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    05 April 2013, Volume 8 Issue 10 Previous Issue    Next Issue
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    Thrombospondin 1 promotes synaptic formation in bone marrow-derived neuron-like cells
    Yun Huang, Mingnan Lu, Weitao Guo, Rong Zeng, Bin Wang, Huaibo Wang
    2013, 8 (10):  869-881.  doi: 10.3969/j.issn.1673-5374.2013.10.001
    Abstract ( 181 )   PDF (359KB) ( 793 )   Save

    In this study, a combination of growth factors was used to induce bone marrow mesenchymal stem cells differentiation into neuron-like cells, in a broader attempt to observe the role of thrombospondin 1 in synapse formation. Results showed that there was no significant difference in the differentiation rate of neuron-like cells between bone marrow mesenchymal stem cells with thrombospondin induction and those without. However, the cell shape was more complex and the neurites were dendritic, with unipolar, bipolar or multipolar morphologies, after induction with thrombospondin 1. The induced cells were similar in morphology to normal neurites. Immunohistochemical staining showed that the number of positive cells for postsynaptic density protein 95 and synaptophysin 1 protein was significantly increased after induction with thrombospondin 1. These findings indicate that thrombospondin 1 promotes synapse formation in neuron-like cells that are differentiated from bone marrow mesenchymal stem cells.

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    Thrombospondin 1 promotes synaptic formation in bone marrow-derived neuron-like cells
    Yanhui Lu, Xiaodong Yuan, Qiaoyu Sun, Ya Ou
    2013, 8 (10):  882-889.  doi: 10.3969/j.issn.1673-5374.2013.10.002
    Abstract ( 281 )   PDF (339KB) ( 1040 )   Save

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    Human umbilical cord Wharton’s jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration
    Hong Chen, Yan Zhang, Zhijun Yang, Hongtian Zhang
    2013, 8 (10):  890-899.  doi: 10.3969/j.issn.1673-5374.2013.10.003
    Abstract ( 330 )   PDF (437KB) ( 951 )   Save

    Human umbilical mesenchymal stem cells from Wharton’s jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths.

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    Effect of minocycline on cerebral ischemia- reperfusion injury
    Yuanyin Zheng, Lijuan Xu, Jinbao Yin, Zhichao Zhong, Hongling Fan, Xi Li, Quanzhong Chang
    2013, 8 (10):  900-908.  doi: 10.3969/j.issn.1673-5374.2013.10.004
    Abstract ( 205 )   PDF (526KB) ( 716 )   Save

    Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-reperfusion (22.5 mg/kg, initially 45 mg/kg) at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein expression.

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    Injury of cortical neurons is caused by the advanced glycation end products-mediated pathway
    Ying Xing, Xu Zhang, Xiangfu Song, Zhongwen Lv, Lingling Hou, Fei Li
    2013, 8 (10):  909-915.  doi: 10.3969/j.issn.1673-5374.2013.10.005
    Abstract ( 197 )   PDF (242KB) ( 679 )   Save

    Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products (50, 100, 200, 400 mg/L), and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage.

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    Transcription factor changes following long term cerebral ischemia/reperfusion injury
    Hongbo Zhang, Weijuan Gao, Tao Qian, Jinglong Tang, Jun Li
    2013, 8 (10):  916-921.  doi: 10.3969/j.issn.1673-5374.2013.10.006
    Abstract ( 182 )   PDF (148KB) ( 667 )   Save

    The present study established a rat model of cerebral ischemia/reperfusion injury using four-vessel occlusion and found that hippocampal CA1 neuronal morphology was damaged, and that there were reductions in hippocampal neuron number and DNA-binding activity of cAMP response element binding protein and CCAAT/enhancer binding protein, accompanied by decreased learning and memory ability. These findings indicate that decline of hippocampal cAMP response element binding protein and CCAAT/enhancer binding protein DNA-binding activities may contribute to neuronal injury and learning and memory ability reduction induced by cerebral ischemia/reperfusion injury.

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    Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain
    Sung Jin Kwon, Jeongsook Park, So Yun Park, Kwang Seop Song, Sun Tae Jung, So Bong Jung, Ik Ryeul Park, Wan Sung Choi, Sun Ok Kwon
    2013, 8 (10):  922-929.  doi: 10.3969/j.issn.1673-5374.2013.10.007
    Abstract ( 170 )   PDF (226KB) ( 1246 )   Save

    The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

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    Diffusion tensor imaging and proton magnetic resonance spectroscopy in brain tumor  Correlation between structure and metabolism
    Zhigang Min, Chen Niu, Netra Rana, Huanmei Ji, Ming Zhang
    2013, 8 (10):  930-937.  doi: 10.3969/j.issn.1673-5374.2013.10.008
    Abstract ( 241 )   PDF (363KB) ( 986 )   Save

    Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individual fractional anisotropy values with N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in tumors, edema, and normal white matter. This study divided the brain parenchyma into tumor, peritumoral edema, and normal-appearing white matter according to MRI data, and analyzed the correlation of metabolites with water molecular diffusion. Results demonstrated that in normal-appearing white matter, N-acetylaspartate/creatine ratios were positively correlated with fractional anisotropy values, negatively correlated with radial diffusivities, and positively correlated with maximum eigenvalues. Maximum eigenvalues and radial diffusivities in peritumoral edema showed a negative correlation with choline, N-acetylaspartate, and creatine. Radial diffusivities in tumor demonstrated a negative correlation with choline. These data suggest that the relationship between metabolism and structure is markedly changed from normal white matter to peritumoral edema and tumor. Neural metabolism in the peritumoral edema area decreased with expanding extracellular space. The normal relationship of neural function and microstructure disappeared in the tumor region.

