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    15 February 2014, Volume 9 Issue 3 Previous Issue    Next Issue
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    Bridging the injured spinal cord with neural stem cells
    Jennifer N. Dulin, Paul Lu
    2014, 9 (3):  229-231.  doi: 10.4103/1673-5374.128212
    Abstract ( 305 )   PDF (692KB) ( 692 )   Save

    Spinal cord injury (SCI) damages not only the gray matter neurons, but also the white matter axonal tracts that carry signals to and from the brain, resulting permanent loss of function below injury. Neural stem cells (NSCs) have high therapeutic potential for reconstruction of the injured spinal cord since they can potentially form neuronal relays to bridge functional connectivity between separated spinal cord segments. This requires host axonal regeneration into and connectivity with donor neurons, and axonal growth and connectivity of donor neurons to host central nervous system (CNS) circuitry. In this minireview, we will discuss key studies that explore novel neuronal relay formation by grafting NSCs in models of SCI, with emphasis on long-distance axonal growth and connectivity of NSCs grafted into injured spinal cord.

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    Gene therapy and the regeneration of retinal ganglion cell axons
    2014, 9 (3):  232-233.  doi: 10.4103/1673-5374.128213
    Abstract ( 555 )   PDF (154KB) ( 620 )   Save

    Because the adult mammalian central nervous system (CNS) has only limited intrinsic capacity to regenerate connections after injury, due to factors both intrinsic and extrinsic to the mature neuron, therapies are required to support the survival of injured neurons and to promote the long-distance regrowth of axons back to their original target structures. The retina and optic nerve (ON) are part of the CNS and this system is much used in experiments designed to test new ways of promoting regeneration after injury. Testing of therapies designed to improve RGC viability also has direct clinical relevance because there is loss of these centrally projecting neurons in many ophthalmic diseases.

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    Magnetic resonance imaging in patients with transient ischemic attack
    Mohamed Al-Khaled
    2014, 9 (3):  234-235.  doi: 10.4103/1673-5374.128211
    Abstract ( 324 )   PDF (148KB) ( 1393 )   Save

    Transient ischemic attack (TIA) is a temporary event, which portends a higher risk of a disabling stroke following the TIA. However, the evaluation and management of TIA vary worldwide and is debated and controversial. Dr. Mohamed Al-Khaled from University of Lübeck in Germany considered With the development of brain imaging, particularly diffusion weighted imaging-magnetic resonance imaging (DWI-MRI), the diagnosis of TIA changed from time-based definition to a tissue-based one. DWI-MRI became a mandatory tool in the TIA workup. The DWI-MRI provides not only the evidence to distinguish between TIA and acute ischemic stroke, furthermore it predicts TIA patients who are at higher risk of disabling stroke, which can be prevented by an immediate evaluation and treatment of TIA These findings, published in the Neural Regeneration Research (Vol. 9, No. 3, 2014).

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    660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment
    Xianchao Li, Wensheng Hou, Xiaoying Wu, Wei Jiang, Haiyan Chen, Nong Xiao, Ping Zhou
    2014, 9 (3):  236-242.  doi: 10.4103/1673-5374.128214
    Abstract ( 270 )   PDF (529KB) ( 2043 )   Save

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600–1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage.

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    Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction
    Yun Xiang, Huihua Liu, Tiebin Yan, Zhiqiang Zhuang, Dongmei Jin, Yuan Peng
    2014, 9 (3):  243-251.  doi: 10.4103/1673-5374.128215
    Abstract ( 190 )   PDF (1937KB) ( 974 )   Save

    Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plasticity, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin (a neural precursor cell marker)-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats.

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    Ginsenoside Rb1 attenuates activated microglia-induced neuronal damage
    Lining Ke, Wei Guo, Jianwen Xu, Guodong Zhang, Wei Wang, Wenhua Huang
    2014, 9 (3):  252-259.  doi: 10.4103/1673-5374.128217
    Abstract ( 212 )   PDF (1403KB) ( 1651 )   Save

    The microglia-mediated inflammatory reaction promotes neuronal damage under cerebral ischemia/hypoxia conditions. We therefore speculated that inhibition of hypoxia-induced microglial activation may alleviate neuronal damage. To test this hypothesis, we co-cultured ginsenoside Rb1, an active component of ginseng, and cortical neurons. Ginsenoside Rb1 protected neuronal morphology and structure in a single hypoxic culture system and in a hypoxic co-culture system with microglia, and reduced neuronal apoptosis and caspase-3 production. The protective effect was observable prior to placing in co-culture. Additionally, ginsenoside Rb1 inhibited levels of tumor necrosis factor-α in a co-culture system containing activated N9 microglial cells. Ginsenoside Rb1 also significantly decreased nitric oxide and superoxide production induced by N9 microglia. Our findings indicate that ginsenoside Rb1 attenuates damage to cerebral cortex neurons by downregulation of nitric oxide, superoxide, and tumor necrosis factor-α expression in hypoxia-activated microglia.

