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Table of Content

    05 January 2014, Volume 9 Issue 1 Previous Issue    Next Issue
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    Facilitating transparency in spinal cord injury studies using data standards and ontologies
    Vance P. Lemmon, Saminda Abeyruwan, Ubbo Visser,John L. Bixby
    2014, 9 (1):  6-7. 
    Abstract ( 281 )   PDF (150KB) ( 1322 )   Save

    Progress in developing robust therapies for spinal cord injury (SCI), traumatic brain injury (TBI) and peripheral nerve injury has been slow. A great deal has been learned over the past 30 years regarding both the intrinsic factors and the environmental factors that regulate axon growth, but this large body of information has not yet resulted in clinically available therapeutics. Prof. Lemmon and his team from University of Miami in USA proposed this therapeutic bottleneck has many root causes, but a consensus is emerging that one contributing factor is a lack of standards for experimental design and reporting. The absence of reporting standards, and even of commonly accepted definitions of key words, also make data mining and bioinformatics analysis of neural plasticity and regeneration difficult, if not impossible. These findings, published in the Neural Regeneration Research (Vol. 9, No. 1, 2014), this short review will consider relevant background and potential solutions to this problem in the axon regeneration domain.

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    Senescence in adipose-derived stem cells and its implications in nerve regeneration
    Cristina Mantovani, Giorgio Terenghi, Valerio Magnaghi
    2014, 9 (1):  10-15. 
    Abstract ( 279 )   PDF (766KB) ( 2201 )   Save
    Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-derived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process whereby stem cells grow old as consequence of intrinsic events (e.g., DNA damage) or environmental cues (e.g., stressful stimuli or diseases), which determine a permanent growth arrest. Several mechanisms are implicated in stem cell senescence, although no one is exclusive of the others. In this review we report some of the most important factors modulating the senescence process, which can influence adipose-derived stem cell morphology and function, and compromise their clinical application for peripheral nerve regenerative cell therapy.
     
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    Mash1 efficiently reprograms rat astrocytes into neurons
    Daofang Ding, Leqin Xu, Hao Xu, Xiaofeng Li, Qianqian Liang, Yongjian Zhao, Yongjun Wang
    2014, 9 (1):  25-32.  doi: 10.4103/1673-5374.125326
    Abstract ( 176 )   PDF (2096KB) ( 1624 )   Save

    To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mash1 and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examined astrocytes from 2-month-old Sprague-Dawley rats, and found that Brn2 was expressed, but Mash1 was not detectable. Thus, we hypothesized that Mash1 alone could be used to reprogram astrocytes into neurons. We transfected a recombinant MSCV-MASH1 plasmid into astrocytes for 72 hours, and saw that all cells expressed Mash1. One week later, we observed the changes in morphology of astrocytes, which showed typical neuronal characteristics. Moreover, β-tubulin expression levels were significantly higher in astrocytes expressing Mash1 than in control cells. These results indicate that Mash1 alone can reprogram astrocytes into neurons.

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    Transfection of the glial cell line-derived neurotrophic factor gene promotes neuronal differentiation
    Jie Du, Xiaoqing Gao, Li Deng, Nengbin Chang, Huailin Xiong, Yu Zheng
    2014, 9 (1):  33-40.  doi: 10.4103/1673-5374.125327
    Abstract ( 206 )   PDF (1555KB) ( 1853 )   Save

    Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, microtubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the supernatant were significantly higher in glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells compared with empty virus plasmid-transfected bone marrow mesenchymal stem cells. Furthermore, microtubule-associated protein 2, glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 mRNA levels in cell pellets were statistically higher in glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells compared with empty virus plasmid-transfected bone marrow mesenchymal stem cells. These results suggest that glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells have a higher rate of induction into neuron-like cells, and this enhanced differentiation into neuron-like cells may be associated with up-regulated expression of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43.

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    Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling
    Lei Song, Yue Gu, Jing Jie, Xiaoxue Bai, Ying Yang, Chaoying Liu, Qun Liu
    2014, 9 (1):  41-50.  doi: 10.4103/1673-5374.125328
    Abstract ( 277 )   PDF (2404KB) ( 1375 )   Save

    Transforming growth factor-beta (TGF-β) type II receptor (TβRII) levels are extremely low in the brain tissue of patients with Alzheimer’s disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specific adapter protein, protects TβRII from degradation and ensures the effective conduction of TGF-β1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippocampus and investigated the regulatory effect of Dab2 protein on TGF-β1/SMAD signaling in a mouse model of Alzheimer’s disease, and the potential neuroprotective effect. The results showed that the TβRII level was lower in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal TβRII and p-SMAD2/3 levels were significantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor-α and interleulin-6 levels and neuronal loss were significantly attenuated in APP/PS1 mouse brain tissue. These results suggest that Dab2 can exhibit neuroprotective effects in Alzheimer’s disease by regulating TGF-β1/SMAD signaling.

