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Table of Content

    05 August 2012, Volume 7 Issue 22 Previous Issue    Next Issue
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    Breaking News in Spinal Cord Injury Research FDA Approved Phase I Clinical Trial of Human, Autologous Schwann Cell Transplantation in Patients with Spinal Cord Injuries
    Xiao-Ming Xu
    2012, 7 (22):  1685-1687. 
    Abstract ( 222 )   PDF (90KB) ( 818 )   Save

    On July 31, 2012, The Miami Project to Cure Paralysis at the University of Miami Miller School of Medicine received permission from the Food and Drug Administration (FDA) to begin a Phase I clinical trial to evaluate the safety of transplanting human autologous Schwann cells to treat patients with spinal cord injuries. This is the only FDA-approved cell therapy-based clinical trial for sub-acute spinal cord injury in the United States.

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    Changes in expression and secretion patterns of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway molecules during murine neural stem/progenitor cell differentiation in vitro
    Jiang Lu, Kehuan Lu, Dongsheng Li
    2012, 7 (22):  1688-1694. 
    Abstract ( 343 )   PDF (207KB) ( 828 )   Save

    In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fi-broblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog ex-pression may be related to the differentiation of neural stem/progenitor cells.

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    Transgene expression and differentiation of baculovirus-transduced adipose-derived stem  cells from dystrophin-utrophin double knock-out mouse
    Qiuling Li, Qiongxiang Zhai, Jia Geng, Hui Zheng, Fei Chen, Jie Kong, Cheng Zhang
    2012, 7 (22):  1695-1702. 
    Abstract ( 198 )   PDF (413KB) ( 853 )   Save

    In this study, recombinant baculovirus carrying the microdystrophin and β-catenin genes was used to infect adipose-derived stem cells from a dystrophin-utrophin double knock-out mouse. Results showed that, after baculovirus transgene infection, microdystrophin and β-catenin genes were effectively expressed in adipose-derived stem cells from the dystrophin-utrophin double knock-out mouse. Furthermore, this transgenic expression promoted adipose-derived stem cell differentiation into muscle cells, but inhibited adipogenic differentiation. In addition, protein expression related to the microdystrophin and Wnt/β-catenin signaling pathway was upregulated. Our experimental findings indicate that baculovirus can successfully deliver the microdystrophin and β-catenin genes into adipose-derived stem cells, and the microdystrophin and Wnt/β-catenin signaling pathway plays an important role in myogenesis of adipose-derived stem cells in the dystrophin-utrophin double knock-out mouse.

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    Sonic hedgehog elevates N-myc gene expression in neural stem cells
    Dongsheng Liu, Shouyu Wang, Yan Cui, Lun Shen, Yanping Du, Guilin Li, Bo Zhang, Renzhi Wang
    2012, 7 (22):  1703-1708. 
    Abstract ( 196 )   PDF (164KB) ( 1101 )   Save

    Proliferation of neural stem cells is regulated by the secreted signaling molecule sonic hedgehog. In this study, neural stem cells were infected with recombinant adeno-associated virus expressing sonic hedgehog-N-enhanced green fluorescent protein. The results showed that overexpression of sonic hedgehog in neural stem cells induced the increased expression of Gli1 and N-myc, a target gene of sonic hedgehog. These findings suggest that N-myc is a direct downstream target of the sonic hedgehog signal pathway in neural stem cells. Sonic hedgehog and N-myc are important mediators of sonic hedgehog-induced proliferation of neural stem cells.

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    Identification of α7 nicotinic acetylcholine receptor on hippocampal astrocytes cultured in vitro and its role on inflammatory mediator secretion
    Yan Wang, Ning Zhu, Kewan Wang, Zhongyi Zhang, Yong Wang
    2012, 7 (22):  1709-1714. 
    Abstract ( 348 )   PDF (288KB) ( 901 )   Save

    The present study found expressions of α7 nicotinic acetylcholine receptor on hippocampal slices and hippocampal astrocytes using double immunofluorescence stainings. Expression of glial fibrillary acidic protein in the cultured hippocampal slices and hippocampal astrocytes significantly increased, and levels of macrophage inflammatory protein 1α, RANTES, interleukin-1β, interleukin-6, and tumor necrosis factor-α increased in the supernatant of cultured astrocytes following exposure to 200 nM amyloid β protein 1-42. Preconditioning of 10 μM nicotine, a nicotinic acetylcholine receptor agonist, could attenuate the influence of amyloid β protein 1-42 in inflammatory mediator secretion of cultured astrocytes. Experimental findings indicated that α7 nicotinic acetylcholine receptor was expressed on the surface of hippocampal astrocytes, and activated α7 nicotinic acetylcholine receptor was shown to inhibit inflammation induced by amyloid β protein 1-42.

