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    05 February 2012, Volume 7 Issue 4 Previous Issue    Next Issue
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    Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer’s disease
    Ping Zhang, Gangyong Zhao, Xianjiang Kang, Likai Su
    2012, 7 (4):  245-250. 
    Abstract ( 227 )   PDF (308KB) ( 1116 )   Save

    In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer’s disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer’s disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.

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    Reconstruction of the adenosine system by bone marrow-derived mesenchymal stem cell transplantation
    Huicong Kang, Qi Hu, Xiaoyan Liu, Yinhe Liu, Feng Xu, Xiang Li, Suiqiang Zhu
    2012, 7 (4):  251-255. 
    Abstract ( 271 )   PDF (277KB) ( 1256 )   Save

    In the present study, we transplanted bone marrow-derived mesenchymal stem cells into the CA3 area of the hippocampus of chronic epilepsy rats kindled by lithium chloride-pilocarpine. Immunofluorescence and western blotting revealed an increase in adenosine A1 receptor expression and a decrease in adenosine A2a receptor expression in the brain tissues of epileptic rats 3 months after transplantation. Moreover, the imbalance in the A1 adenosine receptor/A2a adenosine receptor ratio was improved. Electroencephalograms showed that frequency and amplitude of spikes in the hippocampus and frontal lobe were reduced. These results suggested that mesenchymal stem cell transplantation can reconstruct the normal function of the adenosine system in the brain and greatly improve epileptiform discharges.

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    Dispase rapidly and effectively purifies Schwann cells from newborn mice and adult rats
    Jiaxue Zhu, Jinbao Qin, Zunli Shen, James D. Kretlow, Xiaopan Wang, Zhangyin Liu, Yuqing Jin
    2012, 7 (4):  256-260. 
    Abstract ( 256 )   PDF (325KB) ( 828 )   Save

    In the present study, Schwann cells were isolated from the sciatic nerve of neonatal mice and purified using dispase and collagenase. Results showed that after the first round of purification with dispase, most of the Schwann cells appeared round in shape and floated in culture solution after 15 minutes. In addition, cell yield and cell purity were higher when compared to the collagenase group. After the second round of purification, the final cell yield for the dispase group was higher than that for the collagenase group, but no significant difference was found in cell purity. Moreover, similar results in cell quantity and purity were observed in adult Sprague-Dawley rats. These findings indicate that purification with dispase can result in the rapid isolation of Schwann cells with a high yield and purity.

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    The active principle region of Buyang Huanwu decoction induced differentiation of bone marrow-derived mesenchymal stem cells into neural-like cells Superior effects over original formula of Buyang Huanwu decoction
    Jinghui Zheng, Yi Wan, Jianhuai Chi, Dekai Shen, Tingting Wu, Weimin Li, Pengcheng Du
    2012, 7 (4):  261-267. 
    Abstract ( 234 )   PDF (324KB) ( 956 )   Save

    The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils, and effective components of Buyang Huanwu decoction (active principle region of decoction for invigorating yang for recuperation). After 28 days, nestin and neuron-specific enolase were expressed in the cytoplasm. Reverse transcription-PCR and western blot analyses showed that nestin and neuron-specific enolase mRNA and protein expression was greater in the active principle region group compared with the original formula group. Results demonstrated that the active principle region of Buyang Huanwu decoction induced greater differentiation of rat bone marrow-derived mesenchymal stem cells into neural-like cells in vitro than the original Buyang Huanwu decoction formula.

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    A quantitative study on changes of the myelinated fibers in the cerebral cortex of cortical dysplasia rats
    Xuntai Ma, Yong Tang, Yang Lv, Oumei Cheng, Yong Yan
    2012, 7 (4):  268-272. 
    Abstract ( 274 )   PDF (245KB) ( 937 )   Save

    An animal model of cortical dysplasia was established through X-ray irradiation induced subcortical heterotopic nodules in rats. Transmission electron microscopy detection of the ultrastructure and the stereology examination showed that there was a significant decrease in cerebral white matter and hippocampal volume, the total volume, volume density, length density and total length of the myelinated fibers in the white matter of cortical dysplasia rats. Subcortical heterotopic nodules of the hippocampal CA1 region and synaptic number density in the CA3 region were reduced compared with normal rats. Our experimental findings indicate that erosed subcortical heterotopic nodules, decreased total length of myelinated nerve fibers and demyelination directly lead to a reduction of white matter volume.

