Lenti-Olig2 at lesion site promotes functional recovery of spinal cord injury in rats.

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Tan, Bo-Tao; Jiang, Long; Liu, Li; Yin, Ying; Luo, Ze-Ru-Xin; Long, Zai-Yun; Li, Sen; Yu, Le-Hua; Wu, Ya-Min; Liu, Yuan

2017-06-01

Olig2 is one of the most critical factors during CNS development, which belongs to b-HLH transcription factor family. Previous reports have shown that Olig2 regulates the remyelination processes in CNS demyelination diseases models. However, the role of Olig2 in contusion spinal cord injury (SCI) and the possible therapeutic effects remain obscure. This study aims to investigate the effects of overexpression Olig2 by lentivirus on adult spinal cord injury rats. Lenti-Olig2 expression and control Lenti-eGFP vectors were prepared, and virus in a total of 5 μL (10 8 TU/mL) was locally injected into the injured spinal cord 1.5 mm rostral and caudal near the epicenter. Immunostaining, Western blot, electron microscopy, and CatWalk analyzes were employed to investigate the effects of Olig2 on spinal cord tissue repair and functional recovery. Injection of Lenti-Olig2 significantly increased the number of oligodendrocytes lineage cells and enhanced myelination after SCI. More importantly, the introduction of Olig2 greatly improved hindlimb locomotor performances. Other oligodendrocyte-related transcription factors, which were downregulated or upregulated after injury, were reversed by Olig2 induction. Our findings provided the evidence that overexpression Olig2 promotes myelination and locomotor recovery of contusion SCI, which gives us more understanding of Olig2 on spinal cord injury treatment. © 2017 John Wiley & Sons Ltd.

Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity.

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Yoshiomi Kobayashi

Full Text Available Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs for the repair of spinal cord injury (SCI in a non-human primate model. This study used a pre-evaluated "safe" hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus model of contusive SCI. SCI was induced at the fifth cervical level (C5, followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs. Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic.

Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice.

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Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P; Shields, Christopher B

2013-04-01

Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice. A focal demyelination model was created by stereotaxically injecting lysolecithin into the bilateral ventrolateral funiculus (VLF) of T8 and T9 mouse spinal cords. Immediately after lysolecithin injection mice were treated with COG112, prefix peptide control or vehicle control for 21 days. The locomotor function of the mice was measured by the beam walking test and Basso Mouse Scale (BMS) assessment. The nerve transmission of the VLF of mice was assessed in vivo by transcranial magnetic motor evoked potentials (tcMMEPs). The histological changes were also examined by by eriochrome cyanine staining, immunohistochemistry staining and electron microscopy (EM) method. The area of demyelination in the spinal cord was significantly reduced in the COG112 group. EM examination showed that treatment with COG112 increased the thickness of myelin sheaths and the numbers of surviving axons in the lesion epicenter. Locomotor function was improved in COG112 treated animals when measured by the beam walking test and BMS assessment compared to controls. TcMMEPs also demonstrated the COG112-mediated enhancement of amplitude of evoked responses. The apoE-mimetic COG112 demonstrates a favorable combination of activities in suppressing inflammatory response, mitigating demyelination and in promoting remyelination and associated functional recovery in animal model

Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

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Peters, Erica B; Liu, Betty; Christoforou, Nicolas; West, Jennifer L; Truskey, George A

2015-10-01

Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

The mechanism of Naringin-enhanced remyelination after spinal cord injury

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Wei Rong

2017-01-01

Full Text Available Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway.

Association between presence of pneumonia and pressure ulcer formation following traumatic spinal cord injury.

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Krishnan, Shilpa; Karg, Patricia E; Boninger, Michael L; Brienza, David M

2017-07-01

To determine if the presence of pneumonia and pressure ulcers are associated in individuals with an acute spinal cord injury during acute care and rehabilitation hospitalizations. Retrospective, secondary analyses of data obtained from the Spinal Cord Injury Model Systems enrolled from 1993 until 2006 Setting: Acute care hospitalization and inpatient rehabilitation facilities Participants: A cohort of individuals hospitalized in acute care (n = 3,098) and inpatient rehabilitation (n = 1,768) was included in the analysis. Frequencies of pressure ulcer formation and episodes of pneumonia were noted in both settings. Not applicable. Pressure ulcer formation and diagnosis of pneumonia Results: The development of pressure ulcers, including stage I, was 20.3% acute care and 21.1% during in inpatient rehabilitation. Multivariate logistic regression analyses revealed a significant association of pneumonia with occurrence of pressure ulcers (P ≤ 0.001, OR = 2.3 and 2.2 respectively), the American Spinal Injury Association Impairment Scale grades (P pneumonia, after adjusting for injury severity, age, sex, and utilization of mechanical ventilation. Impaired inflammatory response and decreased mobility in individuals with pneumonia may predispose these individuals to develop pressure ulcers. Surveillance and preventive measures for pressure ulcers should be rigorous in individuals with SCI and pneumonia.

Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation is Essential for Functional Regeneration

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Anne Tscherter

2016-09-01

Full Text Available Presently there exists no cure for spinal cord injury. However, transplantation of embryonic tissue into spinal cord 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 spinal cord circuits. We tested the two hypotheses in an in vitro spinal cord lesion model that is based on propagation of activity between two rat organotypic spinal cord slices in culture. Transplantation of dissociated cells from E14 rat spinal cord or forebrain re-established the relay of activity over the lesion site and, thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse forebrain cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated spinal cord circuits. In contrast, transplantation of neurospheres induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated spinal cord circuits.

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

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

2014-01-01

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

Effect of the anti-androgenic endocrine disruptor vinclozolin on embryonic testis cord formation and postnatal testis development and function.

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Uzumcu, Mehmet; Suzuki, Hiroetsu; Skinner, Michael K

2004-01-01

Vinclozolin is a systemic dicarboximide fungicide that is used on fruits, vegetables, ornamental plants, and turf grass. Vinclozolin and its metabolites are known to be endocrine disruptors and act as androgen receptor antagonists. The hypothesis tested in the current study is that transient embryonic exposure to an anti-androgenic endocrine disruptor at the time of testis determination alters testis development and subsequently influences adult spermatogenic capacity and male reproduction. The effects of vinclozolin on embryonic testicular cord formation in vitro were examined, as well as the effects of transient in utero vinclozolin exposure on postnatal testis development and function. Embryonic day 13 (E13, sperm-positive vaginal smear day = E0) gonads were cultured in the absence or presence of vinclozolin (50-500microM). Vinclozolin treated gonads had significantly fewer cords (P vinclozolin (100 mg/kg/day) between embryonic days 8 and 14 (E8-E14) of development. Testis morphology and function were analyzed from postnatal day (P) 0, pubertal P20, and adult P60. No significant effect of vinclozolin on testis histology or germ cell viability was observed in P0 testis. The pubertal P20 testis from vinclozolin exposed animals had significantly higher numbers of apoptotic germ cells (P vinclozolin exposed males (P vinclozolin exposed animals was higher in adult P60 animals. Observations demonstrate that vinclozolin can effect embryonic testicular cord formation in vitro and that transient in utero exposure to vinclozolin increases apoptotic germ cell numbers in the testis of pubertal and adult animals. This correlated to reduced sperm motility in the adult. In conclusion, transient exposure to vinclozolin during the time of testis differentiation (i.e. cord formation) alters testis development and function. Observations indicate that transient exposure to an anti-androgenic endocrine disruptor during embryonic development causes delayed effects later in adult life

Mdivi-1 inhibits astrocyte activation and astroglial scar formation and enhances axonal regeneration after spinal cord injury in rats

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gang li

2016-10-01

Full Text Available After spinal cord injury (SCI, astrocytes become hypertrophic and proliferative, forming a dense network of astroglial processes at the site of the lesion. This constitutes a physical and biochemical barrier to axonal regeneration. Mitochondrial fission regulates cell cycle progression; inhibiting the cell cycle of astrocytes can reduce expression levels of axon growth-inhibitory molecules as well as astroglial scar formation after SCI. We therefore investigated how an inhibitor of mitochondrial fission, Mdivi-1, would affect astrocyte proliferation, astroglial scar formation, and axonal regeneration following SCI in rats. Western blot and immunofluorescent double-labeling showed that Mdivi-1 markedly reduced the expression of the astrocyte marker glial fibrillary acidic protein (GFAP, and a cell proliferation marker, proliferating cell nuclear antigen, in astrocytes 3 days after SCI. Moreover, Mdivi-1 decreased the expression of GFAP and neurocan, a chondroitin sulfate proteoglycan. Notably, immunofluorescent labeling and Nissl staining showed that Mdivi-1 elevated the production of growth-associated protein-43 and increased neuronal survival at 4 weeks after SCI. Finally, hematoxylin-eosin staining and behavioral evaluation of motor function indicated that Mdivi-1 also reduced cavity formation and improved motor function 4 weeks after SCI. Our results confirm that Mdivi-1 promotes motor function after SCI, and indicate that inhibiting mitochondrial fission using Mdivi-1 can inhibit astrocyte activation and astroglial scar formation and contribute to axonal regeneration after SCI in rats.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

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Adam R Ferguson

2012-10-01

Full Text Available Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI. Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. The mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain pathways in the spinal cord may emerge with certain patterns of activity, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after spinal cord injury. We review these basic phenomena, discuss the cellular and molecular mechanisms, and discuss implications of these findings for improved rehabilitative therapies after spinal cord injury.

Control of nerve cord formation by Engrailed and Gooseberry-Neuro: A multi-step, coordinated process.

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Bonneaud, Nathalie; Layalle, Sophie; Colomb, Sophie; Jourdan, Christophe; Ghysen, Alain; Severac, Dany; Dantec, Christelle; Nègre, Nicolas; Maschat, Florence

2017-12-15

One way to better understand the molecular mechanisms involved in the construction of a nervous system is to identify the downstream effectors of major regulatory proteins. We previously showed that Engrailed (EN) and Gooseberry-Neuro (GsbN) transcription factors act in partnership to drive the formation of posterior commissures in the central nervous system of Drosophila. In this report, we identified genes regulated by both EN and GsbN through chromatin immunoprecipitation ("ChIP on chip") and transcriptome experiments, combined to a genetic screen relied to the gene dose titration method. The genomic-scale approaches allowed us to define 175 potential targets of EN-GsbN regulation. We chose a subset of these genes to examine ventral nerve cord (VNC) defects and found that half of the mutated targets show clear VNC phenotypes when doubly heterozygous with en or gsbn mutations, or when homozygous. This strategy revealed new groups of genes never described for their implication in the construction of the nerve cord. Their identification suggests that, to construct the nerve cord, EN-GsbN may act at three levels, in: (i) sequential control of the attractive-repulsive signaling that ensures contralateral projection of the commissural axons, (ii) temporal control of the translation of some mRNAs, (iii) regulation of the capability of glial cells to act as commissural guideposts for developing axons. These results illustrate how an early, coordinated transcriptional control may orchestrate the various mechanisms involved in the formation of stereotyped neuronal networks. They also validate the overall strategy to identify genes that play crucial role in axonal pathfinding. Copyright © 2017 Elsevier Inc. All rights reserved.

Promoting proximal formative assessment with relational discourse

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Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.

2012-02-01

The practice of proximal formative assessment - the continual, responsive attention to students' developing understanding as it is expressed in real time - depends on students' sharing their ideas with instructors and on teachers' attending to them. Rogerian psychology presents an account of the conditions under which proximal formative assessment may be promoted or inhibited: (1) Normal classroom conditions, characterized by evaluation and attention to learning targets, may present threats to students' sense of their own competence and value, causing them to conceal their ideas and reducing the potential for proximal formative assessment. (2) In contrast, discourse patterns characterized by positive anticipation and attention to learner ideas increase the potential for proximal formative assessment and promote self-directed learning. We present an analysis methodology based on these principles and demonstrate its utility for understanding episodes of university physics instruction.

Combining neurotrophin-transduced schwann cells and rolipram to promote functional recovery from subacute spinal cord injury.

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Flora, Govinder; Joseph, Gravil; Patel, Samik; Singh, Amanpreet; Bleicher, Drew; Barakat, David J; Louro, Jack; Fenton, Stephanie; Garg, Maneesh; Bunge, Mary Bartlett; Pearse, Damien D

2013-01-01

Following spinal cord injury (SCI), both an inhibitory environment and lack of intrinsic growth capacity impede axonal regeneration. In a previous study, prevention of cyclic adenosine monophosphate (AMP) hydrolysis by the phosphodiesterase-4 inhibitor rolipram, in combination with Schwann cell (SC) grafts, promoted significant supraspinal and proprioceptive fiber growth and/or sparing and improved locomotion. In another study, transplanted SCs transduced to generate a bifunctional neurotrophin (D15A) led to significant increases in graft SCs and axons, including supraspinal and myelinated axons. Here we studied the growth and myelination of local and supraspinal axons and functional outcome following the combination of rolipram administration and neurotrophin-transduced SC implantation after SCI. Rolipram was administered subcutaneously for 4 weeks immediately after contusion at vertebral T8 (25.0-mm weight drop, MASCIS impactor). GFP or GFP-D15A-transduced SCs were injected into the injury epicenter 1 week after SCI. GFP-D15A SC grafts and GFP SC grafts with rolipram contained significantly more serotonergic fibers compared to GFP SCs. SC myelinated axons were increased significantly in GFP SC with rolipram-treated animals compared to animals receiving SCI alone. Rolipram administered with either GFP or GFP-D15A SCs significantly increased numbers of brain stem-derived axons below the lesion/implant area and improved hindlimb function. Compared to the single treatments, the combination led to the largest SC grafts, the highest numbers of serotonergic fibers in the grafts, and increased numbers of axons from the reticular formation below the lesion/implant area and provided the greatest improvement in hindlimb function. These findings demonstrate the therapeutic potential for a combination therapy involving the maintenance of cyclic AMP levels and neurotrophin-transduced SCs to repair the subacutely injured spinal cord.

Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization

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Wild, Raphael; Klems, Alina; Takamiya, Masanari

2017-01-01

Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa......-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube. On loss...... of neuronal flt1, ectopic sprouts emanate from veins involving special angiogenic cell behaviours including nuclear positioning and a molecular signature distinct from primary arterial or secondary venous sprouting. Manipulation of arteriovenous identity or Notch signalling established that ectopic sprouting...

Self-Assembled Matrix by Umbilical Cord Stem Cells

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Biagio Saitta

2011-09-01

Full Text Available Corneal integrity is critical for vision. Corneal wounds frequently heal with scarring that impairs vision. Recently, human umbilical cord mesenchymal stem cells (cord stem cells have been investigated for tissue engineering and therapy due to their availability and differentiation potential. In this study, we used cord stem cells in a 3-dimensional (3D stroma-like model to observe extracellular matrix organization, with human corneal fibroblasts acting as a control. For 4 weeks, the cells were stimulated with a stable Vitamin C (VitC derivative ±TGF-b1. After 4 weeks, the mean thickness of the constructs was ~30 mm; however, cord stem cell constructs had 50% less cells per unit volume, indicating the formation of a dense matrix. We found minimal change in decorin and lumican mRNA, and a significant increase in perlecan mRNA in the presence of TGF-b1. Keratocan on the other hand decreased with TGF-b1 in both cell lineages. With both cell types, the constructs possessed aligned collagen fibrils and associated glycosaminoglycans. Fibril diameters did not change with TGF-b1 stimulation or cell lineage; however, highly sulfated glycosaminoglycans associated with the collagen fibrils significantly increased with TGF-b1. Overall, we have shown that cord stem cells can secrete their own extracellular matrix and promote the deposition and sulfation of various proteoglycans. Furthermore, these cells are at least comparable to commonly used corneal fibroblasts and present an alternative for the 3D in vitro tissue engineered model.

Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury.

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Yamaya, Seiji; Ozawa, Hiroshi; Kanno, Haruo; Kishimoto, Koshi N; Sekiguchi, Akira; Tateda, Satoshi; Yahata, Kenichiro; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

2014-12-01

Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether low-energy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI. Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord. In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p

Inflammatory Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Stem Cell-Like Characteristics of Cancer Cells in an IL-1β-Dependent Manner

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Xiaohe Luo

2018-01-01

Full Text Available To ensure the safety of clinical applications of MSCs, thorough understanding of their impacts on tumor initiation and progression is essential. Here, to further explore the complex dialog between MSCs and tumor cells, umbilical cord-derived mesenchymal stem cells (UC-MSCs were employed to be cocultured with either breast or ovarian cancer cells. Though having no obvious influence on proliferation or apoptosis, UC-MSCs exerted intense stem cell-like properties promoting effects on both cancer models. Cocultured cancer cells showed enriched side population, enhanced sphere formation ability, and upregulated pluripotency-associated stem cell markers. Human cytokine array and real-time PCR revealed a panel of MSC-derived prostemness cytokines CCL2, CXCL1, IL-8, and IL-6 which were induced upon coculturing. We further revealed IL-1β, a well-characterized proinflammatory cytokine, to be the inducer of these prostemness cytokines, which was generated from inflammatory UC-MSCs in an autocrine manner. Additionally, with introduction of IL-1RA (an IL-1 receptor antagonist into the coculturing system, the stem cell-like characteristics promoting effects of inflammatory UC-MSCs were partially blocked. Taken together, these findings suggest that transduced inflammatory MSCs work as a major source of IL-1β in tumor microenvironment and initiate the formation of prostemness niche via regulating their secretome in an IL-1β-dependent manner.

UV-activated 7-dehydrocholesterol-coated titanium implants promote differentiation of human umbilical cord mesenchymal stem cells into osteoblasts.

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Satué, María; Ramis, Joana M; Monjo, Marta

2016-01-01

Vitamin D metabolites are essential for bone regeneration and mineral homeostasis. The vitamin D precursor 7-dehydrocholesterol can be used after UV irradiation to locally produce active vitamin D by osteoblastic cells. Furthermore, UV-irradiated 7-dehydrocholesterol is a biocompatible coating for titanium implants with positive effects on osteoblast differentiation. In this study, we examined the impact of titanium implants surfaces coated with UV-irradiated 7-dehydrocholesterol on the osteogenic differentiation of human umbilical cord mesenchymal stem cells. First, the synthesis of cholecalciferol (D3) was achieved through the incubation of the UV-activated 7-dehydrocholesterol coating for 48 h at 23℃. Further, we investigated in vitro the biocompatibility of this coating in human umbilical cord mesenchymal stem cells and its potential to enhance their differentiation towards the osteogenic lineage. Human umbilical cord mesenchymal stem cells cultured onto UV-irradiated 7-dehydrocholesterol-coated titanium implants surfaces, combined with osteogenic supplements, upregulated the gene expression of several osteogenic markers and showed higher alkaline phosphatase activity and calcein blue staining, suggesting increased mineralization. Thus, our results show that the use of UV irradiation on 7-dehydrocholesterol -treated titanium implants surfaces generates a bioactive coating that promotes the osteogenic differentiation of human umbilical cord mesenchymal stem cells, with regenerative potential for improving osseointegration in titanium-based bone anchored implants. © The Author(s) 2015.

Spinal cord injury triggers an intrinsic growth-promoting state in nociceptors.

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Bedi, Supinder S; Lago, Michael T; Masha, Luke I; Crook, Robyn J; Grill, Raymond J; Walters, Edgar T

2012-03-20

Although most investigations of the mechanisms underlying chronic pain after spinal cord injury (SCI) have examined the central nervous system (CNS), recent studies have shown that nociceptive primary afferent neurons display persistent hyperexcitability and spontaneous activity in their peripheral branches and somata in dorsal root ganglia (DRG) after SCI. This suggests that SCI-induced alterations of primary nociceptors contribute to central sensitization and chronic pain after SCI. Does SCI also promote growth of these neurons' fibers, as has been suggested in some reports? The present study tests the hypothesis that SCI induces an intrinsic growth-promoting state in DRG neurons. This was tested by dissociating DRG neurons 3 days or 1 month after spinal contusion injury at thoracic level T10 and measuring neuritic growth 1 day later. Neurons cultured 3 days after SCI exhibited longer neurites without increases in branching ("elongating growth"), compared to neurons from sham-treated or untreated (naïve) rats. Robust promotion of elongating growth was found in small and medium-sized neurons (but not large neurons) from lumbar (L3-L5) and thoracic ganglia immediately above (T9) and below (T10-T11) the contusion site, but not from cervical DRG. Elongating growth was also found in neurons immunoreactive to calcitonin gene-related peptide (CGRP), suggesting that some of the neurons exhibiting enhanced neuritic growth were nociceptors. The same measurements made on neurons dissociated 1 month after SCI revealed no evidence of elongating growth, although evidence for accelerated initiation of neurite outgrowth was found. Under certain conditions this transient growth-promoting state in nociceptors might be important for the development of chronic pain and hyperreflexia after SCI.

From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges.

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Dietz, Volker; Schwab, Martin E

2017-05-01

Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

Energy metabolism during activity-promoting video games practice in subjects with spinal cord injury: evidences for health promotion.

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Gaffurini, P; Bissolotti, L; Calza, S; Calabretto, C; Orizio, C; Gobbo, M

2013-02-01

Activity promoting video game (APVG) practice significantly affects energy metabolism through energy expenditure (EE) increase and has been recently included in strategies for health promotion. It is not known if the APVG practice provides similar outcomes in subjects with spinal cord injury (SCI). Aim of the study was to evaluate cardio-pulmonary and metabolic adaptations during APVG practice and to find whether EE increase above resting condition could suggest the inclusion of this exercise in a more general strategy for health promotion and body weight control in subjects with SCI. Repeated measures study. Rehabilitation Institute. Ten male subjects with SCI (lesion levels from C7 to L1) age 26 to 55 years. We recorded pulmonary ventilation (VE), oxygen consumption (VO2) for EE esteem and heart rate (HR) at rest and while playing virtual bowling, tennis and boxing games using a portable metabolimeter equipped with ECG electrodes. The standard metabolic equivalent of task (METs) was calculated offline. The metabolic and functional parameters were referred to the 10th minute of each activity. Metabolic and functional parameters increased significantly from rest to bowling, tennis and boxing. METs exceeded in average 3 during boxing. One hour of APVG can increase daily EE by about 6% (bowling), 10% (tennis) and 15% (boxing). These considerable results suggest that physical exertion during APVG practice in subjects with SCI could contribute to health promotion as well as caloric balance control, especially when boxing is considered. This can be safely achieved at home with regular activity. These findings substantiate the potential for novel exercise modalities to counteract deconditioning due to inactivity in subjects with SCI by promoting physical activity through implementation of APVG exercise programs.

Evolution and role of corded cell aggregation in Mycobacterium tuberculosis cultures.

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Caceres, Neus; Vilaplana, Cristina; Prats, Clara; Marzo, Elena; Llopis, Isaac; Valls, Joaquim; Lopez, Daniel; Cardona, Pere-Joan

2013-11-01

The aim of this study was to evaluate the evolution and role of corded cell aggregation in Mycobacterium tuberculosis cultures according to growth time and conditions. Thus, in standard culture using aerated 7H9 Middlebrook broth supplemented with 0.05% Tween 80, a dramatic CFU decrease was observed at the end of the exponential phase. This phase was followed by a stable stationary phase that led to dissociation between the optical density (O.D.) and CFU values, together with the formation of opaque colonies in solid culture. Further analysis revealed that this was due to cording. Scanning electron microscopy showed that cording led to the formation of very stable coiled structures and corded cell aggregations which proved impossible to disrupt by any of the physical means tested. Modulation of cording with a high but non-toxic concentration of Tween 80 led to a slower growth rate, avoidance of a sudden drop-off to the stationary phase, the formation of weaker cording structures and the absence of opaque colonies, together with a lower survival at later time-points. An innovative automated image analysis technique has been devised to characterize the cording process. This analysis has led to important practical consequences for the elaboration of M. tuberculosis inocula and suggests the importance of biofilm formation in survival of the bacilli in the extracellular milieu. Copyright © 2013. Published by Elsevier Ltd.

Effects of umbilical cord blood stem cells on healing factors for diabetic foot injuries.

Science.gov (United States)

Çil, N; Oğuz, E O; Mete, E; Çetinkaya, A; Mete, G A

2017-01-01

The use of stem or progenitor cells from bone marrow, or peripheral or umbilical cord blood is becoming more common for treatment of diabetic foot problems. These cells promote neovascularization by angiogenic factors and they promote epithelium formation by stimulating cell replication and migration under certain pathological conditions. We investigated the role of CD34 + stem cells from human umbilical cord blood in wound healing using a rat model. Rats were randomly divided into a control group and two groups with diabetes induced by a single dose of 55 mg/kg intraperitoneal streptozocin. Scarred areas 5 mm in diameter were created on the feet of all rats. The diabetic rats constituted the diabetes control group and a diabetes + stem cell group with local injection into the wound site of 0.5 × 106 CD34 + stem cells from human umbilical cord blood. The newly formed skin in the foot wounds following CD34 + stem cell treatment showed significantly improvement by immunohistochemistry and TUNEL staining, and were closer to the wound healing of the control group than the untreated diabetic animals. The increase in FGF expression that accompanied the local injection of CD34 + stem cells indicates that FGF stimulation helped prevent apoptosis. Our findings suggest a promising new treatment approach to diabetic wound healing.

Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model.

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Desirée L Salazar

2010-08-01

Full Text Available Traumatic spinal cord injury (SCI results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+ and CD24(-/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention.

Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

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Ryu, Hak-Hyun; Kang, Byung-Jae; Park, Sung-Su; Kim, Yongsun; Sung, Gyu-Jin; Woo, Heung-Myong; Kim, Wan Hee; Kweon, Oh-Kyeong

2012-12-01

Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (Pin the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (Pin the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

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Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

2012-01-01

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID

Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review.

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Mazensky, David; Flesarova, Slavka; Sulla, Igor

2017-12-01

Animal models are used to examine the results of experimental spinal cord injury. Alterations in spinal cord blood supply caused by complex spinal cord injuries contribute significantly to the diversity and severity of the spinal cord damage, particularly ischemic changes. However, the literature has not completely clarified our knowledge of anatomy of the complex three-dimensional arterial system of the spinal cord in experimental animals, which can impede the translation of experimental results to human clinical applications. As the literary sources dealing with the spinal cord arterial blood supply in experimental animals are limited and scattered, the authors performed a review of the anatomy of the arterial blood supply to the spinal cord in several experimental animals, including pigs, dogs, cats, rabbits, guinea pigs, rats, and mice and created a coherent format discussing the interspecies differences. This provides researchers with a valuable tool for the selection of the most suitable animal model for their experiments in the study of spinal cord ischemia and provides clinicians with a basis for the appropriate translation of research work to their clinical applications. Anat Rec, 300:2091-2106, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The investigation of influence of adhesion promoters on adhesion bond between vulcanisate and zinc coated steel cord in products based on mixtures of natural and 1,4-cis-polybutadiene rubber

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Gojić Mirko T.

2007-01-01

Full Text Available The mixtures of elastomer compounds based on natural and 1,4-cispolybutadiene rubber of 80:20 ratio, were used for the investigation of adhesion promoters influence on adhesion of vulcanisate to steel cord. Ni-stearate and resorsynol-formaldehyde resin combined with hexamethylenetetramine in various mass ratios were included as adhesion promoters. Elastomer mixtures were prepared using a laboratory double mill, and the rheological and vulcanization characteristics were examined on a vulcameter provided with an oscillating disc, a higher temperature of 145 °C. The crosslinking of the mixture was carried out by press, at a temperature of 145 °C and specific pressure of 40 bar, in period of 45 minutes. A wide number of standardized methods for physical mechanical characterization of vulcanization prior and after accelerated aging were used. The adhesion of vulcanizate bond with zinc coated steel cord was determined according to the so called H-test, by measuring the pulling-out force of the cord from the vulcanized block, and the degree of coverage of cord with vulcanizate after separation. The results of examinations show significant dependence of physico-mechanical characteristics and adhesion forces on the type and amount of used adhesion promoters in experimental elastomer mixtures.

Spinal cord injury reveals multilineage differentiation of ependymal cells.

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Konstantinos Meletis

2008-07-01

Full Text Available Spinal cord injury often results in permanent functional impairment. Neural stem cells present in the adult spinal cord can be expanded in vitro and improve recovery when transplanted to the injured spinal cord, demonstrating the presence of cells that can promote regeneration but that normally fail to do so efficiently. Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal. These cells are recruited by spinal cord injury and produce not only scar-forming glial cells, but also, to a lesser degree, oligodendrocytes. Modulating the fate of ependymal progeny after spinal cord injury may offer an alternative to cell transplantation for cell replacement therapies in spinal cord injury.

Promoting Gait Recovery and Limiting Neuropathic Pain After Spinal Cord Injury.

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Mercier, Catherine; Roosink, Meyke; Bouffard, Jason; Bouyer, Laurent J

2017-04-01

Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growing body of basic science literature supporting this hypothesis and the general belief in rehabilitation research that pain and gait rehabilitation represent two independent problems. First, the main findings from basic research showing interactions between nociception and learning in the spinal cord will be summarized, focusing both on evidence demonstrating the impact of nociception on motor learning and of motor learning on central sensitization. Then, the generalizability of these findings in animal models to humans will be discussed. Finally, the way potential interactions between nociception and motor learning are currently taken into account in clinical research in patients with spinal cord injury will be presented. To conclude, recommendations will be proposed to better integrate findings from basic research into future clinical research in persons with spinal cord injury.

The role of formative feedback in promoting higher order thinking ...

African Journals Online (AJOL)

The role of formative feedback in promoting higher order thinking skills in ... activities, task characteristics, validating students' thinking, and providing feedback. ... Keywords: classroom environment, formative assessment, formative feedback, ...

An anti vimentin antibody promotes tube formation

DEFF Research Database (Denmark)

Jørgensen, Mathias Lindh; Møller, Carina Kjeldahl; Rasmussen, Lasse

2017-01-01

antibody technology, promotes tube formation of endothelial cells in a 2D matrigel assay. By binding vimentin, the antibody increases the tube formation by 21% after 5 hours of incubation. Addition of the antibody directly to cultured endothelial cells does not influence endothelial cell migration...... or proliferation. The enhanced tube formation can be seen for up to 10 hours where after the effect decreases. It is shown that the antibody-binding site is located on the coil 2 domain of vimentin. To our knowledge this is the first study that demonstrates an enhanced tube formation by binding vimentin in a 2D...

Predictive Ability of Pender's Health Promotion Model for Physical Activity and Exercise in People with Spinal Cord Injuries: A Hierarchical Regression Analysis

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Keegan, John P.; Chan, Fong; Ditchman, Nicole; Chiu, Chung-Yi

2012-01-01

The main objective of this study was to validate Pender's Health Promotion Model (HPM) as a motivational model for exercise/physical activity self-management for people with spinal cord injuries (SCIs). Quantitative descriptive research design using hierarchical regression analysis (HRA) was used. A total of 126 individuals with SCI were recruited…

Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury

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Jian-long Wang

2015-01-01

Full Text Available Hydrogen can relieve tissue-damaging oxidative stress, inflammation and apoptosis. Injection of hydrogen-rich saline is an effective method for transporting molecular hydrogen. We hypothesized that hydrogen-rich saline would promote the repair of spinal cord injury induced by Allen′s method in rats. At 0.5, 1, 2, 4, 8, 12 and 24 hours after injury, then once daily for 2 weeks, 0.25 mL/kg hydrogen-rich saline was infused into the subarachnoid space through a catheter. Results at 24 hours, 48 hours, 1 week and 2 weeks after injury showed that hydrogen-rich saline markedly reduced cell death, inflammatory cell infiltration, serum malondialdehyde content, and caspase-3 immunoreactivity, elevated serum superoxide dismutase activity and calcitonin gene-related peptide immunoreactivity, and improved motor function in the hindlimb. The present study confirms that hydrogen-rich saline injected within 2 weeks of injury effectively contributes to the repair of spinal cord injury in the acute stage.

Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

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Yahata, Kenichiro; Kanno, Haruo; Ozawa, Hiroshi; Yamaya, Seiji; Tateda, Satoshi; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

2016-12-01

OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in Neu

Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury.

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Liu, Shengwen; Sandner, Beatrice; Schackel, Thomas; Nicholson, LaShae; Chtarto, Abdelwahed; Tenenbaum, Liliane; Puttagunta, Radhika; Müller, Rainer; Weidner, Norbert; Blesch, Armin

2017-09-15

Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally. In addition, we examined whether SC injection into the caudal spinal parenchyma would further enhance regeneration of descending axons to re-enter the host spinal cord. Our data show that both serotonergic and descending axons traced by biotinylated dextran amine (BDA) extend throughout the scaffolds. The number of regenerating axons is significantly increased when caudal BDNF expression is activated and transient BDNF delivery is able to sustain axons after gene expression is switched off. Descending axons are confined to the caudal graft/host interface even with continuous BDNF expression for 8weeks. Only with a caudal injection of SCs, a pathway facilitating axonal regeneration through the host/graft interface is generated allowing axons to successfully re-enter the caudal spinal cord. Recovery from spinal cord injury is poor due to the limited regeneration observed in the adult mammalian central nervous system. Biomaterials, cell transplantation and growth factors that can guide axons across a lesion site, provide a cellular substrate, stimulate axon growth and have shown some promise in increasing the growth distance of regenerating axons. In the present study, we combined an alginate biomaterial with linear channels with transplantation of Schwann cells within

Transient activation of Wnt/β-catenin signaling reporter in fibrotic scar formation after compression spinal cord injury in adult mice.

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Yamagami, Takashi; Pleasure, David E; Lam, Kit S; Zhou, Chengji J

2018-02-19

After traumatic spinal cord injury (SCI), a scar may form with a fibrotic core (fibrotic scar) and surrounding reactive astrocytes (glial scar) at the lesion site. The scar tissue is considered a major obstacle preventing regeneration both as a physical barrier and as a source for secretion of inhibitors of axonal regeneration. Understanding the mechanism of scar formation and how to control it may lead to effective SCI therapies. Using a compression-SCI model on adult transgenic mice, we demonstrate that the canonical Wnt/β-catenin signaling reporter TOPgal (TCF/Lef1-lacZ) positive cells appeared at the lesion site by 5 days, peaked on 7 days, and diminished by 14 days post injury. Using various representative cell lineage markers, we demonstrate that, these transiently TOPgal positive cells are a group of Fibronectin(+);GFAP(-) fibroblast-like cells in the core scar region. Some of them are proliferative. These results indicate that Wnt/β-catenin signaling may play a key role in fibrotic scar formation after traumatic spinal cord injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice.

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Takahashi, Hiroshi; Koda, Masao; Hashimoto, Masayuki; Furuya, Takeo; Sakuma, Tsuyoshi; Kato, Kei; Okawa, Akihiko; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Takahashi, Kazuhisa; Yamazaki, Masashi; Mannoji, Chikato

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration

Salvianolic acid B protects the myelin sheath around injured spinal cord axons

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Zhe Zhu

2016-01-01

Full Text Available Salvianolic acid B, an active pharmaceutical compound present in Salvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study, in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose was 20 μg/mL. For in vivo investigation, rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks. The amount of myelin sheath and the number of regenerating axons increased, neurological function recovered, and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats. These results indicate that salvianolic acid B can protect axons and the myelin sheath, and can promote the recovery of neurological function. Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

Is early cord clamping, delayed cord clamping or cord milking best?

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Vatansever, Binay; Demirel, Gamze; Ciler Eren, Elif; Erel, Ozcan; Neselioglu, Salim; Karavar, Hande Nur; Gundogdu, Semra; Ulfer, Gozde; Bahadir, Selcen; Tastekin, Ayhan

2018-04-01

To compare the antioxidant status of three cord clamping procedures (early clamping, delayed clamping and milking) by analyzing the thiol-disulfide balance. This randomized controlled study enrolled 189 term infants who were divided into three groups according to the cord clamping procedure: early clamping, delayed clamping and milking. Blood samples were collected from the umbilical arteries immediately after clamping, and the thiol/disulfide homeostasis was analyzed. The native and total thiol levels were significantly (p total thiol ratio was significantly (p = .026) lower in the delayed cord clamping and milking groups compared with the early clamping groups. Early cord clamping causes the production of more disulfide bonds and lower thiol levels, indicating that oxidation reactions are increased in the early cord clamping procedure compared with the delayed cord clamping and milking procedures. The oxidant capacity is greater with early cord clamping than with delayed clamping or cord milking. Delayed cord clamping or milking are beneficial in neonatal care, and we suggest that they be performed routinely in all deliveries.

International Spinal Cord Injury Urinary Tract Infection Basic Data Set

DEFF Research Database (Denmark)

Goetz, L L; Cardenas, D D; Kennelly, M

2013-01-01

To develop an International Spinal Cord Injury (SCI) Urinary Tract Infection (UTI) Basic Data Set presenting a standardized format for the collection and reporting of a minimal amount of information on UTIs in daily practice or research.......To develop an International Spinal Cord Injury (SCI) Urinary Tract Infection (UTI) Basic Data Set presenting a standardized format for the collection and reporting of a minimal amount of information on UTIs in daily practice or research....

Family-directed umbilical cord blood banking.

Science.gov (United States)

Gluckman, Eliane; Ruggeri, Annalisa; Rocha, Vanderson; Baudoux, Etienne; Boo, Michael; Kurtzberg, Joanne; Welte, Kathy; Navarrete, Cristina; van Walraven, Suzanna M

2011-11-01

Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available.

Methylprednisolone promotes recovery of neurological function after spinal cord injury: association with Wnt/β-catenin signaling pathway activation

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Lu, Gong-biao; Niu, Fu-wen; Zhang, Ying-chun; Du, Lin; Liang, Zhi-yuan; Gao, Yuan; Yan, Ting-zhen; Nie, Zhi-kui; Gao, Kai

2016-01-01

Some studies have indicated that the Wnt/β-catenin signaling pathway is activated following spinal cord injury, and expression levels of specific proteins, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β, are significantly altered. We hypothesized that methylprednisolone treatment contributes to functional recovery after spinal cord injury by inhibiting apoptosis and activating the Wnt/β-catenin signaling pathway. In the current study, 30 mg/kg methylprednisolone was injected into rats with spinal cord injury immediately post-injury and at 1 and 2 days post-injury. Basso, Beattie, and Bresnahan scores showed that methylprednisolone treatment significantly promoted locomotor functional recovery between 2 and 6 weeks post-injury. The number of surviving motor neurons increased, whereas the lesion size significantly decreased following methylprednisolone treatment at 7 days post-injury. Additionally, caspase-3, caspase-9, and Bax protein expression levels and the number of apoptotic cells were reduced at 3 and 7 days post-injury, while Bcl-2 levels at 7 days post-injury were higher in methylprednisolone-treated rats compared with saline-treated rats. At 3 and 7 days post-injury, methylprednisolone up-regulated expression and activation of the Wnt/β-catenin signaling pathway, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β phosphorylation. These results indicate that methylprednisolone-induced neuroprotection may correlate with activation of the Wnt/β-catenin signaling pathway. PMID:28123427

Spinal Cord Injury Model System Information Network

Science.gov (United States)

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

Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms

Directory of Open Access Journals (Sweden)

Zhi-yuan Guo

2015-01-01

Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

Mechanisms of spinal cord injury regeneration in zebrafish: a systematic review

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Zeynab Noorimotlagh

2017-12-01

Full Text Available Objective(s:To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish. Materials and Methods: Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software. Results: Wnt/ß-catenin signaling, L1.1, L1.2, Major vault protein (MVP, contactin-2 and High mobility group box1 (HMGB1 had positive promoting effects on axonal re-growth while Ptena had an inhibitory effect. Neurogenesis is stimulated by Wnt/ß-catenin signaling as well as HMGB1, but inhibited by Notch signaling. Glial cells proliferate in response to fibroblast growth factor (fgf signaling and Lysophosphatidic acid (LPA. Furthermore, fgf signaling pathway causes glia bridge formation in favor of axonal regeneration. LPA and HMGB1 in acute phase stimulate inflammatory responses around injury and suppress regeneration. LPA also induces microglia activation and neuronal death in addition to glia cell proliferation, but prevents neurite sprouting. Conclusion: This study provides a comprehensive review of the known molecules and mechanisms in the current literature involved in the spinal cord injury (SCI regeneration in zebrafish, in a time course manner. A better understanding of the whole determining mechanisms for the SCI regeneration should be considered as a main goal for future studies.

Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

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Zhang, S-X; Huang, F; Gates, M; Shen, X; Holmberg, E G

2016-11-01

This is a randomized controlled prospective trial with two parallel groups. The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. This study was conducted in SCS Research Center in Colorado, USA. A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

A 3D nanofibrous hydrogel and collagen sponge scaffold promotes locomotor functional recovery, spinal repair, and neuronal regeneration after complete transection of the spinal cord in adult rats

International Nuclear Information System (INIS)

Kaneko, Ai; Matsushita, Akira; Sankai, Yoshiyuki

2015-01-01

Central nervous system neurons in adult mammals display limited regeneration after injury, and functional recovery is poor following complete transection (>4 mm gap) of a rat spinal cord. A novel combination scaffold composed of 3D nanofibrous hydrogel PuraMatrix and a honeycomb collagen sponge was used to promote spinal repair and locomotor functional recovery following complete transection of the spinal cord in rats. We transplanted this scaffold into 5 mm spinal cord gaps and assessed spinal repair and functional recovery using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. The BBB score of the scaffold-transplanted group was significantly higher than that of the PBS-injected control group from 24 d to 4 months after the operation (P < 0.001–0.01), reaching 6.0  ±  0.75 (mean ± SEM) in the transplant and 0.70  ±  0.46 in the control groups. Neuronal regeneration and spinal repair were examined histologically using Pan Neuronal Marker, glial fibrillary acidic protein, growth-associated protein 43, and DAPI. The scaffolds were well integrated into the spinal cords, filling the 5 mm gaps with higher numbers of regenerated and migrated neurons, astrocytes, and other cells than in the control group. Mature and immature neurons and astrocytes in the scaffolds became colocalized and aligned longitudinally over >2 mm, suggesting their differentiation, maturation, and function. The spinal cord NF200 content of the transplant group, analyzed by western blot, was more than twice that of the control group, supporting the histological results. Transplantation of this novel scaffold promoted functional recovery, spinal repair, and neuronal regeneration. (paper)

High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation

DEFF Research Database (Denmark)

Mouaikel, John; Causse, Sébastien Z; Rougemaille, Mathieu

2013-01-01

The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes...... (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single......-molecule fluorescence insitu hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase...

Anxiolytics may promote locomotor function recovery in spinal cord injury patients

Directory of Open Access Journals (Sweden)

Pierre A Guertin

2008-09-01

Full Text Available Pierre A GuertinNeuroscience Unit, Laval University Medical Center (CHUL, Quebec City, CanadaAbstract: Recent findings in animal models of paraplegia suggest that specific nonbenzodiazepine anxiolytics may temporarily restore locomotor functions after spinal cord injury (SCI. Experiments using in vitro models have revealed, indeed, that selective serotonin receptor (5-HTR ligands such as 5-HTR1A agonists, known as relatively safe anxiolytics, can acutely elicit episodes of rhythmic neuronal activity refered to as fictive locomotion in isolated spinal cord preparations. Along the same line, in vivo studies have recently shown that this subclass of anxiolytics can induce, shortly after systemic administration (eg, orally or subcutaneously, some locomotor-like hindlimb movements during 45–60 minutes in completely spinal cord-transected (Tx rodents. Using ‘knock-out’ mice (eg, 5-HTR7-/- and selective antagonists, it has been clearly established that both 5-HTR1A and 5-HTR7 were critically involved in mediating the pro-locomotor effects induced by 8-OH-DPAT (typically referred to as a 5-HTR1A agonist in Tx animals. Taken together, these in vitro and in vivo data strongly support the idea that 5-HTR1A agonists may eventually become constitutive elements of a novel first-in-class combinatorial treatment aimed at periodically inducing short episodes of treadmill stepping in SCI patients.Keywords: 5-HT agonists, anxiolytics, locomotion, SCI

Taurine Promotes the Cartilaginous Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Vitro.

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Yao, Xiuhua; Huang, Huiling; Li, Zhou; Liu, Xiaohua; Fan, Weijia; Wang, Xinping; Sun, Xuelian; Zhu, Jianmin; Zhou, Hongrui; Wei, Huaying

2017-08-01

Taurine has been reported to influence osteogenic differentiation, but the role of taurine on cartilaginous differentiation using human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) remains unclear. In this study, we investigated the effect of taurine (0, 1, 5 and 10 mM) on the proliferation and chondrogenesis of hUC-MSCs by analyzing cell proliferation, accumulation of glycosaminoglycans and expression of cartilage specific mRNA. The results show though taurine did not affected the proliferation of hUC-MSCs, 5 mM of taurine is sufficient to enhanced the accumulation of glycosaminoglycans and up-regulate cartilage specific mRNA expression, namely collagen type II, aggrecan and SOX9. Taurine also inhibits chondrocyte dedifferentiation by reducing expression of collagen type I mRNA. Taken together, our study reveals that taurine promotes and maintains the chondrogenesis of hUC-MSCs.

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

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Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

2014-08-15

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

Fixed cord

International Nuclear Information System (INIS)

Levy, L.M.; DiChiro, G.; DeSouza, B.; McCullough, D.C.; McVeigh, E.; Hefffez, D.

1989-01-01

Pulsatile longitudinal motion of the spinal cord was examined with MR phase imaging in healthy subjects and in cases involving cord tethering and compression. Asymptomatic patients with a low conus medullaris demonstrated normal cord motion. Clinical improvement was associated with improved cord motion after surgical untethering, provided permanent neurologic damage had not occurred. Decreased and unchanged cord motion was associated with unchanged neurologic deficits. In cases of normal cord motion and possible retethering versus syringomyelia, clinical improvement occurred after shunting only. MR imaging of pulsatile cord motion can be clinically useful in the evaluation of diseases restricting motion of the neuraxis

Recognition of the mycobacterial cord factor by Mincle: relevance for granuloma formation and resistance to tuberculosis

Directory of Open Access Journals (Sweden)

Roland eLang

2013-01-01

Full Text Available The world’s most successful intracellular bacterial pathogen, Mycobacterium tuberculosis (MTB, survives inside macrophages by blocking phagosome maturation and establishes chronic infection characterized by the formation of granulomas. Trehalose-6,6-dimycolate (TDM, the mycobacterial cord factor, is the most abundant cell wall lipid of virulent mycobacteria, is sufficient to cause granuloma formation, and has long been known to be a major virulence factor of MTB. Recently, TDM has been shown to activate the Syk-Card9 signaling pathway in macrophages through binding to the C-type lectin receptor Mincle. The Mincle-Card9 pathway is required for activation of macrophages by TDM in vitro and for granuloma formation in vivo following injection of TDM. Whether this pathway is also exploited by MTB to reprogram the macrophage into a comfortable niche has not been explored yet. Several recent studies have investigated the phenotype of Mincle-deficient mice in mycobacterial infection, yielding divergent results in terms of a role for Mincle in host resistance. Here, we review these studies, discuss possible reasons for discrepant results and highlight open questions in the role of Mincle and other C-type lectin receptors in the infection biology of MTB.

Potential of human dental stem cells in repairing the complete transection of rat spinal cord

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Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

2017-04-01

Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

Science.gov (United States)

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

2016-03-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

Science.gov (United States)

Zareen, N; Shinozaki, M; Ryan, D; Alexander, H; Amer, A; Truong, D Q; Khadka, N; Sarkar, A; Naeem, S; Bikson, M; Martin, J H

2017-11-01

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Cord Blood

Directory of Open Access Journals (Sweden)

Saeed Abroun

2014-05-01

Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

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

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

2016-09-05

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

Concise review: Bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications.

OpenAIRE

Wright, KT; El Masri, W; Osman, A; Chowdhury, J; Johnson, WEB

2011-01-01

Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversi...

Blocking weight-induced spinal cord injury in rats: effects of TRH or naloxone on motor function recovery and spinal cord blood flow

International Nuclear Information System (INIS)

Holtz, A.; Nystroem, B.; Gerdin, B.

1989-01-01

The ability of thyotropin releasing hormone (TRH) or naloxone to reduce the motor function deficit and to improve the spinal cord blood flow (SCBF) was investigated in a rat spinal cord compression injury model. Spinal cord injury was induced by compression for 5 min with a load of 35 g on a 2.2 x 5.0 mm sized compression plate causing a transient paraparesis. One group of animals was given TRH, one group naloxone and one group saline alone. Each drug was administered intravenously as a bolus dose of 2 mg/kg 60 min after injury followed by a continuous infusion of 2 mg/kg/h for 4 h. The motor performance was assessed daily on the inclined plant until Day 4, when SCBF was measured with the 14 C-iodoantipyrine autoradiographic method. It was found that neither TRH nor naloxone had promoted motor function recovery or affected SCBF 4 days after spinal cord injury. (author)

Spinal cord regeneration: lessons for mammals from non-mammalian vertebrates.

Science.gov (United States)

Lee-Liu, Dasfne; Edwards-Faret, Gabriela; Tapia, Víctor S; Larraín, Juan

2013-08-01

Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative-permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. Copyright © 2013 Wiley Periodicals, Inc.

ACOG committee opinion number 399, February 2008: umbilical cord blood banking.

Science.gov (United States)

2008-02-01

Two types of banks have emerged for the collection and storage of umbilical cord blood--public banks and private banks. Public banks promote allogenic (related or unrelated) donation, analogous to the current collection of whole blood units in the United States. Private banks were initially developed to store stem cells from umbilical cord blood for autologous use (taken from an individual for subsequent use by the same individual) by a child if the child develops disease later in life. If a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public versus private banking should be provided. The remote chance of an autologous unit of umbilical cord blood being used for a child or a family member (approximately 1 in 2,700 individuals) should be disclosed. The collection should not alter routine practice for the timing of umbilical cord clamping. Physicians or other professionals who recruit pregnant women and their families for for-profit umbilical cord blood banking should disclose any financial interests or other potential conflicts of interest.

Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury.

Science.gov (United States)

Papastefanaki, Florentia; Jakovcevski, Igor; Poulia, Nafsika; Djogo, Nevena; Schulz, Florian; Martinovic, Tamara; Ciric, Darko; Loers, Gabrielle; Vossmeyer, Tobias; Weller, Horst; Schachner, Melitta; Matsas, Rebecca

2015-06-01

Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.

A Direct Comparison between Norepinephrine and Phenylephrine for Augmenting Spinal Cord Perfusion in a Porcine Model of Spinal Cord Injury.

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Streijger, Femke; So, Kitty; Manouchehri, Neda; Gheorghe, Ana; Okon, Elena B; Chan, Ryan M; Ng, Benjamin; Shortt, Katelyn; Sekhon, Mypinder S; Griesdale, Donald E; Kwon, Brian K

2018-03-28

Current clinical guidelines recommend elevating the mean arterial blood pressure (MAP) to increase spinal cord perfusion in patients with acute spinal cord injury (SCI). This is typically achieved with vasopressors such as norepinephrine (NE) and phenylephrine (PE). These drugs differ in their pharmacological properties and potentially have different effects on spinal cord blood flow (SCBF), oxygenation (PO 2 ), and downstream metabolism after injury. Using a porcine model of thoracic SCI, we evaluated how these vasopressors influenced intraparenchymal SCBF, PO 2 , hydrostatic pressure, and metabolism within the spinal cord adjacent to the injury site. Yorkshire pigs underwent a contusion/compression SCI at T10 and were randomized to receive either NE or PE for MAP elevation of 20 mm Hg, or no MAP augmentation. Prior to injury, a combined SCBF/PO 2 sensor, a pressure sensor, and a microdialysis probe were inserted into the spinal cord adjacent to T10 at two locations: a "proximal" site and a "distal" site, 2 mm and 22 mm from the SCI, respectively. At the proximal site, NE and PE resulted in little improvement in SCBF during cord compression. Following decompression, NE resulted in increased SCBF and PO 2 , whereas decreased levels were observed for PE. However, both NE and PE were associated with a gradual decrease in the lactate to pyruvate (L/P) ratio after decompression. PE was associated with greater hemorrhage through the injury site than that in control animals. Combined, our results suggest that NE promotes better restoration of blood flow and oxygenation than PE in the traumatically injured spinal cord, thus providing a physiological rationale for selecting NE over PE in the hemodynamic management of acute SCI.

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination.

Science.gov (United States)

Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P; Brown, Chester W; John, Gareth R

2014-06-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb(-/-) embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3(-/-) mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. © 2014. Published by The Company of Biologists Ltd.

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination

Science.gov (United States)

Dutta, Dipankar J.; Zameer, Andleeb; Mariani, John N.; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M.; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V.; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P.; Brown, Chester W.; John, Gareth R.

2014-01-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb−/− embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3−/− mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. PMID:24917498

Spinal cord contusion.

Science.gov (United States)

Ju, Gong; Wang, Jian; Wang, Yazhou; Zhao, Xianghui

2014-04-15

Spinal cord injury is a major cause of disability with devastating neurological outcomes and limited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.

Testing the feasibility of training peers with a spinal cord injury to learn and implement brief action planning to promote physical activity to people with spinal cord injury

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Gainforth, Heather L.; Latimer-Cheung, Amy E.; Davis, Connie; Casemore, Sheila; Martin Ginis, Kathleen A.

2015-01-01

Objective The present study tested the feasibility of training peers with spinal cord injury (SCI) to learn brief action planning (BAP), an application of motivational interviewing principles, to promote physical activity to mentees with SCI. Method Thirteen peers with SCI attended a half-day BAP workshop. Using a one-arm, pre-, post-test design, feasibility to learn BAP was assessed in terms of peers' (1) BAP and motivational interviewing spirit competence; (2) training satisfaction; and (3) motivations to use BAP as assessed by measures of the theory of planned behavior constructs. Measures were taken at baseline, immediately post-training, and 1 month follow up. Results Following the training, participants' BAP and motivational interviewing competence significantly increased (P's  2.27). Training satisfaction was very positive with all means falling above the scale midpoint. Participants' perceived behavioral control to use BAP increased from baseline to post (P  0.05). Conclusion Training peers with a SCI to learn to use BAP is feasible. Practical implications BAP is a tool that can be feasibly learned by peers to promote physical activity to their mentees. PMID:25429692

Determinants of participating in life after spinal cord injury - advice for health professionals arising from an examination of shared narratives.

Science.gov (United States)

Amsters, Delena; Duncan, James; Field, Victoria; Smales, Alastair; Zillmann, Leanne; Kendall, Melissa; Kuipers, Pim

2017-08-23

To explore the perceived determinants of participation in life after spinal cord injury and incorporate these into a framework for the promotion of participation suitable for use by rehabilitation professionals. Four people with spinal cord injury and one health service researcher engaged in a process of sharing narratives of life after spinal cord injury over a period of one year. The narratives were distilled using thematic analysis. The relevant subset of data from the narratives categorized as This is what we think determines our participation in life was analyzed in depth to reveal nine themes (1) The world can be my friend or foe; (2) I am who I am; (3) It is a personal journey; (4) Some like to talk, others like to do; (5) We have the technology; (6) A support network is vital and it can be built; (7) Life involves tradeoffs; (8) Push; and (9) Be flexible. These themes were combined into a framework for the promotion of participation to be used by rehabilitation professionals. The collaboratively developed framework has three aspects - Help me, Encourage me and Accept. The proposed participation promotion framework is grounded in the narratives of the research group but needs to be tested before it can be endorsed for practice. Implications for Rehabilitation In order to promote participation in life after spinal cord injury rehabilitation professionals can help people with spinal cord injury to negotiate the world, build and maintain a support crew and access equipment and technology. Spinal cord injury rehabilitation professionals can encourage people with spinal cord injury to push themselves, be assertive and be flexible, as these attributes can assist participation in life after spinal cord injury. In the pursuit of participation goals, rehabilitation professionals must accept the individuality of each person with spinal cord injury, respect that they may or may not be willing to make tradeoffs to achieve participation goals and that they are on an ever

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

Science.gov (United States)

2016-01-01

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

Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms.

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Sakai, Kiyoshi; Yamamoto, Akihito; Matsubara, Kohki; Nakamura, Shoko; Naruse, Mami; Yamagata, Mari; Sakamoto, Kazuma; Tauchi, Ryoji; Wakao, Norimitsu; Imagama, Shiro; Hibi, Hideharu; Kadomatsu, Kenji; Ishiguro, Naoki; Ueda, Minoru

2012-01-01

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

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Parker, David

2017-01-01

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where

Retrograde tracing of fluorescent gold after autogenous nerve transplantation on spinal cord injured in rats

DEFF Research Database (Denmark)

Lin, X; Liu, W; Ding, Ming

2016-01-01

, the transplantation group using autologous sural nerve graft to repair spinal cord injury period and non-transplantation group was only exposed incision without treatment. In the 4, 6 and 8 weeks after operation, the retrograde tracing of FG Fluoro-Gold was performed to discover the recovery of the axial plasma......Objective To investigate the changes of the fluorescent gold retrograde tracing autogenous nerve transplantation on spinal cord injured in rats. Methods The animals were divided into two groups, with modified Allen impact method to establish model of spinal cord injury. After 4 weeks.......01). Conclusion After spinal cord injury, autologous nerve graft was repaired and survived well and promote the recovery of spinal cord injury segment shaft pulp transportation function....

[Three-dimensional parallel collagen scaffold promotes tendon extracellular matrix formation].

Science.gov (United States)

Zheng, Zefeng; Shen, Weiliang; Le, Huihui; Dai, Xuesong; Ouyang, Hongwei; Chen, Weishan

2016-03-01

To investigate the effects of three-dimensional parallel collagen scaffold on the cell shape, arrangement and extracellular matrix formation of tendon stem cells. Parallel collagen scaffold was fabricated by unidirectional freezing technique, while random collagen scaffold was fabricated by freeze-drying technique. The effects of two scaffolds on cell shape and extracellular matrix formation were investigated in vitro by seeding tendon stem/progenitor cells and in vivo by ectopic implantation. Parallel and random collagen scaffolds were produced successfully. Parallel collagen scaffold was more akin to tendon than random collagen scaffold. Tendon stem/progenitor cells were spindle-shaped and unified orientated in parallel collagen scaffold, while cells on random collagen scaffold had disorder orientation. Two weeks after ectopic implantation, cells had nearly the same orientation with the collagen substance. In parallel collagen scaffold, cells had parallel arrangement, and more spindly cells were observed. By contrast, cells in random collagen scaffold were disorder. Parallel collagen scaffold can induce cells to be in spindly and parallel arrangement, and promote parallel extracellular matrix formation; while random collagen scaffold can induce cells in random arrangement. The results indicate that parallel collagen scaffold is an ideal structure to promote tendon repairing.

Acute Thoracolumbar Spinal Cord Injury: Relationship of Cord Compression to Neurological Outcome.

Science.gov (United States)

Skeers, Peta; Battistuzzo, Camila R; Clark, Jillian M; Bernard, Stephen; Freeman, Brian J C; Batchelor, Peter E

2018-02-21

Spinal cord injury in the cervical spine is commonly accompanied by cord compression and urgent surgical decompression may improve neurological recovery. However, the extent of spinal cord compression and its relationship to neurological recovery following traumatic thoracolumbar spinal cord injury is unclear. The purpose of this study was to quantify maximum cord compression following thoracolumbar spinal cord injury and to assess the relationship among cord compression, cord swelling, and eventual clinical outcome. The medical records of patients who were 15 to 70 years of age, were admitted with a traumatic thoracolumbar spinal cord injury (T1 to L1), and underwent a spinal surgical procedure were examined. Patients with penetrating injuries and multitrauma were excluded. Maximal osseous canal compromise and maximal spinal cord compression were measured on preoperative mid-sagittal computed tomography (CT) scans and T2-weighted magnetic resonance imaging (MRI) by observers blinded to patient outcome. The American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades from acute hospital admission (≤24 hours of injury) and rehabilitation discharge were used to measure clinical outcome. Relationships among spinal cord compression, canal compromise, and initial and final AIS grades were assessed via univariate and multivariate analyses. Fifty-three patients with thoracolumbar spinal cord injury were included in this study. The overall mean maximal spinal cord compression (and standard deviation) was 40% ± 21%. There was a significant relationship between median spinal cord compression and final AIS grade, with grade-A patients (complete injury) exhibiting greater compression than grade-C and D patients (incomplete injury) (p compression as independently influencing the likelihood of complete spinal cord injury (p compression. Greater cord compression is associated with an increased likelihood of severe neurological deficits (complete injury) following

Multi-protein delivery by nanodiamonds promotes bone formation.

Science.gov (United States)

Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

2013-11-01

Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

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Yuanyuan Zhao

2015-01-01

Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury.

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Cordelia Ziraldo

2015-06-01

Full Text Available People with spinal cord injury (SCI are predisposed to pressure ulcers (PU. PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM of ischemia/reperfusion-induced inflammation and PU (the PUABM was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to "better" vs. "worse" outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU.

A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury.

Science.gov (United States)

Ziraldo, Cordelia; Solovyev, Alexey; Allegretti, Ana; Krishnan, Shilpa; Henzel, M Kristi; Sowa, Gwendolyn A; Brienza, David; An, Gary; Mi, Qi; Vodovotz, Yoram

2015-06-01

People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to "better" vs. "worse" outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU.

A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury

Science.gov (United States)

Ziraldo, Cordelia; Solovyev, Alexey; Allegretti, Ana; Krishnan, Shilpa; Henzel, M. Kristi; Sowa, Gwendolyn A.; Brienza, David; An, Gary; Mi, Qi; Vodovotz, Yoram

2015-01-01

People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to “better” vs. “worse” outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU. PMID:26111346

3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

Science.gov (United States)

Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

2017-07-17

Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate.

Science.gov (United States)

Le Corre, Marine; Noristani, Harun N; Mestre-Frances, Nadine; Saint-Martin, Guillaume P; Coillot, Christophe; Goze-Bac, Christophe; Lonjon, Nicolas; Perrin, Florence E

2017-11-27

Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obstacles, we first conducted a comparative neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a nonhuman primate), and humans. Next, we developed and characterized a new model of lateral spinal cord hemisection in M. murinus. Over a 3-month period after SCI, we carried out a detailed, longitudinal, behavioral follow-up associated with in vivo magnetic resonance imaging ( 1 H-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo 1 H-MRI, ex vivo 1 H-MRI, and classical histology. The general organization and glial cell distribution/morphology in the spinal cord of M. murinus closely resembles that of humans. Animals assessed at different stages following lateral hemisection of the spinal cord presented specific motor deficits and spinal cord tissue alterations. We also found a close correlation between 1 H-MRI signal and microglia reactivity and/or associated post-trauma phenomena. Spinal cord hemisection in M. murinus provides a reliable new nonhuman primate model that can be used to promote translational research on SCI and represents a novel and more affordable alternative to larger primates.

Cord Blood and Transplants

Science.gov (United States)

... donate their baby’s umbilical cord blood to a public cord blood bank. We have more than 249,000 cord blood ... stored as a cord blood unit at a public cord blood bank for future use. It can then be listed ...

Umbilical cord care in Ethiopia and implications for behavioral change: a qualitative study.

Science.gov (United States)

Amare, Yared

2014-04-18

Infections account for up to a half of neonatal deaths in low income countries. The umbilicus is a common source of infection in such settings. This qualitative study investigates practices and perspectives related to umbilical cord care in Ethiopia. In-depth interviews (IDI) were conducted in a district in each of the four most populous regions in the country: Oromia, Amhara, Tigray and Southern Nations, Nationalities and Peoples Region (SNNPR). In each district, one community was purposively selected; and in each study community, IDIs were conducted with 6 mothers, 4 grandmothers, 2 Traditional Birth Attendants and 2 Health Extension Workers (HEWs). The two main questions in the interview guide related to cord care were: How was the umbilical cord cut and tied? Was anything applied to the cord stump immediately after cutting/in the first 7 days? Why was it applied/not applied? The study elucidates local cord care practices and the rational for these practices. Concepts underlying cord tying practices were how to stem blood flow and facilitate delivery of the placenta. Substances were applied on the cord to moisturize it, facilitate its separation and promote healing. Locally recognized cord problems were delayed healing, bleeding or swelling. Few respondents reported familiarity with redness of the cord - a sign of infection. Grandmothers, TBAs and HEWs were influential regarding cord care. This study highlights local rationale for cord practices, concerns about cord related problems and recognition of signs of infection. Behavioral change messages aimed at improving cord care including cleansing with CHX should address these local perspectives. It is suggested that HEWs and health facility staff target mothers, grandmothers, TBAs and other community women with messages and counseling.

Alleviating Autonomic Dysreflexia after Spinal Cord Injury

Science.gov (United States)

2017-12-01

tracts originating from cortex, we may eventually be able to use cell transplantation as a bridge to promote targeted, functional axon regeneration ...13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS autonomic dysreflexia, spinal cord injury, transplantation, axon regeneration 16. SECURITY...different root causes – i.e. using neural precursor cells to restore more normal innervation of sympathetic preganglionic neurons and

Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

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Changxing Wang

2017-03-01

Full Text Available Background/Aims: Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI. This study investigated the potential for poly (lactic-co-glycolic acid (PLGA complex inoculated with olfactory ensheathing cells (OECs to treat spinal cord injury in a rat model. Methods: OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR p75. The Basso, Beattie, and Bresnahan (BBB score, together with an inclined plane (IP test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP and the microtubule-associated protein-2 (MAP-2, representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation. Results: The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05. Conclusion: PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.

A unified approach for description of gas hydrate formation kinetics in the presence of kinetic promoters in gas hydrate converters

International Nuclear Information System (INIS)

ZareNezhad, Bahman; Varaminian, Farshad

2013-01-01

Highlights: • A unified kinetic model for description of promoted and non-promoted gas hydrate formation processes is presented. • Effects of impeller speed, promoter concentration and different kinetic promoters are investigated. • A unique region of gas hydrate formation is identified regarding gas hydrate formation processes. • The proposed model is useful for understanding the behavior of gas hydrate formation processes and design of GTH converters. - Abstract: The kinetic promoters have found wide applications in enhancing the rate of energy conversion and storage via gas hydrate formation processes. Effects of different kinetic promoters such as anionic surfactants sodium dodecyl sulfate (SDS), dodecylbenzene sulfonic acid (DBSA), and sodium dodecyl benzene sulfonate (SDBS); cationic surfactants, Cetyl trimethyl ammonium bromide (CTAB), dodecyl trimethyl ammonium bromide (DTAB) and non-ionic surfactants, alkylpolyglucoside (APG), dodecyl polysaccharide glycoside (DPG), TritonX-100 (TX100) on methane (CH 4 ), ethane (C 2 H 6 ) and propane (C 3 H 8 ) gas hydrate formation processes are investigated in this work. A macroscopic kinetic model based on the time variations of reaction chemical potential is also presented for global description of gas hydrate formation processes. Experimental gas hydrate formation data are employed to validate the proposed kinetic model. Effects of promoter’s concentrations and agitation intensities on the gas consumption profiles are also investigated. A universal correlation and a unified kinetic map have been proposed for macroscopic description of gas hydrate formation kinetics in the presence or absence of kinetic promoters. According to the presented unified kinetic map, a unique region of gas hydrate formation is identified for the first time. For negligible amounts of kinetic promoters, the presented region disappears and approaches to a unique path at high agitation intensities. The presented unified approach is

Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms*

Science.gov (United States)

Wang, Yong; Yu, Xing; Zhao, Qun-zi; Zheng, Shu; Qing, Wen-jie; Miao, Chun-di; Sanjay, Jaiswal

2016-01-01

We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trβ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis. PMID:27381728

Lentiviral-mediated expression of polysialic acid in spinal cord and conditioning lesion promote regeneration of sensory axons into spinal cord

NARCIS (Netherlands)

Zhang, Yi; Zhang, Xinyu; Wu, Dongsheng; Verhaagen, J.; Richardson, Peter M; Yeh, John; Bo, Xuenong

2007-01-01

In adult mammals, sensory axons that regenerate in the dorsal root are unable to grow across the dorsal root entry zone (DREZ) into the spinal cord. In this study we examined whether, by inducing expression of polysialic acid (PSA) (a large carbohydrate attached to molecules on the cell surface), in

HOXB4 Promotes Hemogenic Endothelium Formation without Perturbing Endothelial Cell Development

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Nadine Teichweyde

2018-03-01

Full Text Available Summary: Generation of hematopoietic stem cells (HSCs from pluripotent stem cells, in vitro, holds great promise for regenerative therapies. Primarily, this has been achieved in mouse cells by overexpression of the homeotic selector protein HOXB4. The exact cellular stage at which HOXB4 promotes hematopoietic development, in vitro, is not yet known. However, its identification is a prerequisite to unambiguously identify the molecular circuits controlling hematopoiesis, since the activity of HOX proteins is highly cell and context dependent. To identify that stage, we retrovirally expressed HOXB4 in differentiating mouse embryonic stem cells (ESCs. Through the use of Runx1(−/− ESCs containing a doxycycline-inducible Runx1 coding sequence, we uncovered that HOXB4 promoted the formation of hemogenic endothelium cells without altering endothelial cell development. Whole-transcriptome analysis revealed that its expression mediated the upregulation of transcription of core transcription factors necessary for hematopoiesis, culminating in the formation of blood progenitors upon initiation of Runx1 expression. : In this article, Klump and colleagues demonstrate that the human homeotic selector protein HOXB4 promotes ESC-derived hematopoiesis by inducing hemogenic endothelium formation, in vitro. It propels hematopoietic specification by upregulating the transcription of genes essential for hematopoietic development, such as those encoding members of the so-called heptad transcription factors. Keywords: HOXB4, hematopoietic stem cells, hemangioblast, hemogenic endothelium, hematopoietic specification, EHT, RUNX1, pluripotent stem cells

Evo-engineering and the cellular and molecular origins of the vertebrate spinal cord.

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Steventon, Ben; Martinez Arias, Alfonso

2017-12-01

The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specific spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posteriorly localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken, Xenopus and zebrafish and relate them to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development. Copyright © 2017. Published by Elsevier Inc.

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

Science.gov (United States)

Hague, D W; Joslyn, S; Bush, W W; Glass, E N; Durham, A C

2015-01-01

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. Multi-institutional retrospective study. Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Therapeutic Effect of Platelet-Rich Plasma in Rat Spinal Cord Injuries

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Nan-Fu Chen

2018-04-01

Full Text Available Platelet-rich plasma (PRP is prepared by centrifuging fresh blood in an anticoagulant state, and harvesting the platelet-rich portion or condensing platelets. Studies have consistently demonstrated that PRP concentrates are an abundant source of growth factors, such as platelet-derived growth factor (PDGF, transforming growth factor β (TGF-β, insulin-like growth factor 1 (IGF-1, and epithelial growth factor (EGF. The complex mechanisms underlying spinal cord injury (SCI diminish intrinsic repair and neuronal regeneration. Several studies have suggested that growth factor-promoted axonal regeneration can occur for an extended period after injury. More importantly, the delivery of exogenous growth factors contained in PRP, such as EGF, IGF-1, and TGF-β, has neurotrophic effects on central nervous system (CNS injuries and neurodegenerative diseases. However, only a few studies have investigated the effects of PRP on CNS injuries or neurodegenerative diseases. According to our review of relevant literature, no study has investigated the effect of intrathecal (i.t. PRP injection into the injured spinal cord and activation of intrinsic mechanisms. In the present study, we directly injected i.t. PRP into rat spinal cords and examined the effects of PRP on normal and injured spinal cords. In rats with normal spinal cords, PRP induced microglia and astrocyte activation and PDGF-B and ICAM-1 expression. In rats with SCIs, i.t. PRP enhanced the locomotor recovery and spared white matter, promoted angiogenesis and neuronal regeneration, and modulated blood vessel size. Furthermore, a sustained treatment (a bolus of PRP followed by a 1/3 dose of initial PRP concentration exerted more favorable therapeutic effects than a single dose of PRP. Our findings suggest by i.t. PRP stimulate angiogenesis, enhancing neuronal regeneration after SCI in rats. Although PRP induces minor inflammation in normal and injured spinal cords, it has many advantages. It is an

Factors influencing bladder stone formation in patients with spinal cord injury.

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Favazza, Terry; Midha, Meena; Martin, Jessicca; Grob, B Mayer

2004-01-01

Bladder stones that form in patients with spinal cord injury (SCI) can cause significant morbidity. This study sought to analyze factors associated with bladder stone formation to determine which patients might be at increased risk to develop bladder stones. A review of 56 SCI patients treated for bladder calculi over a 10-year period at a single institution was performed. These patients were compared with a control population of general SCI patients known to be stone free. The factors compared were patient age, duration of injury, level of injury, completeness of injury, method of bladder management, and the presence of documented urinary tract infections with urease-producing organisms. All patients with stones were male and had a median age of 58.5 years. The median level of injury was C6, the median time since injury was 21 years, 66% had complete injuries, 68% managed their bladders with indwelling catheters or suprapubic tubes, and 83% had a history of infections with urease-producing organisms. When compared with the control group, patients forming bladder stones were older (P = 0.03), were more likely to have indwelling catheters (P < 0.0001), had a history of infections with urease-producing organisms (P = 0.04), and had complete injuries (P = 0.018). This information can be used to identify patients who have an increased risk of bladder stones and measures can be taken to reduce their incidence and morbidity.

Spinal cord injury: overview of experimental approaches used to restore locomotor activity.

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Fakhoury, Marc

2015-01-01

Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord's normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

Reduce, reuse, recycle - Developmental signals in spinal cord regeneration.

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Cardozo, Marcos Julian; Mysiak, Karolina S; Becker, Thomas; Becker, Catherina G

2017-12-01

Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord tissue after injury, generating new neurons that mature and integrate into the spinal circuitry. Elucidating the molecular signals that promote this regeneration is a fundamental question in regeneration research. Model systems, such as salamanders and larval and adult zebrafish are used to analyse successful regeneration. This shows that many developmental signals, such as Notch, Hedgehog (Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF), Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and activate resident spinal progenitor cells. Here we compare the roles of these signals in spinal cord development and regeneration of the much larger and fully patterned adult spinal cord. Understanding how developmental signalling systems are reactivated in successfully regenerating species may ultimately lead to ways to reactivate similar systems in mammalian progenitor cells, which do not show neurogenesis after spinal injury. Copyright © 2017. Published by Elsevier Inc.

A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice

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Liang Dong

2017-01-01

Full Text Available Mesenchymal stem cells (MSCs can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.

Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Cord Injury 101

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Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

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Huie, J. Russell

2016-01-01

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions. PMID:27721996

Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

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Sandra M. Garraway

2016-01-01

Full Text Available Brain-derived neurotrophic factor (BDNF is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions.

Spinal Cord Diseases

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Your spinal cord is a bundle of nerves that runs down the middle of your back. It carries signals back ... of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such ...

Spinal Cord Injury 101

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Full Text Available menu Understanding Spinal Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

Nanog interact with CDK6 to regulates astrocyte cells proliferation following spinal cord injury

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Gu, Jun [Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu (China); Department of Orthopaedics, Xishan People' s Hospital, Wuxi, Jiangsu (China); Ni, Yingjie; Xu, Lin; Xu, Hongliang [Department of Orthopaedics, Xishan People' s Hospital, Wuxi, Jiangsu (China); Cai, Zhengdong, E-mail: caizhengdongsh@163.com [Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu (China)

2016-01-22

Previous research had reported transcription factors Nanog expressed in pluripotent embryonic stem cells (ESCS) that played an important role in regulating the cell proliferation. Nanog levels are frequently elevated in ESCS, but the role in the spinal cord was not clear. To examine the biological relevance of Nanog, we studied its properties in spinal cord injury model. The expression of Nanog and PCNA was gradually increased and reached a peak at 3 day by western blot analysis. The expression of Nanog was further analyzed by immunohistochemistry. Double immunofluorescent staining uncovered that Nanog can co-labeled with PCNA and GFAP in the spinal cord tissue. In vitro, Nanog can promote the proliferation of astrocyte cell by Fluorescence Activating Cell Sorter (FACS) and CCK8. Meanwhile, the cell-cycle protein CDK6 could interact with Nanog in the spinal cord tissue. Taken together, these data suggested that both Nanog may play important roles in spinal cord pathophysiology via interact with CDK6.

Nanog interact with CDK6 to regulates astrocyte cells proliferation following spinal cord injury

International Nuclear Information System (INIS)

Gu, Jun; Ni, Yingjie; Xu, Lin; Xu, Hongliang; Cai, Zhengdong

2016-01-01

Previous research had reported transcription factors Nanog expressed in pluripotent embryonic stem cells (ESCS) that played an important role in regulating the cell proliferation. Nanog levels are frequently elevated in ESCS, but the role in the spinal cord was not clear. To examine the biological relevance of Nanog, we studied its properties in spinal cord injury model. The expression of Nanog and PCNA was gradually increased and reached a peak at 3 day by western blot analysis. The expression of Nanog was further analyzed by immunohistochemistry. Double immunofluorescent staining uncovered that Nanog can co-labeled with PCNA and GFAP in the spinal cord tissue. In vitro, Nanog can promote the proliferation of astrocyte cell by Fluorescence Activating Cell Sorter (FACS) and CCK8. Meanwhile, the cell-cycle protein CDK6 could interact with Nanog in the spinal cord tissue. Taken together, these data suggested that both Nanog may play important roles in spinal cord pathophysiology via interact with CDK6.

Vascular lumen formation.

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Lammert, Eckhard; Axnick, Jennifer

2012-04-01

The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell-cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.

Concise Review: Bone Marrow for the Treatment of Spinal Cord Injury: Mechanisms and Clinical Applications

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Wright, Karina T; Masri, Wagih El; Osman, Aheed; Chowdhury, Joy; Johnson, William E B

2011-01-01

Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversial topic of HSC and MSC transdifferentiation into central nervous system cells but focus on the neurotrophic, tissue sparing, and reparative action of MSC grafts in the context of the spinal cord injury (SCI) milieu. We then discuss some of the specific issues related to the translation of HSC and MSC therapies for patients with SCI and present a comprehensive critique of the current bone marrow cell clinical trials for the treatment of SCI to date. Stem Cells 2011;29:169–178 PMID:21732476

Lifestyle and health conditions of adults with spinal cord injury.

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Xavier de França, Inacia Sátiro; Cruz Enders, Bertha; Silva Coura, Alexsandro; Pereira Cruz, Giovanna Karinny; da Silva Aragão, Jamilly; Carvalho de Oliveira, Déborah Raquel

2014-01-01

. To describe the lifestyle of adults with spinal cord injury and explore its relation with some health conditions. Cross sectional study, in which a questionnaire containing sociodemographic, habits and health conditions variables was used. Forty-seven people with spinal cord injury participated and answered the self-report questionnaire. The group under study was predominantly male (92%), under 40 years of age (47%), and had low educational level (76%). The most frequent risk factors related to the lifestyle were: smoking (28%), alcohol consumption (36%), coffee consumption (92%) and being physically inactive (64%). Association was found between having four or more risk factors related to lifestyle and the loss of appetite, as well as constipation. . The actual inadequate lifestyle is associated with the health conditions of patients, and the nursing team should pay special attention to the education and promotion of health related to people with spinal cord injury.

Modifying Lipid Rafts Promotes Regeneration and Functional Recovery

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Nardos G. Tassew

2014-08-01

Full Text Available Ideal strategies to ameliorate CNS damage should promote both neuronal survival and axon regeneration. The receptor Neogenin promotes neuronal apoptosis. Its ligand prevents death, but the resulting repulsive guidance molecule a (RGMa-Neogenin interaction also inhibits axonal growth, countering any prosurvival benefits. Here, we explore strategies to inhibit Neogenin, thus simultaneously enhancing survival and regeneration. We show that bone morphogenetic protein (BMP and RGMa-dependent recruitment of Neogenin into lipid rafts requires an interaction between RGMa and Neogenin subdomains. RGMa or Neogenin peptides that prevent this interaction, BMP inhibition by Noggin, or reduction of membrane cholesterol all block Neogenin raft localization, promote axon outgrowth, and prevent neuronal apoptosis. Blocking Neogenin raft association influences axonal pathfinding, enhances survival in the developing CNS, and promotes survival and regeneration in the injured adult optic nerve and spinal cord. Moreover, lowering cholesterol disrupts rafts and restores locomotor function after spinal cord injury. These data reveal a unified strategy to promote both survival and regeneration in the CNS.

Abundant expression of guidance and synaptogenic molecules in the injured spinal cord.

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Anne Jacobi

Full Text Available BACKGROUND: Spinal interneurons have emerged as crucial targets of supraspinal input during post-injury axonal remodelling. For example, lesioned corticospinal projections use propriospinal neurons as relay stations to form intraspinal detour circuits that circumvent the lesion site and contribute to functional recovery. While a number of the molecules that determine the formation of neuronal circuits in the developing nervous system have been identified, it is much less understood which of these cues are also expressed in the injured spinal cord and can thus guide growing collaterals and initiate synaptogenesis during circuit remodelling. METHODOLOGY/PRINCIPAL FINDINGS: To address this question we characterized the expression profile of a number of guidance and synaptogenic molecules in the cervical spinal cord of healthy and spinal cord-injured mice by in situ hybridization. To assign the expression of these molecules to distinct populations of interneurons we labeled short and long propriospinal neurons by retrograde tracing and glycinergic neurons using a transgenically expressed fluorescent protein. Interestingly, we found that most of the molecules studied including members of slit-, semaphorin-, synCAM-, neuroligin- and ephrin- families as well as their receptors are also present in the adult CNS. While many of these molecules were abundantly expressed in all interneurons examined, some molecules including slits, semaphorin 7a, synCAM4 and neuroligin 1 showed preferential expression in propriospinal interneurons. Overall the expression pattern of guidance and synaptogenic molecules in the cervical spinal cord appeared to be stable over time and was not substantially altered following a midthoracic spinal cord injury. CONCLUSIONS: Taken together, our study indicates that many of the guidance and synaptogenic cues that regulate neuronal circuit formation in development are also present in the adult CNS and therefore likely contribute to the

Fostering public cord blood banking and research in Canada.

