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    26 May 2014, Volume 9 Issue 10 Previous Issue    Next Issue
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    Visualization of peripheral nerve regeneration
    Ting-Chen Tseng, Chen-Tung Yen, Shan-hui Hsu
    2014, 9 (10):  997-999.  doi: 10.4103/1673-5374.133157
    Abstract ( 222 )   PDF (771KB) ( 843 )   Save

    A variety of treatments for repairing the peripheral nerve injuries have been developed. Monitoring the peripheral nerve regeneration process in vivo without invasion, however, is less reported. This article describes the treatment options for the peripheral nerve regeneration and compares the treatments suitable for nerve injuries. On the other hand, this article provides choices of imaging tools for visualizing the nerve regeneration in real-time. Using the appropriate imaging tool may help understand the process and mechanism of peripheral nerve regeneration under various treatments.

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    Two types of auditory glutamatergic synapses and their implications for repairing damaged central auditory pathways
    Charles C. Lee
    2014, 9 (10):  1000-1002.  doi: 10.4103/1673-5374.133158
    Abstract ( 322 )   PDF (369KB) ( 842 )   Save

    Throughout the entirety of the auditory pathway, excitatory glutamatergic projections primarily link neural stations with one another, act to shape and refine these afferent signals. Dr. Charles C. Lee, who comes from Louisiana State University in USA, thier recent studies suggest an alternative perspective; specifically, that some glutamatergic pathways in the central auditory system instead modulate the information received through the information-bearing glutamatergic pathways. Furthermore, these distinctions among glutamatergic pathways are not limited to the auditory system and are also found in the visual and somatosensory pathways. Furthermore, the putative modulatory glutamatergic pathways, with their distal dendritic synaptic locations and activation of metabotropic glutamate receptors might be more ideally constructed to support sustained and longer-term alterations to synaptic strength and efficacy. Thus, the relative plasticity of these two types of glutamatergic pathways may inherently limit the regenerative capacity of various components in the auditory processing stream. Consequently, regenerating or repairing damage to the central auditory pathways may benefit from targeting selected glutamatergic synaptic types.

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    Intraspinal transplantation of motoneuron-like cell combined with delivery of polymer-based glial cell line-derived neurotrophic factor  for repair of spinal cord contusion injury
    Alireza Abdanipour, Taki Tiraihi, Taher Taheri
    2014, 9 (10):  1003-1013.  doi: 10.4103/1673-5374.133159
    Abstract ( 216 )   PDF (2190KB) ( 751 )   Save

    To evaluate the effects of glial cell line-derived neurotrophic factor transplantation combined with adipose-derived stem cells-transdifferentiated motoneuron delivery on spinal cord contusion injury, we developed rat models of spinal cord contusion injury, 7 days later, injected adipose-derived stem cells-transdifferentiated motoneurons into the epicenter, rostral and caudal regions of the impact site and simultaneously transplanted glial cell line-derived neurotrophic factor-gelfoam complex into the myelin sheath. Motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery reduced cavity formations and increased cell density in the transplantation site. The combined therapy exhibited superior promoting effects on recovery of motor function to transplantation of glial cell line-derived neurotrophic factor, adipose-derived stem cells or motoneurons alone. These findings suggest that motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery holds a great promise for repair of spinal cord injury. 

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    Neural stem cell transplantation in a double-layer collagen membrane with unequal pore sizes for spinal cord injury repair
    Ning Yuan, Wei Tian, Lei Sun, Runying Yuan, Jianfeng Tao, Dafu Chen
    2014, 9 (10):  1014-1019.  doi: 10.4103/1673-5374.133160
    Abstract ( 258 )   PDF (3109KB) ( 1110 )   Save

    A novel double-layer collagen membrane with unequal pore sizes in each layer was designed and tested in this study. The inner, loose layer has about 100-μm-diameter pores, while the outer, compact layer has about 10-μm-diameter pores. In a rat model of incomplete spinal cord injury, a large number of neural stem cells were seeded into the loose layer, which was then adhered to the injured side, and the compact layer was placed against the lateral side. The results showed that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes promoted the differentiation of neural stem cells, attenuated the pathological lesion, and significantly improved the motor function of the rats with incomplete spinal cord injuries. These experimental findings suggest that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes is an effective therapeutic strategy to repair an injured spinal cord.

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    L-carnitine alleviates sciatic nerve crush injury in rats: functional and electron microscopy assessments
    Ümmü Zeynep Avsar, Umit Avsar, Ali Aydin, Muhammed Yayla, Berna Ozturkkaragoz, Harun Un, Murat Saritemur, Tolga Mercantepe
    2014, 9 (10):  1020-1024.  doi: 10.4103/1673-5374.133163
    Abstract ( 248 )   PDF (1202KB) ( 1662 )   Save

    Several studies have demonstrated that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats with diabetes mellitus. It is hypothesized that L-carnitine exhibits neuroprotective effects on injured sciatic nerve of rats. Rat sciatic nerve was crush injured by a forceps and exhibited degenerative changes. After intragastric administration of 50 and 100 mg/kg L-carnitine for 30 days, axon area, myelin sheath area, axon diameter, myelin sheath diameter, and numerical density of the myelinated axons of injured sciatic nerve were similar to normal, and the function of injured sciatic nerve also improved significantly. These findings suggest that L-carnitine exhibits neuroprotective effects on sciatic nerve crush injury in rats.