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    Polysaccharides from Angelica sinensis alleviate neuronal cell injury caused by oxidative stress
    Tao Lei, Haifeng Li, Zhen Fang, Junbin Lin, Shanshan Wang, Lingyun Xiao, Fan Yang, Xin Liu, Junjian Zhang, Zebo Huang,Weijing Liao
    2014, 9 (3):  260-267.  doi: 10.4103/1673-5374.128218
    Abstract ( 234 )   PDF (1251KB) ( 1098 )   Save

    Angelica sinensis has antioxidative and neuroprotective effects. In the present study, we aimed to determine the neuroprotective effect of polysaccharides isolated from Angelica sinensis. In a preliminary experiment, Angelica sinensis polysaccharides not only protected PC12 neuronal cells from H2O2-induced cytotoxicity, but also reduced apoptosis and intracellular reactive oxygen species levels, and increased the mitochondrial membrane potential induced by H2O2 treatment. In a rat model of local cerebral ischemia, we further demonstrated that Angelica sinensis polysaccharides enhanced the antioxidant activity in cerebral cortical neurons, increased the number of microvessels, and improved blood flow after ischemia. Our findings highlight the protective role of polysaccharides isolated from Angelica sinensis against nerve cell injury and impairment caused by oxidative stress.

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    Atorvastatin protects against cerebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects
    Qiuyun Tu, Hui Cao, Wei Zhong, Binrong Ding, Xiangqi Tang
    2014, 9 (3):  268-275.  doi: 10.4103/1673-5374.128220
    Abstract ( 194 )   PDF (1110KB) ( 1153 )   Save

    In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral ischemia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulated, the oxidative stress-related marker malondialdehyde was increased, and superoxide dismutase activity was decreased in the ischemic cerebral cortex. Atorvastatin pretreatment significantly inhibited these changes. Our findings indicate that atorvastatin protects against cerebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects.

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    Vascular changes caused by deep brain stimulation using double-dose gadolinium-enhanced brain MRI
    Byeong Sam Choi, Yong Hwan Kim, Sang Ryong Jeon
    2014, 9 (3):  276-279.  doi: 10.4103/1673-5374.128221
    Abstract ( 238 )   PDF (595KB) ( 762 )   Save

    We retrospectively analyzed the clinical data of 32 patients with medically intractable idiopathic Parkinson’s disease who had undergone staged bilateral deep brain stimulation of the subthalamic nuclei from January 2007 to May 2011. The vascularture of the patients who received two deep brain stimulations was detected using double-dose gadolinium-enhanced brain MRI. The dimensions of straight sinus, superior sagittal sinus, ipsilateral internal cerebral vein in the thalamic branch and ipsilateral anterior caudate vein were reduced. These findings demonstrate that bilateral deep brain stimulation of the subthalamic nuclei affects cerebral venous blood flow.

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    Quantitative volumetric analysis of the optic radiation in the normal human brain using diffusion tensor magnetic resonance imaging-based tractography
    Dong-Hoon Lee, Ji-Won Park, Cheol-Pyo Hong
    2014, 9 (3):  280-284.  doi: 10.4103/1673-5374.128223
    Abstract ( 163 )   PDF (574KB) ( 1040 )   Save

    o attain the volumetric information of the optic radiation in normal human brains, we performed diffusion tensor imaging examination in 13 healthy volunteers. Simultaneously, we used a brain normalization method to reduce individual brain variation and increase the accuracy of volumetric information analysis. In addition, tractography-based group mapping method was also used to investigate the probability and distribution of the optic radiation pathways. Our results showed that the measured optic radiation fiber tract volume was a range of about 0.16% and that the fractional anisotropy value was about 0.53. Moreover, the optic radiation probability fiber pathway that was determined with diffusion tensor tractography-based group mapping was able to detect the location relatively accurately. We believe that our methods and results are helpful in the study of optic radiation fiber tract information.