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Isasi, Rosario; Dalpe, Gratien; Knoppers, Bartha M

2013-12-01

In June 2013, Canadian Blood Services (CBS) established the National Public Cord Blood Bank (NPCBB) accessible to Canadian and international patients and researchers. The NPCBB promotes efforts that contribute to research and improved clinical care by making units not suitable for banking or transplantation available for research. In the context of the NPCBB of the CBS, this article will focus on the practical tools (e.g., consent protocols) developed to optimize umbilical cord blood (UCB) banking and research while enabling ethical provenance of UCB stem cells. The Canadian approach represents an ideal model for comparison as it is a country in which the national public bank (and other regional/provincial public banks) coexists with private companies.

Spinal Cord Injuries

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... forth between your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... down on the nerve parts that carry signals. Spinal cord injuries can be complete or incomplete. With a complete ...

Torakal Ventral Cord Herniation

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Sermin Tok

2015-11-01

Full Text Available  Ventral cord herniation is a rare cause of focal myelopathy due to herniation of the thoracic cord through a dural defect.It is also known by a variety of other terms such as spontaneous thoracic cord herniation or idiopathic spinal cord herniation.The key feature is focal distortion and rotation of the cord with no CSF seen between it and the ventral theca.

Three-dimensional spheroid culture of human umbilical cord mesenchymal stem cells promotes cell yield and stemness maintenance.

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Li, Yi; Guo, Gang; Li, Li; Chen, Fei; Bao, Ji; Shi, Yu-Jun; Bu, Hong

2015-05-01

Mesenchymal stem cell (MSC) transplantation is a promising treatment of many diseases. However, conventional techniques with cells being cultured as a monolayer result in slow cell proliferation and insufficient yield to meet clinical demands. Three-dimensional (3D) culture systems are gaining attention with regard to recreating a complex microenvironment and to understanding the conditions experienced by cells. Our aim is to establish a novel 3D system for the culture of human umbilical cord MSCs (hUC-MSCs) within a real 3D microenvironment but with no digestion or passaging. Primary hUC-MSCs were isolated and grown in serum-free medium (SFM) on a suspension Rocker system. Cell characteristics including proliferation, phenotype and multipotency were recorded. The therapeutic effects of 3D-cultured hUC-MSCs on carbon tetrachloride (CCl4)-induced acute liver failure in mouse models were examined. In the 3D Rocker system, hUC-MSCs formed spheroids in SFM and maintained high viability and active proliferation. Compared with monolayer culture, the 3D-culture system yielded more hUC-MSCs cells within the same volume. The spheroids expressed higher levels of stem cell markers and displayed stronger multipotency. After transplantation into mouse, 3D hUC-MSCs significantly promoted the secretion of interferon-γ and interleukin-6 but inhibited that of tumor necrosis factor-α, thereby alleviating liver necrosis and promoting regeneration following CCl4 injury. The 3D culture of hUC-MSCs thus promotes cell yield and stemness maintenance and represents a promising strategy for hUC-MSCs expansion on an industrial scale with great potential for cell therapy and biotechnology.

Macrophage activation and its role in repair and pathology after spinal cord injury.

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Gensel, John C; Zhang, Bei

2015-09-04

The injured spinal cord does not heal properly. In contrast, tissue repair and functional recovery occur after skin or muscle injuries. The reason for this dichotomy in wound repair is unclear but inflammation, and specifically macrophage activation, likely plays a key role. Macrophages have the ability to promote the repair of injured tissue by regulating transitions through different phase of the healing response. In the current review we compare and contrast the healing and inflammatory responses between spinal cord injuries and tissues that undergo complete wound resolution. Through this comparison, we identify key macrophage phenotypes that are inaptly triggered or absent after spinal cord injury and discuss spinal cord stimuli that contribute to this maladaptive response. Sequential activation of classic, pro-inflammatory, M1 macrophages and alternatively activated, M2a, M2b, and M2c macrophages occurs during normal healing and facilitates transitions through the inflammatory, proliferative, and remodeling phases of repair. In contrast, in the injured spinal cord, pro-inflammatory macrophages potentiate a prolonged inflammatory phase and remodeling is not properly initiated. The desynchronized macrophage activation after spinal cord injury is reminiscent of the inflammation present in chronic, non-healing wounds. By refining the role macrophages play in spinal cord injury repair we bring to light important areas for future neuroinflammation and neurotrauma research. This article is part of a Special Issue entitled SI: Spinal cord injury. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Constitutively reduced sensory capacity promotes better recovery after spinal cord-injury (SCI) in blind rats of the dystrophic RCS strain.

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Rink, Svenja; Bendella, Habib; Alsolivany, Kurdin; Meyer, Carolin; Woehler, Aliona; Jansen, Ramona; Isik, Zeynep; Stein, Gregor; Wennmachers, Sina; Nakamura, Makoto; Angelov, Doychin N

2018-01-01

We compared functional, electrophysiological and morphological parameters after SCI in two groups of rats Sprague Dawley (SD) rats with normal vision and blind rats from a SD-substrain "Royal College of Surgeons" (SD/RCS) who lose their photoreceptor cells after birth due to a genetic defect in the retinal pigment epithelium. For these animals skin-, intramuscular-, and tendon receptors are major available means to resolve spatial information. The purpose of this study was to check whether increased sensitivity in SD/RCS rats would promote an improved recovery after SCI. All rats were subjected to severe compression of the spinal cord at vertebra Th8, spinal cord segment Th10. Recovery of locomotion was analyzed at 1, 3, 6, 9, and 12 weeks after SCI using video recordings of beam walking and inclined ladder climbing. Five functional parameters were studied: foot-stepping angle (FSA), rump-height index (RHI) estimating paw placement and body weight support, respectively, number of correct ladder steps (CLS) assessing skilled hindlimb movements, the BBB-locomotor score and an established urinary bladder score (BS). Sensitivity tests were followed by electrophysiological measurement of M- and H-wave amplitudes from contractions of the plantar musculature after stimulation of the tibial nerve. The closing morphological measurements included lesion volume and expression of astro- and microglia below the lesion. Numerical assessments of BBB, FSA, BS, lesion volume and GFAP-expression revealed no significant differences between both strains. However, compared to SD-rats, the blind SD/RCS animals significantly improved RHI and CLS by 6 - 12 weeks after SCI. To our surprise the withdrawal latencies in the blind SD/RCS rats were longer and the amplitudes of M- and H-waves lower. The expression of IBA1-immunoreactivity in the lumbar enlargement was lower than in the SD-animals. The longer withdrawal latencies suggest a decreased sensitivity in the blind SD/RCS rats, which

Cervical Cord-Canal Mismatch: A New Method for Identifying Predisposition to Spinal Cord Injury.

Science.gov (United States)

Nouri, Aria; Montejo, Julio; Sun, Xin; Virojanapa, Justin; Kolb, Luis E; Abbed, Khalid M; Cheng, Joseph S

2017-12-01

The risk for spinal cord injuries (SCIs) ranging from devastating traumatic injuries, compression because of degenerative pathology, and neurapraxia is increased in patients with congenital spinal stenosis. Classical diagnostic criteria include an absolute anteroposterior diameter of spinal cord, which varies across patients, independent of canal size. Recent large magnetic resonance imaging studies of population cohorts have allowed newer methods to emerge that account for both cord and canal size by measuring a spinal cord occupation ratio (SCOR). A SCOR defined as ≥70% on midsagittal imaging or ≥80% on axial imaging appears to be an effective method of identifying cord-canal mismatch, but requires further validation. Cord-canal size mismatch predisposes patients to SCI because of 1) less space within the canal lowering the amount of degenerative changes needed for cord compression, and 2) less cerebrospinal fluid surrounding the spinal cord decreasing the ability to absorb kinetic forces directed at the spine. Patients with cord-canal mismatch have been reported to be at a substantially higher risk of traumatic SCI, and present with degenerative cervical myelopathy at a younger age than patients without cord-canal mismatch. However, neurologic outcome after SCI has occurred does not appear to be different in patients with or without a cord-canal mismatch. Recognition that canal and cord size are both factors which predispose to SCI supports that cord-canal size mismatch rather than a narrow cervical canal in isolation should be viewed as the underlying mechanism predisposing to SCI. Copyright © 2017. Published by Elsevier Inc.

International standards to document remaining autonomic function after spinal cord injury

DEFF Research Database (Denmark)

Alexander, M S; Biering-Sørensen, Fin; Bodner, D

2008-01-01

-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCo...... function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function....

Lifestyle and health conditions of adults with spinal cord injury

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Inacia Sátiro Xavier de França

2014-07-01

Full Text Available Objective. To describe the lifestyle of adults with spinal cord injury and explore its relation with some health conditions. Methodology. Cross sectional study, in which a questionnaire containing sociodemographic, habits and health conditions variables was used. Forty-seven people with spinal cord injury participated and answered the self-report questionnaire. Results. The group under study was predominantly male (92%, under 40 years of age (47%, and had low educational level (76%. The most frequent risk factors related to the lifestyle were: smoking (28%, alcohol consumption (36%, coffee consumption (92% and being physically inactive (64%. Association was found between having four or more risk factors related to lifestyle and the loss of appetite, as well as constipation. Conclusion. The actual inadequate lifestyle is associated with the health conditions of patients, and the nursing team should pay special attention to the education and promotion of health related to people with spinal cord injury.

Coke formation on hydrodesulphurization catalysts. [Including effects of different promoters

Energy Technology Data Exchange (ETDEWEB)

Ternan, M.; Furimsky, E.; Parsons, B.I.

1979-02-01

The extent of coke formation was measured on a number of different hydrodesulfurization catalysts, primarily as a function of the catalyst chemical composition. Variations in the concentration of MoO/sub 3/ on the alumina, the type of catalyst promoter, the promoter/MoO/sub 3/ ratio, the presulfiding material and the reaction temperature were made. Increases in the reaction rate caused by either changes in the catalyst composition or by moderate changes in the reaction temperature were compared to the catalyst coke content. It was suggested that two types of coke were present on the catalyst, a reactive coke which is subsequently converted to reaction products and an unreactive coke which blocks catalytic sites.

Spinal Cord Independence Measure, version III: applicability to the UK spinal cord injured population.

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Glass, Clive A; Tesio, Luigi; Itzkovich, Malka; Soni, Bakul M; Silva, Pedro; Mecci, Munawar; Chadwick, Raymond; el Masry, Waghi; Osman, Aheed; Savic, Gordana; Gardner, Brian; Bergström, Ebba; Catz, Amiram

2009-09-01

To examine the validity, reliability and usefulness of the Spinal Cord Independence Measure for the UK spinal cord injury population. Multi-centre cohort study. Four UK regional spinal cord injury centres. Eighty-six people with spinal cord injury. Spinal Cord Independence Measure and Functional Independence Measure on admission analysed using inferential statistics, and Rasch analysis of Spinal Cord Independence Measure. Internal consistency, inter-rater reliability, discriminant validity; Spinal Cord Independence Measure subscale match between distribution of item difficulty and patient ability measurements; reliability of patient ability measures; fit of data to Rasch model; unidimensionality of subscales; hierarchical ordering of categories within items; differential item functioning across patient groups. Scale reliability (kappa coefficients range 0.491-0.835; (p Spinal Cord Independence Measure subscales compatible with stringent Rasch requirements; mean infit indices high; distinct strata of abilities identified; most thresholds ordered; item hierarchy stable across clinical groups and centres. Misfit and differences in item hierarchy identified. Difficulties assessing central cord injuries highlighted. Conventional statistical and Rasch analyses justify the use of the Spinal Cord Independence Measure in clinical practice and research in the UK. Cross-cultural validity may be further improved.

Tridax procumbens flavonoids promote osteoblast differentiation and bone formation

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Md. Abdullah Al Mamun

Full Text Available BACKGROUND: Tridaxprocumbens flavonoids (TPFs are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts RESULTS: TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2 CONCLUSION: Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis

Oral Administration of α-Asarone Promotes Functional Recovery in Rats With Spinal Cord Injury

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Min-Jae Jo

2018-05-01

Full Text Available α-asarone, a bioactive compound found in Acorus plant species, has been shown to exhibit neuroprotective, anti-oxidative, anti-inflammatory, and cognitive-enhancing effects. However, the effects of α-asarone on spinal cord injury (SCI have not yet been elucidated. The present study investigated the effects of α-asarone on the mRNA of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis in rats with compressive SCI. α-Asarone was orally administered (10 mg/kg once per day for 14 days following moderate static compression SCI. Compared to controls, α-asarone treatment significantly improved locomotor score, prevented neuroinflammation, and facilitated angiogenesis in the spinal cord at 14 days after SCI. Furthermore, α-asarone significantly reduced the TNF-α, IL-1β, IL-6, monocyte chemoattractant protein 1 (MCP-1, macrophage inflammatory protein 2 (MIP-2, and inducible nitric oxide synthase (iNOS levels but increased the IL-4, IL-10, and arginase 1 levels at 24 h after SCI. At 7 and 14 days after SCI, immunohistochemistry showed reduced reactive gliosis and neuroinflammation and an increased expression of M2 macrophage markers and angiogenesis. The results suggest that the inhibition of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis by α-asarone may be some of the mechanisms underlying the α-asarone-mediated neuroprotective effects on an injured spinal cord.

Microdialysis to optimize cord perfusion and drug delivery in spinal cord injury.

OpenAIRE

Phang, I; Zoumprouli, A; Papadopoulos, MC; Saadoun, S

2016-01-01

OBJECTIVE: There is lack of monitoring from the injury site to guide management of patients with acute traumatic spinal cord injury. Here we describe a bedside microdialysis monitoring technique for optimizing spinal cord perfusion and drug delivery at the injury site. METHODS: 14 patients were recruited within 72 hours of severe spinal cord injury. We inserted intradurally at the injury site a pressure probe, to monitor continuously spinal cord perfusion pressure, and a microdialysis cathete...

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Human Umbilical Cord MSCs as New Cell Sources for Promoting Periodontal Regeneration in Inflammatory Periodontal Defect.

Science.gov (United States)

Shang, Fengqing; Liu, Shiyu; Ming, Leiguo; Tian, Rong; Jin, Fang; Ding, Yin; Zhang, Yongjie; Zhang, Hongmei; Deng, Zhihong; Jin, Yan

2017-01-01

Human periodontal ligament stem cells (hPDLSCs) transplantation represents a promising approach for periodontal regeneration; however, the cell source is limited due to the invasive procedure required for cell isolation. As human umbilical cord mesenchymal stem cells (hUCMSCs) can be harvested inexpensively and inexhaustibly, here we evaluated the regenerative potentials of hUCMSCs as compared with hPDLSCs to determine whether hUCMSCs could be used as new cell sources for periodontal regeneration. Methods The characteristics of hUCMSCs, including multi-differentiation ability and anti-inflammatory capability, were determined by comparison with hPDLSCs. We constructed cell aggregates (CA) using hUCMSCs and hPDLSCs respectively. Then hPDLSCs-CA and hUCMSCs-CA were combined with β-tricalcium phosphate bioceramic (β-TCP) respectively and their regenerative potentials were determined in a rat inflammatory periodontal defect model. Results hPDLSCs showed higher osteogenic differentiation potentials than hUCMSCs. Meanwhile, hUCMSCs showed higher extracellular matrix secretion and anti-inflammatory abilities than hPDLSCs. Similar to hPDLSCs, hUCMSCs were able to contribute to regeneration of both soft and hard periodontal tissues under inflammatory periodontitis condition. There were more newly formed bone and periodontal ligaments in hPDLSCs and hUCMSCs groups than in non-cell treated group. Moreover, no significant differences of regenerative promoting effects between hPDLSCs and hUCMSCs were found. Conclusion : hUCMSCs generated similar promoting effects on periodontal regeneration compared with hPDLSCs, and can be used as new cell sources for periodontal regeneration.

Characterization of Regenerative Phenotype of Unrestricted Somatic Stem Cells (USSC) from Human Umbilical Cord Blood (hUCB) by Functional Secretome Analysis*

Science.gov (United States)

Schira, Jessica; Falkenberg, Heiner; Hendricks, Marion; Waldera-Lupa, Daniel M.; Kögler, Gesine; Meyer, Helmut E.; Müller, Hans Werner; Stühler, Kai

2015-01-01

Stem cell transplantation is a promising therapeutic strategy to enhance axonal regeneration after spinal cord injury. Unrestricted somatic stem cells (USSC) isolated from human umbilical cord blood is an attractive stem cell population available at GMP grade without any ethical concerns. It has been shown that USSC transplantation into acute injured rat spinal cords leads to axonal regrowth and significant locomotor recovery, yet lacking cell replacement. Instead, USSC secrete trophic factors enhancing neurite growth of primary cortical neurons in vitro. Here, we applied a functional secretome approach characterizing proteins secreted by USSC for the first time and validated candidate neurite growth promoting factors using primary cortical neurons in vitro. By mass spectrometric analysis and exhaustive bioinformatic interrogation we identified 1156 proteins representing the secretome of USSC. Using Gene Ontology we revealed that USSC secretome contains proteins involved in a number of relevant biological processes of nerve regeneration such as cell adhesion, cell motion, blood vessel formation, cytoskeleton organization and extracellular matrix organization. We found for instance that 31 well-known neurite growth promoting factors like, e.g. neuronal growth regulator 1, NDNF, SPARC, and PEDF span the whole abundance range of USSC secretome. By the means of primary cortical neurons in vitro assays we verified SPARC and PEDF as significantly involved in USSC mediated neurite growth and therewith underline their role in improved locomotor recovery after transplantation. From our data we are convinced that USSC are a valuable tool in regenerative medicine as USSC's secretome contains a comprehensive network of trophic factors supporting nerve regeneration not only by a single process but also maintained its regenerative phenotype by a multitude of relevant biological processes. PMID:26183719

Spinal Cord Injury 101

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FORMATION AND FURTHER DEVELOPMENT OF MODERN PROMOTION OF PHARMACEUTICAL PRODUCTS

Directory of Open Access Journals (Sweden)

Юрий Владимирович Тарасов

2014-02-01

Full Text Available The articles addresses key notions and elements of marketing of pharmaceutical companies. Key stages and particularities of formation of pharmaceutical marketing are considered. It is proved that in general pharmaceutical market is developing under general marketing rules, however while developing strategy of promotion of pharmaceutical products specific features of the industry must be taken into consideration. The authors describes specific features of modern pharmaceutical market, which must be considered while developing policy of promotion of pharmaceutical products.The analysis is made of modern state of Russian pharmaceutical industry, its place in world pharmaceutical market. It is found that development of pharmaceutical market is directly influenced by the reform of pharmaceutical industry initiated by the Government of our country in 2008. Characteristic of current stage of market development is more strict conditions in marketing sphere and promotion of drugs. DOI: http://dx.doi.org/10.12731/2218-7405-2013-12-2

A specific role of iron in promoting meristematic cell division during adventitious root formation.

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Hilo, Alexander; Shahinnia, Fahimeh; Druege, Uwe; Franken, Philipp; Melzer, Michael; Rutten, Twan; von Wirén, Nicolaus; Hajirezaei, Mohammad-Reza

2017-07-10

Adventitious root (AR) formation is characterized by a sequence of physiological and morphological processes and determined by external factors, including mineral nutrition, the impacts of which remain largely elusive. Morphological and anatomical evaluation of the effects of mineral elements on AR formation in leafy cuttings of Petunia hybrida revealed a striking stimulation by iron (Fe) and a promotive action of ammonium (NH4+). The optimal application period for these nutrients corresponded to early division of meristematic cells in the rooting zone and coincided with increased transcript levels of mitotic cyclins. Fe-localization studies revealed an enhanced allocation of Fe to the nuclei of meristematic cells in AR initials. NH4+ supply promoted AR formation to a lesser extent, most likely by favoring the availability of Fe. We conclude that Fe acts locally by promoting cell division in the meristematic cells of AR primordia. These results highlight a specific biological function of Fe in AR development and point to an unexploited importance of Fe for the vegetative propagation of plants from cuttings. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

International spinal cord injury cardiovascular function basic data set.

Science.gov (United States)

Krassioukov, A; Alexander, M S; Karlsson, A-K; Donovan, W; Mathias, C J; Biering-Sørensen, F

2010-08-01

To create an International Spinal Cord Injury (SCI) Cardiovascular Function Basic Data Set within the framework of the International SCI Data Sets. An international working group. The draft of the data set was developed by a working group comprising members appointed by the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the executive committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review by members of the executive committee of the International SCI Standards and Data Sets, the ISCoS scientific committee, ASIA board, relevant and interested international organizations and societies, individual persons with specific interest and the ISCoS Council. To make the data set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. The variables included in the International SCI Cardiovascular Function Basic Data Set include the following items: date of data collection, cardiovascular history before the spinal cord lesion, events related to cardiovascular function after the spinal cord lesion, cardiovascular function after the spinal cord lesion, medications affecting cardiovascular function on the day of examination; and objective measures of cardiovascular functions, including time of examination, position of examination, pulse and blood pressure. The complete instructions for data collection and the data sheet itself are freely available on the websites of both ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation.

Science.gov (United States)

Avanzi, Mauro P; Goldberg, Francine; Davila, Jennifer; Langhi, Dante; Chiattone, Carlos; Mitchell, William Beau

2014-03-01

The processes of megakaryocyte polyploidization and demarcation membrane system (DMS) formation are crucial for platelet production, but the mechanisms controlling these processes are not fully determined. Inhibition of Rho kinase (ROCK) signalling leads to increased polyploidization in umbilical cord blood-derived megakaryocytes. To extend these findings we determined the effect of ROCK inhibition on development of the DMS and on proplatelet formation. The underlying mechanisms were explored by analysing the effect of ROCK inhibition on the expression of MYC and NFE2, which encode two transcription factors critical for megakaryocyte development. ROCK inhibition promoted DMS formation, and increased proplatelet formation and platelet release. Rho kinase inhibition also downregulated MYC and NFE2 expression in mature megakaryocytes, and this down-regulation correlated with increased proplatelet formation. Our findings suggest a model whereby ROCK inhibition drives polyploidization, DMS growth and proplatelet formation late in megakaryocyte maturation through downregulation of MYC and NFE2 expression. © 2014 John Wiley & Sons Ltd.

MRI signal intensity as a maker of impairment in incomplete cervical spinal cord injuries

International Nuclear Information System (INIS)

Chiba, Hidefumi; Aoki, Haruhito; Hamabe, Masaki; Sasao, Yutaka; Miura, Takehiko

1998-01-01

Incomplete cervical spinal cord injuries such as central cord syndrome may result in prolonged spasticity of the limbs, especially disabilities of the upper extremities, even if the patient is able to walk. In this study, relationship between cord impairment and clinical outcome was investigated using MRI. Results showed that small foci of low signal intensity in T 1 -weighted imaging combined with foci of high signal intensity in T 2 -weighted imaging in follow-up MRI are closely related to the severity of sequelae. Small foci of low signal intensity in T 1 -weighted imaging are considered in the literature to indicate myelomalacia or cyst formation with gliosis. (author)

Change in the profile of traumatic spinal cord injury over 15 years in Spain.

Science.gov (United States)

Bárbara-Bataller, Enrique; Méndez-Suárez, José Luis; Alemán-Sánchez, Carolina; Sánchez-Enríquez, Jesús; Sosa-Henríquez, Manuel

2018-04-05

Traumatic spinal cord injury remains a serious public health and social problem. Although incidence rates are decreasing in our environment, it is a high cost condition that is associated with great disability. The objective of this study was to describe the epidemiological and demographic characteristics of traumatic spinal cord injury and to analyse its epidemiological changes. This study was an observational study with prospective monitoring of all traumatic spinal cord injury patients in the Canary Islands, Spain (2.1 million inhabitants) between 2001 and 2015. Over the specified period of the study, 282 patients suffered a traumatic spinal cord injury. The crude incidence rate was 9.3 cases per million people/year. The patients' mean age increased from 38 years (2001-2005) to 48 years (2011-2015) (p spinal cord injury were falls in 44%, traffic accidents in 36.5%, diving accidents in 8.9% and others in 10.7%. While traffic accidents decreased, falls increased, particularly in the elderly (p injuries and injuries associated with poor functionality (p spinal cord injury in our environment. This change in the profile of new traumatic spinal cord injuries led us to reformulate the functional objectives planned for these patients upon admission to specialized units, to plan destination-upon-discharge in advance and to promote campaigns to prevent spinal cord injury in older adults.

Umbilical cord-care practices in low- and middle-income countries: a systematic review

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Patricia S. Coffey

2017-02-01

Full Text Available Abstract Background Neonatal sepsis is the third leading cause of deaths for infants in their first month of life. The newly cut umbilical cord can be a pathway for bacteria that can cause newborn sepsis and death. Optimal umbilical cord care practices for newborns and during the first week of life, especially in settings with poor hygiene, has the potential to avoid these preventable neonatal deaths. The purpose of this review of cord care practices is to assist in the development of behavior-change strategies to support introduction of novel cord-care regimens, particularly 7.1% chlorhexidine digluconate for umbilical cord care. Methods We searched domestic and international databases for articles that were published in English between January 1, 2000, and August 24, 2016. We found 321 articles and reviewed 65 full-text articles using standardized inclusion criteria. The primary criteria for inclusion was a description of substances applied to the umbilical cord stump in the days following birth. Results We included 46 articles in this review of umbilical cord-care practices. Articles included data from 15 low- and middle-income countries in sub-Saharan Africa (8 countries, Asia (5 countries, North Africa (1 country, and Latin America and the Caribbean (1 country. Findings from this review suggest that documentation of cord-care practices is not consistent throughout low- and middle-income countries, yet existing literature depicts a firm tradition of umbilical cord care in every culture. Cord-care practices vary by country and by regions or cultural groups within a country and employ a wide range of substances. The desire to promote healing and hasten cord separation are the underlying beliefs related to application of substances to the umbilical cord. The frequency of application of the substance (either the number of days or the number of times per day the substance was applied, and source and cost of products used is not well

Spinal Cord Injury 101

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CO_2 capture from flue gas using clathrate formation in the presence of thermodynamic promoters

International Nuclear Information System (INIS)

Kim, Soyoung; Choi, Sung-Deuk; Seo, Yongwon

2017-01-01

Tetrahydrofuran (THF) as a water-soluble sII clathrate former, cyclopentane (CP) as a water-insoluble sII clathrate former, and tetra n-butyl ammonium chloride (TBAC) as a water-soluble semiclathrate former were used to investigate their thermodynamic promotion effects on clathrate-based CO_2 capture from simulated flue gas. The phase equilibria of CO_2 (20%) + N_2 (80%) + promoter clathrates at different promoter concentrations revealed that the presence of THF, CP, and TBAC could significantly reduce the clathrate formation pressure. THF solutions provided the highest gas uptake and steepest CO_2 concentration changes in the vapor phase, whereas TBAC solutions showed the highest CO_2 selectivity (∼61%) in the clathrate phase. CP solutions exhibited a slower formation rate, but their final gas uptake and CO_2 selectivity in the clathrate phase were comparable to the THF solutions. Raman spectroscopy confirmed the enclathration of both CO_2 and N_2 in the clathrate cages and a structural transition due to the inclusion of promoters in the clathrate phase. The overall experimental results indicate that TBAC is a viable thermodynamic promoter for clathrate-based CO_2 capture from simulated flue gas, considering the lower pressure requirement for clathrate formation, higher CO_2 enrichment in the clathrate phase, non-toxicity, and non-volatility. - Highlights: • Clathrate-based CO_2 capture was investigated in the presence of thermodynamic promoters. • THF, CP, and TBAC demonstrated a significant thermodynamic promotion for CO_2 (20%) + N_2 (80%) clathrates. • The highest gas uptake was observed for the THF (5.6 mol%) solution. • TBAC solutions showed the highest CO_2 selectivity in the clathrate phase (∼61%). • Raman spectroscopy confirmed the guest gas enclathration and clathrate structure.

Spinal Cord Injury 101

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Neuromuscular stimulation therapy after incomplete spinal cord injury promotes recovery of interlimb coordination during locomotion

Science.gov (United States)

Jung, R.; Belanger, A.; Kanchiku, T.; Fairchild, M.; Abbas, J. J.

2009-10-01

The mechanisms underlying the effects of neuromuscular electrical stimulation (NMES) induced repetitive limb movement therapy after incomplete spinal cord injury (iSCI) are unknown. This study establishes the capability of using therapeutic NMES in rodents with iSCI and evaluates its ability to promote recovery of interlimb control during locomotion. Ten adult female Long Evans rats received thoracic spinal contusion injuries (T9; 156 ± 9.52 Kdyne). 7 days post-recovery, 6/10 animals received NMES therapy for 15 min/day for 5 days, via electrodes implanted bilaterally into hip flexors and extensors. Six intact animals served as controls. Motor function was evaluated using the BBB locomotor scale for the first 6 days and on 14th day post-injury. 3D kinematic analysis of treadmill walking was performed on day 14 post-injury. Rodents receiving NMES therapy exhibited improved interlimb coordination in control of the hip joint, which was the specific NMES target. Symmetry indices improved significantly in the therapy group. Additionally, injured rodents receiving therapy more consistently displayed a high percentage of 1:1 coordinated steps, and more consistently achieved proper hindlimb touchdown timing. These results suggest that NMES techniques could provide an effective therapeutic tool for neuromotor treatment following iSCI.

Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.

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Banerjee, Dipanjan; Sinha, Archana; Saikia, Sudeshna; Gogoi, Bhaskarjyoti; Rathore, Arvind K; Das, Anindhya Sundar; Pal, Durba; Buragohain, Alak K; Dasgupta, Suman

2018-06-05

The transformation of macrophages into lipid loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger receptors expression and macrophage foam cell formation. Thus, present research explored the signaling pathway involved in inflammation induced macrophage foam cells formation and therefore, targeting this pathway might be useful for preventing macrophage foam cell formation. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Edaravone combined with Schwann cell transplantation may repair spinal cord injury in rats

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Shu-quan Zhang

2015-01-01

Full Text Available Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for the treatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T 9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-labeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-labeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined withSchwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

Science.gov (United States)

Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology

The combined effect of thermodynamic promoters tetrahydrofuran and cyclopentane on the kinetics of flue gas hydrate formation

DEFF Research Database (Denmark)

Daraboina, Nagu; von Solms, Nicolas

2015-01-01

) hydrate formation using a rocking cell apparatus. Hydrate formation and decomposition kinetics were investigated by constant cooling (hydrate nucleation temperature) and isothermal (hydrate nucleation time) methods. Improved (synergistic) hydrate formation kinetics (hydrate nucleation and growth) were...... of these two promoters is favorable both thermodynamically and kinetically for hydrate formation from flue gas....

Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho-associated kinase II in spinal cord injury rats

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You-jiang Min

2017-01-01

Full Text Available Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase (ROCK signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan (GV3, Dazhui (GV14, Zusanli (ST36 and Ciliao (BL32 and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the mRNA and protein expression of Rho-A and Rho-associated kinase II (ROCKII of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKII. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKII. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of RhoA and ROCKII. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.

Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

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Sarah E. Mondello

2014-02-01

Full Text Available Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury. This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

Spinal Cord Injury 101

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ROCK inhibition with Y27632 promotes the proliferation and cell cycle progression of cultured astrocyte from spinal cord.

Science.gov (United States)

Yu, Zhiyuan; Liu, Miao; Fu, Peicai; Xie, Minjie; Wang, Wei; Luo, Xiang

2012-12-01

Rho-associated Kinase (ROCK) has been identified as an important regulator of proliferation and cell cycle progression in a number of cell types. Although its effects on astrocyte proliferation have not been well characterized, ROCK has been reported to play important roles in gap junction formation, morphology, and migration of astrocytes. In the present study, our aim was to investigate the effect of ROCK inhibition by [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride] (Y27632) on proliferation and DNA synthesis in cultured astrocytes from rat spinal cord and the possible mechanism involved. Western blots showed that treatment of astrocytes with Y27632 increased their expression of cyclin D1, CDK4, and cyclin E, thereby causing cell cycle progression. Furthermore, Y27632-induced astrocyte proliferation was mediated through the extracellular-signal-regulated kinase signaling cascade. These results indicate the importance of ROCK in astrocyte proliferation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway

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Kai Gao

2015-01-01

Full Text Available The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, ca-spase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental findings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

Umbilical Cord Blood Banking for Transplantation in Morocco: Problems and opportunities

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Mazini L

2014-11-01

Full Text Available Since the success of the first umbilical cord blood (UCB transplantation in a child with Fanconi anaemia in 1989, great interests have emerged for this source of stem cells. UCB provides an unlimited source of ethnically diverse stem cells and is an alternative for bone marrow (BM and peripheral blood (PB heamatopoietic stem cell transplantation (HSCT. Thus, UCB and manipulated stem cells are now collected and banked according to international accreditation standards for listing on registries allowing rapid search and accessibility worldwide. This work aims to identify problems limiting the creation of a Moroccan cord blood bank and to highlight opportunities and issues of a new legislation promoting additional applications of cell therapy.

Stem Cells: New Hope For Spinal Cord Injury

Directory of Open Access Journals (Sweden)

Gazdic Marina

2015-03-01

Full Text Available Stem cell therapy offers several attractive strategies for spinal cord repair. The regenerative potential of pluripotent stem cells was confirmed in an animal model of Spinal Cord Injury (SCI; nevertheless, optimized growth and differentiation protocols along with reliable safety assays should be established prior to the clinical application of hESCs and iPSCs. Th e therapeutic effects of mesenchymal stem cells (MSCs in SCI result from neurotrophin secretion, angiogenesis, and antiinflammatory actions. Several preclinical SCI studies have reported that the occurrence of axonal extension, remyelination and neuroprotection occur after the transplantation of olfactory ensheathing cells (OECs. The transplantation of neural stem cells NSCs (NSCs promotes partial functional improvement after SCI because of their potential to differentiate into neurons, oligodendrocytes, and astrocytes. The ideal source of stem cells for safe and efficient cell-based therapy for SCI remains a challenging issue that requires further investigation.

Spinal Cord Injury 101

Medline Plus

Full Text Available ... the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

Maresin 1 Promotes Inflammatory Resolution, Neuroprotection, and Functional Neurological Recovery After Spinal Cord Injury.

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Francos-Quijorna, Isaac; Santos-Nogueira, Eva; Gronert, Karsten; Sullivan, Aaron B; Kopp, Marcel A; Brommer, Benedikt; David, Samuel; Schwab, Jan M; López-Vales, Ruben

2017-11-29

Resolution of inflammation is defective after spinal cord injury (SCI), which impairs tissue integrity and remodeling and leads to functional deficits. Effective pharmacological treatments for SCI are not currently available. Maresin 1 (MaR1) is a highly conserved specialized proresolving mediator (SPM) hosting potent anti-inflammatory and proresolving properties with potent tissue regenerative actions. Here, we provide evidence that the inappropriate biosynthesis of SPM in the lesioned spinal cord hampers the resolution of inflammation and leads to deleterious consequences on neurological outcome in adult female mice. We report that, after spinal cord contusion injury in adult female mice, the biosynthesis of SPM is not induced in the lesion site up to 2 weeks after injury. Exogenous administration of MaR1, a highly conserved SPM, propagated inflammatory resolution after SCI, as revealed by accelerated clearance of neutrophils and a reduction in macrophage accumulation at the lesion site. In the search of mechanisms underlying the proresolving actions of MaR1 in SCI, we found that this SPM facilitated several hallmarks of resolution of inflammation, including reduction of proinflammatory cytokines (CXCL1, CXCL2, CCL3, CCL4, IL6, and CSF3), silencing of major inflammatory intracellular signaling cascades (STAT1, STAT3, STAT5, p38, and ERK1/2), redirection of macrophage activation toward a prorepair phenotype, and increase of the phagocytic engulfment of neutrophils by macrophages. Interestingly, MaR1 administration improved locomotor recovery significantly and mitigated secondary injury progression in a clinical relevant model of SCI. These findings suggest that proresolution, immunoresolvent therapies constitute a novel approach to improving neurological recovery after acute SCI. SIGNIFICANCE STATEMENT Inflammation is a protective response to injury or infection. To result in tissue homeostasis, inflammation has to resolve over time. Incomplete or delayed

Spinal cord stimulation

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... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

CD14+ monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

International Nuclear Information System (INIS)

Wang, Ding; Chen, Ke; Du, Wei Ting; Han, Zhi-Bo; Ren, He; Chi, Ying

2010-01-01

Here, the effect of CD14 + monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-γ (IFN-γ) secretion capacities of CD4 + and CD8 + T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E 2 (PGE 2 ) as an important soluble mediator. CD14 + monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1β, either exogenously added or produced by CD14 + monocytes in culture, could trigger expression of high levels of PGE 2 by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE 2 expression, but also reversed the promotional effect of CD14 + monocytes and partially restored CD4 + and CD8 + T cell proliferation and IFN-γ secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

Spinal Cord Injury 101

Medline Plus

Full Text Available ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

Cord Blood Chimerism And Relapse After Haplo-Cord Transplantation

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van Besien, Koen; Koshy, Nebu; Gergis, Usama; Mayer, Sebastian; Cushing, Melissa; Rennert, Hannah; Slotky, Ronit; Mark, Tomer; Pearse, Roger; Rossi, Adriana; Phillips, Adrienne; Vasovic, Liljana; Ferrante, Rosanna; Hsu, Michael; Shore, Tsiporah

2018-01-01

Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic GVHD. But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with AML and MDS, engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% vs 11% Pdisease recurrence (46% vs 12%, P=0.007) Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% vs 15%, P=0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful GVL effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high. PMID:27333804

Fixed cord in spinal stenosis

International Nuclear Information System (INIS)

Levy, L.M.; Wang, H.; Francomano, C.; Hurko, O.; Carson, B.; Heffez, D.S.; DiChiro, G.; Bryan, R.N.

1990-01-01

This paper evaluates patients with cervical spinal canal compromise due to congenital anomalies (achondroplasia, Chiari malformation) and degenerative diseases using MR cord motion and cerebrospinal fluid (CSF) flow studies. Pulsatile longitudinal motion of the cervical cord was determined by means of cardiac-gated velocity phase contrast methods, including cine. Pathology included dwarfism (n = 15), Chiari malformation (n = 10), spondylosis (n = 10), and acute cord compression (n = 9). Symptomatic cases of congenital cervical stenosis had decreased cord motion, although CSF flow was not always significantly compromised. Postoperative cases demonstrated good cord and CSF motion, unless compression or obstruction was present

Regenerative Potential of Ependymal Cells for Spinal Cord Injuries Over Time

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Xiaofei Li

2016-11-01

Full Text Available Stem cells have a high therapeutic potential for the treatment of spinal cord injury (SCI. We have shown previously that endogenous stem cell potential is confined to ependymal cells in the adult spinal cord which could be targeted for non-invasive SCI therapy. However, ependymal cells are an understudied cell population. Taking advantage of transgenic lines, we characterize the appearance and potential of ependymal cells during development. We show that spinal cord stem cell potential in vitro is contained within these cells by birth. Moreover, juvenile cultures generate more neurospheres and more oligodendrocytes than adult ones. Interestingly, juvenile ependymal cells in vivo contribute to glial scar formation after severe but not mild SCI, due to a more effective sealing of the lesion by other glial cells. This study highlights the importance of the age-dependent potential of stem cells and post-SCI environment in order to utilize ependymal cell's regenerative potential.

What is the potential of oligodendrocyte progenitor cells to successfully treat human spinal cord injury?

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Yeung Trevor M

2011-09-01

Full Text Available Abstract Background Spinal cord injury is a serious and debilitating condition, affecting millions of people worldwide. Long seen as a permanent injury, recent advances in stem cell research have brought closer the possibility of repairing the spinal cord. One such approach involves injecting oligodendrocyte progenitor cells, derived from human embryonic stem cells, into the injured spinal cord in the hope that they will initiate repair. A phase I clinical trial of this therapy was started in mid 2010 and is currently underway. Discussion The theory underlying this approach is that these myelinating progenitors will phenotypically replace myelin lost during injury whilst helping to promote a repair environment in the lesion. However, the importance of demyelination in the pathogenesis of human spinal cord injury is a contentious issue and a body of literature suggests that it is only a minor factor in the overall injury process. Summary This review examines the validity of the theory underpinning the on-going clinical trial as well as analysing published data from animal models and finally discussing issues surrounding safety and purity in order to assess the potential of this approach to successfully treat acute human spinal cord injury.

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats

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Marta Rocha Araujo

2016-06-01

Full Text Available Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI with and without mesenchymal stem cells (MSC, to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV. Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1, decreased immunoreactivity of astrocytes (GFAP+ and greater activation of endogenous stem cells (nestin+ in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.

Early elective colostomy following spinal cord injury.

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Boucher, Michelle

Elective colostomy is an accepted method of bowel management for patients who have had a spinal cord injury (SCI). Approximately 2.4% of patients with SCI have a colostomy, and traditionally it is performed as a last resort several years after injury, and only if bowel complications persist when all other methods have failed. This is despite evidence that patients find a colostomy easier to manage and frequently report wishing it had been performed earlier. It was noticed in the author's spinal unit that increasing numbers of patients were requesting colostomy formation during inpatient rehabilitation following SCI. No supporting literature was found for this; it appears to be an emerging and untested practice. This article explores colostomy formation as a method of bowel management in patients with SCI, considers the optimal time for colostomy formation after injury and examines issues for health professionals.