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    Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injury
    Luigi Aloe, Patrizia Bianchi, Alberto De Bellis, Marzia Soligo, Maria Luisa Rocco
    2014, 9 (10):  1025-1030.  doi: 10.4103/1673-5374.133161
    Abstract ( 299 )   PDF (1197KB) ( 1442 )   Save

    The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an increased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deficits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

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    Differential expression of microRNAs in dorsal root ganglia after sciatic nerve injury
    Anjie Lu, Zufa Huang, Chaoyue Zhang, Xianfang Zhang, Jiuhong Zhao, Haiying Zhang, Quanpeng Zhang, Song Wu, Xinan Yi
    2014, 9 (10):  1031-1040.  doi: 10.4103/1673-5374.133164
    Abstract ( 203 )   PDF (2459KB) ( 1104 )   Save

    This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identified whose expression was significantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization verified that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a combination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neurons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that microRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.

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    A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair
    Dong Wang, Xijun Huang, Guo Fu, Liqiang Gu, Xiaolin Liu, Honggang Wang, Jun Hu, Jianhua Yi, Xiaofeng Niu, Qingtang Zhu
    2014, 9 (10):  1041-1046.  doi: 10.4103/1673-5374.133166
    Abstract ( 202 )   PDF (1527KB) ( 1170 )   Save

    Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripheral nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration.

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    The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells
    Huanling Yao, Tianshi Wang, Jiexin Deng, Ding Liu, Xiaofei Li, Jinbo Deng
    2014, 9 (10):  1047-1054.  doi: 10.4103/1673-5374.133169
    Abstract ( 205 )   PDF (3556KB) ( 831 )   Save

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    Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain
    Yanbing He, Shiyuan Xu, Junjie Huang, Qingjuan Gong
    2014, 9 (10):  1055-1062.  doi: 10.4103/1673-5374.133170
    Abstract ( 289 )   PDF (1997KB) ( 1020 )   Save

    Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the specific sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression increased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These findings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassium-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassium-chloride co-transporter 1.

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    Chemokine receptor 4 gene silencing blocks neuroblastoma metastasis in vitro
    Xin Chen, Yongjie Zhu, Lulu Han, Hongting Lu, Xiwei Hao, Qian Dong
    2014, 9 (10):  1063-1067.  doi: 10.4103/1673-5374.133172
    Abstract ( 180 )   PDF (676KB) ( 1231 )   Save

    This study investigated the effects of small interfering RNA (siRNA)-mediated silencing of chemokine receptor 4 (CXCR4) on the invasion capacity of human neuroblastoma cell line SH-SY5Y in vitro. Three siRNAs targeting CXCR4 were chemically synthesized and individually transfected into SH-SY5Y cells. Expression of CXCR4 mRNA and protein was significantly suppressed in transfected cells by all three sequence-specific siRNAs compared with control groups. Furthermore, the invasion capacity of SH-SY5Y cells was significantly decreased following transfection with CXCR4-specific siRNA compared with the control groups. These data demonstrate that down-regulation of CXCR4 can inhibit in vitro invasion of neuroblastoma.

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    The human δ2 glutamate receptor gene is not mutated in patients with spinocerebellar ataxia
    Jinxiang Huang, Aiyu Lin, Haiyan Dong, Chaodong Wang
    2014, 9 (10):  1068-1074.  doi: 10.4103/1673-5374.133173
    Abstract ( 259 )   PDF (520KB) ( 1237 )   Save

    The human glutamate receptor delta 2 gene (GRID2) shares 90% homology with the orthologous mouse gene. The mouse Grid2 gene is involved with functions of the cerebellum and spontaneous mutation of Grid2 leads to a spinocerebellar ataxia-like phenotype. To investigate whether such mutations occur in humans, we screened for mutations in the coding sequence of GRID2 in 24 patients with familial or sporadic spinocerebellar ataxia and in 52 normal controls. We detected no point mutations or insertion/deletion mutations in the 16 exons of GRID2. However, a polymorphic 4 nucleotide deletion (IVS5-121_-118 GAGT) and two single nucleotide polymorphisms (c.1251G>T and IVS14-63C>G) were identified. The frequency of these polymorphisms was similar between spinocerebellar ataxia patients and normal controls. These data indicate that spontaneous mutations do not occur in GRID2 and that the incidence of spinocerebellar ataxia in humans is not associated with GRID2 mutation or polymorphisms.

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    Bridging peripheral nerves using a deacetyl chitin conduit combined with short-term electrical stimulation
    Zhongli Zhang, Xin Li, Songjie Zuo, Jie Xin, Peixun Zhang
    2014, 9 (10):  1075-1078.  doi: 10.4103/1673-5374.133168
    Abstract ( 216 )   PDF (224KB) ( 864 )   Save

    Previous studies have demonstrated that deacetyl chitin conduit nerve bridging or electrical stimulation can effectively promote the regeneration of the injured peripheral nerve. We hypothesized that the combination of these two approaches could result in enhanced regeneration. Rats with right sciatic nerve injury were subjected to deacetyl chitin conduit bridging combined with electrical stimulation (0.1 ms, 3 V, 20 Hz, for 1 hour). At 6 and 12 weeks after treatment, nerve conduction velocity, myelinated axon number, fiber diameter, axon diameter and the thickness of the myelin sheath in the stimulation group were better than in the non-stimulation group. The results indicate that deacetyl chitin conduit bridging combined with temporary electrical stimulation can promote peripheral nerve repair.

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    Attenuated inhibition of medium spiny neurons participates in the pathogenesis of childhood depression
    Dandan Liu, Linghan Hu, Junqi Zhang, Ping Zhang, Shengtian Li
    2014, 9 (10):  1079-1088.  doi: 10.4103/1673-5374.133171
    Abstract ( 412 )   PDF (540KB) ( 872 )   Save

    Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of antidepressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental findings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.

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