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    Can amino-functionalized carbon nanotubes carry functional nerve growth factor?
    Wen Chen, Qing Xiong, Quanxia Ren, Yake Guo, Gao Li
    2014, 9 (3):  285-292.  doi: 10.4103/1673-5374.128225
    Abstract ( 184 )   PDF (1922KB) ( 1046 )   Save

    Carbon nanotubes can carry protein into cells to induce biological effects. Amino-functionalized carbon nanotubes are soluble and biocompatible, have high reactivity and low toxicity, and can help promote nerve cell growth. In this study, amino-functionalized ethylenediamine-treated multi-walled carbon nanotubes were used to prepare carbon nanotubes-nerve growth factor complexes by non-covalent grafting. The physicochemical properties, cytotoxicity to PC12 and chick embryo dorsal root ganglion, and biological activity of the carbon nanotubes-nerve growth factor complexes were investigated. The results showed that amino functionalization improved carbon nanotubes-nerve growth factor complex dispersibility, reduced their toxicity to PC12 cells, and promoted PC12 cell differentiation and chick embryo dorsal root ganglion.

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    Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study
    Ji Qi, Junqi Chen, Yong Huang, Xinsheng Lai, Chunzhi Tang, Junjun Yang, Hua Chen, Shanshan Qu
    2014, 9 (3):  293-300.  doi: 10.4103/1673-5374.128227
    Abstract ( 157 )   PDF (1762KB) ( 910 )   Save

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    Normalization of ventral tegmental area structure following acupuncture in a rat model of heroin relapse
    Rongjun Zhang, Xinghui Cai, Xiaoge Song, Chaoyang Dong, Xiaorong Hou, Lei Lv
    2014, 9 (3):  301-307.  doi: 10.4103/1673-5374.128228
    Abstract ( 202 )   PDF (1218KB) ( 1312 )   Save

    Drugs can cause obvious damage to the brain. To verify the relationship between acupuncture, neurotrophic factor expression and brain cell structural changes, this study established a rat model of heroin relapse using intramuscular injection of increasing amounts of heroin. During the detoxification period, rat models received acupuncture at Baihui (DU20) and Dazhui (DU14). Electron microscopy demonstrated that the structure of the ventral tegmental area in heroin relapse rats gradually became normalized after acupuncture treatment. Immunohistochemical staining exhibited that the expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the ventral tegmental area following acupuncture. Moreover, the effects were similar to that of methadone, a type of medicine called an opioid. Results suggested that acupuncture at Baihui and Dazhui protected brain neurons against injury in rats with heroin relapse by promoting brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression.

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    Special function of nestin+ neurons in the medial septum-diagonal band of Broca in adult rats
    Yuhong Zhao, Kaihua Guo, Dongpei Li, Qunfang Yuan, Zhibin Yao
    2014, 9 (3):  308-317.  doi: 10.4103/1673-5374.128229
    Abstract ( 246 )   PDF (2255KB) ( 924 )   Save

    Nestin+ neurons have been shown to express choline acetyltransferase (ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin+ neurons to the olfactory bulb and the time course of nestin+ neurons in the medial septum-diagonal band of Broca in adult rats during injury recovery after olfactory nerve transection. This study observed that all nestin+ neurons were double-labeled with ChAT in the medial septum-diagonal band of Broca. Approximately 53.6% of nestin+ neurons were projected to the olfactory bulb and co-labeled with fast blue. A large number of nestin+ neurons were not present in each region of the medial septum-diagonal band of Broca. Nestin+ neurons in the medial septum and vertical limb of the diagonal band of Broca showed obvious compensatory function. The number of nestin+ neurons decreased to a minimum later than nestin–/ChAT+ neurons in the medial septum-diagonal band of Broca. The results suggest that nestin+ cholinergic neurons may have a closer connection to olfactory bulb neurons. Nestin+ cholinergic neurons may have a stronger tolerance to injury than Nestin–/ChAT+ neurons. The difference between nestin+ and nestin–/ChAT+ neurons during the recovery process requires further investigations.

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    Short-term environmental enrichment exposure induces proliferation and maturation of  doublecortin-positive cells in the prefrontal cortex
    Chunling Fan, Mengqi Zhang, Lei Shang, Ngobe Akume Cynthia, Zhi Li, Zhenyu Yang, Dan Chen, Jufang Huang, Kun Xiong
    2014, 9 (3):  318-328.  doi: 10.4103/1673-5374.128231
    Abstract ( 203 )   PDF (4830KB) ( 764 )   Save

    Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine (a marker of cell proliferation), c-Fos (a marker of cell viability) and NeuN (a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.

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    The Olig family affects central nervous system development and disease
    Botao Tan, Jing Yu, Ying Yin, Gongwei Jia, Wei Jiang, Lehua Yu
    2014, 9 (3):  329-336.  doi: 10.4103/1673-5374.128232
    Abstract ( 192 )   PDF (551KB) ( 1549 )   Save

    Neural cell differentiation and maturation is a critical step during central nervous system development. The oligodendrocyte transcription family (Olig family) is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system development and related diseases.

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