Anterior spinal cord syndrome of unknown etiology

OpenAIRE

Klakeel, Merrine; Thompson, Justin; Srinivasan, Rajashree; McDonald, Frank

2015-01-01

A spinal cord injury encompasses a physical insult to the spinal cord. In the case of anterior spinal cord syndrome, the insult is a vascular lesion at the anterior spinal artery. We present the cases of two 13-year-old boys with anterior spinal cord syndrome, along with a review of the anatomy and vasculature of the spinal cord and an explanation of how a lesion in the cord corresponds to anterior spinal cord syndrome.

The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation

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Machova Urdzikova, Lucia; Karova, Kristyna; Ruzicka, Jiri; Kloudova, Anna; Shannon, Craig; Dubisova, Jana; Murali, Raj; Kubinova, Sarka; Sykova, Eva; Jhanwar-Uniyal, Meena; Jendelova, Pavla

2015-01-01

Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9–T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury. PMID:26729105

Spinal cord injury with central cord syndrome from surfing.

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Steinfeld, Yaniv; Keren, Yaniv; Haddad, Elias

2018-01-01

Central cord syndrome (CCS) is an injury to the center of the spinal cord. It is well known as a hyperextension injury, but it has never been described as a surfing injury. Our report describes this injury in detail. A 35-year-old male novice surfer presented to the emergency department with acute tetraplegia following falling off his surfboard and hitting sea floor at a shallow beach break. He was rescued by a fellow surfer while floating in the sea and unable to raise his head above sea level. Upon arrival at the hospital, tetraplegia and sensory deficits were noted. Radiological investigations showed advanced spinal stenosis at C4-6 levels. T2 magnetic resonance imaging (MRI) demonstrated myelopathy at C5-C6 level. He was diagnosed as having central cord syndrome, treated conservatively, and regained near full neurologic recovery after a month of rehabilitation. Unique sport activities lead to unique injuries. It is important to accurately describe these injuries in order to create protective measures against them. Neurologic injuries in surfers are uncommon. With low-energy trauma, surfer's myelopathy is still the most common diagnosis, but central cord syndrome should be in the differential diagnosis.

Optimal method for collection of umbilical cord blood: an Egyptian trial for a public cord blood bank.

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Bassiouny, M R; El-Chennawi, F; Mansour, A K; Yahia, S; Darwish, A

2015-06-01

Umbilical cord blood (UCB) contains stem cells and can be used as an alternative to bone marrow transplantation. Engraftment is dependent on the total nucleated cell (TNC) and CD34+ cell counts of the cord blood units. This study was designed to evaluate the effect of the method of collection of the UCB on the yield of the cord blood units. Informed consent was obtained from 100 eligible mothers for donation of cord blood. Both in utero and ex utero methods were used for collection. The cord blood volume was measured. The TNC and the CD34+ cell counts were enumerated. We have found that in utero collection gave significantly larger volumes of cord blood and higher TNC counts than ex utero collection. There was no significant difference between both methods regarding the CD34+ cell counts. This study revealed a significant correlation between the volume of the collected cord blood and both TNC and CD34+ cell counts. It is better to collect cord blood in utero before placental delivery to optimize the quality of the cord blood unit. © 2015 AABB.

[Impact of animal-assisted intervention on rehabilitation of patients with spinal cord injury].

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Zsoldos, Amanda; Sátori, Agnes; Zana, Agnes

2014-09-28

The animal-assisted programs represent an interdisciplinary approach. They can be integrated into preventive, therapeutic and rehabilitative processes as complementary methods. The aim of the study was to promote the psychological adaptation and social reintegration of patients who suffered spinal cord injury, as well as reducing depression and feelings of isolation caused by the long hospitalization. The hypothesis of the authors was that the animal-assisted intervention method can be effectively inserted into the rehabilitation process of individuals with spinal cord injury as complementary therapy. 15 adults with spinal cord injury participated in the five-week program, twice a week. Participants first filled out a questionnaire on socio-demographics, and after completion of the program they participated in a short, directed interview with open questions. During the field-work, after observing the participants, qualitative data analysis was performed. The results suggest that the therapeutic animal induced a positive effect on the emotional state of the patients. Participants acquired new skills and knowledge, socialization and group cohesion had been improved. The authors conclude that the animal-assisted activity complemented by therapeutic elements can be beneficial in patients undergoing spinal cord injury rehabilitation and that knowledge obtained from the study can be helpful in the development of a future animal-assisted therapy program for spinal cord injury patients.

Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins.

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Wang, Yaping; Cheng, Xiaoxin; He, Qian; Zheng, Yiyan; Kim, Dong H; Whittemore, Scott R; Cao, Qilin L

2011-04-20

Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cord could lead to new therapeutic strategies to enhance remyelination and functional recovery after SCI. In the present study, we show that reactive astrocytes from the injured rat spinal cord or their conditioned media inhibit OL differentiation of adult OPCs with concurrent promotion of astrocyte differentiation. The expression of bone morphogenetic proteins (BMP) is dramatically increased in the reactive astrocytes and their conditioned media. Importantly, blocking BMP activity by BMP receptor antagonist, noggin, reverse the effects of active astrocytes on OPC differentiation by increasing the differentiation of OL from OPCs while decreasing the generation of astrocytes. These data indicate that the upregulated bone morphogenetic proteins in the reactive astrocytes are major factors to inhibit OL differentiation of OPCs and to promote its astrocyte differentiation. These data suggest that manipulation of BMP signaling in the endogenous or grafted NSCs or OPCs may be a useful therapeutic strategy to increase their OL differentiation and remyelination and enhance functional recovery after SCI.

Role of biomaterials in neurorestoration after spinal cord injuries

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Ioana Stanescu

2016-05-01

Full Text Available Despite advances in knowledge and technology SCI remains one of the most severe and disabling disorders affecting young people. Spinal cord lesions result in permanent loss of motor, sensory and autonomic functions, causing an enormous impact on patient’s personal, social, familial and professional life. There is currently no effective treatment available to improve severe neurologic deficits and to decrease disability. Tissue-engineering techniques have developed a variety of scaffolds, made by biomaterials, used alone, incapsulated with cells or embedded with molecules, which are delivered to lesion site to achieve neural regeneration. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Biomaterials acts like cell-carriers for the injury site, but also as reservoirs for growth factors or biomolecules. Hydrogels are a promising therapeutical strategy in spinal cord repair. Nano-fibers provide a three-dimensional network, which mimic closely the native extracellular matrix, thus offering a better support for cell attachment and proliferation than traditional micro-structure. New strategies like pharmacologic treatments, cell therapies, gene therapies and biomaterial tissue engineering should combine to increase their synergistic effect and to obtain the expected functional recovery in spinal cord injured patients

Study on the Promotion Effect of Ionic Liquid on CH4 Hydrate Formation

International Nuclear Information System (INIS)

Shin, Ju-Young; Mun, Sungyong; Kang, Seong-Pil; Kim, Kisub

2013-01-01

In this study, we investigated the kinetics of gas hydrate formation in the presence of ionic liquid (IL). Hydroxyethyl-methyl-morpholinium chloride (HEMM-Cl) was chosen as a material for the promotion effect test. Phase equilibrium curve for CH 4 hydrate with aqueous IL solution was obtained and its induction time and consumed amount of CH 4 gas were also measured. Aqueous solutions containing 20-20,000 ppm of HEMM-Cl was prepared and studied at 70 bar and 274.15 K. To compare the measured results to those of the conventional promoter, sodium dodecyl sulfate was also tested at the same condition. Result showed that the hydrate equilibrium curve was shifted toward higher pressure and lower temperature region. In addition, the induction time on CH 4 hydrate formation in the presence of IL was not shown. The amount of consumed CH 4 was increased with the whole range of tested concentration of IL and the highest consumption of CH 4 happened at 1,000 ppm of HEMM-Cl. HEMM-Cl induced and enhanced the CH 4 hydrate formation with a small amount of addition. Obtained result is expected to be applied for the development of technologies such as gas storage and transport using gas hydrates

Media(ted) fabrications: how the science-media symbiosis helped 'sell' cord banking.

Science.gov (United States)

Michelle, Carolyn

2006-01-01

This paper considers the problematic role of the science-media symbiosis in the dissemination of misleading and emotionally manipulative information regarding services offered by CordBank, New Zealand's only umbilical cord blood banking facility. As this case study illustrates, the growing reliance of health and science reporters on the knowledge capital of medical specialists, biogenetic researchers, and scientists potentially enhances the ability of 'expert' sources to set the agenda for media representations of emerging medical and scientific developments, and may undermine the editorial independence of journalists and editors, many of whom in this case failed to critically evaluate deeply problematic claims regarding the current and future benefits of cord banking. Heavy reliance on established media frames of anecdotal personalization and technoboosterism also reinforced a proscience journalistic culture in which claims by key sources were uncritically reiterated and amplified, with journalistic assessments of the value of cord banking emphasizing potential benefits for individual consumers. It is argued that use of these media frames potentially detracts from due consideration of the broader social, ethical, legal, and health implications of emerging biomedical developments, along with the professional, personal, and increasingly also financial interests at stake in their public promotion, given the growing commercialization of biogenetic technologies.

Host-race formation: promoted by phenology, constrained by heritability.

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Whipple, A V; Abrahamson, W G; Khamiss, M A; Heinrich, P L; Urian, A G; Northridge, E M

2009-04-01

Host-race formation is promoted by genetic trade-offs in the ability of herbivores to use alternate hosts, including trade-offs due to differential timing of host-plant availability. We examined the role of phenology in limiting host-plant use in the goldenrod gall fly (Eurosta solidaginis) by determining: (1) whether phenology limits alternate host use, leading to a trade-off that could cause divergent selection on Eurosta emergence time and (2) whether Eurosta has the genetic capacity to respond to such selection in the face of existing environmental variation. Experiments demonstrated that oviposition and gall induction on the alternate host, Solidago canadensis, were the highest on young plants, whereas the highest levels of gall induction on the normal host, Solidago gigantea, occurred on intermediate-age plants. These findings indicate a phenological trade-off for host-plant use that sets up the possibility of divergent selection on emergence time. Heritability, estimated by parent-offspring regression, indicated that host-race formation is impeded by the amount of genetic variation, relative to environmental, for emergence time.

SPINAL CORD- A CADAVERIC STUDY

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Vijayamma K. N

2018-01-01

Full Text Available BACKGROUND Spinal cord is situated within the vertebral canal extending from the lower end of the medulla oblongata at the upper border of first cervical vertebra. In early foetal life, it extends throughout the length of the vertebral canal, and at the time of birth, it reaches the level of third lumbar vertebra. In adult, it ends at the lower border of first lumbar vertebra and thereafter continued as filum terminale, which gets attached to tip of coccyx. Spinal cord is covered by three protective membranes called spinal meninges, diameter, arachnoid and pia mater. The diameter and arachnoid mater extent up to second sacral vertebra and the pia mater forms filum terminale and extend at the tip of coccyx. MATERIALS AND METHODS Forty spinal cord cadaveric specimen were studied by dissection method after exposing the vertebral canal. The roots of spinal nerve were sectioned on both sides and the cord is released along with its coverings. The dura and arachnoid mater were incised longitudinally and the subarachnoid space, blood vessels, nerve roots, ligament denticulata, cervical and lumbar enlargements were observed. The blood vessels including radicular arteries were also studied photographed. RESULTS The spinal cord is a highly vascular structure situated within the vertebral canal, covered by diameter, arachnoid mater and pia mater. Spinal dura is thicker anteriorly than posteriorly. The pia mater forms linea splendens, which extend along the whole length of the cord in front of the anterior median fissure. The average length of the cord is 38 cm. The length and breadth of cervical enlargement was more compared to lumbar enlargement. The number of rootlets in both dorsal and ventral roots accounts more in cervical compared to other regions of the cord. The ligament denticulata is a thin transparent bands of pia mater attached on either sides of the cord between the dorsal and ventral roots of spinal nerves. The tooth like extensions are well

Optogenetics of the Spinal Cord: Use of Channelrhodopsin Proteins for Interrogation of Spinal Cord Circuits.

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Rahman, Habibur; Nam, Youngpyo; Kim, Jae-Hong; Lee, Won-Ha; Suk, Kyoungho

2017-12-29

Spinal cord circuits play a key role in receiving and transmitting somatosensory information from the body and the brain. They also contribute to the timing and coordination of complex patterns of movement. Under disease conditions, such as spinal cord injury and neuropathic pain, spinal cord circuits receive pain signals from peripheral nerves, and are involved in pain development via neurotransmitters and inflammatory mediators released from neurons and glial cells. Despite the importance of spinal cord circuits in sensory and motor functions, many questions remain regarding the relationship between activation of specific cells and behavioral responses. Optogenetics offers the possibility of understanding the complex cellular activity and mechanisms of spinal cord circuits, as well as having therapeutic potential for addressing spinal cord-related disorders. In this review, we discuss recent findings in optogenetic research employing the channelrhodopsin protein to assess the function of specific neurons and glia in spinal cord circuits ex vivo and in vivo. We also explore the possibilities and challenges of employing optogenetics technology in future therapeutic strategies for the treatment of spinal disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vocal cord dysfunction in children.

Science.gov (United States)

Noyes, Blakeslee E; Kemp, James S

2007-06-01

Vocal cord dysfunction is characterised by paradoxical vocal cord adduction that occurs during inspiration, resulting in symptoms of dyspnoea, wheeze, chest or throat tightness and cough. Although the condition is well described in children and adults, confusion with asthma often triggers the use of an aggressive treatment regimen directed against asthma. The laryngoscopic demonstration of vocal cord adduction during inspiration has been considered the gold standard for the diagnosis of vocal cord dysfunction, but historical factors and pulmonary function findings may provide adequate clues to the correct diagnosis. Speech therapy, and in some cases psychological counselling, is often beneficial in this disorder. The natural course and prognosis of vocal cord dysfunction are still not well described in adults or children.

Banking on cord blood stem cells.

Science.gov (United States)

Sullivan, Michael J

2008-07-01

Umbilical cord blood gifted to non-profit public cord blood banks is now routinely used as an alternative source of haematopoietic stem cells for allogeneic transplantation for children and adults with cancer, bone marrow failure syndromes, haemoglobinopathies and many genetic metabolic disorders. Because of the success and outcomes of public cord banking, many companies now provide private cord banking services. However, in the absence of any published transplant evidence to support autologous and non-directed family banking, commercial cord banks currently offer a superfluous service.

Spinal Cord Dysfunction (SCD)

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Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

Hybrid equation/agent-based model of ischemia-induced hyperemia and pressure ulcer formation predicts greater propensity to ulcerate in subjects with spinal cord injury.

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Alexey Solovyev

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

International bowel function extended spinal cord injury data set

DEFF Research Database (Denmark)

Krogh, K; Perkash, I; Stiens, S A

2008-01-01

and the ASIA Board. Relevant and interested scientific and professional organizations and societies (around 40) were also invited to review the data set and it was posted on the ISCoS and ASIA websites for 3 months to allow comments and suggestions. The ISCoS Scientific Committee, ISCoS Council and ASIA Board......STUDY DESIGN: International expert working group.Objective:To develop an International Bowel Function Extended Spinal Cord Injury (SCI) Data Set presenting a standardized format for the collection and reporting of an extended amount of information on bowel function. SETTING: Working group...... consisting of members appointed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS). METHODS: A draft prepared by the working group was reviewed by Executive Committee of the International SCI Standards and Data Sets and later by the ISCoS Scientific Committee...

International bowel function basic spinal cord injury data set

DEFF Research Database (Denmark)

Krogh, K; Perkash, I; Stiens, S A

2008-01-01

S Scientific Committee and the ASIA Board. Relevant and interested scientific and professional (international) organizations and societies (approximately 40) were also invited to review the data set and it was posted on the ISCoS and ASIA websites for 3 months to allow comments and suggestions. The ISCo......STUDY DESIGN: International expert working group. OBJECTIVE: To develop an International Bowel Function Basic Spinal Cord Injury (SCI) Data Set presenting a standardized format for the collection and reporting of a minimal amount of information on bowel function in daily practice or in research....... SETTING: Working group consisting of members appointed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS). METHODS: A draft prepared by the working group was reviewed by Executive Committee of the International SCI Standards and Data Sets, and later by ISCo...

Spinal cord swelling and candidiasis

International Nuclear Information System (INIS)

Ho, K.; Gronseth, G.; Aldrich, M.; Williams, A.

1982-01-01

Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was cauused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunsupporessed cancer patient. (orig.)

The use of recombinant nAG protein In spinal cord crush injury in a rat model

International Nuclear Information System (INIS)

Al-Qattan, M.M.; Al-Motairi, M.; Ah-Habib, A.

2017-01-01

Objective: To evaluate the therapeutic properties of nAG protein during the recovery following acute spinal cord injuries in the rat. Study Design: An experimental study. Place and Duration of Study: King Saud University, Riyadh, Saudi Arabia, from September 2014 to September 2015. Methodology: Eight rats were studied (4 control rats and 4 experimental rats; and hence 50% were controls and 50% were experimental). All rats were subjected to an acute spinal cord injury using the aneurysmal clip injury model. Immediately after the injury, a single intra-dural injection of either normal saline (in the control group) or the nAG protein (in the experimental group) was done. Assessment of both groups was done over a 6-week period with regard to weight maintenance, motor recovery scores, MRI and histopathology of the injury site. Results: Weight maintenance was seen in the experimental and not in the control rats. Starting at 3 weeks after injury, the motor recovery was significantly (p<0.05) better in the experimental group. MRI assessment at 6 weeks showed better maintenance of cord continuity and less fluid accumulation at the injury site in the nAG-treated group. Just proximal to the injury site, there was less gliosis in the experimental group compared to the control group. At the crush injury site, there was less tissue architecture distortion, less vacuole formation, and less granulation tissue formation in the experimental group. Conclusion: The local injection nAG protein enhances neuro-restoration, reduces gliosis, and reduces vacuole/ granulation tissue formation following acute spinal cord crush injury in the rat aneurysmal clip animal model. (author)

Spinal Cord Injury 101

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CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

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Wang, Ding, E-mail: qqhewd@gmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Chen, Ke, E-mail: chenke_59@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Du, Wei Ting, E-mail: duwtpumc@yahoo.com.cn [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); Han, Zhi-Bo, E-mail: zhibohan@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Ren, He, E-mail: knifesharp2000@hotmail.com [National Engineering Research Center of Cell Products, AmCellGene Co. Ltd, TEDA, Tianjin (China); Chi, Ying, E-mail: caizhuying@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); and others

2010-09-10

Here, the effect of CD14{sup +} monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-{gamma} (IFN-{gamma}) secretion capacities of CD4{sup +} and CD8{sup +} T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E{sub 2} (PGE{sub 2}) as an important soluble mediator. CD14{sup +} monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1{beta}, either exogenously added or produced by CD14{sup +} monocytes in culture, could trigger expression of high levels of PGE{sub 2} by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE{sub 2} expression, but also reversed the promotional effect of CD14{sup +} monocytes and partially restored CD4{sup +} and CD8{sup +} T cell proliferation and IFN-{gamma} secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

Wheelchair Tai Chi as a Therapeutic Exercise for Individuals with Spinal Cord Injury

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Wang, Yong Tai; Chang, Li-Shan; Chen, Shihui; Zhong, Yaping; Yang, Yi; Li, Zhanghua; Madison, Timothy

2015-01-01

Individuals with spinal cord injuries (SCI) rarely participate in health-promotion programs or wellness screenings due to the lack of accessibility, adaptations, and tertiary healthcare providers. An unconditioned body is more prone to suffer injury and is at risk for more severe health problems than a conditioned one. As is common in individuals…

MR imaging and spinal cord injury

International Nuclear Information System (INIS)

Azar-Kia, B.; Fine, M.; Naheedy, M.; Elias, D.

1987-01-01

MR imaging has significantly improved diagnostic capability of spinal cord injuries. Other available diagnostic modalities such as plain films, myelography, CT, and post-CT myelography have failed to consistently show the secific evidence of spinal cord injuries and their true extent. The authors are presenting our experiences with MR imaging in spinal column injury. They have found MR imaging to be the procedure of choice for prognostic evaluation of spinal cord trauma. They are showing examples of recent and old spinal cord injury such as hematomyelia, myelomalacia, transection, spinal cord edema, and cavitation

Spinal cord swelling and candidiasis

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Ho, K.; Gronseth, G.; Aldrich, M.; Williams, A.

1982-11-01

Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was caused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunosuppressed cancer patient.

Spinal-cord swelling in acute multiple sclerosis

International Nuclear Information System (INIS)

Kikuchi, Seiji; Tashiro, Kunio; Naganuma, Mutsuo; Hida, Kazutoshi; Iwasaki, Yoshinobu; Abe, Hiroshi; Miyasaka, Kazuo

1986-01-01

Despite the frequent involvement of the spinal cord by multiple sclerosis, reports concerning neuroradiological findings regarding these lesions have been limited; most of them have demonstrated a normal or small spinal cord. Two cases of acute paraparesis showed evidence of spinal-cord swelling on myelography and CT myelography, initially suggesting the diagnosis of an intramedullary tumor. Spinal-cord swelling was demonstrated more clearly on CT myelography than on conventional myelography. The diagnosis of multiple sclerosis was made with the aid of the CSF findings, the clinical course, and the contracting-cord sign. The ''contracting-cord sign'' means the diminution of the spinal-cord diameter in the chronic stage. Since acute multiple sclerosis may produce spinal-cord swelling simulating a tumor, careful investigations are necessary to avoid unwarranted surgical interventions. (author)

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

Science.gov (United States)

Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

Focal Anterior Displacement of the Thoracic Spinal Cord without Evidence of Spinal Cord Herniation or an Intradural Mass

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Lee, Jong Yoon; Lee, Joon Woo; Lee, Guen Young; Kang, Heung Sik [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of)

2014-07-01

We report magnetic resonance imaging (MRI) findings on focal anterior displacement of the thoracic spinal cord in asymptomatic patients without a spinal cord herniation or intradural mass. We identified 12 patients (male:female = 6:6; mean age, 51.7; range, 15-83 years) between 2007 and 2011, with focal anterior displacement of the spinal cord and without evidence of an intradural mass or spinal cord herniation. Two radiologists retrospectively reviewed the MRI findings in consensus. An asymmetric spinal cord deformity with a focal dented appearance was seen on the posterior surface of the spinal cord in all patients, and it involved a length of 1 or 2 vertebral segments in the upper thoracic spine (thoracic vertebrae 1-6). Moreover, a focal widening of the posterior subarachnoid space was also observed in all cases. None of the patients had myelopathy symptoms, and they showed no focal T2-hyperintensity in the spinal cord with the exception of one patient. In addition, cerebrospinal fluid (CSF) flow artifacts were seen in the posterior subarachnoid space of the affected spinal cord level. Computed tomography myelography revealed preserved CSF flow in the two available patients. Focal anterior spinal cord indentation can be found in the upper thoracic level of asymptomatic patients without a spinal cord herniation or intradural mass.

Focal Anterior Displacement of the Thoracic Spinal Cord without Evidence of Spinal Cord Herniation or an Intradural Mass

International Nuclear Information System (INIS)

Lee, Jong Yoon; Lee, Joon Woo; Lee, Guen Young; Kang, Heung Sik

2014-01-01

We report magnetic resonance imaging (MRI) findings on focal anterior displacement of the thoracic spinal cord in asymptomatic patients without a spinal cord herniation or intradural mass. We identified 12 patients (male:female = 6:6; mean age, 51.7; range, 15-83 years) between 2007 and 2011, with focal anterior displacement of the spinal cord and without evidence of an intradural mass or spinal cord herniation. Two radiologists retrospectively reviewed the MRI findings in consensus. An asymmetric spinal cord deformity with a focal dented appearance was seen on the posterior surface of the spinal cord in all patients, and it involved a length of 1 or 2 vertebral segments in the upper thoracic spine (thoracic vertebrae 1-6). Moreover, a focal widening of the posterior subarachnoid space was also observed in all cases. None of the patients had myelopathy symptoms, and they showed no focal T2-hyperintensity in the spinal cord with the exception of one patient. In addition, cerebrospinal fluid (CSF) flow artifacts were seen in the posterior subarachnoid space of the affected spinal cord level. Computed tomography myelography revealed preserved CSF flow in the two available patients. Focal anterior spinal cord indentation can be found in the upper thoracic level of asymptomatic patients without a spinal cord herniation or intradural mass

Spinal Cord Injury 101

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Full Text Available ... spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

Aging promotes todorokite formation from layered manganese oxide at near-surface conditions

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Cui, Haojie [Chinese Academy of Sciences, Xiamen (China). Key Lab. of Urban Environment and Health; Huazhong Agricultural Univ., Ministry of Agriculture, Wuhan (China). Key Lab. of Subtropical Agricultural Resources and Environment; Liu, Fan; Feng, Xionghan; Tan, Wenfeng [Huazhong Agricultural Univ., Ministry of Agriculture, Wuhan (China). Key Lab. of Subtropical Agricultural Resources and Environment; Wang, Ming Kuang [National Taiwan Univ., Taipei (China). Dept. of Agricultural Chemistry

2010-12-15

Todorokite is one common manganese oxide in soils and sediments and is commonly formed from layered Na-buserite. Aging processes can alter the physicochemical properties of freshly formed Na-buserite in natural environments. However, it is not clear whether and how aging affects the formation of todorokites. In the present paper, Na-buserite with aging treatment was employed to prepare todorokite at atmospheric pressure to investigate the effects of aging treatment of Na-buserite on the formation of todorokite. Four aged Na-buserite samples, which are produced through oxidation of Mn{sup 2+} in concentrated NaOH medium by O{sub 2} with aging for 3, 6, 9, and 12 months, were employed to investigate the effects of aging processes on the transformation from Na-buserite to todorokite by Mg{sup 2+}-templating reaction at atmospheric pressure. The manganese oxides were examined using X-ray diffraction (XRD), elemental analysis, determinations of the average manganese oxidation number, infrared spectroscopy (IR), and transmission electron microscopy (TEM). The XRD, IR, and elemental analyses indicate that aging treatment can alter the substructure of the freshly synthesized Na-buserite. During the aging process, some of the Mn(III) may migrate into the interlayer region or disproportionate to form Mn{sup 2+} and Mn{sup 4+} from the layer of Na-buserite and the concomitant formation of layer vacancies. The interlayer Mn{sup 3+} or Mn{sup 2+} occupied above or below the layer vacancy sites and become corner-sharing octahedral. XRD analyses and TEM clearly show that the transformation from Na-buserite to todorokite was promoted by aging treatments. The alterations of substructure of aged Na-buserites can promote the rearrangement of manganese to construct a tunnel structure during the transformation from layered manganese oxides to tunnel-structure todorokite at atmospheric pressure. The transformation from Na-buserite to todorokite was promoted by aging treatments at

Spinal Cord Injury 101

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Full Text Available ... of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury

Science.gov (United States)

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

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.

Spinal Cord Injury 101

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Full Text Available ... About Media Donate Spinal Cord Injury Medical Expert Videos ... Home Kim Eberhardt Muir, MS Coping with a New Injury Robin Dorman, PsyD Sex and Fertility After Spinal Cord Injury Diane M. ...

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation.

Science.gov (United States)

Dou, John; Schmidt, Rebecca J; Benke, Kelly S; Newschaffer, Craig; Hertz-Picciotto, Irva; Croen, Lisa A; Iosif, Ana-Maria; LaSalle, Janine M; Fallin, M Daniele; Bakulski, Kelly M

2018-01-01

Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (P PC1 = 1.4 × 10 -9 ; P PC2 = 2.9 × 10 -5 ; P PC3 = 3.8 × 10 -5 ; P PC4 = 4.2 × 10 -6 ; P PC5 = 9.9 × 10 -13 , P PC6 = 1.3 × 10 -11 ) and not with sample type (P PC1-6 >0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted Pcoat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models.

Science.gov (United States)

Abdullahi, Dauda; Annuar, Azlina Ahmad; Mohamad, Masro; Aziz, Izzuddin; Sanusi, Junedah

2017-01-01

It has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

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

Science.gov (United States)

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

2016-10-01

We review the pathophysiology and imaging findings of acute traumatic spinal cord injury (SCI), cervical spondylotic myelopathy, and briefly review the much less common cord herniation as a unique cause of myelopathy. Acute traumatic SCI is devastating to the patient and the costs to society are staggering. There are currently no "cures" for SCI and the only accepted pharmacologic treatment regimen for traumatic SCI is currently being questioned. Evaluation and prognostication of SCI is a demanding area with significant deficiencies, including lack of biomarkers. Accurate classification of SCI is heavily dependent on a good clinical examination, the results of which can vary substantially based upon the patient׳s condition or comorbidities and the skills of the examiner. Moreover, the full extent of a patients׳ neurologic injury may not become apparent for days after injury; by then, therapeutic response may be limited. Although magnetic resonance imaging (MRI) is the best imaging modality for the evaluation of spinal cord parenchyma, conventional MR techniques do not appear to differentiate edema from axonal injury. Recently, it is proposed that in addition to characterizing the anatomic extent of injury, metrics derived from conventional MRI and diffusion tensor imaging, in conjunction with the neurological examination, can serve as a reliable objective biomarker for determination of the extent of neurologic injury and early identification of patients who would benefit from treatment. Cervical spondylosis is a common disorder affecting predominantly the elderly with a potential to narrow the spinal canal and thereby impinge or compress upon the neural elements leading to cervical spondylotic myelopathy and radiculopathy. It is the commonest nontraumatic cause of spinal cord disorder in adults. Imaging plays an important role in grading the severity of spondylosis and detecting cord abnormalities suggesting myelopathy. Copyright © 2016 Elsevier Inc. All rights

Spinal Cord Injury 101

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Full Text Available ... of Spinal Cord Injury Rehabilitation Kristine Cichowski, MS Occupational Therapy after Spinal Cord Injury Katie Powell, OT ... does not provide medical advice, recommend or endorse health care products or services, or control the information ...

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Full Text Available ... play_arrow What are the chances of regaining feeling and mobility after a spinal cord injury? play_arrow How long does it usually take for feeling and movement to return after a spinal cord ...

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Full Text Available ... Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ... a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? ...

Long-Term Safety Issues of iPSC-Based Cell Therapy in a Spinal Cord Injury Model: Oncogenic Transformation with Epithelial-Mesenchymal Transition

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Satoshi Nori

2015-03-01

Full Text Available Previously, we described the safety and therapeutic potential of neurospheres (NSs derived from a human induced pluripotent stem cell (iPSC clone, 201B7, in a spinal cord injury (SCI mouse model. However, several safety issues concerning iPSC-based cell therapy remain unresolved. Here, we investigated another iPSC clone, 253G1, that we established by transducing OCT4, SOX2, and KLF4 into adult human dermal fibroblasts collected from the same donor who provided the 201B7 clone. The grafted 253G1-NSs survived, differentiated into three neural lineages, and promoted functional recovery accompanied by stimulated synapse formation 47 days after transplantation. However, long-term observation (for up to 103 days revealed deteriorated motor function accompanied by tumor formation. The tumors consisted of Nestin+ undifferentiated neural cells and exhibited activation of the OCT4 transgene. Transcriptome analysis revealed that a heightened mesenchymal transition may have contributed to the progression of tumors derived from grafted cells.

Multiple roles for apoptosis facilitating condensation of the Drosophila ventral nerve cord.

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Page, Damon T; Olofsson, Birgitta

2008-02-01

At the end of embryogenesis, the ventral nerve cord (VNC) of Drosophila undergoes a shape change, termed condensation. During condensation the length of the VNC shortens by 25%, a process dependent on extracellular matrix deposited by hemocytes, an intact cytoskeleton of glia and neurons and neural activity. Here we show that cell death contributes to nerve cord shortening. Firstly, apoptosis occurs at the interface of the epidermis and the nerve cord where it plays a role in the separation of these two tissues. Separation precedes condensation and in conditions where separation is prevented, condensation fails. Secondly, many cells undergo apoptosis within VNC during condensation. This cell death is localized mainly to the posterior part of the nerve cord where more than half of all cell death occurs. Preventing apoptosis either in neurons or glia partially inhibits VNC shortening during condensation. Despite the importance of midline glia in axon tract development, preventing midline glia cell death results in normal hatching and adult formation. We find that undead midline glia are eliminated from the midline and become mispositioned or expelled from the nervous system. We suggest that this represent a form of pattern repair that operates to reduce the impact of the additional cells. (c) 2008 Wiley-Liss, Inc.

Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats

Directory of Open Access Journals (Sweden)

Braniff de la Torre Valdovinos

2016-01-01

Full Text Available We performed experiments in cats with a spinal cord penetrating hemisection at T13-L1 level, with and without tamoxifen treatment. The results showed that the numbers of the ipsilateral and contralateral ventral horn neurons were reduced to less than half in the nontreated animals compared with the treated ones. Also, axons myelin sheet was preserved to almost normal values in treated cats. On the contrary, in the untreated animals, their myelin sheet was reduced to 28% at 30 days after injury (DAI, in both the ipsilateral and contralateral regions of the spinal cord. Additionally, we made hindlimb kinematics experiments to study the effects of tamoxifen on cat locomotion after the injury: at 4, 16, and 30 DAI. We observed that the ipsilateral hindlimb angular displacement (AD of the pendulum-like movements (PLM during gait locomotion was recovered to almost normal values in treated cats. Contralateral PLM acquired similar values to those obtained in intact cats. At 4 DAI, untreated animals showed a compensatory increment of PLM occurring in the contralateral hindlimb, which was partially recovered at 30 DAI. Our findings indicate that tamoxifen exerts a neuroprotective effect and preserves or produces myelinated axons, which could benefit the locomotion recovery in injured cats.

Spinal Cord Injury 101

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Full Text Available ... Cord Injury Allen Heinemann, PhD How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a ...

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Full Text Available ... spinal cord injuries? play_arrow What is “Braingate” research? play_arrow How would stem-cell therapies work ... cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can ...

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Full Text Available ... Spinal Cord Injury Guy W. Fried, MD Substance Abuse and Spinal Cord Injury Allen Heinemann, PhD How ... arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

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Tethered Spinal Cord Syndrome

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... cord over time and may be exacerbated during sports or pregnancy, or may be due to narrowing of the ... cord over time and may be exacerbated during sports or pregnancy, or may be due to narrowing of the ...

Extending technology-aided leisure and communication programs to persons with spinal cord injury and post-coma multiple disabilities.

Science.gov (United States)

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Ricciuti, Riccardo A; Trignani, Roberto; Oliva, Doretta; Signorino, Mario; D'Amico, Fiora; Sasanelli, Giovanni

2015-01-01

These two studies extended technology-aided programs to promote leisure and communication opportunities to a man with cervical spinal cord injury and a post-coma man with multiple disabilities. The studies involved the use of ABAB designs, in which A and B represented baseline and intervention phases, respectively. The programs focused on enabling the participants to activate songs, videos, requests, text messages, and telephone calls. These options were presented on a computer screen and activated through a small pressure microswitch by the man with spinal cord injury and a special touch screen by the post-coma man. To help the latter participant, who had no verbal skills, with requests and telephone calls, series of words and phrases were made available that he could activate in those situations. Data showed that both participants were successful in managing the programs arranged for them. The man with spinal cord injury activated mean frequencies of above five options per 10-min session. The post-coma man activated mean frequencies of about 12 options per 20-min session. Technology-aided programs for promoting leisure and communication opportunities might be successfully tailored to persons with spinal cord injury and persons with post-coma multiple disabilities. Implications for Rehabilitation Technology-aided programs may be critical to enable persons with pervasive motor impairment to engage in leisure activities and communication events independently. Persons with spinal cord injury, post-coma extended brain damage, and forms of neurodegenerative disease, such as amyotrophic lateral sclerosis, may benefit from those programs. The programs could be adapted to the participants' characteristics, both in terms of technology and contents, so as to improve their overall impact on the participants' functioning and general mood.

TMEM59 potentiates Wnt signaling by promoting signalosome formation.

Science.gov (United States)

Gerlach, Jan P; Jordens, Ingrid; Tauriello, Daniele V F; van 't Land-Kuper, Ineke; Bugter, Jeroen M; Noordstra, Ivar; van der Kooij, Johanneke; Low, Teck Y; Pimentel-Muiños, Felipe X; Xanthakis, Despina; Fenderico, Nicola; Rabouille, Catherine; Heck, Albert J R; Egan, David A; Maurice, Madelon M

2018-04-09

Wnt/β-catenin signaling controls development and adult tissue homeostasis by regulating cell proliferation and cell fate decisions. Wnt binding to its receptors Frizzled (FZD) and low-density lipoprotein-related 6 (LRP6) at the cell surface initiates a signaling cascade that leads to the transcription of Wnt target genes. Upon Wnt binding, the receptors assemble into large complexes called signalosomes that provide a platform for interactions with downstream effector proteins. The molecular basis of signalosome formation and regulation remains elusive, largely due to the lack of tools to analyze its endogenous components. Here, we use internally tagged Wnt3a proteins to isolate and characterize activated, endogenous Wnt receptor complexes by mass spectrometry-based proteomics. We identify the single-span membrane protein TMEM59 as an interactor of FZD and LRP6 and a positive regulator of Wnt signaling. Mechanistically, TMEM59 promotes the formation of multimeric Wnt-FZD assemblies via intramembrane interactions. Subsequently, these Wnt-FZD-TMEM59 clusters merge with LRP6 to form mature Wnt signalosomes. We conclude that the assembly of multiprotein Wnt signalosomes proceeds along well-ordered steps that involve regulated intramembrane interactions. Copyright © 2018 the Author(s). Published by PNAS.

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Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

Science.gov (United States)

Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Regulation of autophagy by AMP-activated protein kinase/sirtuin 1 pathway reduces spinal cord neurons damage.

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Yan, Peng; Bai, Liangjie; Lu, Wei; Gao, Yuzhong; Bi, Yunlong; Lv, Gang

2017-09-01

AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI). The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI) in vitro . The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining. We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro , indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro . Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI. Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

Morphological changes in different populations of bladder afferent neurons detected by herpes simplex virus (HSV) vectors with cell-type-specific promoters in mice with spinal cord injury.

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Shimizu, Nobutaka; Doyal, Mark F; Goins, William F; Kadekawa, Katsumi; Wada, Naoki; Kanai, Anthony J; de Groat, William C; Hirayama, Akihide; Uemura, Hirotsugu; Glorioso, Joseph C; Yoshimura, Naoki

2017-11-19

Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell-type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter. Two weeks after vector inoculation into the bladder wall, L1 and L6 dorsal root ganglia (DRG) were removed bilaterally for immunofluorescent staining using anti-mCherry antibody. The number of CMV promoter vector-labeled neurons was not altered after SCI. The number of CGRP and TRPV1 promoter vector-labeled neurons was significantly increased whereas the number of NF200 vector-labeled neurons was decreased in L6 DRG after SCI. The median size of CGRP promoter-labeled C-fiber neurons was increased from 247.0 in SI mice to 271.3μm 2 in SCI mice whereas the median cell size of TRPV1 promoter vector-labeled neurons was decreased from 245.2 in SI mice to 216.5μm 2 in SCI mice. CGRP and TRPV1 mRNA levels of laser-captured bladder afferent neurons labeled with Fast Blue were significantly increased in SCI mice compared to SI mice. Thus, using a novel HSV vector-mediated neuronal labeling technique, we found that SCI induces expansion of the CGRP- and TRPV1-expressing C-fiber cell population, which could contribute to C-fiber afferent hyperexcitability and NDO after SCI. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

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Bonnet Amandine

2012-09-01

Full Text Available Abstract Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1 is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.

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Bonnet, Amandine; Randrianarison-Huetz, Voahangy; Nzounza, Patrycja; Nedelec, Martine; Chazal, Maxime; Waast, Laetitia; Pene, Sabrina; Bazarbachi, Ali; Mahieux, Renaud; Bénit, Laurence; Pique, Claudine

2012-09-25

The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4⁺ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4⁺ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the

Pericytes Make Spinal Cord Breathless after Injury.

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Almeida, Viviani M; Paiva, Ana E; Sena, Isadora F G; Mintz, Akiva; Magno, Luiz Alexandre V; Birbrair, Alexander

2017-09-01

Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.

Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction.

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Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

2011-12-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Copyright © 2011 AlphaMed Press.

'The hospital was just like a home': self, service and the 'McCord Hospital Family'.

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Noble, Vanessa; Parle, Julie

2014-04-01

For more than a century, McCord Hospital, a partly private and partly state-subsidised mission hospital has provided affordable health-care services, as well as work and professional training opportunities for thousands of people in Durban, a city on the east coast of South Africa. This article focuses on one important aspect of the hospital's longevity and particular character, or 'organisational culture': the ethos of a 'McCord Family', integral to which were faith and a commitment to service. While recognising that families - including 'hospital families' like that at McCord - are contentious social constructs, with deeply embedded hierarchies and inequalities based on race, class and gender, we also consider however how the notion of 'a McCord family' was experienced and shared in complex ways. Indeed, during the twentieth century, this ethos was avidly promoted by the hospital's founders and managers and by a wide variety of employees and trainees. It also extended to people at a far geographical remove from Durban. Moreover, this ethos became so powerful that many patients felt that it shaped their convalescence experience positively. This article considers how this 'family ethos' was constructed and what made it so attractive to this hospital's staff, trainees and patients. Furthermore, we consider what 'work' it did for this mission hospital, especially in promoting bonds of multi-racial unity in the contexts of segregation and apartheid society. More broadly, it suggests that critical histories of the ways in which individuals, hospitals, faith and 'families' intersect may be of value for the future of hospitals as well as of interest in their past.