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    N-methyl-D-aspartate receptor subtype 3A promotes apoptosis in developing mouse brain exposed to hyperoxia
    Jimei Li, Shanping Yu, Zhongyang Lu, Osama Mohamad, Ling Wei
    2012, 7 (4):  273-277. 
    Abstract ( 190 )   PDF (188KB) ( 814 )   Save

    In the present study, 7 day postnatal C57/BL6 wild-type mice (hyperoxia group) and 7 day postnatal N-methyl-D-aspartate receptor subtype 3A knockout mice (NR3A KO group) were exposed to 75% oxygen and 15% nitrogen in a closed container for 5 days. Wild-type mice raised in normoxia served as controls. TdT-mediated dUTP nick end labeling (TUNEL)/neuron-specific nuclear protein (NeuN) and 5-bromo-2’-deoxyuridine (BrdU)/NeuN immunofluorescence staining showed that the number of apoptotic cells and the number of proliferative cells in the dentate subgranular zone significantly increased in the hyperoxia group compared with the control group. However, in the same hyperoxia environment, the number of apoptotic cells and the number of proliferative cells significantly decreased in the NR3A KO group compared with hyperoxia group. TUNEL+/NeuN+ and BrdU+/NeuN+ cells were observed in the NR3A KO and the hyperoxia groups. These results demonstrated that the NR3A gene can promote cell apoptosis and mediate the potential damage in the developing brain induced by exposure to non-physiologically high concentrations of oxygen.

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    Increased CD133+ cell infiltration in the rat brain following fluid percussion injury
    Ming Wei, Ziwei Zhou, Shenghui Li, Chengwei Jing, Dashi Zhi, Jianning Zhang
    2012, 7 (4):  278-282. 
    Abstract ( 170 )   PDF (281KB) ( 1013 )   Save

    The prominin-1/CD133 epitope is expressed in undifferentiated cells. Studies have reported that craniocerebral trauma in animal models of fluid percussion injury induces production of a specific stem cell subgroup. It has been hypothesized that fluid percussion injury induces CD133+ cell infiltration in the brain tissue. The present study established a traumatic brain injury model through fluid percussion injury. Immunohistochemical staining showed significantly increased CD133 antigen expression in the rat brain following injury. CD133+ cells were mainly distributed in hippocampal CA1-3 regions, as well as the dentate gyrus and hilus, of the lesioned hemisphere. Occasional cells were also detected in the cortex. In addition, reverse transcription-PCR revealed that no change in CD133 mRNA expression in injured brain tissue. These results suggested that fluid percussion injury induced CD133 antigen expression in the brain tissues as a result of conformational epitope changes, but not transcriptional expression.

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    Effects of fulvestrant on biological activity and Wnt expression in rat GH3 cells
    Jiwei Bai, Yan Wang, Chuzhong Li, Yazhuo Zhang
    2012, 7 (4):  283-289. 
    Abstract ( 197 )   PDF (347KB) ( 793 )   Save

    The present study investigated the influence of anti-estrogen treatment (fulvestrant) on pituitary adenoma cell line GH3 biological activity, the estrogen receptor α pathway, the WnT pathway, and mechanisms of decreased Wnt inhibitory factor-1 expression in GH3 cells. Results showed that fulvestrant suppressed GH3 cell proliferation and reduced hormone secretion in a dose-dependent manner. Estrogen receptor α and Wnt4 expression decreased, but Wnt inhibitory factor-1 expression increased in a dose-dependent manner following fulvestrant treatment, and β-catenin expression remained unchanged. Inhibitors of DNA methylation and histone modification upregulated Wnt inhibitory factor-1 expression. Results suggested that fulvestrant suppressed biological activity of GH3 cells via the estrogen receptor α and Wnt pathways. These results suggested that decreased Wnt inhibitory factor-1 expression in GH3 cells played a role in epigenetic mechanisms. Anti-estrogen therapies could provide novel treatments for growth hormone adenomas.

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    DNA degradation within mouse brain and dental pulp cells 72 hours postmortem
    Jilong Zheng, Xiaona Li, Di Shan, Han Zhang, Dawei Guan
    2012, 7 (4):  290-294. 
    Abstract ( 215 )   PDF (214KB) ( 1055 )   Save

    In this study, we sought to elucidate the process of DNA degradation in brain and dental pulp cells of mice, within postmortem 0-72 hours, by using the single cell gel electrophoresis assay and professional comet image analysis and processing techniques. The frequency of comet-like cells, the percentage of tail DNA, tail length, tail moment, Olive moment and tail area increased in tandem with increasing postmortem interval. In contrast, the head radius, the percentage of head DNA and head area showed a decreasing trend. Linear regression analysis revealed a high correlation between these parameters and the postmortem interval. The findings suggest that the single cell gel electrophoresis assay is a quick and sensitive method to detect DNA degradation in brain and dental pulp cells, providing an objective and accurate new way to estimate postmortem interval.

