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05 April 2012, Volume 7 Issue 10 Previous Issue    Next Issue

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Dose-dependent and combined effects of N-methyl- D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters Yaoyu Li, An’an Yang, Tingting Zhu, Zhao Liu, Siwei You, Kwok-Fai So 2012, 7 (10):  725-730.  Abstract ( 227 )   PDF (431KB) ( 766 )   Save This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine (L-NA) on the survival of retinal ganglion cells (RGCs) at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 (1.0, 3.0 and 4.5 mg/kg) and L-NA (1.5, 3.0, 4.5 and 6.0 mg/kg) increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect. Related Articles | Metrics

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Alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor antagonist inhibits apoptosis of retinal ganglion cells in a rabbit model of optic nerve injury Ruijia Wang, Xinping Luan, Yiti Mu, Hongyu Jia, Jingxuan Xu 2012, 7 (10):  731-735.  Abstract ( 219 )   PDF (224KB) ( 750 )   Save A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor antagonist. Related Articles | Metrics

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X-box-binding protein 1-modified neural stem cells for treatment of Parkinson’s disease Lihui Si, Tianmin Xu, Fengzhang Wang, Qun Liu, Manhua Cui 2012, 7 (10):  736-740.  Abstract ( 205 )   PDF (241KB) ( 831 )   Save X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson’s disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson’s disease in rats. Related Articles | Metrics

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Transplantation of human umbilical cord blood mesenchymal stem cells to treat a rat model of traumatic brain injury Junjian Zhao, Naiyao Chen, Na Shen, Hui Zhao, Dali Wang, Jun Shi, Yang Wang, Xiufeng Cui, Zhenyu Yan, Hui Xue 2012, 7 (10):  741-748.  Abstract ( 238 )   PDF (324KB) ( 1001 )   Save In the present study, human umbilical cord blood mesenchymal stem cells were injected into a rat model of traumatic brain injury via the tail vein. Results showed that 5-bromodeoxyuridine-labeled cells aggregated around the injury site, surviving up to 4 weeks post-transplantation. In addition, transplantation-related death did not occur, and neurological functions significantly improved. Histological detection revealed attenuated pathological injury in rat brain tissues following human umbilical cord blood mesenchymal stem cell transplantation. In addition, the number of apoptotic cells decreased. Immunohistochemistry and in situ hybridization showed increased expression of brain-derived neurotrophic factor, nerve growth factor, basic fibroblast growth factor, and vascular endothelial growth factor, along with increased microvessel density in surrounding areas of brain injury. Results demonstrated migration of transplanted human umbilical cord blood mesenchymal stem cells into the lesioned boundary zone of rats, as well as increased angiogenesis and expression of related neurotrophic factors in the lesioned boundary zone. Related Articles | Metrics

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Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia Dong Wang, Jianjun Zhang 2012, 7 (10):  749-755.  Abstract ( 175 )   PDF (233KB) ( 922 )   Save Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours (mild hypothermia). Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells (bromodeoxyuridine-positive cells), better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury. References | Related Articles | Metrics

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Uric acid promotes neuronal differentiation of human placenta-derived mesenchymal stem cells in a time- and concentration-dependent manner Nailong Yang, Lili Xu, Peng Lin, Jing Cui 2012, 7 (10):  756-760.  Abstract ( 173 )   PDF (181KB) ( 897 )   Save Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time- and concentration-dependent manner. References | Related Articles | Metrics

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Basic fibroblast growth factor increases the number of endogenous neural stem cells and inhibits the expression of amino methyl isoxazole propionic acid receptors in amyotrophic lateral sclerosis mice Weihui Huang, Dawei Zang, Yi Lu, Ping Jiang 2012, 7 (10):  761-765.  Abstract ( 239 )   PDF (185KB) ( 769 )   Save This study aimed to investigate the number of amino methyl isoxazole propionic acid (AMPA) receptors and production of endogenous neural stem cells in the SOD1G93AG1H transgenic mouse model of amyotrophic lateral sclerosis, at postnatal day 60 following administration of basic fibroblast growth factor (FGF-2). A radioligand binding assay and immunohistochemistry were used to estimate the number of AMPA receptors and endogenous neural stem cells respectively. Results showed that the number of AMPA receptors and endogenous neural stem cells in the brain stem and sensorimotor cortex were significantly increased, while motor function was significantly decreased at postnatal days 90 and 120. After administration of FGF-2 into mice, numbers of endogenous neural stem cells increased, while expression of AMPA receptors decreased, whilst motor functions were recovered. At postnatal day 120, the number of AMPA receptors was negatively correlated with the number of endogenous neural stem cells in model mice and FGF-2-treated mice. Our experimental findings indicate that FGF-2 can inhibit AMPA receptors and increase the number of endogenous neural stem cells, thus repairing neural injury in amyotrophic lateral sclerosis mice. Related Articles | Metrics