Cord Blood Banking for Potential Future Transplantation.

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Shearer, William T; Lubin, Bertram H; Cairo, Mitchell S; Notarangelo, Luigi D

2017-11-01

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that

Spinal Cord Injury 101

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Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

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Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

2014-03-18

SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

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Z.H. Wang

2014-04-01

Full Text Available SRY-related high-mobility-group box 9 (Sox9 gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs. After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

International Nuclear Information System (INIS)

Wang, Z.H.; Li, X.L.; He, X.J.; Wu, B.J.; Xu, M.; Chang, H.M.; Zhang, X.H.; Xing, Z.; Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y.

2014-01-01

SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering

CT-myelography of cervical cord injury

International Nuclear Information System (INIS)

Koyanagi, Izumi; Isu, Toyohiko; Iwasaki, Yoshinobu

1986-01-01

We reported seven cases of acute cervical cord injuries who were examined by CT-Myelography (CTM) within 7 days after trauma. The presence or absence of spinal cord enlargement, the initial neurological status and the neurological prognosis of these patients were studied. The neurological status of each patient was graded by the method of Frankel who defined five grades from A to E according to the severity of neurological deficits. Seven patients were all males. The youngest was 18 and the oldest was 73 years old, with a mean age of 40.7 years. Follows up periods ranged from 7 to 23 months. Result: CTM revealed the enlargement of spinal cord in two cases, who had severe neurological deficits and were graded to A. No neurological improvements were obtained in these cases. Five cases without cord enlargement were graded to A in one patient, B in one patient and C in three patients. Four of these five patients improved neurologically. One grade C patient remained grade C. Complete block of subarachnoid space was observed in two out of seven cases. Cord enlargement was present in one of them. Another case of complete block improved from C to D. Conclusion: We consider the presence of cord enlargement which can be demonstrated by CTM well correlates the severity of the cord damage and presume poor neurological prognosis. Internal decompression, such as posterior longitudinal myelotomy may be recommended to the case of cord enlargement. When the cord enlargement is absent, improvement of neurological grade is expected although the initial neurological status shows severe deficits. (author)

Twiddler's syndrome in spinal cord stimulation.

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Al-Mahfoudh, Rafid; Chan, Yuen; Chong, Hsu Pheen; Farah, Jibril Osman

2016-01-01

The aims are to present a case series of Twiddler's syndrome in spinal cord stimulators with analysis of the possible mechanism of this syndrome and discuss how this phenomenon can be prevented. Data were collected retrospectively between 2007 and 2013 for all patients presenting with failure of spinal cord stimulators. The diagnostic criterion for Twiddler's syndrome is radiological evidence of twisting of wires in the presence of failure of spinal cord stimulation. Our unit implants on average 110 spinal cord stimulators a year. Over the 5-year study period, all consecutive cases of spinal cord stimulation failure were studied. Three patients with Twiddler's syndrome were identified. Presentation ranged from 4 to 228 weeks after implantation. Imaging revealed repeated rotations and twisting of the wires of the spinal cord stimulators leading to hardware failure. To the best of our knowledge this is the first reported series of Twiddler's syndrome with implantable pulse generators (IPGs) for spinal cord stimulation. Hardware failure is not uncommon in spinal cord stimulation. Awareness and identification of Twiddler's syndrome may help prevent its occurrence and further revisions. This may be achieved by implanting the IPG in the lumbar region subcutaneously above the belt line. Psychological intervention may have a preventative role for those who are deemed at high risk of Twiddler's syndrome from initial psychological screening.

Astrocytes from the Contused Spinal Cord Inhibit Oligodendrocyte Differentiation of Adult Oligodendrocyte Precursor Cells by Increasing the Expression of Bone Morphogenetic Proteins

OpenAIRE

Wang, Yaping; Cheng, Xiaoxin; He, Qian; Zheng, Yiyan; Kim, Dong H.; Whittemore, Scott R.; Cao, Qilin L.

2011-01-01

Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cor...

Combination of autologous bone marrow mesenchymal stem cells and cord blood mononuclear cells in the treatment of chronic thoracic spinal cord injury in 27 cases

Directory of Open Access Journals (Sweden)

Lian-zhong WANG

2012-08-01

autologous bone marrow mesenshymal stem cells in combination with umbilical cord blood mononuclear cells could improve AIS grade, AISA motor and sensory scores to some extent in patients with chronic thoracic spinal cord injury by promoting the recovery of late spinal cord injury.

Diagnosis and surgical treatment of terminal syringomyelia within spinal cord combined with tethered cord syndrome

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Jing-cheng XIE

2016-04-01

Full Text Available Objective To summarize the clinical manifestations, imaging characteristics and experience of surgical treatment of spinal cord terminal syringomyelia with tethered cord syndrome (TCS.  Methods and Results Clinical data of 10 patients with spinal cord syringomyelia combined with TCS surgically treated under microscope from January 1999 to March 2014 in our hospital were retrospectively analyzed. There were 3 males and 7 females with average age of 15.06 years old (ranged from 2 to 35 years old. The course of disease ranged from 3 months to 20 years (average 42.17 months. Among those patients, one patient presented hydromyelia, 8 patients suffered from meningeal cyst within the sacral canal, and one patient were concurrent with sacral dermal sinus. The weakness of lower extremities, especially distal limbs, was the main clinical manifestation. Five patients were accompanied with bowel and bladder dysfunction and 5 patients with sensory disturbance below the level of syringomyelia, especially hypesthesia. Preoperative MRI showed conus medullaris disappeared at the end of spinal cord, and there was fluid signal in the lower spinal cord with hypo-intensity signal in T1WI and hyper-intensity signal in T2WI without enhancement. All patients underwent surgical procedures. Under microscope, filum terminale was cut off, drainage was performed, meningeal cyst within the sacral canal was removed, and tethered cord was released. The success rate of operations was 100%. The duration of surgery ranged from 1.52 to 3.07 h (average 2.15 h, with average intraoperative blood loss 220 ml (ranged from 100 to 410 ml. The tethering filum had been totally resected and histological examination showed typical filum tissue in all cases. No operative complication was found. Visual Analogue Scale (VAS score was decreased, and the lower limbs weakness as well as bowel and bladder dysfunction was gradually relieved after operation. The period of follow-up was ranged from 6

The Protective Effect of Spinal Cord Stimulation Postconditioning Against Spinal Cord Ischemia/Reperfusion Injury in Rabbits.

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Li, Huixian; Dong, Xiuhua; Jin, Mu; Cheng, Weiping

2018-01-18

Delayed paraplegia due to spinal cord ischemia/reperfusion injury (IRI) remains one of the most severe complications of thoracoabdominal aneurysm surgery, for which effective prevention and treatment is still lacking. The current study investigates whether spinal cord stimulation (SCS) postconditioning has neuroprotective effects against spinal cord IRI. Ninety-six New Zealand white male rabbits were randomly divided into four groups as follows: a sham group and three experimental groups (C group, 2 Hz group, and 50 Hz group) n = 24/group. Spinal cord ischemia was induced by transient infrarenal aortic balloon occlusion for 28 min, after which rabbits in group C underwent no additional intervention, while rabbits in the other two experimental groups underwent 2 Hz or 50 Hz epidural SCS for 30 min at the onset of reperfusion and then daily until sacrifice. Hind limb neurologic function of rabbits was assessed using Jacob scale. Lumbar spinal cords were harvested immediately after sacrifice for histological examination and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The number of viable α-motor neurons in ventral horn was counted and TUNEL-positive rate of α-motor neurons was calculated. Spinal cord IRI was caused by transient infrarenal aorta occlusion for 28 min. Both 2 Hz and 50 Hz SCS postconditioning had neuroprotective effects, particularly the 2 Hz SCS postconditioning. Comparing to C group and 50 Hz group, rabbits in the 2 Hz group demonstrated better hind limb motor function and a lower rate of TUNEL-positive α-motor neuron after eight hours, one day, three days, and seven days of spinal cord reperfusion. More viable α-motor neurons were preserved after one and three days of spinal cord reperfusion in 2 Hz group rabbits than in C group and 50 Hz group rabbits. SCS postconditioning at 2 Hz protected the spinal cord from IRI. © 2018 International Neuromodulation Society.

Neurorehabilitation and neuroprosthetic technologies to regain motor function following spinal cord injury

OpenAIRE

van den Brand, Rubia

2014-01-01

Spinal cord injury (SCI) leads to a range of disabilities, including locomotor impairments that seriously diminish the patients’ quality of life. Strategies to promote functional recovery after severe SCI will undoubtedly include approaches to regenerate injured pathways. The present work pursues a less ambitious, but potentially more rapidly applicable approach to improve function after SCI by applying neurorehabilitation augmented with neuroprosthetic technologies. In an intact situation, t...

Electroacupuncture improves microcirculation and neuronal morphology in the spinal cord of a rat model of intervertebral disc extrusion

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Dai-xun Jiang

2015-01-01

Full Text Available Most studies on spinal cord neuronal injury have focused on spinal cord tissue histology and the expression of nerve cell damage and repair-related genes. The importance of the microcirculation is often ignored in spinal cord injury and repair research. Therefore, in this study, we established a rat model of intervertebral disc extrusion by inserting a silica gel pad into the left ventral surface of T 13 . Electroacupuncture was used to stimulate the bilateral Zusanli point (ST36 and Neiting point (ST44 for 14 days. Compared with control animals, blood flow in the first lumbar vertebra (L 1 was noticeably increased in rats given electroacupuncture. Microvessel density in the T 13 segment of the spinal cord was increased significantly as well. The number of normal neurons was higher in the ventral horn of the spinal cord. In addition, vacuolation in the white matter was lessened. No obvious glial cell proliferation was visible. Furthermore, hindlimb motor function was improved significantly. Collectively, our results suggest that electroacupuncture can improve neuronal morphology and microcirculation, and promote the recovery of neurological functions in a rat model of intervertebral disc extrusion.

Reliable and fast volumetry of the lumbar spinal cord using cord image analyser (Cordial).

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Tsagkas, Charidimos; Altermatt, Anna; Bonati, Ulrike; Pezold, Simon; Reinhard, Julia; Amann, Michael; Cattin, Philippe; Wuerfel, Jens; Fischer, Dirk; Parmar, Katrin; Fischmann, Arne

2018-04-30

To validate the precision and accuracy of the semi-automated cord image analyser (Cordial) for lumbar spinal cord (SC) volumetry in 3D T1w MRI data of healthy controls (HC). 40 3D T1w images of 10 HC (w/m: 6/4; age range: 18-41 years) were acquired at one 3T-scanner in two MRI sessions (time interval 14.9±6.1 days). Each subject was scanned twice per session, allowing determination of test-retest reliability both in back-to-back (intra-session) and scan-rescan images (inter-session). Cordial was applied for lumbar cord segmentation twice per image by two raters, allowing for assessment of intra- and inter-rater reliability, and compared to a manual gold standard. While manually segmented volumes were larger (mean: 2028±245 mm 3 vs. Cordial: 1636±300 mm 3 , p<0.001), accuracy assessments between manually and semi-automatically segmented images showed a mean Dice-coefficient of 0.88±0.05. Calculation of within-subject coefficients of variation (COV) demonstrated high intra-session (1.22-1.86%), inter-session (1.26-1.84%), as well as intra-rater (1.73-1.83%) reproducibility. No significant difference was shown between intra- and inter-session reproducibility or between intra-rater reliabilities. Although inter-rater reproducibility (COV: 2.87%) was slightly lower compared to all other reproducibility measures, between rater consistency was very strong (intraclass correlation coefficient: 0.974). While under-estimating the lumbar SCV, Cordial still provides excellent inter- and intra-session reproducibility showing high potential for application in longitudinal trials. • Lumbar spinal cord segmentation using the semi-automated cord image analyser (Cordial) is feasible. • Lumbar spinal cord is 40-mm cord segment 60 mm above conus medullaris. • Cordial provides excellent inter- and intra-session reproducibility in lumbar spinal cord region. • Cordial shows high potential for application in longitudinal trials.

Surgical treatment of hip ankylosis due to heterotopic ossification secondary to spinal cord injury.

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Romero-Muñoz, L M; Barriga-Martín, A; DeJuan-García, J

2018-02-21

To expose our experience in the diagnostic and surgical treatment of neurogenic heterotopic ossification of the hip. We designed an observational retrospective descriptive study including 20 patients (30 hips) with neurogenic heterotopic ossification of the hip secondary to spinal cord injury attended in our institution in the last 10 years, with a minimum of one year follow-up. Medical files and imaging studies were reviewed. The study variables analyzed were: type and localization of neurogenic heterotopic ossification, pre-post excision range of motion, level and aetiology of spinal cord injury, ASIA score, smoking history, surgical approach and complications associated with surgery. A total of 20 patients were treated with resection of heterotopic ossification in 30 hips. 16 patients presented ASIA A spinal cord injury and 4 ASIA B spinal cord injury. Preoperatively all the patients had severe ankylosis in the hip that made sitting in a wheel chair and activities such as repositioning and hygiene difficult. The average postoperative motion at the follow-up evaluation was 90° in flexion, 20° of internal rotation and 40° of external rotation. Immediately after surgery all the patients followed a specific intensive physiotherapy regime for the hip and celecoxib 200 mg was administrated daily orally for a month to prevent recurrence of heterotopic bone formation. None of the patients reviewed suffered a recurrence of heterotopic bone formation. Surgical excision of hip ossification in order to achieve functional ROM of the hip is the best treatment for patients with neurogenic heterotopic ossification of the hip. Copyright © 2018 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Impact of 4.0% chlorhexidine cleansing of the umbilical cord on mortality and omphalitis among newborns of Sylhet, Bangladesh: design of a community-based cluster randomized trial

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Ahmed Saifuddin

2009-10-01

Full Text Available Abstract Background The World Health Organization recommends dry cord care for newborns but this recommendation may not be optimal in low resource settings where most births take place in an unclean environment and infections account for up to half of neonatal deaths. A previous trial in Nepal indicated that umbilical cord cleansing with 4.0% chlorhexidine could substantially reduce mortality and omphalitis risk, but policy changes await additional community-based data. Methods The Projahnmo Chlorhexidine study was a three-year, cluster-randomized, community-based trial to assess the impact of three cord care regimens on neonatal mortality and omphalitis. Women were recruited mid-pregnancy, received a basic package of maternal and neonatal health promotion messages, and were followed to pregnancy outcome. Newborns were visited at home by local village-based workers whose areas were randomized to either 1 single- or 2 7-day cord cleansing with 4.0% chlorhexidine, or 3 promotion of dry cord care as recommended by WHO. All mothers received basic messages regarding hand-washing, clean cord cutting, and avoidance of harmful home-base applications to the cord. Death within 28 days and omphalitis were the primary outcomes; these were monitored directly through home visits by community health workers on days 1, 3, 6, 9, 15, and 28 after birth. Discussion Due to report in early 2010, the Projahnmo Chlorhexidine Study examines the impact of multiple or single chlorhexidine cleansing of the cord on neonatal mortality and omphalitis among newborns of rural Sylhet District, Bangladesh. The results of this trial will be interpreted in conjunction with a similarly designed trial previously conducted in Nepal, and will have implications for policy guidelines for optimal cord care of newborns in low resource settings in Asia. Trial Registration ClinicalTrials.gov (NCT00434408

Umbilical Cord Blood: Counselling, Collection, and Banking.

Science.gov (United States)

Armson, B Anthony; Allan, David S; Casper, Robert F

2015-09-01

To review current evidence regarding umbilical cord blood counselling, collection, and banking and to provide guidelines for Canadian health care professionals regarding patient education, informed consent, procedural aspects, and options for cord blood banking in Canada. Selective or routine collection and banking of umbilical cord blood for future stem cell transplantation for autologous (self) or allogeneic (related or unrelated) treatment of malignant and non-malignant disorders in children and adults. Cord blood can be collected using in utero or ex utero techniques. Umbilical cord blood counselling, collection, and banking, education of health care professionals, indications for cord blood collection, short- and long-term risk and benefits, maternal and perinatal morbidity, parental satisfaction, and health care costs. Published literature was retrieved through searches of Medline and PubMed beginning in September 2013 using appropriate controlled MeSH vocabulary (fetal blood, pregnancy, transplantation, ethics) and key words (umbilical cord blood, banking, collection, pregnancy, transplantation, ethics, public, private). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to September 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Umbilical cord blood is a readily available source of hematopoetic stem cells used with increasing frequency as an alternative to

Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury.

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Cheng, Xiaoxin; Zheng, Yiyan; Bu, Ping; Qi, Xiangbei; Fan, Chunling; Li, Fengqiao; Kim, Dong H; Cao, Qilin

2018-01-01

Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role in lipid and cholesterol metabolism, has also been implicated in many neurological diseases. In this study, we examined the effect of apoE on the pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant (apoE -/- ) and wild-type mice received a T9 moderate contusion SCI and were evaluated using histological and behavioral analyses after injury. At 3days after injury, the permeability of spinal cord-blood-barrier, measured by extravasation of Evans blue dye, was significantly increased in apoE -/- mice compared to wild type. The inflammation and spared white matter was also significantly increased and decreased, respectively, in apoE -/- mice compared to the wild type ones. The apoptosis of both neurons and oligodendrocytes was also significantly increased in apoE -/- mice. At 42days after injury, the inflammation was still robust in the injured spinal cord in apoE -/- but not wild type mice. CD45+ leukocytes from peripheral blood persisted in the injured spinal cord of apoE -/- mice. The spared white matter was significantly decreased in apoE -/- mice compared to wild type ones. Locomotor function was significantly decreased in apoE -/- mice compared to wild type ones from week 1 to week 8 after contusion. Treatment of exogenous apoE mimetic peptides partially restored the permeability of spinal cord-blood-barrier in apoE -/- mice after SCI. Importantly, the exogenous apoE peptides decreased inflammation, increased spared white matter and promoted locomotor recovery in apoE -/- mice after SCI. Our results indicate that endogenous apoE plays important roles in maintaining the spinal cord-blood-barrier and decreasing inflammation and spinal cord tissue loss after SCI, suggesting its important neuroprotective function after SCI. Our results further suggest that exogenous apoE mimetic peptides could be a novel and promising neuroprotective reagent for SCI. Copyright �

Distribution of elements in human spinal cord

International Nuclear Information System (INIS)

Yukawa, Masae; Kobayashi, T.; Qiu, Y.; Kameda, N.; Ito, Y.; Otomo, E.

1992-01-01

The distribution of elements in human spinal cord was investigated on unfixed frozen cord material using PIXE technique. Distribution of Cu, Zn and Fe were not uniform in the cross section of the spinal cord and concentrations of these elements were higher in the anterior gray horn than in the other areas, while K and Cl distributed uniformly. The content of K changed along the spinal cord from the cervical to the lumbar level. These findings are discussed in relation to current understanding of the physiology of the spinal cord. (author)

Reassembly of adult human testicular cells: can testis cord-like structures be created in vitro?

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Mincheva, M; Sandhowe-Klaverkamp, R; Wistuba, J; Redmann, K; Stukenborg, J-B; Kliesch, S; Schlatt, S

2018-02-01

Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. In vitro approaches using dispersed single cell suspensions of human testes to generate seminiferous tubule structures and to initiate their functionality have as yet shown only limited success. Testes from 15 adult gender dysphoria patients (mean ± standard deviation age 35 ± 9.3 years) showing spermatogonial arrest became available for this study after sex-reassignment surgery. In vitro primary testicular somatic cell cultures were generated to explore the self-organizing ability of testicular somatic cells to form testis cords over a 2-week period. Morphological phenotype, protein marker expression and temporal dynamics of cell reassembly were analyzed. Cell suspensions obtained by two-step enzymatic digestion were plated onto glass coverslips in 24-well plates. To obtain adherent somatic cells, the supernatant was discarded on Day 2. The culture of the attached cell population was continued. Reassembly into cord-like structures was analyzed daily by microscopic observations. Endpoints were qualitative changes in morphology. Cell types were characterized by phase-contrast microscopy and immunohistochemistry. Dynamics of cord formation were recorded by time-lapse microscopy. Primary adult human testicular cells underwent sequential morphological changes including compaction and reaggregation resulting in round or elongated cord-like structures. Time-lapse video recordings within the first 4 days of culture revealed highly dynamic processes of migration and coalescence of reaggregated cells. The cellular movements were mediated by peritubular cells. Immunohistochemical analysis showed that both SRY-related high mobility box 9-positive Sertoli and α-smooth muscle actin-positive peritubular myoid cells

Radiation treatment of spinal cord neoplasms

International Nuclear Information System (INIS)

Smirnov, R.V.

1982-01-01

Results of radiation treatment of spinal cord neoplasms are presented. The results of combined (surgical and radiation) treatment of tumors are studied. On the whole it is noted that radiation treatment of initial spinal cord tumours is not practised on a large scale because of low radiostability of spinal cord

Spinal cord involvement in tuberculous meningitis.

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Garg, R K; Malhotra, H S; Gupta, R

2015-09-01

To summarize the incidence and spectrum of spinal cord-related complications in patients of tuberculous meningitis. Reports from multiple countries were included. An extensive review of the literature, published in English, was carried out using Scopus, PubMed and Google Scholar databases. Tuberculous meningitis frequently affects the spinal cord and nerve roots. Initial evidence of spinal cord involvement came from post-mortem examination. Subsequent advancement in neuroimaging like conventional lumbar myelography, computed tomographic myelography and gadolinium-enhanced magnetic resonance-myelography have contributed immensely. Spinal involvement manifests in several forms, like tuberculous radiculomyelitis, spinal tuberculoma, myelitis, syringomyelia, vertebral tuberculosis and very rarely spinal tuberculous abscess. Frequently, tuberculous spinal arachnoiditis develops paradoxically. Infrequently, spinal cord involvement may even be asymptomatic. Spinal cord and spinal nerve involvement is demonstrated by diffuse enhancement of cord parenchyma, nerve roots and meninges on contrast-enhanced magnetic resonance imaging. High cerebrospinal fluid protein content is often a risk factor for arachnoiditis. The most important differential diagnosis of tuberculous arachnoiditis is meningeal carcinomatosis. Anti-tuberculosis therapy is the main stay of treatment for tuberculous meningitis. Higher doses of corticosteroids have been found effective. Surgery should be considered only when pathological confirmation is needed or there is significant spinal cord compression. The outcome in these patients has been unpredictable. Some reports observed excellent recovery and some reported unfavorable outcomes after surgical decompression and debridement. Tuberculous meningitis is frequently associated with disabling spinal cord and radicular complications. Available treatment options are far from satisfactory.

Locomotor recovery after spinal cord hemisection/contusion injures in bonnet monkeys: footprint testing--a minireview.

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Rangasamy, Suresh Babu

2013-07-01

Spinal cord injuries usually produce loss or impairment of sensory, motor and reflex function below the level of damage. In the absence of functional regeneration or manipulations that promote regeneration, spontaneous improvements in motor functions occur due to the activation of multiple compensatory mechanisms in animals and humans following the partial spinal cord injury. Many studies were performed on quantitative evaluation of locomotor recovery after induced spinal cord injury in animals using behavioral tests and scoring techniques. Although few studies on rodents have led to clinical trials, it would appear imperative to use nonhuman primates such as macaque monkeys in order to relate the research outcomes to recovery of functions in humans. In this review, we will discuss some of our research evidences concerning the degree of spontaneous recovery in bipedal locomotor functions of bonnet monkeys that underwent spinal cord hemisection/contusion lesions. To our knowledge, this is the first report to discuss on the extent of spontaneous recovery in bipedal locomotion of macaque monkeys through the application of footprint analyzing technique. In addition, the results obtained were compared with the published data on recovery of quadrupedal locomotion of spinally injured rodents. We propose that the mechanisms underlying spontaneous recovery of functions in spinal cord lesioned monkeys may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Moreover, based on analysis of motor functions observed in locomotion in these subjected monkeys, we understand that spinal automatism and development of responses by afferent stimuli from outside the cord could possibly contribute to recovery of paralyzed hindlimbs. This report also emphasizes the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed

Regulation of autophagy by AMP-activated protein kinase/ sirtuin 1 pathway reduces spinal cord neurons damage

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Peng Yan

2017-09-01

Full Text Available Objective(s: AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1 signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI. Materials and Methods:The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI in vitro. The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining. Results: We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro, indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro. Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI. Conclusion: Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

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Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

2017-12-01

Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Therapeutic approaches for spinal cord injury

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Alexandre Fogaça Cristante

2012-10-01

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

Umbilical cord blood for unrelated bone marrow replacement; Asia bank and Japan cord blood bank network update.

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Mugishima, Hideo; Takahashi, Tuneo; Nagamura, Tokiko; Asano, Sigetaka; Saito, Hidehiko

2002-08-01

Cord blood offers many advantages including a high concentration of hematopoietic stem cells, a large number of potential donors, and ease of harvest. Furthermore, since there is no risk for either the mother or baby, few people refuse to donate. There is thought to be a low risk for virus contamination and also probably a low incidence and severity of GVHD. Cord blood can be obtained quickly without the assistance of a coordinator and one or 2 locus-mismatched HLA is usually acceptable. In Japan, there are 10 cord blood banks supported by the government. Between 1996 and June 2002, 9,500 units were registered with the Japan cord blood bank network (JCBBN). 630 units were delivered and most of these were transplanted. The status of registered cord blood units worldwide is shown. 59,081 units have been registered by NETCORD. The Japan cord blood bank network accounts for 13% of these units. I will discuss the Tokyo cord blood tank (TCBB). The bank at Tokyo, to which we belong, is one of the largest banks in Japan. We helped to establish Asia CORD in 2000 and have held annual conferences and meetings in Tokyo to exchange information. So far, China, Korea, Taiwan, Thailand, Viet Nam and Japan have participated. We accepted three trainees from the Ho Chi Minh City Blood Transfusion and Hematology Center for training in cord blood transplantation in May 2001. In January 2002, a patient with ALL received cord blood and was successfully engrafted at Ho Chi Minh City Blood Transfusion and Hematology Center. We present here the clinical outcome of these patients through Tokyo cord blood bank and Japan cord blood bank network. First, the number of CB units stored and registered at JCBBN and TCBB has increased rapidly over the past two years. Second, the survival rate of acute leukemia patients in release was significantly lower than that in patients in CR. Third, the engraftment rate in patients with metabolic disease (50%) was lower than that in patients with leukemia

Trauma: Spinal Cord Injury.

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Eckert, Matthew J; Martin, Matthew J

2017-10-01

Injuries to the spinal column and spinal cord frequently occur after high-energy mechanisms of injury, or with lower-energy mechanisms, in select patient populations like the elderly. A focused yet complete neurologic examination during the initial evaluation will guide subsequent diagnostic procedures and early supportive measures to help prevent further injury. For patients with injury to bone and/or ligaments, the initial focus should be spinal immobilization and prevention of inducing injury to the spinal cord. Spinal cord injury is associated with numerous life-threatening complications during the acute and long-term phases of care that all acute care surgeons must recognize. Published by Elsevier Inc.

Spinal-Cord-Injured Individual's Experiences of Having a Partner

DEFF Research Database (Denmark)

Angel, Sanne

2015-01-01

Having a partner is a strong factor in adaptation to the new life situation with a spinal cord injury (SCI). Still, more knowledge in detail about the partner's influences according to the experiences of individuals with SCI could contribute to the understanding of the situation after an injury. ...... and allowed SCI individuals the ability to self-realize. This promoted feelings of profound gratitude but also dependency. Thus, the SCI individual benefitted from the partner's support mentally and physically, which enabled a life that would not otherwise be possible....

The age factor in axonal repair after spinal cord injury: A focus on neuron-intrinsic mechanisms.

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Geoffroy, Cédric G; Meves, Jessica M; Zheng, Binhai

2017-06-23

Age is an important consideration for recovery and repair after spinal cord injury. Spinal cord injury is increasingly affecting the middle-aged and aging populations. Despite rapid progress in research to promote axonal regeneration and repair, our understanding of how age can modulate this repair is rather limited. In this review, we discuss the literature supporting the notion of an age-dependent decline in axonal growth after central nervous system (CNS) injury. While both neuron-intrinsic and extrinsic factors are involved in the control of axon growth after injury, here we focus on possible intrinsic mechanisms for this age-dependent decline. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Umbilical cord cell banking-implications for the future

International Nuclear Information System (INIS)

Gunning, Jennifer

2005-01-01

The first successful cord cell transplant to a sibling with Fanconi's anaemia took place 15 years ago. This proven utility of cord blood led to the establishment of cord blood banks both private and public and there are now nearly 100 cord blood banks worldwide. It is estimated that over 200,000 cord blood units (CBU) are held by the private sector and over 160,000 CBU are registered with the largest public cord blood registry. There is a tension between private cord blood banks, which store CBU for autologous or family use, and public banks, which store CBU for unrelated use and the ethics of private cord blood storage has been questioned. But more general ethical questions also arise regarding ownership, consent, confidentiality, costs and quality standards and patenting. In looking at these ethical issues one also needs to look at potential future use of cord blood stem cells. Up until now cord cells have principally been used in the treatment of paediatric blood and immune disorders. Improvements in cell expansion technology will make CBU more appropriate also for treating adults with such disorders. However, it has also been demonstrated that cord blood stem cells have the capacity to differentiate into other types of cells, neuronal, bone, epithelial and muscle which would have a future role to play in cell therapy and regenerative medicine

Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews

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Liu-Lin Xiong

2017-06-01

Full Text Available Hemi-sectioned spinal cord injury (hSCI can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient’s daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10. Hoechst 33342-labeled BMSCs derived from adult tree shrews were isolated, cultured, and implanted into the spinal cord around the injury site at 9 days after injury. The isolated BMSCs were able to survive, proliferate and release a variety of neurotrophic factors (NTFs both in vitro and in vivo. At 28 days after injury, compared with the sham group, the hSCI group displayed scar formation and dramatic elevations in the mean interleukin 1 beta (IL-1β density and cell apoptosis level, whereas the expression of signal transducer and activator of transcription 3 (STAT3 and ciliary neurotrophic factor (CNTF mRNA was reduced. Following BMSC transplantation, motoneurons extent of shrinkage were reduced and the animals’ Basso, Beattie, and Bresnahan (BBB locomotion scale scores were significantly higher at 21 and 28 days after injury when compared with the injured group. Moreover, the hSCI-induced elevations in scar formation, IL-1β, and cell apoptosis were reduced by BMSC transplantation to levels that were close to those of the sham group. Corresponding elevations in the expression of STAT3 and CNTF mRNA were observed in the hSCI + BMSCs group, and the levels were not significantly different from those observed in the sham group. Together, our results support that grafted BMSCs can significantly improve locomotor function in tree shrews subjected to hSCI and that this improvement is associated with the upregulation of CNTF and STAT3

Motor Axonal Regeneration After Partial and Complete Spinal Cord Transection

Science.gov (United States)

Lu, Paul; Blesch, Armin; Graham, Lori; Wang, Yaozhi; Samara, Ramsey; Banos, Karla; Haringer, Verena; Havton, Leif; Weishaupt, Nina; Bennett, David; Fouad, Karim; Tuszynski, Mark H.

2012-01-01

We subjected rats to either partial mid-cervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor (BDNF) gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared to several control groups. Combinatorial treatment generated motor axon regeneration beyond both C5 hemisection and complete transection sites. Yet despite formation of synapses with neurons below the lesion, motor outcomes worsened after partial cervical lesions and spasticity worsened after complete transection. These findings highlight the complexity of spinal cord repair, and the need for additional control and shaping of axonal regeneration. PMID:22699902

Thrombin binding to human brain and spinal cord

International Nuclear Information System (INIS)

McKinney, M.; Snider, R.M.; Richelson, E.

1983-01-01

Thrombin, a serine protease that regulates hemostasis, has been shown to stimulate the formation of cGMP in murine neuroblastoma cells. The nervous system in vivo thus may be postulated to respond to this blood-borne factor after it breaches the blood-brain barrier, as in trauma. Human alpha-thrombin was radiolabeled with 125I and shown to bind rapidly, reversibly, and with high affinity to human brain and spinal cord. These findings indicate the presence of specific thrombin-binding sites in nervous tissue and may have important clinical implications

The oblique cord of the forearm in man.

Science.gov (United States)

Tubbs, R Shane; O'Neil, James T; Key, Christopher D; Zarzour, Jessica G; Fulghum, Sarah B; Kim, Eugenia J; Lyerly, Michael J; Shoja, Mohammadali M; George Salter, E; Jerry Oakes, W

2007-05-01

There is minimal and often conflicting data in the literature regarding the oblique cord of the forearm. The current study seeks to elucidate further the anatomy of this structure of the upper extremity. In adult cadavers, the oblique cord was observed for and, when found, measurements were made of it. Ranges of motion were carried out while observation of the oblique cord was made. An oblique cord was found on 52.6% of sides. Gantzer's muscle was found on 55% of sides and, when present, had attachment into the oblique cord on five sides. The oblique cord was present on 13 sides with a Gantzer's muscle. Of the 20 sides with an oblique cord, no Gantzer's muscle was found on 10. The mean length of the oblique cord was 3.4 cm. In the majority of specimens, this cord tapered from proximal to distal. The proximal, middle, and distal widths of this structure had means 9, 7, and 4 mm, respectively. The oblique cord was found to travel approximately 45 degrees from a line drawn through the ulna and more or less traveled perpendicular to the insertion site of the bicipital tendon. This ligament was lax in the neutral position and with pronation became lax in all specimens. The oblique cord progressively became taut with increased supination from the neutral position and was maximally taut with the forearm fully supinated. Tautness of this cord was also found with distal distraction of the radius. Following the transection of the oblique cord, no discernable difference was observed in regard to maximal supination of the forearm or distal distraction of the radius. No obvious instability of the proximal forearm was found following transection of the oblique cord. Functionally, although the oblique cord may resist supination, it is unlikely that this structure affords significant stability to the proximal forearm, as it was often absent, of a very small caliber, and based on our observations, following its transection, the amount of supination of the forearm did not increase

Pregnancy Complications: Umbilical Cord Abnormalities

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... Umbilical cord abnormalities Umbilical cord abnormalities Now playing: E-mail to a friend Please fill in all fields. ... blood supply) to the baby. The two arteries transport waste from the baby to the placenta (where ...

Different phase delays of peripheral input to primate motor cortex and spinal cord promote cancellation at physiological tremor frequencies.

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Koželj, Saša; Baker, Stuart N

2014-05-01

Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to cycles of physiological tremor, but with opposite phases. Convergence of spinal and cortical activity onto motoneurons may thus produce phase cancellation and a reduction in tremor amplitude. The mechanisms underlying this phase difference are unknown. We investigated coherence between spinal and M1 activity with sensory input. In two anesthetized monkeys, we electrically stimulated the medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as independent Poisson processes (rate 10 Hz). Single units were recorded from M1 (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were additionally classified according to M1 subdivision (rostral/caudal, M1r/c). Spike-stimulus coherence analysis revealed significant coupling over a broad range of frequencies, with the strongest coherence at <50 Hz. Delays implied by the slope of the coherence phase-frequency relationship were greater than the response onset latency, reflecting the importance of late response components for the transmission of oscillatory inputs. The spike-stimulus coherence phase over the 6-13 Hz physiological tremor band differed significantly between M1 and spinal cells (phase differences relative to the cord of 2.72 ± 0.29 and 1.72 ± 0.37 radians for PTNs from M1c and M1r, respectively). We conclude that different phases of the response to peripheral input could partially underlie antiphase M1 and spinal cord activity during motor behavior. The coordinated action of spinal and cortical feedback will act to reduce tremulous oscillations, possibly improving the overall stability and precision of motor control. Copyright © 2014 the American Physiological Society.

Diffusion tensor imaging in spinal cord injury

International Nuclear Information System (INIS)

Kamble, Ravindra B; Venkataramana, Neelam K; Naik, Arun L; Rao, Shailesh V

2011-01-01

To assess the feasibility of spinal tractography in patients of spinal cord injury vs a control group and to compare fractional anisotropy (FA) values between the groups. Diffusion tensor imaging (DTI) was performed in the spinal cord of 29 patients (18 patients and 11 controls). DTI was done in the cervical region if the cord injury was at the dorsal or lumbar region and in the conus region if cord injury was in the cervical or dorsal region. FA was calculated for the patients and the controls and the values were compared. The mean FA value was 0.550±0.09 in the control group and 0.367±0.14 in the patients; this difference was statistically significant (P=0.001). Spinal tractography is a feasible technique to assess the extent of spinal cord injury by FA, which is reduced in patients of spinal cord injury, suggesting possible Wallerian degeneration. In future, this technique may become a useful tool for assessing cord injury patients after stem cell therapy, with improvement in FA values indicating axonal regeneration

Granulocyte Colony-Stimulating Factor Combined with Methylprednisolone Improves Functional Outcomes in Rats with Experimental Acute Spinal Cord Injury

Directory of Open Access Journals (Sweden)

William Gemio Jacobsen Teixeira

2018-02-01

Full Text Available OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment; G-CSF (G-CSF at the time of injury and daily over the next five days; methylprednisolone (methylprednisolone for 24 h; and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days. Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001. This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001. The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75. CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.

An adaptive neuromuscular controller for assistive lower-limb exoskeletons : A preliminary study on subjects with spinal cord injury

NARCIS (Netherlands)

Wu, Amy R.; Dzeladini, Florin; Brug, Tycho J.H.; Tamburella, Federica; Tagliamonte, Nevio L.; Van Asseldonk, Edwin H.F.; van der Kooij, H.; Ijspeert, Auke J.

2017-01-01

Versatility is important for a wearable exoskeleton controller to be responsive to both the user and the environment. These characteristics are especially important for subjects with spinal cord injury (SCI), where active recruitment of their own neuromuscular system could promote motor recovery.

An adaptive neuromuscular controller for assistive lower-limb exoskeletons : A preliminary study on subjects with spinal cord injury

NARCIS (Netherlands)

Wu, Amy R.; Dzeladini, Florin; Brug, Tycho J.H.; Tamburella, Federica; Tagliamonte, Nevio L.; Van Asseldonk, Edwin H.F.; Van Der Kooij, Herman; IJspeert, Auke Jan

2017-01-01

Versatility is important for a wearable exoskeleton controller to be responsive to both the user and the environment. These characteristics are especially important for subjects with spinal cord injury (SCI), where active recruitment of their own neuromuscular system could promote motor recovery.

Directly measuring spinal cord blood flow and spinal cord perfusion pressure via the collateral network: correlations with changes in systemic blood pressure.

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Kise, Yuya; Kuniyoshi, Yukio; Inafuku, Hitoshi; Nagano, Takaaki; Hirayasu, Tsuneo; Yamashiro, Satoshi

2015-01-01

During thoracoabdominal surgery in which segmental arteries are sacrificed over a large area, blood supply routes from collateral networks have received attention as a means of avoiding spinal cord injury. The aim of this study was to investigate spinal cord blood supply through a collateral network by directly measuring spinal cord blood flow and spinal cord perfusion pressure experimentally. In beagle dogs (n = 8), the thoracoabdominal aorta and segmental arteries L1-L7 were exposed, and a temporary bypass was created for distal perfusion. Next, a laser blood flow meter was placed on the spinal dura mater in the L5 region to measure the spinal cord blood flow. The following were measured simultaneously when the direct blood supply from segmental arteries L2-L7 to the spinal cord was stopped: mean systemic blood pressure, spinal cord perfusion pressure (blood pressure within the aortic clamp site), and spinal cord blood flow supplied via the collateral network. These variables were then investigated for evidence of correlations. Positive correlations were observed between mean systemic blood pressure and spinal cord blood flow during interruption of segmental artery flow both with (r = 0.844, P flow with and without distal perfusion (r = 0.803, P network from outside the interrupted segmental arteries, and high systemic blood pressure (∼1.33-fold higher) was needed to obtain the preclamping spinal cord blood flow, whereas 1.68-fold higher systemic blood pressure was needed when distal perfusion was halted. Spinal cord blood flow is positively correlated with mean systemic blood pressure and spinal cord perfusion pressure under spinal cord ischemia caused by clamping a wide range of segmental arteries. In open and endovascular thoracic and thoracoabdominal surgery, elevating mean systemic blood pressure is a simple and effective means of increasing spinal cord blood flow, and measuring spinal cord perfusion pressure seems to be useful for monitoring

Umbilical cord blood banking in the worldwide hematopoietic stem cell transplantation system: perspectives for Ukraine.

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Kalynychenko, T O

2017-09-01

Significant progress in the promotion of procedural technologies associated with the transplantation of hematopoietic stem cells caused a rapid increase in activity. The exchange of hematopoietic stem cells for unrelated donor transplantations is now much easier due to the relevant international professional structures and organizations established to support cooperation and standard setting, as well as rules for the functioning of both national donor registries and cord blood banks. These processes are increasing every year and are contributing to the outpacing rates of development in this area. Products within their country should be regulated by the competent government authorities. This study analyzes the work of international and national levels of support for transplantation activity in the field of unrelated hematopoietic stem cell transplantation, the standardization order of technologies, as well as data that justify the need to create a network of donated umbilical cord blood banks in Ukraine as a factor in the development of allogeneic transplantation. This will promote the accessibility of international standards for the treatment of serious diseases for Ukrainian citizens.

Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma.

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Bernhard, Wolfgang; Raith, Marco; Kunze, Rebecca; Koch, Vera; Heni, Martin; Maas, Christoph; Abele, Harald; Poets, Christian F; Franz, Axel R

2015-08-01

Choline is essential to human development, particularly of the brain in the form of phosphatidylcholine, sphingomyelin and acetylcholine, for bile and lipoprotein formation, and as a methyl group donator. Choline is actively transported into the fetus, and maternal supply correlates with cognitive outcome. Interruption of placental supply may therefore impair choline homeostasis in preterm infants. Determination of postnatal plasma concentrations of choline and its derivatives betaine and dimethylglycine (DMG) in preterm infants compared to cord and maternal blood matched for postmenstrual age (PMA). We collected plasma of very low-birth-weight infants undergoing neonatal intensive care (n = 162), cord plasma of term and preterm infants (n = 176, 24-42-week PMA), serum of parturients (n = 36), and plasma of healthy premenopausal women (n = 40). Target metabolites were analyzed with tandem mass spectrometry and reported as median (25th/75th percentiles). Cord plasma choline concentration was 41.4 (31.8-51.2) µmol/L and inversely correlated with PMA. In term but not in preterm infants, cord plasma choline was lower in girls than in boys. Prenatal glucocorticoid treatment did not affect choline levels in cord plasma, whereas betaine was decreased and DMG increased. In parturients and non-pregnant women, choline concentrations were 14.1 (10.3-16.9) and 8.8 (5.7-11.2) µmol/L, respectively, whereas betaine was lowest in parturients. After delivery, preterm infant plasma choline decreased to 20.8 (16.0-27.6) µmol/L within 48 h. Betaine and DMG correlated with plasma choline in all groups. In preterm infants, plasma choline decreases to 50 % of cord plasma concentrations, reflecting choline undernourishment and postnatal metabolic adaptation, and potentially contributing to impaired outcome.

Cost-effectiveness of private umbilical cord blood banking.

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Kaimal, Anjali J; Smith, Catherine C; Laros, Russell K; Caughey, Aaron B; Cheng, Yvonne W

2009-10-01

To investigate the cost-effectiveness of private umbilical cord blood banking. A decision-analytic model was designed comparing private umbilical cord blood banking with no umbilical cord blood banking. Baseline assumptions included a cost of $3,620 for umbilical cord blood banking and storage for 20 years, a 0.04% chance of requiring an autologous stem cell transplant, a 0.07% chance of a sibling requiring an allogenic stem cell transplant, and a 50% reduction in risk of graft-versus-host disease if a sibling uses banked umbilical cord blood. Private cord blood banking is not cost-effective because it cost an additional $1,374,246 per life-year gained. In sensitivity analysis, if the cost of umbilical cord blood banking is less than $262 or the likelihood of a child needing a stem cell transplant is greater than 1 in 110, private umbilical cord blood banking becomes cost-effective. Currently, private umbilical cord blood banking is cost-effective only for children with a very high likelihood of needing a stem cell transplant. Patients considering private blood banking should be informed of the remote likelihood that a unit will be used for a child or another family member. III.

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

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Xiujun Li

2017-06-01

Full Text Available Background/Aims: Mesenchymal stem cells (MSCs play an important role in regulating angiogenesis and immune balance. Abnormal proliferation and function of MSCs were reported at maternal fetal interface in patients with pre-eclampsia (PE. Micro-RNA-495 was known to be upregulated in the MSCs derived from patients with PE. However, it is not clear whether the up-regulated miR-495 is related to the pathogenesis of PE. Methods: We analyzed the expression of miR-495 in MSCs and umbilical cords derived from healthy pregnancies (NC and PE, then we upregulated or downregulated the expression of miR-495 in MSCs derived from NC and tested the proliferation, apoptosis, migration, invasion, tube formation and senescence. Results: In the current study, we found that the expression of miR-495 was significantly increased in both umbilical cord tissues and MSCs in patients with severe PE. Overexpressing miR-495 arrested cell cycle in S phase and promoted cell apoptosis. The supernatants from miR-495-overexpressed-MSCs inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-miR-495 had the opposite effects. Furthermore, we analyzed the senescence related β-galactosidase activity and CD146 and found that miR-495 induced the senescence of MSCs. Molecular mechanism studies confirmed that Bmi-1 mediated these effects of miR-495 on MSCs. Conclusion: Taken together, our data demonstrated that miR-495 induced senescence of MSCs may be involved in the pathogenesis of PE.

Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

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Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

2006-12-01

Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

Development of protective autoimmunity by immunization with a neural-derived peptide is ineffective in severe spinal cord injury.

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Susana Martiñón

Full Text Available Protective autoimmunity (PA is a physiological response to central nervous system trauma that has demonstrated to promote neuroprotection after spinal cord injury (SCI. To reach its beneficial effect, PA should be boosted by immunizing with neural constituents or neural-derived peptides such as A91. Immunizing with A91 has shown to promote neuroprotection after SCI and its use has proven to be feasible in a clinical setting. The broad applications of neural-derived peptides make it important to determine the main features of this anti-A91 response. For this purpose, adult Sprague-Dawley rats were subjected to a spinal cord contusion (SCC; moderate or severe or a spinal cord transection (SCT; complete or incomplete. Immediately after injury, animals were immunized with PBS or A91. Motor recovery, T cell-specific response against A91 and the levels of IL-4, IFN-γ and brain-derived neurotrophic factor (BDNF released by A91-specific T (T(A91 cells were evaluated. Rats with moderate SCC, presented a better motor recovery after A91 immunization. Animals with moderate SCC or incomplete SCT showed significant T cell proliferation against A91 that was characterized chiefly by the predominant production of IL-4 and the release of BDNF. In contrast, immunization with A91 did not promote a better motor recovery in animals with severe SCC or complete SCT. In fact, T cell proliferation against A91 was diminished in these animals. The present results suggest that the effective development of PA and, consequently, the beneficial effects of immunizing with A91 significantly depend on the severity of SCI. This could mainly be attributed to the lack of T(A91 cells which predominantly showed to have a Th2 phenotype capable of producing BDNF, further promoting neuroprotection.

‘The Hospital was just like a Home’: Self, Service and the ‘McCord Hospital Family’

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Noble, Vanessa; Parle, Julie

2014-01-01

For more than a century, McCord Hospital, a partly private and partly state-subsidised mission hospital has provided affordable health-care services, as well as work and professional training opportunities for thousands of people in Durban, a city on the east coast of South Africa. This article focuses on one important aspect of the hospital’s longevity and particular character, or ‘organisational culture’: the ethos of a ‘McCord Family’, integral to which were faith and a commitment to service. While recognising that families – including ‘hospital families’ like that at McCord – are contentious social constructs, with deeply embedded hierarchies and inequalities based on race, class and gender, we also consider however how the notion of ‘a McCord family’ was experienced and shared in complex ways. Indeed, during the twentieth century, this ethos was avidly promoted by the hospital’s founders and managers and by a wide variety of employees and trainees. It also extended to people at a far geographical remove from Durban. Moreover, this ethos became so powerful that many patients felt that it shaped their convalescence experience positively. This article considers how this ‘family ethos’ was constructed and what made it so attractive to this hospital’s staff, trainees and patients. Furthermore, we consider what ‘work’ it did for this mission hospital, especially in promoting bonds of multi-racial unity in the contexts of segregation and apartheid society. More broadly, it suggests that critical histories of the ways in which individuals, hospitals, faith and ‘families’ intersect may be of value for the future of hospitals as well as of interest in their past. PMID:24775429

Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury.

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Ozturk, Anil Murat; Sozbilen, Murat Celal; Sevgili, Elvin; Dagci, Taner; Özyalcin, Halit; Armagan, Guliz

2018-03-22

Spinal cord injury (SCI) leads to vascular damage and disruption of blood-spinal cord barrier which participates in secondary nerve injury. Epidermal growth factor (EGF) is an endogenous protein which regulates cell proliferation, growth and differention. Previous studies reported that EGF exerts neuroprotective effect in spinal cord after SCI. However, the molecular mechanisms underlying EGF-mediated protection in different regions of nervous system have not shown yet. In this study, we aimed to examine possible anti-apoptotic and protective roles of EGF not only in spinal cord but also in brain following SCI. Twenty-eight adult rats were divided into four groups of seven animals each as follows: sham, trauma (SCI), SCI + EGF and SCI + methylprednisolone (MP) groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic protein levels and antioxidant enzyme activities were measured in spinal cord and frontal cortex. In our study, EGF promoted locomotor recovery and motor neuron survival of SCI rats. EGF treatment significantly decreased Bax and increased Bcl-2 protein expressions both in spinal cord and brain when compared to SCI group. Moreover, antioxidant enzyme activities including catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were increased following EGF treatment similar to MP treatment. Our experiment also suggests that alteration of the ratio of Bcl-2 to Bax may result from decreased apoptosis following EGF treatment. As a conclusion, these results show, for the first time, that administration of EGF exerts its protection via regulating apoptotic and oxidative pathways in response to spinal cord injury in different regions of central nervous system. Copyright © 2018 Elsevier Ltd. All rights reserved.

Topologically preserving straightening of spinal cord MRI.

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De Leener, Benjamin; Mangeat, Gabriel; Dupont, Sara; Martin, Allan R; Callot, Virginie; Stikov, Nikola; Fehlings, Michael G; Cohen-Adad, Julien

2017-10-01

To propose a robust and accurate method for straightening magnetic resonance (MR) images of the spinal cord, based on spinal cord segmentation, that preserves spinal cord topology and that works for any MRI contrast, in a context of spinal cord template-based analysis. The spinal cord curvature was computed using an iterative Non-Uniform Rational B-Spline (NURBS) approximation. Forward and inverse deformation fields for straightening were computed by solving analytically the straightening equations for each image voxel. Computational speed-up was accomplished by solving all voxel equation systems as one single system. Straightening accuracy (mean and maximum distance from straight line), computational time, and robustness to spinal cord length was evaluated using the proposed and the standard straightening method (label-based spline deformation) on 3T T 2 - and T 1 -weighted images from 57 healthy subjects and 33 patients with spinal cord compression due to degenerative cervical myelopathy (DCM). The proposed algorithm was more accurate, more robust, and faster than the standard method (mean distance = 0.80 vs. 0.83 mm, maximum distance = 1.49 vs. 1.78 mm, time = 71 vs. 174 sec for the healthy population and mean distance = 0.65 vs. 0.68 mm, maximum distance = 1.28 vs. 1.55 mm, time = 32 vs. 60 sec for the DCM population). A novel image straightening method that enables template-based analysis of quantitative spinal cord MRI data is introduced. This algorithm works for any MRI contrast and was validated on healthy and patient populations. The presented method is implemented in the Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1209-1219. © 2017 International Society for Magnetic Resonance in Medicine.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

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van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, Pdisease (HR=0.26, Pdisease (HR=0.06, Pdisease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Development of a 3D matrix for modeling mammalian spinal cord injury in vitro

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Juan Felipe Diaz Quiroz

2016-01-01

Full Text Available Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difficulty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells after exposure to drugs.

Risk factors in iatrogenic spinal cord injury.

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Montalva-Iborra, A; Alcanyis-Alberola, M; Grao-Castellote, C; Torralba-Collados, F; Giner-Pascual, M

2017-09-01

In the last years, there has been a change in the aetiology of spinal cord injury. There has been an increase in the number of elderly patients with spinal cord injuries caused by diseases or medical procedures. The aim of this study is to investigate the frequency of the occurrence of iatrogenic spinal cord injury in our unit. The secondary aim is to study what variables can be associated with a higher risk of iatrogenesis. A retrospective, descriptive, observational study of patients with acute spinal cord injury admitted from June 2009 to May 2014 was conducted. The information collected included the patient age, aetiology, neurological level and grade of injury when admitted and when discharged, cardiovascular risk factors, a previous history of depression and any prior treatment with anticoagulant or antiplatelet drugs. We applied a logistic regression. The grade of statistical significance was established as Pinjury was the thoracic level (48%). The main aetiology of spinal cord injury caused by iatrogenesis was surgery for degenerative spine disease, in patients under the age of 30 were treated with intrathecal chemotherapy. Iatrogenic spinal cord injury is a frequent complication. A statistically significant association between a patient history of depression and iatrogenic spinal cord injury was found as well as with anticoagulant and antiplatelet drug use prior to iatrogenic spinal cord injury.

Spinal cord injury arising in anaesthesia practice.

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Hewson, D W; Bedforth, N M; Hardman, J G

2018-01-01

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury - vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis - will be discussed in turn. For each condition, we draw attention to practical, evidence-based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Exercise Guidelines to Promote Cardiometabolic Health in Spinal Cord Injured Humans: Time to Raise the Intensity?

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Nightingale, Tom E; Metcalfe, Richard S; Vollaard, Niels B; Bilzon, James L

2017-08-01

Spinal cord injury (SCI) is a life-changing event that, as a result of paralysis, negatively influences habitual levels of physical activity and hence cardiometabolic health. Performing regular structured exercise therefore appears extremely important in persons with SCI. However, exercise options are mainly limited to the upper body, which involves a smaller activated muscle mass compared with the mainly leg-based activities commonly performed by nondisabled individuals. Current exercise guidelines for SCI focus predominantly on relative short durations of moderate-intensity aerobic upper-body exercise, yet contemporary evidence suggests this is not sufficient to induce meaningful improvements in risk factors for the prevention of cardiometabolic disease in this population. As such, these guidelines and their physiological basis require reappraisal. In this special communication, we propose that high-intensity interval training (HIIT) may be a viable alternative exercise strategy to promote vigorous-intensity exercise and prevent cardiometabolic disease in persons with SCI. Supplementing the limited data from SCI cohorts with consistent findings from studies in nondisabled populations, we present strong evidence to suggest that HIIT is superior to moderate-intensity aerobic exercise for improving cardiorespiratory fitness, insulin sensitivity, and vascular function. The potential application and safety of HIIT in this population is also discussed. We conclude that increasing exercise intensity could offer a simple, readily available, time-efficient solution to improve cardiometabolic health in persons with SCI. We call for high-quality randomized controlled trials to examine the efficacy and safety of HIIT in this population. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Delayed expression of cell cycle proteins contributes to astroglial scar formation and chronic inflammation after rat spinal cord contusion

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Wu Junfang

2012-07-01

Full Text Available Abstract Background Traumatic spinal cord injury (SCI induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model. Methods Adult male rats were subjected to moderate spinal cord contusion injury at T8 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 weeks or 4 months post-injury, and processed for protein expression and lesion volume. Functional recovery was assessed over the 4 months after injury. Results Immunoblot analysis demonstrated a marked continued upregulation of cell cycle-related proteins − including cyclin D1 and E, CDK4, E2F5 and PCNA − for 4 months post-injury that were highly expressed by GFAP+ astrocytes and microglia, and co-localized with inflammatory-related proteins. CR8 administrated systemically 3 h post-injury and continued for 7 days limited the sustained elevation of cell cycle proteins and immunoreactivity of GFAP, Iba-1 and p22PHOX − a key component of NADPH oxidase − up to 4 months after SCI. CR8 treatment significantly reduced lesion volume, which typically progressed in untreated animals between 1 and 4 months after trauma. Functional recovery was also significantly improved by CR8 treatment after SCI from week 2 through week 16. Conclusions These data demonstrate that cell cycle-related proteins are chronically upregulated after SCI and may contribute to astroglial scar

Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation.

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Takeuchi, Shinji; Fukuda, Koji; Yamada, Tadaaki; Arai, Sachiko; Takagi, Satoshi; Ishii, Genichiro; Ochiai, Atsushi; Iwakiri, Shotaro; Itoi, Kazumi; Uehara, Hisanori; Nishihara, Hiroshi; Fujita, Naoya; Yano, Seiji

2017-04-01

Malignant pleural mesothelioma (MPM) is characterized by dissemination and aggressive growth in the thoracic cavity. Podoplanin (PDPN) is an established diagnostic marker for MPM, but the function of PDPN in MPM is not fully understood. The purpose of this study was to determine the pathogenetic function of PDPN in MPM. Forty-seven of 52 tumors (90%) from Japanese patients with MPM and 3/6 (50%) MPM cell lines tested positive for PDPN. Knocking down PDPN in PDPN-high expressing MPM cells resulted in decreased cell motility. In contrast, overexpression of PDPN in PDPN-low expressing MPM cells enhanced cell motility. PDPN stimulated motility was mediated by activation of the RhoA/ROCK pathway. Moreover, knocking down PDPN with short hairpin (sh) RNA in PDPN-high expressing MPM cells resulted in decreased development of a thoracic tumor in mice with severe combined immune deficiency (SCID). In sharp contrast, transfection of PDPN in PDPN-low expressing MPM cells resulted in an increase in the number of Ki-67-positive proliferating tumor cells and it promoted progression of a thoracic tumor in SCID mice. Interestingly, PDPN promoted focus formation in vitro, and a low level of E-cadherin expression and YAP1 activation was observed in PDPN-high MPM tumors. These findings indicate that PDPN is a diagnostic marker as well as a pathogenetic regulator that promotes MPM progression by increasing cell motility and inducing focus formation. Therefore, PDPN might be a pathogenetic determinant of MPM dissemination and aggressive growth and may thus be an ideal therapeutic target. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

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Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

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

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

2017-01-15

For the past 25 years, the field of neuroimaging has witnessed the development of several software packages for processing multi-parametric magnetic resonance imaging (mpMRI) to study the brain. These software packages are now routinely used by researchers and clinicians, and have contributed to important breakthroughs for the understanding of brain anatomy and function. However, no software package exists to process mpMRI data of the spinal cord. Despite the numerous clinical needs for such advanced mpMRI protocols (multiple sclerosis, spinal cord injury, cervical spondylotic myelopathy, etc.), researchers have been developing specific tools that, while necessary, do not provide an integrative framework that is compatible with most usages and that is capable of reaching the community at large. This hinders cross-validation and the possibility to perform multi-center studies. In this study we introduce the Spinal Cord Toolbox (SCT), a comprehensive software dedicated to the processing of spinal cord MRI data. SCT builds on previously-validated methods and includes state-of-the-art MRI templates and atlases of the spinal cord, algorithms to segment and register new data to the templates, and motion correction methods for diffusion and functional time series. SCT is tailored towards standardization and automation of the processing pipeline, versatility, modularity, and it follows guidelines of software development and distribution. Preliminary applications of SCT cover a variety of studies, from cross-sectional area measures in large databases of patients, to the precise quantification of mpMRI metrics in specific spinal pathways. We anticipate that SCT will bring together the spinal cord neuroimaging community by establishing standard templates and analysis procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Religious perspectives on umbilical cord blood banking.

Science.gov (United States)

Jordens, Christopher F C; O'Connor, Michelle A C; Kerridge, Ian H; Stewart, Cameron; Cameron, Andrew; Keown, Damien; Lawrence, Rabbi Jeremy; McGarrity, Andrew; Sachedina, Abdulaziz; Tobin, Bernadette

2012-03-01

Umbilical cord blood is a valuable source of haematopoietic stem cells. There is little information about whether religious affiliations have any bearing on attitudes to and decisions about its collection, donation and storage. The authors provided information about umbilical cord blood banking to expert commentators from six major world religions (Catholicism, Anglicanism, Islam, Judaism, Hinduism and Buddhism) and asked them to address a specific set of questions in a commentary. The commentaries suggest there is considerable support for umbilical cord blood banking in these religions. Four commentaries provide moral grounds for favouring public donation over private storage. None attach any particular religious significance to the umbilical cord or to the blood within it, nor place restrictions on the ethnicity or religion of donors and recipients. Views on ownership of umbilical cord blood vary. The authors offer a series of general points for those who seek a better understanding of religious perspectives on umbilical cord blood banking.

Measurements of the vertebral foramen and the spinal cord by means of x-ray computed tomography (corpse)

International Nuclear Information System (INIS)

Kimura, Kazue; Katakura, Toshihiko; Suzuki, Kenji; Sato, Takanori; Azuma, Koji; Okuaki, Koju; Mizukoshi, Hitoshi; Kageyama, Kazuhiro; Suzuki, Sigeki

1985-01-01

It is important for orthopedics to measure the sizes of the vertebral canal and the spinal cord. Owing to the development of X-ray computed tomography (XCT), clear cross section images of the vertebral foramen and the spinal cord are now available, facilitating the measurement of these sizes, so that many literatures on this subject have been reported. The authors studied the errors of measurements of the anteroposterior diameterers of the vertebral foramen and the spinal cord by means of XCT (EMI CT 5005 type, slice thickness: 14mm). Method: Cross section images by XCT at the mid-plane of each vertebral body of cadaver were taken, and then, sawed cross sections were prepared for actual survey of the antero-posterior diameters of the vertebral foramen and the spinal cord. Measurements by XCT were made with the CT-number profile method and the multi-format film method. Results: The errors at the measurement of the antero-posterior diameters of the vertebral foramen and the spinal cord were about +- 2.0 - +- 4.5 %. The slice thickness of XCT pictures at present is thinner than 14mm and if we can make the tomographic plane at a right angle to the long axis of the vertebral column, the errors may be more minimized. (author)

Tailless-like (TLX) protein promotes neuronal differentiation of dermal multipotent stem cells and benefits spinal cord injury in rats.

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Wang, Tao; Ren, Xiaobao; Xiong, Jianqiong; Zhang, Lei; Qu, Jifu; Xu, Wenyue

2011-04-01

Spinal cord injury (SCI) remains a formidable challenge in the clinic. In the current study, we examined the effects of the TLX gene on the proliferation and neuronal differentiation of dermal multipotent stem cells (DMSCs) in vitro and the potential of these cells to improve SCI in rats in vivo. DMSCs were stably transfected with TLX-expressing plasmid (TLX/DMSCs). Cell proliferation was examined using the MTT assay, and neuronal differentiation was characterized by morphological observation combined with immunocytochemical/immunofluorescent staining. The in vivo functions of these cells were evaluated by transplantation into rats with SCI, followed by analysis of hindlimb locomotion and post-mortem histology. Compared to parental DMSCs, TLX/DMSCs showed enhanced proliferation and preferential differentiation into NF200-positive neurons in contrast to GFAP-positive astrocytes. When the undifferentiated cells were transplanted into rats with SCI injury, TLX/DMSCs led to significant improvement in locomotor recovery and healing of SCI, as evidenced by reduction in scar tissues and cavities, increase in continuous nerve fibers/axons and enrichment of NF200-positive neurons on the histological level. In conclusion, TLX promotes the proliferation and neuronal differentiation of DMSCs and thus, may serve as a promising therapy for SCI in the clinic.

Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function

DEFF Research Database (Denmark)

Mirastschijski, Ursula; Schnabel, Reinhild; Claes, Juliane

2010-01-01

applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-beta1 (TGF-beta1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined......, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP...... and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-beta1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound...

Clinical Use and Patentability of Cord Blood

Science.gov (United States)

Cavusoglu, Turker; Kilic, Kubilay Dogan; Yigitturk, Gurkan; Tomruk, Canberk; Turgut, Mehmet; Uyanikgil, Yigit

2018-03-14

The blood in the umbilical cord that provides the connection between mother and fetus during pregnancy is called cord blood. The blood of umbilical cord which is usually got rid of following birth, is a very rich stem cell source. Cord blood collection gives no harm to the mother and baby. Besides, its allogeneic and au-tologous usage, the most important disadvantage is that the number of cells is insufficient in adults. Today, it is predominantly used for therapeutic purposes for many diseases. The aim of this review is giving a detailed information about groups of stem cells in cord blood and determining the point of clinical use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Re-theorising mobility and the formation of culture and language among the Corded Ware Culture in Europe

DEFF Research Database (Denmark)

Kristiansen, Kristian; Allentoft, Morten E.; Frei, Karin M.

2017-01-01

Recent genetic, isotopic and linguistic research has dramatically changed our understanding of how the Corded Ware Culture in Europe was formed. Here the authors explain it in terms of local adaptations and interactions between migrant Yamnaya people from the Pontic-Caspian steppe and indigenous ...

Vibration acceleration promotes bone formation in rodent models.

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Ryohei Uchida

BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group. BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%. On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models.

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

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Gori, Jennifer L.; Butler, Jason M.; Chan, Yan-Yi; Chandrasekaran, Devikha; Poulos, Michael G.; Ginsberg, Michael; Nolan, Daniel J.; Elemento, Olivier; Wood, Brent L.; Adair, Jennifer E.; Rafii, Shahin; Kiem, Hans-Peter

2015-01-01

Pluripotent stem cells (PSCs) represent an alternative hematopoietic stem cell (HSC) source for treating hematopoietic disease. The limited engraftment of human PSC–derived (hPSC-derived) multipotent progenitor cells (MPP) has hampered the clinical application of these cells and suggests that MPP require additional cues for definitive hematopoiesis. We hypothesized that the presence of a vascular niche that produces Notch ligands jagged-1 (JAG1) and delta-like ligand-4 (DLL4) drives definitive hematopoiesis. We differentiated hes2 human embryonic stem cells (hESC) and Macaca nemestrina–induced PSC (iPSC) line-7 with cytokines in the presence or absence of endothelial cells (ECs) that express JAG1 and DLL4. Cells cocultured with ECs generated substantially more CD34+CD45+ hematopoietic progenitors compared with cells cocultured without ECs or with ECs lacking JAG1 or DLL4. EC-induced cells exhibited Notch activation and expressed HSC-specific Notch targets RUNX1 and GATA2. EC-induced PSC-MPP engrafted at a markedly higher level in NOD/SCID/IL-2 receptor γ chain–null (NSG) mice compared with cytokine-induced cells, and low-dose chemotherapy-based selection further increased engraftment. Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction were similar to levels achieved for cord blood–derived MPP and up to 20-fold higher than those achieved with hPSC-derived MPP engraftment. Our findings indicate that endothelial Notch ligands promote PSC-definitive hematopoiesis and production of long-term engrafting CD34+ cells, suggesting these ligands are critical for HSC emergence. PMID:25664855

Traumatic spinal cord injury in MR imaging

International Nuclear Information System (INIS)

Bronarski, J.; Wozniak, E.

1993-01-01

Spinal cord injuries in tetraplegics were briefly discussed on the basis of MR imaging. It was found that severe cervical spine trauma usually results in concussion - the complete transection of the cord is rare. A case of 19 years old male with total cord transection confirmed by MR imaging is described. (author)

A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

Science.gov (United States)

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-01-01

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational

Cord lactate, pH, and blood gases from healthy neonates.

Science.gov (United States)

Shirey, T; St Pierre, J; Winkelman, J

1996-01-01

Lactate, pH, pO2, and pCO2 were determined in arterial, venous, and free-flowing mixed umbilical cord blood obtained from deliveries of apparently healthy neonates. The goals of this study were to establish reference ranges for lactate and pH against which results in cases of high-risk labor and delivery could be compared, to see how the gases correlated with these values, and to determine whether easily accessible mixed umbilical cord blood can serve as the sample in lieu of cord arterial or cord venous blood. Arterial and venous cord lactates were 2.98 mmol/l (+/- 1.40) and 2.80 mmol/l (+/- 1.35), respectively, from 85 cords obtained from vaginal and cesarean deliveries. Mixed cord blood lactate, obtained on 48 cords, was 2.72 mmol/l (+/- 1.28) versus 3.14 and 2.97 mmol/l for the arterial and venous samples from those cords, respectively, and correlated quite well with lactate from the venous specimens (r = 0.97). Differences of > 0.5 mmol/l occurred between mixed and arterial cord bloods in 21 patients, and between mixed and venous cord bloods in 6 of the 48 patients, respectively. We conclude that (1) less than 2.5% of deliveries of apparently healthy neonates have arterial, venous, or mixed cord lactates > or = 7.0 mmol/l and pH pO2 nor pCO2 correlate well with cord venous lactate, and (3) readily available mixed cord blood is a satisfactory specimen for the measurement of venous cord latate.

CORD PROLAPSE, ASSOCIATED FACTORS AND FETAL OUTCOME

African Journals Online (AJOL)

Several factors predispose to cord prolapse, amongst which are breech presentation, abnormal lie and presentation, hydramnios and long cord [2-3, 5-7]. Perinatal mortality is the most feared complication and often seen in up to 91% of cases [8-9]. Little is known about the pattern of umbilical cord prolapse in Cameroon as ...

Propofol combined with bone marrow mesenchymal stem cell transplantation improves electrophysiological function in the hindlimb of rats with spinal cord injury better than monotherapy

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Yue-xin Wang

2015-01-01

Full Text Available The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

A behavioural intervention increases physical activity in people with subacute spinal cord injury: a randomised trial

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Carla FJ Nooijen

2016-01-01

Full Text Available Questions: For people with subacute spinal cord injury, does rehabilitation that is reinforced with the addition of a behavioural intervention to promote physical activity lead to a more active lifestyle than rehabilitation alone? Design: Randomised, controlled trial with concealed allocation, intention-to-treat analysis, and blinded assessors. Participants: Forty-five adults with subacute spinal cord injury who were undergoing inpatient rehabilitation and were dependent on a manual wheelchair. The spinal cord injuries were characterised as: tetraplegia 33%; motor complete 62%; mean time since injury 150 days (SD 74. Intervention: All participants received regular rehabilitation, including handcycle training. Only the experimental group received a behavioural intervention promoting an active lifestyle after discharge. This intervention involved 13 individual sessions delivered by a coach who was trained in motivational interviewing; it began 2 months before and ended 6 months after discharge from inpatient rehabilitation. Outcome measures: The primary outcome was physical activity, which was objectively measured with an accelerometer-based activity monitor 2 months before discharge, at discharge, and 6 and 12 months after discharge from inpatient rehabilitation. The accelerometry data were analysed as total wheeled physical activity, sedentary time and motility. Self-reported physical activity was a secondary outcome. Results: The behavioural intervention significantly increased wheeled physical activity (overall between-group difference from generalised estimating equation 21 minutes per day, 95% CI 8 to 35. This difference was evident 6 months after discharge (28 minutes per day, 95% CI 8 to 48 and maintained at 12 months after discharge (25 minutes per day, 95% CI 1 to 50. No significant intervention effect was found for sedentary time or motility. Self-reported physical activity also significantly improved. Conclusion: The behavioural

The experience of attempting to return to work following spinal cord injury: a systematic review of the qualitative literature.

Science.gov (United States)

Hilton, Gillean; Unsworth, Carolyn; Murphy, Gregory

2018-07-01

This review sought to answer the question "What are the barriers and facilitators influencing people's experience of return to work following spinal cord injury?" Studies that met the selection criteria were identified, presented and critically appraised using National Institute for Health and Care Excellence guidelines. Thematic synthesis was completed with studies possessing strong methodological rigor. Synthesis and interpretation involved three stages; coding of primary data; development of descriptive themes reflective of the primary data; and establishment of analytical themes to answer the review question. Data from nine papers were included in the thematic synthesis. Several descriptive themes and three analytical themes were drawn from the data to answer the research question. Analytical themes included: a matrix of personal and environmental factors exists requiring complex navigation in order to create possibilities and opportunities for postinjury employment; the process of seeking or gaining employment shares a reciprocal relationship with the temporal nature of adjustment to spinal cord injury; and there is an intrinsic need for occupational engagement through paid employment. Returning to or gaining employment after spinal cord injury is a fundamentally difficult experience for people. Multiple strategies are required to support the navigation of the process. There is, however, a need in people with spinal cord injury, to be a worker, and with that comes the inherent benefits of being employed. Implications for rehabilitation Returning to work should be a significant focus of spinal cord injury rehabilitation. Employment is both possible and health promoting following spinal cord injury. Multiple strategies are required to support people to navigate the return to work process. It is important to be cognizant of the individual motivations for being a worker and the complexity of the adjustment process. Spinal cord injury centers can provide a

Cord blood banking and transplantation: advances and controversies.

Science.gov (United States)

Yoder, Mervin C

2014-04-01

A review of articles published since January 2012 on the topic of cord blood banking and cord blood stem cell transplantation was conducted for this the 25th anniversary year of the first cord blood transplant performed in a human. Cord blood banking is performed throughout the world. Umbilical cord blood (UCB) transplantation is recognized as an acceptable alternative stem cell source for paediatric and adults requiring a haematopoietic transplant, particularly for patients of racial and ethnic minorities. To further advance the use of UCB, methods to enhance UCB stem cell expansion, engraftment and maintenance may be required. Controversy on the most effective and economically sustainable model for banking and storing an optimal UCB product continues to persist. Cord blood banking and transplantation of cord blood stem cells has advanced rapidly over the initial 25 years, as more than 30 ,000 patients have benefited from the therapy. New concepts on the use of methods to expand UCB stem cells for transplantation and use for nonhaematopoietic indications may increase demand for UCB over the next few decades.

Effect of intravenous transplantation of bone marrow mesenchymal stem cells on neurotransmitters and synapsins in rats with spinal cord injury

Science.gov (United States)

Chen, Shaoqiang; Wu, Bilian; Lin, Jianhua

2012-01-01

Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3–5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time (1–5 weeks). Expressions of choline acetyltransferase, glutamic acid decarboxylase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury. PMID:25657678

Different strategies to improve the use of the umbilical cord and cord blood for hematopoietic and other regenerative cell therapies

NARCIS (Netherlands)

Garde, Mark Paul van der

2016-01-01

The umbilical cord and cord blood contain stem cells that can be used for regenerative cell therapies such as hematopoietic stem cell transplantation. However, the application of cord blood is hindered by the slow engraftment of the cells and delayed immune reconstitution compared to stem cells of

Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping improves systemic and cerebral oxygenation in preterm lambs.

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Graeme R Polglase

Full Text Available As measurement of arterial oxygen saturation (SpO2 is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2 were measured continuously in apnoeic preterm lambs (126±1 day gestation. Positive pressure ventilation was initiated either 1 prior to umbilical cord clamping, or 2 after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.

Utility of MR imaging in pediatric spinal cord injury

International Nuclear Information System (INIS)

Felsberg, G.J.; Tien, R.D.; Osumi, A.K.; Cardenas, C.A.

1995-01-01

We evaluated the utility of MR imaging in pediatric patients with acute and subacute spinal cord injuries. MR imaging of 22 pediatric patients with suspected traumatic spinal cord injuries was reviewed. MR findings were correlated with physical examination and compared to available radiographs and CT examinations performed at time of presentation. Twelve patients had abnormalities on MR imaging. Seven had spinal cord contusions; five contusions were hemorrhagic. Five of seven patients with cord contusion had normal radiographs and CT exams. Six patients with normal radiographs and CT examinations had abnormal MR studies revealing cord contusion, ligamentous injury, disc herniation, and epidural hematoma. MR is useful in initial evaluation of pediatric patients with spinal cord injuries and in prognosis of future neurologic function. In the setting of spinal cord symptomatology and negative radiographic studies, MR imaging should be performed. Surgically correctable causes of cord compression demonstrated by MR imaging include disc herniation, epidural hematoma, and retropulsed fracture fragments. The entity of spinal cord injury without radiographic abnormality is a diagnosis of exclusion which should only be made after radiologic investigation with radiographs, high-resolution thin-section CT, and MR imaging. (orig.)

Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with Collagen-Induced Arthritis

Science.gov (United States)

Tanida, Atsushi; Kishimoto, Yuji; Okano, Toru; Hagino, Hiroshi

2013-01-01

Background Various clinical reports suggest etanercept (ETN) has some efficacy in bone formation in rheumatoid arthritis (RA). To examine this effect, we investigated the gene expression of cytokines relevant to osteoblast/osteoclast differentiation, and evaluated histomorphometric findings in mature rats with collagen-induced arthritis (CIA). Methods Total RNA was extracted from knee joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the infiltrating pannus volume and pannus surface, and the following items in contact with pannus surface were measured: osteoclast number, osteoid surface, osteoid volume and labeling surface. These were evaluated in the distal femur with CIA with or without ETN administration. Results TNF-alpha, RANKL and OPG mRNA expressions, linked to osteoclastogenesis, were not significantly different with or without ETN administration. ETN administration significantly increased Wnt-1 mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression, the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus surface and osteoclast number, parameters of bone destruction, were not significantly different among groups. Osteoid volume, osteoid surface and labeling surface, parameters of bone formation, increased significantly with ETN administration. Conclusion Our results suggest that ETN suppresses DDK-1 expression, and, as a result, Wnt expression is promoted and osteoblastogenesis becomes more active, independent of the regulation of osteoclast activity. Marked bone formation is attributed to the fact that ETN directly promotes osteoblastogenesis, not as a result of suppressing osteoclastogenesis. PMID:24031147

Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia.

Science.gov (United States)

Wang, Xu-Yang; Gu, Pei-Yuan; Chen, Shi-Wen; Gao, Wen-Wei; Tian, Heng-Li; Lu, Xiang-He; Zheng, Wei-Ming; Zhuge, Qi-Chuan; Hu, Wei-Xing

2015-11-01

In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury

Science.gov (United States)

Feng, Linjie; Gan, Hongquan; Zhao, Wenguo; Liu, Yingjie

2017-01-01

Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium-induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium-treated group; group B, normal BMSC-treated group; group C, OEC conditioned medium-induced BMSC-treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein-43 and neuron-specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results. PMID:28656221

Spinal Cord Stimulation

DEFF Research Database (Denmark)

Meier, Kaare

2014-01-01

Spinal cord stimulation (SCS) is a surgical treatment for chronic neuropathic pain that is refractory to other treatment. Originally described by Shealy et al. in 1967(1), it is used to treat a range of conditions such as complex regional pain syndrome (CRPS I)(2), angina pectoris(3), radicular...... pain after failed back surgery syndrome (FBSS)(4), pain due to peripheral nerve injury, stump pain(5), peripheral vascular disease(6) and diabetic neuropathy(7,8); whereas phantom pain(9), postherpetic neuralgia(10), chronic visceral pain(11), and pain after partial spinal cord injury(12) remain more...

Comparison of the effect of topical application of human milk and dry cord care on the bacterial colonization of umbilical cord in newborn infants

Directory of Open Access Journals (Sweden)

Fatemeh Abbaszadeh

2014-04-01

Full Text Available Background: Breast milk contains significant amounts of compounds that act as natural antimicrobial agents. This study was conducted to compare the effect of topical application of human milk and dry cord care on bacterial colonization in the umbilical cord of newborn infants. Methods: This clinical trial study was carried out on 174 infants in Kashan. The newborns were randomized to mother's milk group and dry cord care group from the birth. In group 1, the mother rubbed her own milk on the cord stump every 12 hours from 3 hours after birth to 2 days after the umbilical cord separation. In group 2, the mother was recommended not to use any material on the cord. Then, the cord samples were taken four times; 3hours after birth, at days 3 and 7, and 2 days after the umbilical cord separation. Results: The findings of the culture two days after umbilical cord separation indicated that low percentage of neonates in the breast milk (23.1% and dry cord care (28.8% groups had bacterial colonization. Moreover, no significant difference was found between the two groups in terms of growth of pathogenic organisms and normal flora of the skin (P>0.05. Conclusion: Given the low prevalence of pathogenic microorganisms in the two groups, it seems using breast milk and dry cord care are equally effective methods of taking care of umbilical cord.

Nitrite promotes protein carbonylation and Strecker aldehyde formation in experimental fermented sausages: are both events connected?

Science.gov (United States)

Villaverde, A; Ventanas, J; Estévez, M

2014-12-01

The role played by curing agents (nitrite, ascorbate) on protein oxidation and Strecker aldehyde formation is studied. To fulfill this objective, increasing concentrations of nitrite (0, 75 and 150ppm) and ascorbate (0, 250 and 500ppm) were added to sausages subjected to a 54day drying process. The concurrence of intense proteolysis, protein carbonylation and formation of Strecker aldehydes during processing of sausages suggests that α-aminoadipic semialdehyde (AAS) and γ-glutamic semialdehyde (GGS) may be implicated in the formation of Strecker aldehydes. The fact that nitrite (150ppm, ingoing amount) significantly promoted the formation of protein carbonyls at early stages of processing and the subsequent formation of Strecker aldehydes provides strength to this hypothesis. Ascorbate (125 and 250ppm) controlled the overall extent of protein carbonylation in sausages without declining the formation of Strecker aldehydes. These results may contribute to understanding the chemistry fundamentals of the positive influence of nitrite on the flavor and overall acceptability of cured muscle foods. Copyright © 2014 Elsevier Ltd. All rights reserved.

Service Innovation by Industrial Cluster Formation and Export Promotion

Directory of Open Access Journals (Sweden)

Noleen Pisa

2017-12-01

Full Text Available Service innovation drives economic growth and structural change by stimulating the development of new sectors and productivity improvements in existing sectors. Resource based sectors are the main contributors to South Africa’s North West province’s economic output This paper illustrates how such a region can use industrial cluster formation and focused export promotion as a strategy to enhance service innovation. Four service clusters were identified within the above mentioned province through structural path analysis and power of pull methods. An export market selection model is applied to the identified service industrial clusters to reveal realistic export opportunities associated with each cluster. Finally, trade multipliers are used to show the spill-over benefits given an increase in the clusters’ exports. Policymakers can use these results to inform actions that may assist in the development of these services clusters to strengthen the province’s competitive advantage and diversify its output.