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    Erythropoietin upregulates growth associated protein-43 expression and promotes retinal ganglion cell axonal regeneration in vivo after optic nerve crush
    Haibo Tan, Xin Kang, Yisheng Zhong, Xi Shen, Yu Cheng, Qin Jiao, Lianfu Deng
    2012, 7 (4):  295-301. 
    Abstract ( 261 )   PDF (295KB) ( 1062 )   Save

    In this study, we established a rat model of optic nerve crush to explore the effects of erythropoietin on retinal ganglion cell axonal regeneration. At 15 days after injury in erythropoietin treated rats, retinal ganglion cell densities in regions corresponding to the 1/6, 3/6 and 5/6 ratios of the retinal radius were significantly increased. In addition, the number of growth associated protein-43 positive axons was significantly increased at different distances (50, 250 and 500 μm) from the crush site after erythropoietin treatment. Erythropoietin significantly increased growth associated protein-43 protein levels in the retina after crush injury, as determined by western blot and immunofluorescence analysis. These results demonstrate that erythropoietin protects injured retinal ganglion cells and promotes axonal regeneration.

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    Nerve growth factor and inducible nitric oxide synthase expression in the mesencephalon and diencephalon, as well as visual- and auditory-related nervous tissues, in a macaque model of type 2 diabetes
    Qihui Luo, Wentao Liu, Jingyao Chen, Mingshu Wang, Wen Zeng, Zhengli Chen, Anchun Cheng
    2012, 7 (4):  302-307. 
    Abstract ( 429 )   PDF (270KB) ( 1114 )   Save

    The present study detected distribution and expression of nerve growth factor and inducible nitric oxide synthase in the mesencephalon and diencephalon, as well as visual- and auditory-related nervous tissues, in a macaque model of type 2 diabetes using immunohistochemistry. Results showed that nerve growth factor expression decreased, but inducible nitric oxide synthase expression increased, in the mesencephalon and diencephalon, as well as visual- and auditory- related nervous tissues. These results suggested that nerve growth factor and inducible nitric oxide synthase play an important role in regulating the development of diabetic visual- and auditory-related diseases.

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    Skin electrodes transduced signals to the bladder resulting in ameliorated hypomotility in a rabbit model of diabetes
    Xinmin Wang, Qirui Fu, Qingmei Zhang, Ping Xu, Lin Cao, Meng Xue, Wei Wang
    2012, 7 (4):  308-312. 
    Abstract ( 201 )   PDF (165KB) ( 820 )   Save

    Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projection area using three levels of exporting voltage (5.84 V, 8.00 V, and 11.00 V). Results demonstrated significantly attenuated electric signals from both groups, in particular the diabetes group. The skin electrode signals were conducted to the bladders, and all vesical signals increased according to strength of stimulating signals from the skin electrode. However, vesical signals from diabetic rabbits were less than those from normal rabbits at the same stimulating strength of exporting voltage. Vesical pressures from the two groups increased along with increased vesical signals, but vesical pressure was less those from diabetic rabbits than in normal rabbits (basic status and different stimulating levels). Linear correlation analysis showed a significantly positive correlation between vesical pressure and signal. These results demonstrated that electric signals from skin electrodes resulted in increased vesical pressure, and vesical pressure increased along with stimulation strength.

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    Rationale for the use of multifunctional drugs as neuroprotective agents for glaucoma
    Jiahua Fang, Fagang Jiang, Jingbo Li, Yanhua Zhu
    2012, 7 (4):  313-318. 
    Abstract ( 216 )   PDF (147KB) ( 1110 )   Save

    Glaucoma, the leading cause globally of irreversible blindness, is a neurodegenerative disease characterized by progressive retinal ganglion cell death. To date, no drug has been shown to prevent the retinal ganglion cell loss associated with glaucoma. Multiple mechanisms lead to ganglion cell death in glaucoma, suggesting that a neuroprotectant that has a single mode of action, like memantine, would have a limited positive effect at slowing down ganglion cell death. Conversely, simultaneously targeting several factors may be the best therapeutic approach to improve outcomes. Multifunctional drugs are fast gaining acceptance as a strategy for the treatment of complex disorders of the central nervous system, such as Parkinson’s disease, Alzheimer’s disease and other progressive neurodegenerative diseases. In this paper, we review the current literature on multifunctional drugs and propose a rationale for the use of multifunctional drugs in glaucomatous optic neuropathy.

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