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    Neuroprotective effects of bovine colostrum on intracerebral hemorrhage-induced apoptotic neuronal cell death in rats
    Sung Eun Kim, Il Gyu Ko, Mal Soon Shin, Chang Ju Kim, Young Gwan Ko, Hanjin Cho
    2012, 7 (22):  1715-1721. 
    Abstract ( 190 )   PDF (351KB) ( 997 )   Save

    Brain cell death after intracerebral hemorrhage may be mediated in part by an apoptotic mechanism. Colostrum is the first milk produced by mammals for their young. It plays an important role in pro-tection and development by providing various antibodies, growth factors and nutrients, and has been used for various diseases in many countries. In the present study, we investigated the an-ti-apoptotic effects of bovine colostrum using organotypic hippocampal slice cultures and an intracerebral hemorrhage animal model. We performed densitometric measurements of propidium iodide uptake, a step-down avoidance task, Nissl staining, and caspase-3 immunohistochemistry. The present results revealed that colostrum treatment significantly suppressed N-methyl-D-aspartic acid-induced neuronal cell death in the rat hippocampus. Moreover, colostrum treatment improved short-term memory by suppressing hemorrhage-induced apoptotic neuronal cell death and de-creasing the volume of the lesion induced by intracerebral hemorrhage in the rat hippocampus. These results suggest that colostrum may have a beneficial role in recovering brain function fol-lowing hemorrhagic stroke by suppressing apoptotic cell death.

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    5-hydroxymethyl-2-furfural prolongs survival and inhibits oxidative stress in a mouse model of forebrain ischemia
    Bailiu Ya, Lan Zhang, Li Zhang, Yali Li, Lin Li
    2012, 7 (22):  1722-1728. 
    Abstract ( 233 )   PDF (129KB) ( 1125 )   Save

    In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfural 30 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.

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    Early hyperbaric oxygen therapy inhibits aquaporin 4 and adrenocorticotropic hormone expression in the pituitary gland of rabbits with blast-induced craniocerebral injury
    Jian Huo, Jiachuan Liu, Jinbiao Wang, Yongming Zhang, Chunlin Wang, Yanyan Yang, Wenjiang Sun, Shaonian Xu
    2012, 7 (22):  1729-1735. 
    Abstract ( 195 )   PDF (301KB) ( 1056 )   Save

    In the present study, rabbits were treated with hyperbaric oxygen for 1 hour after detonator-blast- induced craniocerebral injury. Immunohistochemistry showed significantly reduced aquaporin 4 expression and adrenocorticotropic hormone expression in the pituitary gland of rabbits with craniocerebral injury. Aquaporin 4 expression was positively correlated with adrenocorticotropic hormone expression. These findings indicate that early hyperbaric oxygen therapy may suppress adrenocorticotropic hormone secretion by inhibiting aquaporin 4 expression.

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    Thrombospondins and synaptogenesis
    Bin Wang, Weitao Guo, Yun Huang
    2012, 7 (22):  1737-1743. 
    Abstract ( 228 )   PDF (203KB) ( 952 )   Save

    Here, we review research on the mechanisms underlying the ability of thrombospondin to promote synaptogenesis and examine its role in central nervous system diseases and drug actions. Thrombospondin secreted by glial cells plays a critical role in synaptogenesis and maintains synapse stability. Thrombospondin regulates synaptogenesis through receptor α2δ-1 and neuro-ligin 1, and promotes the proliferation and differentiation of neural progenitor cells. It also parti-cipates in synaptic remodeling following injury and in the action of some nervous system drugs.

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    Stem cell transplantation for treating Duchenne muscular dystrophy
    Xiaofeng Yang
    2012, 7 (22):  1744-1751. 
    Abstract ( 228 )   PDF (87KB) ( 953 )   Save

    OBJECTIVE: To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science.
    DATA RETRIEVAL: We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science.
    SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers.
    MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to subject areas; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) distribution according to institution in China; (7) distribution according to institution that cooperated with Chinese institutions; (8) top-cited articles from 2002 to 2006; (9) top-cited articles from 2007 to 2011.
    RESULTS: A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy.
    CONCLUSION: The publications on stem cell transplantation for treating Duchenne muscular dystrophy were relatively few. It also needs more research to confirm that stem cell therapy is a reliable treatment for Duchenne muscular dystrophy.

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    Precision radiotherapy for brain tumors
    Ying Yan, Zhanwen Guo, Haibo Zhang, Ning Wang, Ying Xu
    2012, 7 (22):  1752-1759. 
    Abstract ( 191 )   PDF (141KB) ( 899 )   Save

    OBJECTIVE: Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science.
    DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science.
    SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: 2002-2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) Corrected papers or book chapters.
    MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) top cited publications; (5) distribution according to journals; and (6) comparison of study results on precision radiotherapy for brain tumors.
    RESULTS: The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies.
    CONCLUSION: Precision radiotherapy for brain tumors remains a highly active area of research and development. 

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