Spinal column shortening for tethered cord syndrome associated with myelomeningocele, lumbosacral lipoma, and lipomyelomeningocele in children and young adults.

Science.gov (United States)

Aldave, Guillermo; Hansen, Daniel; Hwang, Steven W; Moreno, Amee; Briceño, Valentina; Jea, Andrew

2017-06-01

OBJECTIVE Tethered cord syndrome is the clinical manifestation of an abnormal stretch on the spinal cord, presumably causing mechanical injury, a compromised blood supply, and altered spinal cord metabolism. Tethered cord release is the standard treatment for tethered cord syndrome. However, direct untethering of the spinal cord carries potential risks, such as new neurological deficits from spinal cord injury, a CSF leak from opening the dura, and retethering of the spinal cord from normal scar formation after surgery. To avoid these risks, the authors applied spinal column shortening to children and transitional adults with primary and secondary tethered cord syndrome and report treatment outcomes. The authors' aim with this study was to determine the safety and efficacy of spinal column shortening for tethered cord syndrome by analyzing their experience with this surgical technique. METHODS The authors retrospectively reviewed the demographic and procedural data of children and young adults who had undergone spinal column shortening for primary or secondary tethered cord syndrome. RESULTS Seven patients with tethered cord syndrome caused by myelomeningocele, lipomyelomeningocele, and transitional spinal lipoma were treated with spinal column shortening. One patient with less than 24 months of follow-up was excluded from further analysis. There were 3 males and 4 females; the average age at the time was surgery was 16 years (range 8-30 years). Clinical presentations for our patients included pain (in 5 patients), weakness (in 4 patients), and bowel/bladder dysfunction (in 4 patients). Spinal column osteotomy was most commonly performed at the L-1 level, with fusion between T-12 and L-2 using a pedicle screw-rod construct. Pedicle subtraction osteotomy was performed in 6 patients, and vertebral column resection was performed in 1 patient. The average follow-up period was 31 months (range 26-37 months). Computed tomography-based radiographic outcomes showed solid

Spinal cord magnetic resonance imaging in suspected multiple sclerosis

International Nuclear Information System (INIS)

Lycklama a Nijeholt, G.J.; Bergers, E.; Castelijns, J.A.; Barkhof, F.; Uitdehaag, B.M.J.; Polman, C.H.

2000-01-01

We examined the value of spinal cord magnetic resonance imaging (MRI) in the diagnostic work-up of multiple sclerosis (MS). Forty patients suspected of having MS were examined within 24 months after the start of symptoms. Disability was assessed, and symptoms were categorized as either brain or spinal cord. Work-up further included cerebrospinal fluid analysis and standard proton-density, T2-, and T1-weighted gadolinium-enhanced brain and spinal cord MRI. Patients were categorized as either clinically definite MS (n = 13), laboratory-supported definite MS (n = 14), or clinically probable MS (n = 4); four patients had clinically probable MS, and in nine MS was suspected. Spinal cord abnormalities were found in 35 of 40 patients (87.5 %), consisting of focal lesions in 31, only diffuse abnormalities in two, and both in two. Asymptomatic spinal cord lesions occurred in six patients. All patients with diffuse spinal cord abnormality had clear spinal cord symptoms and a primary progressive disease course. In clinically definite MS, the inclusion of spinal imaging increased the sensitivity of MRI to 100 %. Seven patients without a definite diagnosis had clinically isolated syndromes involving the spinal cord. Brain MRI was inconclusive, while all had focal spinal cord lesions which explained symptoms and ruled out other causes. Two other patients had atypical brain abnormalities suggesting ischemic/vascular disease. No spinal cord abnormalities were found, and during follow-up MS was ruled out. Spinal cord abnormalities are common in suspected MS, and may occur asymptomatic. Although diagnostic classification is seldom changed, spinal cord imaging increases diagnostic sensitivity of MRI in patients with suspected MS. In addition, patients with primary progressive MS may possibly be earlier diagnosed. Finally, differentiation with atypical lesions may be improved. (orig.)

Magnetic resonance imaging of experimental spinal cord injury

International Nuclear Information System (INIS)

Nakamura, Tsutomu; Kumano, Kouichi; Kadoya, Satoru

1989-01-01

Correlation between pathological findings and magnetic resonance imaging (MRI) of experimental cord injury were investigated. Cord injuries were made on ten Wistar rats weighing 80-170 gm by epidural compression of the thoracic cord with a Biemer cerebral vascular clip for 5-20 seconds. Several hours after the procedure animals were examined by spin echo axial MR images with a pulse sequence of TR/TE=1000/36 msec. MR studies were repeated on 4 animals 3-7 days after the initial examination. Immediately after the latest MRI examination animals were sacrificed and fixed with 10% formalin. Three micron thickness paraffin sections stained with hematoxylin and eosin were evaluated under a microscope. The pathological finding was hemorrhagic necrosis with edema of various severity depending on duration of clip application. The hemorrhagic necrosis was observed either unilaterally or bilaterally to the cord. MR findings of the cord were of high intensity in five animals which were severely injured, while central low intensity of the injured cord appeared in three mildly injured animals. Of the remaining two animals which had mild injury, one showed unilateral high intensity, while no definitive change was demonstrated in the other. The high intensity in the MRI suggested edema associated with hemorrhagic necrosis rather than hemorrhage. The central low intensity appearing in the mildly injured cord might be hemorrhage in the gray matter. It is concluded that MRI was useful to diagnose not only the level and severity but also the pathological process in the injured cord, and thus to estimate the prognosis of the cord injuries. (author)

Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury

Directory of Open Access Journals (Sweden)

Aysegul Gunduz

2017-01-01

Full Text Available We conducted a systematic review of studies using non-invasive brain stimulation (NIBS: repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS as a research and clinical tool aimed at improving motor and functional recovery or spasticity in patients following spinal cord injury (SCI under the assumption that if the residual corticospinal circuits could be stimulated appropriately, the changes might be accompanied by functional recovery or an improvement in spasticity. This review summarizes the literature on the changes induced by NIBS in the motor and functional recovery and spasticity control of the upper and lower extremities following SCI.

Spinal cord motion. Influence of respiration and cardiac cycle

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Winklhofer, S. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; Schoth, F. [RWTH Aachen University Hospital (Germany). Dept. of Diagnostic Radiology; Stolzmann, P. [University Hospital Zurich (Switzerland). Inst. of Diagnostic and Interventional Radiology; Krings, T. [Toronto Western Hospital, ON (Canada). Div. of Neuroradiology; Mull, M.; Wiesmann, M. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; Stracke, C.P. [RWTH Aachen University Hospital (Germany). Dept. of Neuroradiology; Alfried-Krupp-Hospital, Essen (Germany). Dept. of Neuroradiology

2014-11-15

To assess physiological spinal cord motion during the cardiac cycle compared with the influence of respiration based on magnetic resonance imaging (MRI) measurements. Anterior-posterior spinal cord motion within the spinal canal was assessed in 16 healthy volunteers (median age, 25 years) by cardiac-triggered and cardiac-gated gradient echo pulse sequence MRI. Image acquisition was performed during breath-holding, normal breathing, and forced breathing. Normal spinal cord motion values were computed using descriptive statistics. Breathing-dependent differences were assessed using the Wilcoxon signed-rank test and compared with the cardiac-based cord motion. A normal value table was set up for the spinal cord motion of each vertebral cervico-thoracic-lumbar segment. Significant differences in cord motion were found between cardiac-based motion while breath-holding and the two breathing modalities (P < 0.01 each). Spinal cord motion was found to be highest during forced breathing, with a maximum in the lower cervical spinal segments (C5; mean, 2.1 mm ± 1.17). Image acquisition during breath-holding revealed the lowest motion. MRI permits the demonstration and evaluation of cardiac and respiration-dependent spinal cord motion within the spinal canal from the cervical to lumbar segments. Breathing conditions have a considerably greater impact than cardiac activity on spinal cord motion.

Spinal cord motion. Influence of respiration and cardiac cycle

International Nuclear Information System (INIS)

Winklhofer, S.; University Hospital Zurich; Schoth, F.; Stolzmann, P.; Krings, T.; Mull, M.; Wiesmann, M.; Stracke, C.P.; Alfried-Krupp-Hospital, Essen

2014-01-01

To assess physiological spinal cord motion during the cardiac cycle compared with the influence of respiration based on magnetic resonance imaging (MRI) measurements. Anterior-posterior spinal cord motion within the spinal canal was assessed in 16 healthy volunteers (median age, 25 years) by cardiac-triggered and cardiac-gated gradient echo pulse sequence MRI. Image acquisition was performed during breath-holding, normal breathing, and forced breathing. Normal spinal cord motion values were computed using descriptive statistics. Breathing-dependent differences were assessed using the Wilcoxon signed-rank test and compared with the cardiac-based cord motion. A normal value table was set up for the spinal cord motion of each vertebral cervico-thoracic-lumbar segment. Significant differences in cord motion were found between cardiac-based motion while breath-holding and the two breathing modalities (P < 0.01 each). Spinal cord motion was found to be highest during forced breathing, with a maximum in the lower cervical spinal segments (C5; mean, 2.1 mm ± 1.17). Image acquisition during breath-holding revealed the lowest motion. MRI permits the demonstration and evaluation of cardiac and respiration-dependent spinal cord motion within the spinal canal from the cervical to lumbar segments. Breathing conditions have a considerably greater impact than cardiac activity on spinal cord motion.

Age-related changes of the spinal cord: A biomechanical study.

Science.gov (United States)

Okazaki, Tomoya; Kanchiku, Tsukasa; Nishida, Norihiro; Ichihara, Kazuhiko; Sakuramoto, Itsuo; Ohgi, Junji; Funaba, Masahiro; Imajo, Yasuaki; Suzuki, Hidenori; Chen, Xian; Taguchi, Toshihiko

2018-03-01

Although it is known that aging plays an important role in the incidence and progression of cervical spondylotic myelopathy (CSM), the underlying mechanism is unclear. Studies that used fresh bovine cervical spinal cord report the gray matter of the cervical spinal cord as being more rigid and fragile than the white matter. However, there are no reports regarding the association between aging an tensile and Finite Element Method (FEM). Therefore, FEM was used based on the data pertaining to the mechanical features of older bovine cervical spinal cord to explain the pathogenesis of CSM in elderly patients. Tensile tests were conducted for white and gray matter separately in young and old bovine cervical spinal cords, and compared with their respective mechanical features. Based on the data obtained, FEM analysis was further performed, which included static and dynamic factors to describe the internal stress distribution changes of the spinal cord. These results demonstrated that the mechanical strength of young bovine spinal cords is different from that of old bovine spinal cords. The gray matter of the older spinal cord was significantly softer and more resistant to rupture compared with that of younger spinal cords (Pspinal cords in response to similar compression, when compared with young spinal cords. These results demonstrate that in analyzing the response of the spinal cord to compression, the age of patients is an important factor to be considered, in addition to the degree of compression, compression speed and parts of the spinal cord compression factor.

Spinal cord regeneration: moving tentatively towards new perspectives.

Science.gov (United States)

Jones, D G; Anderson, E R; Galvin, K A

2003-01-01

The failure of the adult human spinal cord to regenerate following injury is not absolute, but appears to be amenable to therapeutic manipulation. Recent work has shown that the provision of a growth permissive environment by the neutralization of inhibitory influences, or the grafting of fetal tissue, peripheral nerve, Schwann cells, or olfactory ensheathing cells can enhance regeneration in animal models of spinal cord injury. Stem cells are gaining ever-increasing favour as a treatment option for spinal cord injury. The potential of neural stem cells, embryonic stem cells, and bone marrow stromal cells is discussed. Additional treatment options such as pharmacological interventions, functional electrical stimulation and physiotherapy approaches are also explored. Basic science insights are used as a foundation for a discussion of a variety of clinical perspectives including repair of the chronically injured spinal cord, animal models of human spinal cord injuries and clinical trials. A more holistic approach towards spinal cord injury is suggested, one where a hierarchy of needs is recognised and quality of life is paramount. Finally, this review cautions against overly grandiose claims of an imminent miracle cure for human spinal cord injury.

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

Science.gov (United States)

Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

2013-03-05

Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

Diffusion tensor imaging of spinal cord parenchyma lesion in rat with chronic spinal cord injury.

Science.gov (United States)

Zhao, Can; Rao, Jia-Sheng; Pei, Xiao-Jiao; Lei, Jian-Feng; Wang, Zhan-Jing; Zhao, Wen; Wei, Rui-Han; Yang, Zhao-Yang; Li, Xiao-Guang

2018-04-01

Adequate evaluation of spinal cord parenchyma and accurate identification of injury range are considered two premises for the research and treatment of chronic spinal cord injury (SCI). Diffusion tensor imaging (DTI) provides information about water diffusion in spinal cord, and thus makes it possible to realize these premises. In this study, we conducted magnetic resonance imaging (MRI) for Wistar rats 84days after spinal cord contusion. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) from different positions of the injured cord were collected, analyzed, and compared with the histological results and locomotor outcomes. Moreover, we performed fiber tractography, and examined the difference in cavity percentage obtained respectively via conventional MRI, DTI and histology. Results showed that the chronic SCI rats had the largest changes of all DTI metrics at the epicenter; the farther away from the epicenter, the smaller the variation. FA, AD and RD were all influenced by SCI in a greater space range than MD. The good consistency of FA values and histological results in specific regions evidenced FA's capability of reflecting Wallerian degeneration after SCI. DTI metrics at the epicenter in ventral funiculus also showed a close correlation with the BBB scores. Additionally, supported by the histological results, DTI enables a more accurate measurement of cavity percentage compared to the conventional MRI. DTI parameters might comprehensively reflect the post-SCI pathological status of spinal cord parenchyma at the epicenter and distal parts during the chronic stage, while showing good consistency with locomotor performance. DTI combined with tractography could intuitively display the distribution of spared fibers after SCI and accurately provide information such as cavity area. This may shed light on the research and treatment of chronic SCI. Copyright © 2017 Elsevier Inc. All rights

[Varices of the vocal cord: report of 21 cases].

Science.gov (United States)

Li, Jin-rang; Sun, Jian-jun

2006-04-01

To study the diagnosis and treatment of varices of the vocal cord. The clinical data of 21 cases with varix of vocal cord were analyzed. All the patients presented hoarseness. There were 15 female and 6 male cases with their ages ranged from 23 to 68 years (median 44 years old). The varix was found on the right vocal cord in 12 cases, on the left vocal cord in 9 cases. Isolated varix existed on the vocal cord in 10 cases, varix with vocal cord polyps or nodules in 10 cases, varix with vocal cord paralysis in 1 case. All the patients were diagnosed under the laryngovideoscopy. The lesions appeared on the superior surface of the vocal cord. Varices manifested as abnormally dilated capillary running in the anterior to posterior direction in 6 cases, as clusters of capillary in 3 cases, as a dot or small sheet or short line of capillary in 12 cases. The varices were disappeared in 2 of 8 cases with vocal cord varices and polyps after removed the polyps. The varices of others patients had no change after following up for more than 6 months, but one patient happened hemorrhage of the contralateral vocal cord. Varices are most commonly seen in female. Laryngovideoscopy is the key in determining the vocal fold varices. Management of patients with a varix includes medical therapy, speech therapy, and occasionally surgical vaporization.

International spinal cord injury bowel function basic data set (Version 2.0)

DEFF Research Database (Denmark)

Krogh, K; Emmanuel, A; Perrouin-Verbe, B

2017-01-01

: Working group appointed by the American Spinal injury association (ASIA) and the International Spinal Cord Society (ISCoS). METHODS: The draft prepared by the working group was reviewed by the International SCI Data Set Committee and later by members of the ISCoS Executive and Scientific Committees......STUDY DESIGN: International expert working group. OBJECTIVES: To revise the International Spinal Cord Injury (SCI) Bowel Function Basic Data Set as a standardized format for the collecting and reporting of a minimal amount of information on bowel function in clinical practice and research. SETTING...... and the ASIA board. The revised data set was posted on the ASIA and ISCoS websites for 1 month to allow further comments and suggestions. Changes resulting from a Delphi process among experts in children with SCI were included. Members of ISCoS Executive and Scientific Committees and the ASIA board made...

CORDSPW - Windows computer program package for graphical interpretation of CORD-2 data

International Nuclear Information System (INIS)

Slavic, S.; Kromar, M.

2007-01-01

The CORD-2 package, developed at Jozef Stefan Institute, enables determination of the core power distribution and reactivity. Core distributions data generated during the calculation process are stored in CORlib files. CORDSP code, which is a part of the CORD-2 package, displays and compares data contained in CORlib files. Since it runs in the DOS environment, there are several limitations in the presentation of desired data. A CORDSPW package runs in the Windows environment and offers better graphical interpretation of the CORlib data. Core distributions can be displayed, compared, rewritten in the new files and sent to the printer. The user can select the appropriate display of the presented data such as core symmetry, colour and fonts. Core radial and axial distributions can be presented and compared. There are several options to store and print data. The user can choose between standard ASCII and graphical JPG format. (author)

Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury

Science.gov (United States)

Hansen, Christopher N.; Norden, Diana M.; Faw, Timothy D.; Deibert, Rochelle; S.Wohleb, Eric; Sheridan, John F.; P.Godbout, Jonathan; Basso, D. Michele

2016-01-01

Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24 hours and 7 days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24 hours after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7 days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9. PMID:27191729

PCP and SAX-3/Robo Pathways Cooperate to Regulate Convergent Extension-Based Nerve Cord Assembly in C. elegans.

Science.gov (United States)

Shah, Pavak K; Tanner, Matthew R; Kovacevic, Ismar; Rankin, Aysha; Marshall, Teagan E; Noblett, Nathaniel; Tran, Nhan Nguyen; Roenspies, Tony; Hung, Jeffrey; Chen, Zheqian; Slatculescu, Cristina; Perkins, Theodore J; Bao, Zhirong; Colavita, Antonio

2017-04-24

Formation and resolution of multicellular rosettes can drive convergent extension (CE) type cell rearrangements during tissue morphogenesis. Rosette dynamics are regulated by both planar cell polarity (PCP)-dependent and -independent pathways. Here we show that CE is involved in ventral nerve cord (VNC) assembly in Caenorhabditis elegans. We show that a VANG-1/Van Gogh and PRKL-1/Prickle containing PCP pathway and a Slit-independent SAX-3/Robo pathway cooperate to regulate, via rosette intermediaries, the intercalation of post-mitotic neuronal cell bodies during VNC formation. We show that VANG-1 and SAX-3 are localized to contracting edges and rosette foci and act to specify edge contraction during rosette formation and to mediate timely rosette resolution. Simultaneous loss of both pathways severely curtails CE resulting in a shortened, anteriorly displaced distribution of VNC neurons at hatching. Our results establish rosette-based CE as an evolutionarily conserved mechanism of nerve cord morphogenesis and reveal a role for SAX-3/Robo in this process. Copyright © 2017 Elsevier Inc. All rights reserved.

Isolation of mesenchymal stem cells from equine umbilical cord blood

DEFF Research Database (Denmark)

Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl

2007-01-01

. The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results: Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5o......Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low...

Diffusion tensor imaging in spinal cord compression

International Nuclear Information System (INIS)

Wang, Wei; Qin, Wen; Hao, Nanxin; Wang, Yibin; Zong, Genlin

2012-01-01

Background Although diffusion tensor imaging has been successfully applied in brain research for decades, several main difficulties have hindered its extended utilization in spinal cord imaging. Purpose To assess the feasibility and clinical value of diffusion tensor imaging and tractography for evaluating chronic spinal cord compression. Material and Methods Single-shot spin-echo echo-planar DT sequences were scanned in 42 spinal cord compression patients and 49 healthy volunteers. The mean values of the apparent diffusion coefficient and fractional anisotropy were measured in region of interest at the cervical and lower thoracic spinal cord. The patients were divided into two groups according to the high signal on T2WI (the SCC-HI group and the SCC-nHI group for with or without high signal). A one-way ANOVA was used. Diffusion tensor tractography was used to visualize the morphological features of normal and impaired white matter. Results There were no statistically significant differences in the apparent diffusion coefficient and fractional anisotropy values between the different spinal cord segments of the normal subjects. All of the patients in the SCC-HI group had increased apparent diffusion coefficient values and decreased fractional anisotropy values at the lesion level compared to the normal controls. However, there were no statistically significant diffusion index differences between the SCC-nHI group and the normal controls. In the diffusion tensor imaging maps, the normal spinal cord sections were depicted as fiber tracts that were color-encoded to a cephalocaudal orientation. The diffusion tensor images were compressed to different degrees in all of the patients. Conclusion Diffusion tensor imaging and tractography are promising methods for visualizing spinal cord tracts and can provide additional information in clinical studies in spinal cord compression

MR imaging of stable posttraumatic spinal cord injury

International Nuclear Information System (INIS)

Braun, I.F.; Hoffman, J.C. Jr.; Murphy, C.; Davis, P.C.

1986-01-01

Posttraumatic spinal cord cysts have been thought to be infrequent sequelae of spinal trauma. To evaluate the incidence of spinal cord abnormalities in patients who have previously sustained cord trauma, the authors studied the incidence of these changes in clinically stable patients following injury. Twenty-five patients with a history of previous cord injury and stable neurologic status volunteered for MR imaging studies. Studies performed using a 0.5-T and 1.5-T unit revealed focal kinking of the cord at the trauma site as well as intramedullary hypointense areas on T1-weighted images in most volunteers. There was close clinical correlation between MR imaging findings and experimental pathologic data, which suggests that these lesions are much more prevalent than once thought

Transplante de sangue de cordão umbilical - SCU Umbilical cord blood transplantation

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Celso A. Rodrigues

2010-05-01

Full Text Available A frequente utilização de sangue de cordão umbilical - SCU como fonte de células- tronco hematopoéticas - CTH, tanto em crianças, como em adultos, que não dispõem de doador na família, tem levado ao estabelecimento da padronização de critérios em sua seleção, objetivando a obtenção de melhores resultados. A escolha da unidade de SCU deve basear-se no número total de células nucleadas e no número de diferenças de antígenos leucocitários humanos (HLA. Diante de uma unidade com celularidade mínima, deve-se considerar a possibilidade da utilização de duplo cordão. Frente a mais de uma unidade com características semelhantes, a realização da contagem de células CD34 e da compatibilidade ABO, assim como a qualidade e a rapidez para obtenção da unidade, podem definir a escolha.The frequent use of umbilical cord blood as the source of hematopoietic stem cells, both in children and adults who do not have related donors, has led to the establishment of a better standardization of selection criteria aiming at improving the results. The choice of the umbilical cord blood unit should be based on the total number of nucleated cells and the number of differences in the human leukocyte antigen (HLA system. When a unit has minimal cellularity, the use of a double cord blood transplant should be considered. When two or more units have similar characteristics, the choice may be determined by the CD34 count, ABO compatibility and the quality and speed to obtain the unit.

Tolerance of the human spinal cord to single dose radiosurgery

International Nuclear Information System (INIS)

Ryu, S.; Zhu, G.; Yin, F.-F.; Ajlouni, M.; Kim, J.H.

2003-01-01

Tolerance of the spinal cord to the single dose of radiation is not well defined. Although there are cases of human spinal cord tolerance from re-irradiation to the same cord level, the information about the tolerance of human spinal cord to single large dose of radiosurgery is not available. We carried out spinal radiosurgery to treat spinal metastasis and studied the single dose tolerance of the human spinal cord in an ongoing dose escalation paradigm. A total of 39 patients with 48 lesions of spinal metastasis were treated with single dose radiosurgery at Henry Ford Hospital. The radiosurgery dose was escalated from 8 Gy to 16 Gy at 2 Gy increment. The radiation dose was prescribed to periphery of the spinal tumor. The radiation dose to the spinal cord was estimated by computerized dosimetry. The median follow-up time was 10 months (range 6-18 months) from the radiosurgery. The endpoint of the study was to demonstrate the efficacy of the spinal radiosurgery and to determine the tolerance of human spinal cord to single dose radiosurgery. The dose to the spinal cord was generally less than 50 % of the prescribed radiation dose. The volume of the spinal cord that received higher than this dose was less than 20 % of the anterior portion of the spinal cord. Maximum single dose of 8 Gy was delivered to the anterior 20 % of the spinal cord in this dose escalation study. The dose volume histogram will be presented. There was no acute or subacute radiation toxicity detected clinically and radiologically during the maximum follow-up of 20 months. Further dose escalation is in progress. The single tolerance dose of the human spinal cord appears to be at least 8 Gy when it was given to the 20 % of the cord volume, although the duration of follow up is not long enough to detect severe late cord toxicity. This study offers a valuable radiobiological basis of the normal spinal cord tolerance, and opens spinal radiosurgery as a safe treatment for spinal metastasis

Spermatic Cord Knot: A Clinical Finding in Patients with Spermatic Cord Torsion

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Abdullatif Al-Terki

2011-01-01

Full Text Available Pertinent history taking and careful examination often taper the differentials of the acute scrotum; congruently the ability to diagnose acute spermatic cord torsion (SCT when radiological adjuncts are not available is highly imperative. This observational study serves to present a series of 46 cases of spermatic cord torsion whereby we hypothesize the identification of a clinical knot on scrotal examination as an important clinical aid in making a decision to surgical exploration in patients with acute and subacute SCT, especially in centers where imaging resources are unavailable.

Simplified spinal cord phantom for evaluation of SQUID magnetospinography

International Nuclear Information System (INIS)

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

2014-01-01

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

Human amniotic epithelial cells combined with silk fibroin scaffold in the repair of spinal cord injury

Directory of Open Access Journals (Sweden)

Ting-gang Wang

2016-01-01

Full Text Available Treatment and functional reconstruction after central nervous system injury is a major medical and social challenge. An increasing number of researchers are attempting to use neural stem cells combined with artificial scaffold materials, such as fibroin, for nerve repair. However, such approaches are challenged by ethical and practical issues. Amniotic tissue, a clinical waste product, is abundant, and amniotic epithelial cells are pluripotent, have low immunogenicity, and are not the subject of ethical debate. We hypothesized that amniotic epithelial cells combined with silk fibroin scaffolds would be conducive to the repair of spinal cord injury. To test this, we isolated and cultured amniotic epithelial cells, and constructed complexes of these cells and silk fibroin scaffolds. Implantation of the cell-scaffold complex into a rat model of spinal cord injury resulted in a smaller glial scar in the damaged cord tissue than in model rats that received a blank scaffold, or amniotic epithelial cells alone. In addition to a milder local immunological reaction, the rats showed less inflammatory cell infiltration at the transplant site, milder host-versus-graft reaction, and a marked improvement in motor function. These findings confirm that the transplantation of amniotic epithelial cells combined with silk fibroin scaffold can promote the repair of spinal cord injury. Silk fibroin scaffold can provide a good nerve regeneration microenvironment for amniotic epithelial cells.

Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

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Jennifer M Colón

2016-01-01

Full Text Available Spinal cord injury (SCI is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

Neuroimaging for spine and spinal cord surgery

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Koyanagi, Izumi [Hokkaido Neurosurgical Memorial Hospital (Japan); Iwasaki, Yoshinobu; Hida, Kazutoshi

2001-01-01

Recent advances in neuroimaging of the spine and spinal cord are described based upon our clinical experiences with spinal disorders. Preoperative neuroradiological examinations, including magnetic resonance (MR) imaging and computerized tomography (CT) with three-dimensional reconstruction (3D-CT), were retrospectively analyzed in patients with cervical spondylosis or ossification of the posterior longitudinal ligament (130 cases), spinal trauma (43 cases) and intramedullary spinal cord tumors (92 cases). CT scan and 3D-CT were useful in elucidating the spine pathology associated with degenerative and traumatic spine diseases. Visualization of the deformity of the spine or fracture-dislocation of the spinal column with 3D-CT helped to determine the correct surgical treatment. MR imaging was most important in the diagnosis of both spine and spinal cord abnormalities. The axial MR images of the spinal cord were essential in understanding the laterality of the spinal cord compression in spinal column disorders and in determining surgical approaches to the intramedullary lesions. Although non-invasive diagnostic modalities such as MR imaging and CT scans are adequate for deciding which surgical treatment to use in the majority of spine and spinal cord disorders, conventional myelography is still needed in the diagnosis of nerve root compression in some cases of cervical spondylosis. (author)

Lithium chloride contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux.

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Tong, Minji; He, Zili; Lin, Xiaoxiao; Zhou, Yulong; Wang, Qingqing; Zheng, Zengming; Chen, Jian; Xu, Huazi; Tian, Naifeng

2018-01-22

Blood-spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) significantly compromises functional neuronal recovery. Autophagy is a potential therapeutic target when seeking to protect the BSCB. We explored the effects of lithium chloride (LiCl) on BSCB permeability and autophagy-induced SCI both in a rat model of SCI and in endothelial cells subjected to oxygen-glucose deprivation. We evaluated BSCB status using the Evans Blue dye extravasation test and measurement of tight junction (TJ) protein levels; we also assessed functional locomotor recovery. We detected autophagy-associated proteins in vivo and in vitro using both Western blotting and immunofluorescence staining. We found that, in a rat model of SCI, LiCl attenuated the elevation in BSCB permeability, improved locomotor recovery, and inhibited the degradation of TJ proteins including occludin and claudin-5. LiCl significantly induced the extent of autophagic flux after SCI by increasing LC3-II and ATG-5 levels, and abolishing p62 accumulation. In addition, a combination of LiCl and the autophagy inhibitor chloroquine not only partially eliminated the BSCB-protective effect of LiCl, but also exacerbated TJ protein degradation both in vivo and in vitro. Together, these findings suggest that LiCl treatment alleviates BSCB disruption and promotes locomotor recovery after SCI, partly by stimulating autophagic flux. Copyright © 2017 Elsevier Inc. All rights reserved.

Central nociceptive sensitization vs. spinal cord training: Opposing forms of plasticity that dictate function after complete spinal cord injury

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Adam R Ferguson

2012-10-01

Full Text Available The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome learning. Instrumental flexion training produces a central change in spinal plasticity that enables future spinal learning on both the ipsilateral and contralateral leg. However, if stimulation is given in a response-independent manner, the spinal cord develops central maladaptive plasticity that undermines future spinal learning on both legs. The present paper tests for interactions between spinal cord training and central nociceptive sensitization after complete spinal cord transection. We found that spinal training alters future central sensitization by intradermal formalin (24 h post-training. Conversely intradermal formalin impaired future spinal learning (24 h post-injection. Because the NMDA receptor has been implicated in formalin-induced central sensitization, we tested whether pretreatment with NMDA affects spinal learning. We found intrathecal NMDA impaired learning in a dose-dependent fashion, and that this effect endures for at least 24h. These data provide strong evidence for an

Platelet rich plasma promotes skeletal muscle cell migration in association with up-regulation of FAK, paxillin, and F-Actin formation.

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Tsai, Wen-Chung; Yu, Tung-Yang; Lin, Li-Ping; Lin, Mioa-Sui; Tsai, Ting-Ta; Pang, Jong-Hwei S

2017-11-01

Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The aim of this study was to investigate the effect and molecular mechanism of PRP on migration of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP. The cell migration was evaluated by transwell filter migration assay and electric cell-substrate impedance sensing. The spreading of cells was evaluated microscopically. The formation of filamentous actin (F-actin) cytoskeleton was assessed by immunofluorescence staining. The protein expressions of paxillin and focal adhesion kinase (FAK) were assessed by Western blot analysis. Transfection of paxillin small-interfering RNA (siRNAs) to muscle cells was performed to validate the role of paxillin in PRP-mediated promotion of cell migration. Dose-dependently PRP promotes migration of and spreading and muscle cells. Protein expressions of paxillin and FAK were up-regulated dose-dependently. F-actin formation was also enhanced by PRP treatment. Furthermore, the knockdown of paxillin expression impaired the effect of PRP to promote cell migration. It was concluded that PRP promoting migration of muscle cells is associated with up-regulation of proteins expression of paxillin and FAK as well as increasing F-actin formation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2506-2512, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The spinal cord: a review of functional neuroanatomy.

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

2013-02-01

The spinal cord controls the voluntary muscles of the trunk and limbs and receives sensory input from these areas. It extends from the medulla oblongata to the lower border of the first lumbar vertebra. A basic knowledge of spinal cord anatomy is essential for interpretation of clinical signs and symptoms and for understanding of pathologic processes involving the spinal cord. In this article, anatomic structures are correlated with relevant clinical signs and symptoms and a step-wise approach to spinal cord diagnosis is outlined. Copyright © 2013 Elsevier Inc. All rights reserved.

Spinal cord injury drives chronic brain changes

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Ignacio Jure

2017-01-01

Full Text Available Only a few studies have considered changes in brain structures other than sensory and motor cortex after spinal cord injury, although cognitive impairments have been reported in these patients. Spinal cord injury results in chronic brain neuroinflammation with consequent neurodegeneration and cognitive decline in rodents. Regarding the hippocampus, neurogenesis is reduced and reactive gliosis increased. These long-term abnormalities could explain behavioral impairments exhibited in humans patients suffering from spinal cord trauma.

A single cysteine post-translational oxidation suffices to compromise globular proteins kinetic stability and promote amyloid formation

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Patrizia Marinelli

2018-04-01

Full Text Available Oxidatively modified forms of proteins accumulate during aging. Oxidized protein conformers might act as intermediates in the formation of amyloids in age-related disorders. However, it is not known whether this amyloidogenic conversion requires an extensive protein oxidative damage or it can be promoted just by a discrete, localized post-translational modification of certain residues. Here, we demonstrate that the irreversible oxidation of a single free Cys suffices to severely perturb the folding energy landscape of a stable globular protein, compromise its kinetic stability, and lead to the formation of amyloids under physiological conditions. Experiments and simulations converge to indicate that this specific oxidation-promoted protein aggregation requires only local unfolding. Indeed, a large scale analysis indicates that many cellular proteins are at risk of undergoing this kind of deleterious transition; explaining how oxidative stress can impact cell proteostasis and subsequently lead to the onset of pathological states. Keywords: Protein oxidation, Protein misfolding, Protein aggregation, Oxidative stress, Post-translational modification

Sonographic findings of normal newborn spinal cord

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Park, Chan Sup; Kim, Dong Gyu

1988-01-01

The authors performed spinal cord ultrasonography of 21 healthy newborn infants in Gyeongsang National University Hospital. Normal spinal cord revealed low echogenecity at that of cerebrospinal fluid and was demarcated by intense reflections from its dorsal and ventral surfaces. The central canal was routinely seen as a thin linear reflection in the center of the cord. The nerve roots making up the cauda equina formed a poorly defined collection of intense linear echoes extending from the conus. On real time image, the normal spinal cord exhibited rather slow and rhythmical anteroposterior movement within the subarachnoid fluid. A distinct and rapid vascular pulsation of the spinal cord was usually recognizable. The approximate level of vertebral bodies was determined as follows; most ventrally located vertebral body was thought to be L5 and S1 was seen slightly posterior to the L5 directed inferoposteriorly. According to the above criteria terminal portions of spinal cord were seen around the L2 body in 5 MHz and pointed termination of conus medullaris was clearly seen at L2-3 junction and in upper body of L3 by 7.5 MHz. So it would be better to examine by 5 MHz for spatial orientation and then by 7.5 MHz for more accurate examination. High-resolution, real-time ultrasonography was a safe, rapid screening technique for evaluation of the spinal cord in infants. Additional applications of spinal sonography may be possible in the evaluation of neonatal syringohydromyelia and meningocele as well as intraspinal cyst localization for possible percutaneous puncture by ultrasound guidance

Spinal cord stimulation therapy for localized central pain

International Nuclear Information System (INIS)

Hirato, Masafumi; Takahashi, Akio; Watanabe, Katsushige; Kazama, Ken; Yoshimoto, Yuhei

2008-01-01

We studied the pathophysiology of localized central pain and the surgical result of spinal cord stimulation. There were 10 cases; 7 males and 3 females from 24 to 77 years old. Pain was caused by peripheral nerve injury in one case, spinal cord injury in two cases and cerebrovascular disease (CVD) (thalamic pain) in 7 cases. All cases were treated by epidural spinal cord stimulation and followed from 0.8 to 8.8 years. Sufficient pain relief was achieved in one case of peripheral nerve and spinal cord injury and in 4 cases of CVD. Moderate pain control was achieved in 2 cases of CVD. In one each case of spinal cord injury and of CVD, pain control was ineffective. In cases with thalamic pain, we studied the correlation between the surgical result of spinal cord stimulation and the clinical features, MRI, fluoro-deoxyglucose (FDG)-positron emission tomography (PET), and somatosensory evoked potentials (SEP) findings before operation. MRI revealed a small to moderate sized lesion on the thalamus or putamen in each case. PET also showed decreased accumulation of FDG on the affected thalamus. In all cases without one fair responder to spinal cord stimulation, we could recognize definite SEP originating in the sensory cortex ipsilateral side to the CVD lesion during contralateral median or posterior tibial nerve stimulation. In the good responders, we could recognize SEP originating in the sensory cortex of the lesion side with less delayed latency or decreased amplitude than in the moderate responders. In this group, test stimulation with low voltage on the spinal cord evoked a sensory effect (paresthesia) over the painful part of the body. Spinal cord stimulation proved to be an effective treatment for localized central pain. In cases with localized central pain after CVD, we could expect to ameliorate the intractable pain in those cases in which SEP or spinal cord test stimulation revealed that the thalamo-cortical system was preserved. (author)

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

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Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

2013-08-01

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Spinal cord toxoplasmosis in AIDS

International Nuclear Information System (INIS)

Carteret, M.; Petit, E.; Granat, O.; Marichez, M.; Gilquin, J.

1995-01-01

Toxoplasmosis is the most common brain parasitic infection in acquired immunodeficiency syndrome (AIDS). Spinal cord localizations are still rare (2 cases with cerebral involvement, 2 cases without). A case of both spinal cord and cerebral involvement is reported. Magnetic resonance imaging (MR imaging) was performed because of sensory level (L 1). A focal conus medullaris enlargement was seen, iso intense on T 1 weighted images. This lesion was hyperintense on T 2 weighted sequence, and was homogeneously enhanced after Gadolinium on T 1 weighted images. A medullary oedema was noted. A toxoplasmosis treatment was initiated, without cortico therapy. MR imaging performed one month later (D 30), while important clinical improvements were seen, pointed out normal thickness of conus medullaris, without enhancement after Gadolinium. Disease lesions in AIDS with focal spinal cord processes are reviewed, and diagnostic work-up is discussed. Spinal cord single lesion, associated or not with brain involvements should be treated as a toxoplasmic infection, with MR imaging follow up. This work up should avoid medullary biopsy, still required in case of treatment failure. Cerebral involvements, with multiples lesions can mask medullary localization. (authors). 8 refs., 2 figs

Jomon pottery: cord-imitating decoration

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Irina Zhushchikhovskaya

2007-12-01

Full Text Available The paper discusses the decoration of pottery of the Neolithic Jomon culture (Japanese Archipelago, 13600–900 BC. The comb-impressed pattern produced by various kinds of cord or rope stamps is considered as the ‘calling card’ of Jomon pottery from the earliest cultural periods to the latest. Another kind of decoration recognized recently uses the cord not as a patterning tool, but as an essential motif of decorative composition. High relief elements imitate cordage forms and structures – knots, loops, hanging cord, net, etc. This kind of decoration corresponds to the pottery of Mid-dle Jomon period (3500–2500 BC sites located in northern and north-eastern Honshu and southern Hokkaido. It is supposed that the introduction of images of real material object into the field of decorative art was reasoned by the meaning of cord and cordage as cultural signs during the Middle Jomon period. Interesting parallels to some cordage structures reconstructed on Middle Jomon pottery decoration are well known in traditional Japanese culture of VI–XX cc. Analytical interpretation of this resemblance may became the subject of special research.

Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

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Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

2006-07-01

Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

Enhanced Engraftment of a Very Low-Dose Cord Blood Unit in an Adult Haemopoietic Transplant by Addition of Six Mismatched Viable Cord Units

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Stephen J. Proctor

2010-01-01

, supported by six mismatched cord blood units (one unit per 10 kg recipient weight. No adverse reaction occurred following the infusion of mismatched units and engraftment of the suboptimal-dose matched unit occurred rapidly, with no molecular evidence of engraftment of mismatched cords. Early molecular remission of ALL was demonstrated using a novel PCR for a mitochondrial DNA mutation in the leukaemic clone. The cell dose of the matched cord was well below that recommended to engraft a 70 kg recipient. We suggest that a factor or factors in the mismatched cords enhanced/supported engraftment of the matched cord.

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

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

2013-08-01

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.

Apolipoprotein E in umbilical cord blood plasma

International Nuclear Information System (INIS)

Forte, T.M.; Davis, P.A.; Blum, C.B.

1983-01-01

Adolipoprotein E (apo E), with a molecular weight of approximately 37,000 daltons, is a minor apolipoprotein constituent in adult plasma lipoproteins. This apolipoprotein, like apolipoprotein B, is a ligand recognized by specific lipoprotein receptor sites (B-E receptors) on cell surfaces. We have recently shown that a pronounced apo E band appears in umbilical cord blood low-density (LDL) lipoproteins and also in high density (HDL) lipoproteins. Densitometric scans of Coomassie blue G-250 stained polyacrylamide gels suggested that apo E was probably elevated in cord blood lipoproteins. To pursue this suggestion, apo E in cord blood was quantitated by radioimmunoassay and correlated with cord blood lipid levels. In addition, apo E levels in 20 normal adult volunteers were also examined

Characterization of axon formation in the embryonic stem cell-derived motoneuron.