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    Therapeutic effects and safety of olcegepant and telcagepant for migraine A meta-analysis
    Gang Yao, Tingmin Yu, Ximei Han, Xijing Mao1, Bo Li
    2013, 8 (10):  938-947.  doi: 10.3969/j.issn.1673-5374.2013.10.009
    Abstract ( 378 )   PDF (410KB) ( 1580 )   Save

    OBJECTIVE: To evaluate the therapeutic effects and adverse reactions of olcegepant and telcagepant for the treatment of migraine.
    DATA RETRIEVAL: We identified studies using Medline (1966-01/2012-06), PubMed (1966-01/2012-06), Scopus (1980-01/2012-06), Cochrane Central Register of Controlled Trials (1980-01/2012-06) and China National Knowledge Infrastructure (1980-01/2012-06).
    SELECTION CRITERIA: The included studies were double-blind, randomized and placebo-controlled trials of olcegepant or telcagepant for the treatment of single acute migraine in patients with or without aura. Adverse reaction data were also included. Two independent investigators performed quality evaluation and data extraction using Jadad scoring. Meta-analyses were undertaken using RevMan 5.0.25 software.
    MAIN OUTCOME MEASURES: Pain relief rate, pain-free rate, and incidence of adverse reactions were measured in patients 2 and 24 hours after injection of olcegepant and oral telcagepant.
    RESULTS: Six randomized, controlled trials were included. Meta-analysis demonstrated that compared with placebo, the pain relief rate (odds ratio, OR = 5.21, 95% confidence interval, CI: 1.91–14.2, P < 0.01) and pain-free rate (OR = 31.11, 95% CI: 3.80–254.98, P < 0.01) significantly increased 2 hours after 2.5 mg/d olcegepant treatment. Pain relief rate and pain-free rate 2 and 24 hours after treatment with telcagepant 150 mg/d and 300 mg/d were superior to placebo (P < 0.01). Moreover, the remission rate of unrelenting headache was higher after 24 hours of 300 mg/d telcagepant treatment compared with 150 mg/d (OR = 0.78, 95% CI: 0.62–0.97, P < 0.05). The incidence of adverse reactions with olcegepant was not significantly greater than placebo (P = 0.28), but within 48 hours of administration of telcagepant 300 mg/d, the incidence of adverse reactions was higher than placebo (OR = 1.21, 95% CI: 1.04–1.42, P < 0.01). Few studies have compared the therapeutic effects of olcegepant and telcagepant.
    CONCLUSION: The calcitonin-gene-related peptide receptor antagonists olcegepant and telcagepant have shown good therapeutic effects in the treatment of migraine. Moreover, the incidence of adverse reactions compares favorably with placebo, although liver transaminases may become elevated after long-term use.

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    Prognosis in prolonged coma patients with diffuse axonal injury assessed by somatosensory evoked potential
    Xiujue Zheng, Mantao Chen, Jingqi Li, Fei Cao
    2013, 8 (10):  948-954.  doi: 10.3969/j.issn.1673-5374.2013.10.010
    Abstract ( 242 )   PDF (173KB) ( 815 )   Save

    A total of 43 prolonged coma patients with diffuse axonal injury received the somatosensory evoked potential examination one month after injury in the First Affiliated Hospital, School of Medicine, Zhejiang University in China. Somatosensory evoked potentials were graded as normal, abnormal or absent (grades I–III) according to N20 amplitude and central conduction time. The outcome in patients with grade III somatosensory evoked potential was in each case unfavorable. The prognostic accuracy of grade III somatosensory evoked potential for unfavorable and non-awakening outcome was 100% and 80%, respectively. The prognostic accuracy of grade I somatosensory evoked potential for favorable and wakening outcome was 86% and 100%, respectively. These results suggest that somatosensory evoked potential grade is closely correlated with coma severity and degree of recovery. Somatosensory evoked potential is a valuable diagnostic tool to assess prognosis in prolonged coma patients with diffuse axonal injury.

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    A novel mutation in the sodium channel α1 subunit gene in a child with Dravet syndrome in Turkey
    Mutluay Arslan, Uluç Yiş, Hande Çağlayan, Rıdvan Akin
    2013, 8 (10):  955-958.  doi: 10.3969/j.issn.1673-5374.2013.10.011
    Abstract ( 169 )   PDF (268KB) ( 868 )   Save

    Dravet syndrome is a rare epileptic encephalopathy characterized by frequent seizures beginning in the first year of life and behavioral disorders. Mutations in the sodium channel α1 subunit gene are the main cause of this disease. We report two patients with refractory seizures and psychomotor retardation in whom the final diagnosis was Dravet syndrome with confirmed mutations in the sodium channel α1 subunit gene. The mutation identified in the second patient was a novel frame shift mutation, which resulted from the deletion of five nucleotides in exon 24.

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