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    Changes in brain functional network connectivity after stroke
    Wei Li, Yapeng Li, Wenzhen Zhu, Xi Chen
    2014, 9 (1):  51-60.  doi: 10.4103/1673-5374.125330
    Abstract ( 282 )   PDF (1195KB) ( 1603 )   Save

    Studies have shown that functional network connection models can be used to study brain network changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlated to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea-lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.

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    Mechanism underlying the protective effect of Kaixin Jieyu Fang on vascular depression following cerebral white matter damage
    Ying Zhang, Shijing Huang, Yanyun Wang, Junhua Pan, Jun Zheng, Xianhui Zhang, Yuxia Chen, Duojiao Li
    2014, 9 (1):  61-68.  doi: 10.4103/1673-5374.125331
    Abstract ( 213 )   PDF (2475KB) ( 925 )   Save

    The Chinese compound Kaixin Jieyu Fang can be used to treat vascular depression; however, the underlying mechanism remains unclear. This study established a rat model of chronic cerebral ischemia-caused white matter damage by ligation of the bilateral common carotid arteries. Rats received daily intragastric administration of a suspension of Kaixin Jieyu Fang powder. After 3, 7 and 21 days of treatment, the degree of white matter damage in the cerebral ischemia rat model was alleviated, Bcl-2 protein and mRNA expression in brain tissue increased, and Bax protein and mRNA expression decreased. These results indicate that Kaixin Jieyu Fang can alleviate cerebral white matter damage, and the underlying mechanism is associated with regulation of Bcl-2/Bax protein and mRNA expression, which is one of possible mechanism behind the protective effect of Kaixin Jieyu Fang against vascular depression.

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    A non-invasive, rapid method to genotype late-onset Alzheimer’s disease-related apolipoprotein E gene polymorphisms
    Li Yi, Ting Wu, Wenyuan Luo, Wen Zhou, Jun Wu
    2014, 9 (1):  69-75.  doi: 10.4103/1673-5374.125332
    Abstract ( 241 )   PDF (1450KB) ( 2628 )   Save

    The apolipoprotein E gene ε4 allele is considered a negative factor for neural regeneration in late-onset Alzheimer’s disease cases. The aim of this study was to establish a non-invasive, rapid method to genotype apolipoprotein E gene polymorphisms. Genomic DNA from mouth swab specimens was extracted using magnetic nanoparticles, and genotyping was performed by real-time PCR using TaqMan-BHQ probes. Genotyping accuracy was validated by DNA sequencing. Our results demonstrate 100% correlation to DNA sequencing, indicating reliability of our protocol. Thus, the method we have developed for apolipoprotein E genotyping is accurate and reliable, and also suitable for genotyping large samples, which may help determine the role of the apolipoprotein E ε4 allele in neural regeneration in late-onset Alzheimer’s disease cases.

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    Hippocampal gene expression in a rat model of depression after electroacupuncture at the Baihui and Yintang acupoints
    Dongmei Duan, Xiuyan Yang, Ya Tu, Liping Chen
    2014, 9 (1):  76-83.  doi: 10.4103/1673-5374.125333
    Abstract ( 316 )   PDF (343KB) ( 1714 )   Save

    Preliminary basic research and clinical findings have demonstrated that electroacupuncture therapy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level; there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we profiled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depression-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui (DU20) and Yintang (EX-HN3) regulates the expression of 21 genes. Real-time PCR showed that the genes Vgf, Igf2, Tmp32, Loc500373, Hif1a, Folr1, Nmb, and Rtn were upregulated or downregulated in depression and that their expression tended to normalize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui  and Yintang modulates depression by regulating the expression of particular genes.

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    Electro-acupuncture at Conception and Governor vessels and transplantation of umbilical cord blood-derived mesenchymal stem cells for treating cerebral ischemia/reperfusion injury
    Haibo Yu, Pengdian Chen, Zhuoxin Yang, Wenshu Luo, Min Pi, Yonggang Wu, Ling Wang
    2014, 9 (1):  84-91.  doi: 10.4103/1673-5374.125334
    Abstract ( 204 )   PDF (1089KB) ( 1310 )   Save

    Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reperfusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at     24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry findings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the ischemic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These findings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promoting neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.

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    Lipid rafts participate in aberrant degradative autophagic-lysosomal pathway of amyloid-beta peptide in Alzheimer’s disease
    Xin Zhou, Chun Yang, Yufeng Liu, Peng Li, Huiying Yang, Jingxing Dai, Rongmei Qu, Lin Yuan
    2014, 9 (1):  92-100.  doi: 10.4103/1673-5374.125335
    Abstract ( 272 )   PDF (325KB) ( 2550 )   Save

    Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzheimer’s disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer’s disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant degradative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer’s disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer’s disease treatment.

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    Critical illness polyneuropathy and myopathy: a systematic review
    Chunkui Zhou, Limin Wu, Fengming Ni, Wei Ji, Jiang Wu, Hongliang Zhang
    2014, 9 (1):  101-110.  doi: 10.4103/1673-5374.125337
    Abstract ( 294 )   PDF (1283KB) ( 3379 )   Save

    Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitating neurological disease.

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