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Pan, Hung-Chuan; Wu, Ya-Ting; Shen, Shih-Cheng; Wang, Chi-Chung; Tsai, Ming-Shiun; Cheng, Fu-Chou; Lin, Shinn-Zong; Chen, Ching-Wen; Liu, Ching-San; Su, Hong-Lin

2011-01-01

The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

Independent spinal cord atrophy measures correlate to motor and sensory deficits in individuals with spinal cord injury

DEFF Research Database (Denmark)

Lundell, Hans Magnus Henrik; Barthelemy, Dorothy; Skimminge, A.

2011-01-01

touch and pinprick, and muscle strength. Antero-posterior width (APW), left-right width (LRW) and cross-sectional spinal cord area (SCA) were extracted from MRI at the spinal level of C2. The angular variation of the spinal cord radius over the full circle was also extracted and compared...... with the clinical scores.Results:The motor score was correlated to LRW and the sensory scores were correlated to APW. The scores correlated also well with decreases in spinal cord radius in oblique angles in coherent and non-overlapping sectors for the sensory and motor qualities respectively.Conclusion:APW and LRW...

Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation after Acute Spinal Cord Injury

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2017-09-01

model in anesthetized (immobile) animals. Task 1: Evaluating the NIRS system function in a pig model of SCI in conjunction with IP measurements...started. We are collecting spinal cord NIRS data, using the V1 and OXT5 NIRS systems, in conjunction with IP measurements of spinal cord tissue...model of SCI in conjunction with IP measurements of oxygen, perfusion, pressure, and metabolism. SC150178 Kwon - Anual Report – Sep 01 2016 – Aug 31

Pretreatment with AQP4 and NKCC1 Inhibitors Concurrently Attenuated Spinal Cord Edema and Tissue Damage after Spinal Cord Injury in Rats.

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Yan, Xiaodong; Liu, Juanfang; Wang, Xiji; Li, Wenhao; Chen, Jingyuan; Sun, Honghui

2018-01-01

Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na + -K + -Cl - cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored. Additionally, aforementioned parameters in rats treated with AQP4 and/or NKCC1 inhibitors were assessed 2 days after SCI. Spinal cord water content was significantly increased 1 h after SCI while AQP4 and NKCC1 expression and spinal fluid LDH activity elevated 6 h after SCI. Spinal cord edema and spinal cord destruction peaked around 24 h after SCI and maintained at high levels thereafter. Treating rats with AQP4 inhibitor TGN-020 and NKCC1 antagonist bumetanide significantly reduced spinal cord edema, tissue destruction, and AQP4 and NKCC1 expression after SCI in an additive manner. These results demonstrated the benefits of simultaneously inhibiting both AQP4 and NKCC1 after SCI.

ROLE OF MONOCYTE PHAGOCYTIC SYSTEM IN FORMATION OF ANTIVIRAL RESISTANCE IN MICE AFTER PRELIMINARY INJECTION OF CRYOPRESERVED CORD BLOOD

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Kozhina OYu

2013-03-01

Full Text Available Now the task of preventive maintenance and search of biologically active substances, capable to make active the nonspecific immune response, remains an actual during flu epidemic. It has been previously established, that cryopreserved leucoconcentrate of human cord blood (cLHCB can act as modulator of activity of immunity. In the given work there was estimated influence of preventive injection of cLHCB and its components on functional activity of monocyte phagocytic system cells (MPSC in mice in the conditions of the induced influenzal infection. Preliminary introduction of cLHCB and its components 6 months prior to infection by flu virus makes 2 times increase of functional activity of macrophages, preventing inhibition of a nonspecific link of immunity. Thus, cLHCB inhibit of secondary immune deficiency development. The found increase in phagocytic activity of peritoneal cavity cells and 3 times increasesing of CD11b-marker expression after preventive injection of cLHCB testifies to rise of adherence and protective potential of MPSC that is one of possible mechanisms of formation of resistance to a flu virus. It is shown, that intranasal cLHCB injection before development of viral infection it can be o recommended as the method of preventive maintenance of flu.

Gd-DTPA MR imaging enhancement of spinal cord tumors

International Nuclear Information System (INIS)

Dillon, W.P.; Bolla, K.; Mark, A.S.; Tsudura, J.S.; Norman, D.; Newton, T.H.

1987-01-01

Nineteen patients with suspected spinal cord tumors were imaged with T1- and T2-weighted sequences before and after the administration of Gd-DTPA (0.1 mmol/kg). Eleven of the 19 patients had spinal cord tumors (three unproven). Eight of 11 patients had intramedullary tumors (four astrocytomas, two ependymomas) and two had extra-medullary tumors (one meningioma, one metastatic melanoma). Other lesions studied include idiopathic syringomyelia (two), spinal arteriovenous malformation (AVM) (one), posttraumatic arachnoiditis (one), and cord infarct (one). All of the tumors enhanced after the administration of Gd-DTPA. Spinal cord enhancement was also noted in association with a spinal cord AVM, a suspected cord infarct, and in the patient with severe arachnoiditis. No enhancement was present in patients with idiopathic or posttraumatic syringomyelia or in the three normal patients. In six of the patients, enhancement was critical in confirming disease that was questionable on the precontrast MR images. Gadolinium enhancement allowed differentiation of tumor from postoperative changes in two patients with spinal cord tumors. Enhanced images localized the lesion more accurately than precontrast MR images in eight patients. In four patients a lesion could only be detected after the administration of contrast. The postcontrast images better defined the margin of tumor from surrounding edema, operative scarring, and cord cavitation. The AVM case had enhancement of slowly flowing veins with Gd-DTPA posterior to an ischemic cord segment. Gd-DTPA enhancement is extremely useful in the detection and therapeutic assessment of spinal cord tumors; however, enhancement is not specific for tumors and should be interpreted in light of the clinical setting

Spinal Cord Subependymoma Surgery : A Multi-Institutional Experience.

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Yuh, Woon Tak; Chung, Chun Kee; Park, Sung-Hye; Kim, Ki-Jeong; Lee, Sun-Ho; Kim, Kyoung-Tae

2018-03-01

A spinal cord subependymoma is an uncommon, indolent, benign spinal cord tumor. It is radiologically similar to a spinal cord ependymoma, but surgical findings and outcomes differ. Gross total resection of the tumor is not always feasible. The present study was done to determine the clinical, radiological and pathological characteristics of spinal cord subependymomas. We retrospectively reviewed the medical records of ten spinal cord subependymoma patients (M : F=4 : 6; median 38 years; range, 21-77) from four institutions. The most common symptoms were sensory changes and/or pain in eight patients, followed by motor weakness in six. The median duration of symptoms was 9.5 months. Preoperative radiological diagnosis was ependymoma in seven and astrocytoma in three. The tumors were located eccentrically in six and were not enhanced in six. Gross total resection of the tumor was achieved in five patients, whereas subtotal or partial resection was inevitable in the other five patients due to a poor dissection plane. Adjuvant radiotherapy was performed in two patients. Neurological deterioration occurred in two patients; transient weakness in one after subtotal resection and permanent weakness after gross total resection in the other. Recurrence or regrowth of the tumor was not observed during the median 31.5 months follow-up period (range, 8-89). Spinal cord subependymoma should be considered when the tumor is located eccentrically and is not dissected easily from the spinal cord. Considering the rather indolent nature of spinal cord subependymomas, subtotal removal without the risk of neurological deficit is another option.

Structural remodeling of the heart and its premotor cardioinhibitory vagal neurons following T(5) spinal cord transection.

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Lujan, Heidi L; Janbaih, Hussein; DiCarlo, Stephen E

2014-05-01

Midthoracic spinal cord injury (SCI) is associated with enhanced cardiac sympathetic activity and reduced cardiac parasympathetic activity. The enhanced cardiac sympathetic activity is associated with sympathetic structural plasticity within the stellate ganglia, spinal cord segments T1-T4, and heart. However, changes to cardiac parasympathetic centers rostral to an experimental SCI are relatively unknown. Importantly, reduced vagal activity is a predictor of high mortality. Furthermore, this autonomic dysregulation promotes progressive left ventricular (LV) structural remodeling. Accordingly, we hypothesized that midthoracic spinal cord injury is associated with structural plasticity in premotor (preganglionic parasympathetic neurons) cardioinhibitory vagal neurons located within the nucleus ambiguus as well as LV structural remodeling. To test this hypothesis, dendritic arborization and morphology (cholera toxin B immunohistochemistry and Sholl analysis) of cardiac projecting premotor cardioinhibitory vagal neurons located within the nucleus ambiguus were determined in intact (sham transected) and thoracic level 5 transected (T5X) rats. In addition, LV chamber size, wall thickness, and collagen content (Masson trichrome stain and structural analysis) were determined. Midthoracic SCI was associated with structural changes within the nucleus ambiguus and heart. Specifically, following T5 spinal cord transection, there was a significant increase in cardiac parasympathetic preganglionic neuron dendritic arborization, soma area, maximum dendritic length, and number of intersections/animal. This parasympathetic structural remodeling was associated with a profound LV structural remodeling. Specifically, T5 spinal cord transection increased LV chamber area, reduced LV wall thickness, and increased collagen content. Accordingly, results document a dynamic interaction between the heart and its parasympathetic innervation.

Interactive and individual effects of sensory potentiation and region-specific changes in excitability after spinal cord injury.

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Hoffman, N; Parker, D

2011-12-29

While promoting regeneration across lesion sites is a main focus of research into spinal injury, changes also occur in the sublesion spinal cord and its sensory inputs. However, how these varied effects relate to recovery remains largely unknown. Here, we have examined changes in sensory inputs and region-specific changes in spinal cord excitability after spinal cord lesions in the lamprey, a model system for studying regeneration and functional recovery, and related the changes to the degree of locomotor recovery.Proprioceptive responses below lesion sites were potentiated and their rate of adaptation reduced 8-10 weeks after lesioning (i.e. when animals usually showed significant locomotor recovery). These effects were associated with changes in cellular properties that were consistent with an increase in proprioceptor excitability. However, the changes in proprioceptive inputs did not correlate with the degree of locomotor recovery. There were region-specific changes in spinal cord excitability below lesion sites. In isolation, these excitability changes also did not correlate with the degree of locomotor recovery, but in this case, there were significant interactions between the magnitude of stimulation-evoked responses across the lesion site (used to assess the extent of regeneration) and sublesion changes in excitability. These interactions differed in animals that recovered well or poorly, suggesting that the nature of this interaction influenced recovery. These results add to the evidence for diverse changes in the spinal cord after injury, and suggest that regenerated inputs and their interactions with sublesion networks influence the degree of functional recovery. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Myelosuppressive conditioning using busulfan enables bone marrow cell accumulation in the spinal cord of a mouse model of amyotrophic lateral sclerosis.

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Coral-Ann B Lewis

Full Text Available Myeloablative preconditioning using irradiation is the most commonly used technique to generate rodents having chimeric bone marrow, employed for the study of bone marrow-derived cell accumulation in the healthy and diseased central nervous system. However, irradiation has been shown to alter the blood-brain barrier, potentially creating confounding artefacts. To better study the potential of bone marrow-derived cells to function as treatment vehicles for neurodegenerative diseases alternative preconditioning regimens must be developed. We treated transgenic mice that over-express human mutant superoxide dismutase 1, a model of amyotrophic lateral sclerosis, with busulfan to determine whether this commonly used chemotherapeutic leads to stable chimerism and promotes the entry of bone marrow-derived cells into spinal cord. Intraperitoneal treatment with busulfan at 60 mg/kg or 80 mg/kg followed by intravenous injection of green fluorescent protein-expressing bone marrow resulted in sustained levels of chimerism (~80%. Bone marrow-derived cells accumulated in the lumbar spinal cord of diseased mice at advanced stages of pathology at both doses, with limited numbers of bone marrow derived cells observed in the spinal cords of similarly treated, age-matched controls; the majority of bone marrow-derived cells in spinal cord immunolabelled for macrophage antigens. Comparatively, significantly greater numbers of bone marrow-derived cells were observed in lumbar spinal cord following irradiative myeloablation. These results demonstrate bone marrow-derived cell accumulation in diseased spinal cord is possible without irradiative preconditioning.

An Exploration of Teachers' Narratives: What Are the Facilitators and Constraints Which Promote or Inhibit "Good" Formative Assessment Practices in Schools?

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Sach, Elizabeth

2015-01-01

This paper set out to explore teachers' narratives in order to understand some of the facilitators and constraints which promote or inhibit good formative assessment practices in schools. A "responsive interview" approach was used to probe a small sample of lower and middle school teachers' perceptions of formative assessment.…

High-field MR imaging of spinal cord multiple sclerosis

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De La Paz, R.L.; Floris, R.; Norman, D.; Enzmann, D.R.

1987-01-01

Fifty-one high-field MR imaging studies (1.5 T, General Electric Signa) of the spinal cord were performed in 42 patients (27 female, 15 male; mean age, 40 years) with clinically definitive (n = 34) or probable (n = 8) multiple sclerosis and suspected spinal cord lesions. MR imaging showed focal spinal cord abnormalities in 38 (75%) of 51 studies. T2-weighted images were abnormal (showing foci of high signal intensity) in 38 studies, T1-weighted images were abnormal (showing areas of low signal intensity or mass effect) in 16 (42%) of 38, and GRASS images were abnormal (showing foci of high signal intensity) in 9 (82%) of 11 cases. Brain MR imaging showed periventricular lesions typical of multiple sclerosis in 34 (81%) of 42 studies. Spinal cord studies were positive in eight cases with normal brain MR images, and brain studies were positive in 13 instances of normal spinal cord MR images. Four lesions were at the cervicomedullary junction, 44 in the cervical spinal cord, and three in the thoracic cord. Mass effect in cord lesions, simulating neoplasm, was seen in seven patients during the acute symptomatic phase. Serial studies in three patients with decreasing symptoms showed a reduction after 3-4 weeks and resolution of the mass effect after 2-6 months

Regeneration of supraspinal axons after transection of the thoracic spinal cord in the developing opossum, Didelphis virginiana.

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Wang, X M; Terman, J R; Martin, G F

1998-08-17

When the thoracic spinal cord of the North American opossum is transected early in development, supraspinal axons grow through the lesion. In the experiments reported here, we asked whether regeneration of cut axons contributes to such growth. Fast Blue (FB) was injected into the lumbar cord on postnatal day (PD)5, 8, 15, or 20. Five days later, FB was removed by gentle suction, and the spinal cord was transected at thoracic levels. Fourteen days later, rhodamine B dextran was injected between the site of the FB injection and the lesion. The pups were maintained for an additional 7-10 days before killing and perfusion. We assumed that supraspinal neurons that contained FB survived axotomy and those that contained both FB and rhodamine B dextran supported regenerating axons. In the PD5 group (lesioned at PD10), regenerative growth was documented for axons originating in all of the supraspinal nuclei that innervate the lumbar cord by PD10. When the injections were made at the later ages, however, neurons that supported regenerative growth were fewer in number and regionally restricted. In some cases, they were limited primarily to the red nucleus, the medullary raphe, and the adjacent reticular formation. Our results show that regeneration of cut axons contributes to growth of supraspinal axons through the lesion after transection of the thoracic cord in developing opossums and that the critical period for regenerative growth is not the same for all axons.

Differential gene expression in the EphA4 knockout spinal cord and analysis of the inflammatory response following spinal cord injury.

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Kathryn M Munro

Full Text Available Mice lacking the axon guidance molecule EphA4 have been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips™. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wildtype spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage/microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages/activated microglia in injured EphA4 knockout compared to wild-type spinal cords at 2, 4 or 14 days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages/activated microglia was observed in EphA4 knockout spinal cords at 4 days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury.

[Retention cysts of the vocal cords (author's transl)].

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Grundmann, E W

1979-05-01

Present day knowledge in laryngology maintains that the free edge of the true cord mucosa is devoid of glands so that retention cysts should not occur in this tissue. When such cysts do occur, it is difficult to define their pathogenesis. Reference is made to the author's earlier study which found a regular occurrence of mucous glands in the squamous epithelial region of the vocal cords. A retention cyst in the true cord is described histologically in the present report. The glands responsible for these cysts are believed to function by moistening the mucous membrane of the vocal cords.

International urodynamic basic spinal cord injury data set.

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Biering-Sørensen, F; Craggs, M; Kennelly, M; Schick, E; Wyndaele, J-J

2008-07-01

To create the International Urodynamic Basic Spinal Cord Injury (SCI) Data Set within the framework of the International SCI Data Sets. International working group. The draft of the data set was developed by a working group consisting of members appointed by the Neurourology Committee of the International Continence Society, the European Association of Urology, the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the Executive Committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review and comments by members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA Board, relevant and interested (international) organizations and societies (around 40) and persons and the ISCoS Council. Endorsement of the data set by relevant organizations and societies will be obtained. To make the data set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. Variables included in the International Urodynamic Basic SCI Data Set are date of data collection, bladder sensation during filling cystometry, detrusor function, compliance during filing cystometry, function during voiding, detrusor leak point pressure, maximum detrusor pressure, cystometric bladder capacity and post-void residual volume.

Spinal meningioma: relationship between degree of cord compression and outcome.

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Davies, Simon; Gregson, Barbara; Mitchell, Patrick

2017-04-01

The aim of this study was to find the relationships between the degree of cord compression as seen on MRIs with persisting cord atrophy after decompression and patient outcomes in spinal meningiomas. We undertook a retrospective analysis of 31 patients' pre- and postoperative MRIs, preoperative functional status and their outcomes at follow-up. The following metrics were analysed; percentage cord area at maximum compression, percentage tumour occupancy and percentage cord occupancy. These were then compared with outcome as measured by the Nurick scale. Of the 31 patients, 27 (87%) had thoracic meningiomas, 3 (10%) cervical and 1 (3%) cervicothoracic. The meningiomas were pathologically classified as grade 1 (29) or grade 2 (2) according to the WHO classification. The average remaining cord cross-sectional area was 61% of the estimated original value. The average tumour occupancy of the canal was 72%. The average cord occupancy of the spinal canal at maximum compression was 20%. No correlation between cord cross-section area and Nurick Scale was seen. On the postoperative scan, the average cord area had increased to 84%. No correlation was seen between this value and outcome. We found that cross-section area measurements on MRI scans have no obvious relationship with function before or after surgery. This is a base for future research into the mechanism of cord recovery and other compressive cord conditions.

Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

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Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

2016-09-01

We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1-10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633-0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926-0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.

A study of spinal cord tumors by magnetic resonance imaging

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Gushiken, Isao; Nishihira, Takeshi; Nakasone, Tomohiro [Ryukyu Univ., Nishihara, Okinawa (Japan). School of Medicine; Takara, Hiroaki; Oshiro, Yutaka; Oshiro, Takashi; Isa, Makoto; Kinjo, Yukio; Ibaraki, Kunio

1989-10-01

We studied 17 cases of spinal cord tumors using magnetic resonance imaging. According to the intensity of image and histological feature of spinal cord tumors, we identified two groups in T2 weighted imaging. One was a hypointensity group showing cystic or vascular tumors, and the other was hyperintensity group of solid tumors. Preoperative images of swelling, narrowing, deviation of the spinal cord were remained after the operations. Grafted free fatty tissue for the prevention of adhesion was recognized well also after the operation. Postoperative imagings sometime showed pseudo-deviation of the spinal cord which was easy to be mistaken as the remains of tumors and narrowing of the spinal cord. In conclusion, the magnetic resonance imaging makes very early detection of spinal cord tumors possible, and it is valuable for a diagnosis of the spinal cord tumor associated with brain tumor. (author).

A study of spinal cord tumors by magnetic resonance imaging

International Nuclear Information System (INIS)

Gushiken, Isao; Nishihira, Takeshi; Nakasone, Tomohiro; Takara, Hiroaki; Oshiro, Yutaka; Oshiro, Takashi; Isa, Makoto; Kinjo, Yukio; Ibaraki, Kunio.

1989-01-01

We studied 17 cases of spinal cord tumors using magnetic resonance imaging. According to the intensity of image and histological feature of spinal cord tumors, we identified two groups in T2 weighted imaging. One was a hypointensity group showing cystic or vascular tumors, and the other was hyperintensity group of solid tumors. Preoperative images of swelling, narrowing, deviation of the spinal cord were remained after the operations. Grafted free fatty tissue for the prevention of adhesion was recognized well also after the operation. Postoperative imagings sometime showed pseudo-deviation of the spinal cord which was easy to be mistaken as the remains of tumors and narrowing of the spinal cord. In conclusion, the magnetic resonance imaging makes very early detection of spinal cord tumors possible, and it is valuable for a diagnosis of the spinal cord tumor associated with brain tumor. (author)

A rat model of chronic syringomyelia induced by epidural compression of the lumbar spinal cord.

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Lee, Ji Yeoun; Kim, Shin Won; Kim, Saet Pyoul; Kim, Hyeonjin; Cheon, Jung-Eun; Kim, Seung-Ki; Paek, Sun Ha; Pang, Dachling; Wang, Kyu-Chang

2017-10-01

OBJECTIVE There has been no established animal model of syringomyelia associated with lumbosacral spinal lipoma. The research on the pathophysiology of syringomyelia has been focused on Chiari malformation, trauma, and inflammation. To understand the pathophysiology of syringomyelia associated with occult spinal dysraphism, a novel animal model of syringomyelia induced by chronic mechanical compression of the lumbar spinal cord was created. METHODS The model was made by epidural injection of highly concentrated paste-like kaolin solution through windows created by partial laminectomy of L-1 and L-5 vertebrae. Behavioral outcome in terms of motor (Basso-Beattie-Bresnahan score) and urinary function was assessed serially for 12 weeks. Magnetic resonance images were obtained in some animals to confirm the formation of a syrinx and to monitor changes in its size. Immunohistochemical studies, including analysis for glial fibrillary acidic protein, NeuN, CC1, ED-1, and caspase-3, were done. RESULTS By 12 weeks after the epidural compression procedure, syringomyelia formation was confirmed in 85% of the rats (34 of 40) on histology and/or MRI. The syrinx cavities were found rostral to the epidural compression. Motor deficit of varying degrees was seen immediately after the procedure in 28% of the rats (11 of 40). In 13 rats (33%), lower urinary tract dysfunction was seen. Motor deficit improved by 5 weeks after the procedure, whereas urinary dysfunction mostly improved by 2 weeks. Five rats (13%, 5 of 40) died 1 month postoperatively or later, and 3 of the 5 had developed urinary tract infection. At 12 weeks after the operation, IHC showed no inflammatory process, demyelination, or accelerated apoptosis in the spinal cords surrounding the syrinx cavities, similar to sham-operated animals. CONCLUSIONS A novel experimental model for syringomyelia by epidural compression of the lumbar spinal cord has been created. The authors hope that it will serve as an important research

Spinal cord blood flow measured by 14C-iodoantipyrine autoradiography during and after graded spinal cord compression in rats

International Nuclear Information System (INIS)

Holtz, A.; Nystroem, B.G.; Gerdin, B.

1989-01-01

The relations between degree of thoracic spinal cord compression causing myelographic block, reversible paraparesis, and extinction of the sensory evoked potential on one hand, and spinal cord blood flow on the other, were investigated. This was done in rats using the blocking weight-technique and 14 C-iodoantipyrine autoradiography. A load of 9 g caused myelographic block. Five minutes of compression with that load caused a reduction of spinal cord blood flow to about 25%, but 5 and 60 minutes after the compression spinal cord blood flow was restored to 60% of the pretrauma value. A load of 35 g for 5 minutes caused transient paraparesis. Recovery to about 30% was observed 5 and 60 minutes thereafter. During compression at a load of 55 g, which caused almost total extinction of sensory evoked potential and irreversible paraplegia, spinal cord blood flow under the load ceased. The results indicate that myelographic block occurs at a load which does not cause irreversible paraparesis and that a load which permits sensory evoked potential to be elicited results in potentially salvageable damage

MRI in diagnosis of spinal cord diseases

International Nuclear Information System (INIS)

Kobayashi, Naotoshi; Ono, Yuko; Kakinoki, Yoshio; Kimura, Humiko; Ebihara, Reiko; Nagayama, Takashi; Okada, Takaharu; Watanabe, Hiromi

1985-01-01

64 MRI studies of 57 cases of spinal cord diseases were reviewed, and following results were obtained. (1) MRI is usefull for screening method of spinal cord diseases, as CT in cerebral diseases. (2) MRI might replaces myelography in most of spinal cord disease, and more reliable informations might be obtained by MRI than in myelography in some cases, but (3) in detection of small organic changes, some technological problems are layed regarding to the image resolution of MRI. (author)

Incarcerated umbilical cord hernia containing the gallbladder

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Ann M. Kulungowski

2017-06-01

Full Text Available A 16 day-old boy infant with an umbilical mass underwent operative exploration of the umbilicus. The mass proved to be a gallbladder incarcerated in a hernia of the umbilical cord. Distinguishing an omphalocele from an umbilical cord hernia is not obvious and can be arbitrary. Morphologically, the two terms both describe congenital abdominal wall defects covered by a membrane, typically containing abdominal organs. Subtle differences and clinical features between omphalocele and umbilical cord hernia are highlighted in this report.

Contrast enhanced CT of spinal cord angioma

International Nuclear Information System (INIS)

Nakamura, Takahiko; Ebitani, Tsutomu; Honma, Takao; Sofue, Muroto; Nakamura, Shigeru

1982-01-01

Contrast enhanced CT on 6 patients with spinal cord angioma showed enhancement in 2 of them. The conditions to produce contrast enhancement were the window width of 100 - 200, and the window level of 0 - 50. In spinal cord angioma, contrast enhanced CT is presently only an adjunct to angiography and myelography. Nevertheless, contrast enhanced CT is useful in the screening test for spinal cord angioma, in the patients who are nonindicated to angiography, and in the postoperative follow-up. (Ueda, J.)

Nanomedicine for treating spinal cord injury

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

2013-09-01

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

Teaching nonlinear dynamics through elastic cords

International Nuclear Information System (INIS)

Chacon, R; Galan, C A; Sanchez-Bajo, F

2011-01-01

We experimentally studied the restoring force of a length of stretched elastic cord. A simple analytical expression for the restoring force was found to fit all the experimental results for different elastic materials. Remarkably, this analytical expression depends upon an elastic-cord characteristic parameter which exhibits two limiting values corresponding to two nonlinear springs with different Hooke's elastic constants. Additionally, the simplest model of elastic cord dynamics is capable of exhibiting a great diversity of nonlinear phenomena, including bifurcations and chaos, thus providing a suitable alternative model system for discussing the basic essentials of nonlinear dynamics in the context of intermediate physics courses at university level.

Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells.

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Powan, Phattrakorn; Luanpitpong, Sudjit; He, Xiaoqing; Rojanasakul, Yon; Chanvorachote, Pithi

2017-11-01

The epithelial-to-mesenchymal transition is proposed to be a key mechanism responsible for metastasis-related deaths. Similarly, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the link between the two events and their control mechanisms is unclear. We used a three-dimensional (3D) tumor spheroid assay and other CSC-indicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial-to-mesenchymal transition in lung cancer cells. Ectopic overexpression and knockdown of E-cadherin were found to promote and retard, respectively, the formation of tumor spheroids in vitro but had opposite effects on tumor formation and metastasis in vivo in a xenograft mouse model. We explored the discrepancy between the in vitro and in vivo results and demonstrated, for the first time, that E-cadherin is required as a component of a major survival pathway under detachment conditions. Downregulation of E-cadherin increased the stemness of lung cancer cells but had an adverse effect on their survival, particularly on non-CSCs. Such downregulation also promoted anoikis resistance and invasiveness of lung cancer cells. These results suggest that anoikis assay could be used as an alternative method for in vitro assessment of CSCs that involves dysregulated adhesion proteins. Our data also suggest that agents that restore E-cadherin expression may be used as therapeutic agents for metastatic cancers. Copyright © 2017 the American Physiological Society.

Inter-organizational relationships: promoters and restrictive factors in the formation of cooperation network

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Marcos Antonio Gaspar

2014-04-01

Full Text Available The present paper had as aim to identify factors of inter-organizational relationships which promotes and restricts the formation of companies’ cooperation network, from two levels of analysis (organizational and inter-organizational. To achieve this goal, it was developed a descriptive-qualitative study, with prospecting for primary and secondary data on a cooperation network. The universe was composed by 41 participating companies associated to the analyzed network. The sampling procedure was for researcher’s accessibility and convenience. As a result, it was identified that the network is guided by goals of cooperation among the participating companies, in addition to representing the sector and provide services in the interests of the associates. The main factors influencing the formation of the network were: business center, marketing and training; but only training has been achieved satisfactorily. The business center and marketing factors have not yet been fully developed, being both identified as restrictive factors.

Induction of Fos protein immunoreactivity by spinal cord contusion

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E.A. Del-Bel

2000-05-01

Full Text Available The objective of the present study was to identify neurons in the central nervous system that respond to spinal contusion injury in the rat by monitoring the expression of the nuclear protein encoded by the c-fos gene, an activity-dependent gene, in spinal cord and brainstem regions. Rats were anesthetized with urethane and the injury was produced by dropping a 5-g weight from 20.0 cm onto the exposed dura at the T10-L1 vertebral level (contusion group. The spinal cord was exposed but not lesioned in anesthetized control animals (laminectomy group; intact animals were also subjected to anesthesia (intact control. Behavioral alterations were analyzed by Tarlov/Bohlman scores, 2 h after the procedures and the animals were then perfused for immunocytochemistry. The patterns of Fos-like immunoreactivity (FLI which were site-specific, reproducible and correlated with spinal laminae that respond predominantly to noxious stimulation or injury: laminae I-II (outer substantia gelatinosa and X and the nucleus of the intermediolateral cell column. At the brain stem level FLI was detected in the reticular formation, area postrema and solitary tract nucleus of lesioned animals. No Fos staining was detected by immunocytochemistry in the intact control group. However, detection of FLI in the group submitted to anesthesia and surgical procedures, although less intense than in the lesion group, indicated that microtraumas may occur which are not detected by the Tarlov/Bohlman scores. There is both a local and remote effect of a distal contusion on the spinal cord of rats, implicating sensory neurons and centers related to autonomic control in the reaction to this kind of injury.

Prognosis by tumor location for pediatric spinal cord Ependymomas

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Oh, MC; Sayegh, ET; Safaee, M; Sun, MHZ; Kaur, G; Kim, JM; Aranda, D; Molinaro, AM; Gupta, N; Parsa, AT

2013-01-01

Object. Ependymoma is a common CNS tumor in children, with spinal cord ependymomas making up 13.1% of all ependymomas in this age group. The clinical features that affect prognosis in pediatric spinal cord ependymomas are not well understood. A comprehensive literature review was performed to determine whether a tumor location along the spinal cord is prognostically significant in children undergoing surgery for spinal cord ependymomas. Methods. A PubMed search was performed to identify all p...

Are there endogenous stem cells in the spinal cord?

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Ferrucci, Michela; Ryskalin, Larisa; Busceti, Carla L; Gaglione, Anderson; Biagioni, Francesca; Fornai, Francesco

2017-12-01

Neural progenitor cells (NPC) represent the stem-like niche of the central nervous system that maintains a regenerative potential also in the adult life. Despite NPC in the brain are well documented, the presence of NPC in the spinal cord has been controversial for a long time. This is due to a scarce activity of NPC within spinal cord, which also makes difficult their identification. The present review recapitulates the main experimental studies, which provided evidence for the occurrence of NPC within spinal cord, with a special emphasis on spinal cord injury and amyotrophic lateral sclerosis. By using experimental models, here we analyse the site-specificity, the phenotype and the main triggers of spinal cord NPC. Moreover, data are reported on the effect of specific neurogenic stimuli on these spinal cord NPC in an effort to comprehend the endogenous neurogenic potential of this stem cell niche.

Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury.

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Hanna, Amgad; Thompson, Daniel L; Hellenbrand, Daniel J; Lee, Jae-Sung; Madura, Casey J; Wesley, Meredith G; Dillon, Natalie J; Sharma, Tapan; Enright, Connor J; Murphy, William L

2016-07-01

Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin-3 (NT-3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT-3 binding and release were characterized in vitro. Then, the NT-3-loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP-coated sutures exhibited a burst release of NT-3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT-3-loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT-3-loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT-3-loaded sutures had significantly more axons per graft than rats treated with an NT-3 injection and rats without NT-3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP-coated sutures can efficiently release NT-3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Insulin Promotes the Proliferation of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells by Activating the Akt-Cyclin D1 Axis

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Peng Li

2017-01-01

Full Text Available Background. The functions of insulin in mesenchymal stem cells (MSC remain poorly understood. Methods. MSC from human umbilical cord matrix (UCM cultured in serum-free media (SFM with or without insulin were subjected to various molecular biological analyses to determine their proliferation and growth states, expression levels of Akt-cyclin D1 signaling molecules, and in vitro differentiation capacities. Results. Insulin accelerated the G1-S cell cycle progression of UCM-MSC and significantly stimulated their proliferation and growth in SFM. The pro-proliferative action of insulin was associated with augmented cyclin D1 and phosphorylated Akt expression levels. Akt inactivation remarkably abrogated insulin-induced increases in cyclin D1 expression and cell proliferation, indicating that insulin enhances the proliferation of UCM-MSC via acceleration of the G1-S transition mediated by the Akt-cyclin D1 pathway. Additionally, the UCM-MSC propagated in SFM supplemented with insulin exhibited similar specific surface antigen profiles and differentiation capacities as those generated in conventional media containing fetal bovine serum. Conclusions. These findings suggest that insulin acts solely to promote UCM-MSC proliferation without affecting their immunophenotype and differentiation potentials and thus have important implications for utilizing insulin to expand clinical-grade MSC in vitro.

Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats

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Chen, Bo; He, Jianyu; Yang, Hao; Zhang, Qian; Zhang, Lingling; Zhang, Xian; Xie, En; Liu, Cuicui; Zhang, Rui; Wang, Yi; Huang, Linhong; Hao, Dingjun

2015-03-01

There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.

Subinhibitory concentrations of triclosan promote Streptococcus mutans biofilm formation and adherence to oral epithelial cells.

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Telma Blanca Lombardo Bedran

Full Text Available Triclosan is a general membrane-active agent with a broad-spectrum antimicrobial activity that is commonly used in oral care products. In this study, we investigated the effect of sub-minimum inhibitory concentrations (MICs of triclosan on the capacity of the cariogenic bacterium Streptococcus mutans to form biofilm and adhere to oral epithelial cells. As quantified by crystal violet staining, biofilm formation by two reference strains of S. mutans was dose-dependently promoted, in the range of 2.2- to 6.2-fold, by 1/2 and 1/4 MIC of triclosan. Observations by scanning electron microscopy revealed the presence of a dense biofilm attached to the polystyrene surface. Growth of S. mutans in the presence of triclosan at sub-MICs also increased its capacity to adhere to a monolayer of gingival epithelial cells. The expression of several genes involved in adherence and biofilm formation in S. mutans was investigated by quantitative RT-PCR. It was found that sub-MICs of triclosan significantly increased the expression of comD, gtfC, and luxS, and to a lesser extent of gtfB and atlA genes. These findings stress the importance of maintaining effective bactericidal concentrations of therapeutic triclosan since sub-MICs may promote colonization of the oral cavity by S. mutans.

Magnetic resonance imaging of acute spinal-cord injury

International Nuclear Information System (INIS)

Yamamoto, Hideki; Nakagawa, Hiroshi; Yamada, Takahisa; Iwata, Kinjiro; Okumura, Terufumi; Hoshino, Daisaku.

1992-01-01

Magnetic resonance imaging (MRI) provides a noninvasive and very important method of investigating spinal-cord injuries. By means of MRI we examined 36 patients with spinal injuries, 34 of them in the acute stage. 19 cases had complete spinal-cord injury with paraplegia, while 17 cases had incomplete spinal-cord injury. MRI showed the injured spinal-cord in the acute stage to be partially swollen, with a high signal intensity in the T 2 -weighted images. In the chronic stage, the injured cord may show atrophic changes with a post-traumatic cavity or myelomalacia, which appears as a high-signal-intensity lesion in the T 2 -weighted images and as a low-signal intensity in the T 1 -weighted images. The cases with complete spinal injuries showed a high signal intensity at the wide level, and these prognoses were poor. The cases with incomplete injuries showed normal findings or a high-signal-intensity spot. In the Gd-DTPA enhanced images, the injured cords were enhanced very well in the subchronic stage. MRI is thus found to be useful in the diagnosis of spinal injuries; it also demonstrates a potential for predicting the neurological prognosis. (author)

Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats.

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Lingying Liu

Full Text Available BACKGROUND: Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs could on wound healing in a rat model of severe burn and its potential mechanism. METHODS: Adult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI, and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA. RESULTS: We found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation. CONCLUSION: The study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.

Suicide in a spinal cord injured population

DEFF Research Database (Denmark)

Hartkopp, A; Brønnum-Hansen, Henrik; Seidenschnur, A M

1998-01-01

To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI).......To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI)....

MRI diagnosis of acute spinal cord decompression sickness

International Nuclear Information System (INIS)

Tang Xiaofeng; Yuan Fengmei; Ma Heng; Xu Yongzhong; Gai Qingzhu; Wang Ying

2008-01-01

Objective: To describe MRI findings of acute spinal cord decompression sickness. Methods: MRI findings of 5 cases with clinical definite acute spinal cord decompression sickness were retrospectively analyzed. The main clinical informations included underwater performance history against regulations, short-term complete or incomplete spinal cord injury symptoms after fast going out of water, sensory disability and urinary and fecal incontinence, etc. Results: Spinal cord vacuole sign was found in all 5 cases. Iso-signal intensity (n=3), high signal intensity (n=1), and low signal intensity (n=1) was demonstrated on T 1 WI, and high signal intensity (n=5) was found on T 2 WI. Owl eye sign was detected in 3 cases, and lacune foci were seen in 2 cases. Conclusion: MRI findings of acute spinal cord decompression sickness had some characteristics, and it was easy to diagnose by combining diving history with clinical manifestations. (authors)

Cisplatin upregulates mitochondrial nitric oxide synthase and peroxynitrite formation to promote renal injury

International Nuclear Information System (INIS)

Jung, Michaela; Hotter, Georgina; Vinas, Jose Luis; Sola, Anna

2009-01-01

The mitochondria are a critical target for cisplatin-associated nephrotoxicity. Though nitric oxide formation has been implicated in the toxicity of cisplatin, this formation has not so far been related to a possible activation of mitochondrial nitric oxide synthase (mNOS). We show here that the upregulation of oxide mNOS and peroxynitrite formation in cisplatin treatment are key events that influence the development of the harmful parameters described in cisplatin-associated kidney failure. We confirm this by isolating the mitochondrial fraction of the kidney and across different access routes such as the use of a specific inhibitor of neuronal NOS, L-NPA, a peroxynitrite scavenger, FeTMPyP, and a peroxynitrite donor, SIN-1. The in vitro studies corroborated the information obtained in the in vivo experiments. The administration of cisplatin reveals a clear upregulation in the transcription of neuronal NOS and an increase in the levels of nitrites in the mitochondrial fractions of the kidneys. The upregulated transcription directly affects the cytoskeleton structure and the apoptosis. The inhibition of neuronal NOS reduces the levels of nitrites, cell death, and cytoskeleton derangement. Peroxynitrite is involved in the mechanism promoting the NOS transcription. In addition, in controls SIN-1 imitates the effects of cisplatin. In summary, we demonstrate that upregulation of mNOS in cisplatin treatment is a key component in both the initiation and the spread of cisplatin-associated damage in the kidney. Furthermore, peroxynitrite formation is directly involved in this process

Relationship between newborn Acid-Base status and umbilical cord morphology

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Marssosi V

2001-06-01

Full Text Available ess the relationship between umbilical cord blood gases at birth and morphology of umbilical cord, in a prospective study of 200 consecutive term delivery, we investigated the relationship between umbilical cord morphology characteristics (umbilical crd length, number of vascular coil, coiling index and color of amniotic fluid and umbilical vessel blood gases. Statistically significant linear correlation was found between umblicial venous PH and the umbilical cord length (r=0.39, 95% CI 0.25, 0.53, P<0.03, umber of vascular coils (r=0.45 95% CI 0.31-0.59 P<0.012, and coiling index (r=0.34, 95% CI 0.12-0.48, P<0.04, and also negative linear correlation was found between umbilical venous partial pressure of carbon dioxide & of coli (r=0.3, 95% CI –0.44, -0.16 P<0.03. No relation was found between umbilical cord indices and meconium staining of amniotic fluid.Placental weight also correlated with umbilical cord length (r=0.17, 95% CI 0.03-0.31, P<0.03, but not with umbilical cord coils or coiling index.Umbilical venous pH is related to umbilical cord morphology but umbilical venous PCO2 was only related to the number of coils and umbilicat artery pH wa only related to the number of coils and not related to length or coiling index of umbilical cord morphology. The morphology of umbilical cord can affect maternal-fetal gas exchange