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Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model Haisheng Liu, Zhili Ni, Yetao Chen, Dong Wang, Yan Qi, Qiuhang Zhang, Shijie Wang 2012, 7 (10):  766-771.  Abstract ( 231 )   PDF (222KB) ( 1525 )   Save The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil® (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system. References | Related Articles | Metrics

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Calcium-mediated paired pulse depression in juvenile rat dorsal striatum Yufeng Xie, Michael F. Jackson, John F. MacDonald 2012, 7 (10):  772-777.  Abstract ( 298 )   PDF (293KB) ( 842 )   Save As the major division of the basal ganglia, neostriatum forms mutual connections with multiple brain areas and is critically involved in motor control and learning/memory. Long-term synaptic plasticity has been widely studied in different species recently. However, there are rare reports about the short-term synaptic plasticity in neostratium. In the present study, using field excitatory postsynaptic potentials recording, we reported one form of short-term synaptic plasticity that is paired pulse depression in juvenile rat dorsal striatum slices induced by stimuli of the white matter. The field excitatory postsynaptic potentials could be abolished by α-amino-3-hydroxy-5-methylizoxazole-4- propionic acid receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, but not by gamma-aminobutyric acid type A receptor antagonist bicuculline or dopamine D1 receptor antagonist SKF-81297. The paired pulse depression in the corticostratial pathway was different from paired pulse facilitation in the hippocampal CA1 synapse. In addition, the paired pulse depression was not affected by bath application of gamma-aminobutyric acid type A receptor antagonist or dopamine D1 receptor antagonist. However, low calcium and high magnesium could attenuate the paired pulse depression. These findings suggest a more complicated plasticity form in the dorsal striatum of juvenile rats that is different from that in the hippocampus, which is related with extracellular calcium. Related Articles | Metrics

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Increased hypoxia-inducible factor 1alpha expression in rat brain tissues in response to aging Huqing Wang, Haiqin Wu, Hena Guo, Guilian Zhang, Ru Zhang, Shuqin Zhan 2012, 7 (10):  778-782.  Abstract ( 224 )   PDF (345KB) ( 1012 )   Save The present study observed changes in rat neural cells at various ages (3, 18, 24, and 30 months). With age, neural cells became large and were sparsely arranged, and the number of Nissl bodies decreased. In addition, hypoxia-inducible factor 1α expression increased with increasing age in hippocampal CA1 and CA3 regions, motor cortex, and the first subfolium, especially from 3 to 18 months. In the open-field test, grid crossing decreased with increasing age, especially from 18 months. The number of rearings reached a peak in the 18 months group, and then subsequently decreased. The results suggested that hypoxia-inducible factor 1α played an important role in the nervous system aging process. References | Related Articles | Metrics

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Research progress in muscle-derived stem cells Literature retrieval results based on international database Li Zhang, Wei Wang 2012, 7 (10):  784-791.  Abstract ( 195 )   PDF (237KB) ( 845 )   Save OBJECTIVE: To identify global research trends of muscle-derived stem cells (MDSCs) using a bibliometric analysis of the Web of Science, Research Portfolio Online Reporting Tools of the National Institutes of Health (NIH), and the Clinical Trials registry database (ClinicalTrials.gov). DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for MDSCs from 2002 to 2011 using the Web of Science, NIH, and ClinicalTrials.gov. SELECTION CRITERIA: Inclusion criteria: (1) Web of Science: (a) peer-reviewed articles on MDSCs that were published and indexed in the Web of Science. (b) Type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items. (c) Year of publication: 2002–2011. (d) Citation databases: Science Citation Index-Expanded (SCI-E), 1899–present; Conference Proceedings Citation Index-Science (CPCI-S), 1991–present; Book Citation Index-Science (BKCI-S), 2005–present. (2) NIH: (a) Projects on MDSCs supported by the NIH. (b) Fiscal year: 1988–present. (3) ClinicalTrials.gov: All clinical trials relating to MDSCs were searched in this database. Exclusion criteria: (1) Web of Science: (a) Articles that required manual searching or telephone access. (b) We excluded documents that were not published in the public domain. (c) We excluded a number of corrected papers from the total number of articles. (d) We excluded articles from the following databases: Social Sciences Citation Index (SSCI), 1898–present; Arts & Humanities Citation Index (A&HCI), 1975–present; Conference Proceedings Citation Index – Social Science & Humanities (CPCI-SSH), 1991–present; Book Citation Index – Social Sciences & Humanities (BKCI-SSH), 2005–present; Current Chemical Reactions (CCR-EXPANDED), 1985–present; Index Chemicus (IC), 1993–present. (2) NIH: (a) We excluded publications related to MDSCs that were supported by the NIH. (b) We limited the keyword search to studies that included MDSCs within the title or abstract. (3) ClinicalTrials.gov: (a) We excluded clinical trials that were not in the ClinicalTrials.gov database. (b) We excluded clinical trials that dealt with stem cells other than MDSCs in the ClinicalTrials.gov database. MAIN OUTCOME MEASURES: (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) top cited authors over the last 10 years; (7) projects financially supported by the NIH; and (8) clinical trials registered. RESULTS: (1) In all, 802 studies on MDSCs appeared in the Web of Science from 2002 to 2011, almost half of which derived from American authors and institutes. The number of studies on MDSCs has gradually increased over the past 10 years. Most papers on MDSCs appeared in journals with a particular focus on cell biology research, such as Experimental Cell Research, Journal of Cell Science, and PLoS One. (2) Eight MDSC research projects have received over US$6 billion in funding from the NIH. The current project led by Dr. Johnny Huard of the University of Pittsburgh—―Muscle-Based Tissue Engineering to Improve Bone Healing‖—is supported by the NIH. Dr. Huard has been the most productive and top-cited author in the field of gene therapy and adult stem cell research in the Web of Science over last 10 years. (3) On ClinicalTrials.gov, ―Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence‖ Phase 1 is registered and sponsored by Johns Hopkins University and has been led by Dr. John P. Gearhart since November 2009. CONCLUSION: From our analysis of the literature and research trends, we found that MDSCs may offer further benefits in regenerative medicine. Related Articles | Metrics

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Scientific literature addressing detection of monosialoganglioside A 10-year bibliometric analysis Yanli Xu, Miaojing Li, Zhijun Liu, Aiping Xi, Chaoxian Zhao, Jianzhong Zhang 2012, 7 (10):  792-799.  Abstract ( 242 )   PDF (189KB) ( 774 )   Save OBJECTIVE: The study was undertaken to explore a bibliometric approach to quantitatively assess the research on detection of monosialoganglioside from 2002 to 2011. DATA RETRIEVAL: A bibliometric analysis based on the publications on Web of Science was performed using key words such as “monosialoganglioside”, “colloidal gold”, “high performance liquid chromatography” and “detection”. SELECTION CRITERIA: (1) Research articles on the detection of monosialoganglioside; (2) researches on human and animal fundamentals, clinical trials and case reports; (3) article types: article, review, proceedings paper, note, letter, editorial material, discussion, book chapter; (4) Publication year: 2002-2011. Exclusion criteria: (1) unrelated articles; (2) type of articles: correction; (3) articles from following databases: all databases related to social science and  arts & humanities in Web of Science were excluded. MAIN OUTCOME MEASURES: (1) distribution of subject areas; (2) number of publications annually; (3) document type and language of publications; (4) distribution of institutions; (5) distribution of output in journals; (6) the number of countries in which the article is published; (7) top cited paper. RESULTS: Overall population stands at 1 880 research articles addressing detection of monosialoganglioside in Web of Science during the study period. Articles (1 599) were the most frequently used document type comprising 85.05%, followed by meeting abstracts, reviews and proceedings papers. The distribution of subject categories showed that monosialoganglioside research covered both clinical and basic science research. The USA, Japan, and Italy were the three most productive countries, and the publication numbers in the USA were highest with 559 papers. The University of Milan, Nagoya University, and Kinki University are the most productive institutions regarding detection of monosialoganglioside. In 559 articles published by Americans, Medical College of Georgia ranked the first with 30 articles, followed by University of Medicine and Dentistry of New Jersey (28 articles), Cornell University (24 articles) and Johns Hopkins University (24 articles). In 442 articles published by Japanese, Nagoya University ranked the first with 40 articles, followed by Kinki University (36 articles), and Dokkyo University (31 articles). Though the total number of publications by Japanese is smaller than Americans, the top three institutions published more publications than American institutions. There is a markedly increase in the number of publications on the subject detection of monosialoganglioside in 2004, which the peak in the past 10 years. The valley bottom of the subject appeared in 2005. In total, the research is increased with time prolonged. Journal of Neurochemistry, Journal of Biological Chemistry and Journal of Neuroimmunology were core subject journals in monosialoganglioside studies. CONCLUSION: This study highlights the topics in detection of monosialoganglioside research that are being published around the world. Related Articles | Metrics