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    24 July 2015, Volume 10 Issue 7 Previous Issue    Next Issue
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    Connexins in neurons and glia: targets for intervention in disease and injury
    Keith B. Moore, John O’Brien
    2015, 10 (7):  1013-1017.  doi: 10.4103/1673-5374.160092
    Abstract ( 535 )   PDF (389KB) ( 833 )   Save

    Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Among neurons, gap junctions form electrical synapses that function primarily for communication. However, in neurodegenerative states due to disease or injury gap junctions may be detrimental to survival. Electrical synapses may facilitate hyperactivity and bystander killing among neurons, while gap junction hemichannels in glia may facilitate inflammatory signaling and scar formation. Advances in understanding mechanisms of plasticity of electrical synapses and development of molecular therapeutics to target glial gap junctions and hemichannels offer new hope to pharmacologically limit neuronal degeneration and enhance recovery.

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    The treatment of Parkinson’s disease with deep brain stimulation: current issues
    Alexia-Sabine Moldovan, Stefan Jun Groiss, Saskia Elben, Martin Südmeyer, Alfons Schnitzler, Lars Wojtecki
    2015, 10 (7):  1018-1022.  doi: :10.4103/1673-5374.160094
    Abstract ( 280 )   PDF (216KB) ( 613 )   Save

    Deep brain stimulation has become a well-established symptomatic treatment for Parkinson’s disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

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    Glycogen and amyloid-beta: key players in the shift from neuronal hyperactivity to hypoactivity observed in Alzheimer’s disease?
    Britanny Bass, Sarah Upson, Kamolika Roy, Emily L. Montgomery, Tuula O. Jalonen, Ian V.J. Murray
    2015, 10 (7):  1023-1025.  doi: 10.4103/1673-5374.160059
    Abstract ( 201 )   PDF (284KB) ( 597 )   Save
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    Role of mitochondria in regulating microRNA activity and its relevance to the central nervous system
    Wang-Xia Wang, Joe E. Springer
    2015, 10 (7):  1026-1028.  doi: 10.4103/1673-5374.160061
    Abstract ( 284 )   PDF (333KB) ( 1041 )   Save
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    Dendrimer nanocarriers drug action: perspective for neuronal pharmacology
    Felipe Vidal, Leonardo Guzman
    2015, 10 (7):  1029-1031.  doi: 10.4103/1673-5374.160063
    Abstract ( 167 )   PDF (960KB) ( 736 )   Save
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    Subcellular localization of Rho GTPases: implications for axon regeneration
    DiAnna L. Hynds
    2015, 10 (7):  1032-1033.  doi: 10.4103/1673-5374.160064
    Abstract ( 173 )   PDF (290KB) ( 491 )   Save
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    Acetylation as a mechanism that regulates axonal regeneration
    Shen Lin, George M. Smith
    2015, 10 (7):  1034-1036.  doi: 10.4103/1673-5374.160066
    Abstract ( 175 )   PDF (811KB) ( 502 )   Save
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    Magnetic nanotechnology to study and promote axon growth
    Wolfgang Pita-Thomas
    2015, 10 (7):  1037-1039.  doi: 10.4103/1673-5374.160067
    Abstract ( 182 )   PDF (467KB) ( 560 )   Save
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    “To measure is to know”: how advances in image analysis are supporting neural repair strategies
    Pascal Vallotton, Robert Michail Ivan Kapsa
    2015, 10 (7):  1040-1042.  doi: 10.4103/1673-5374.160069
    Abstract ( 171 )   PDF (322KB) ( 509 )   Save
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    Argon: a novel therapeutic option to treat neuronal ischemia and reperfusion injuries?
    Felix Ulbrich, Ulrich Goebel
    2015, 10 (7):  1043-1044.  doi: 10.4103/1673-5374.160071
    Abstract ( 188 )   PDF (151KB) ( 445 )   Save
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    Circuit reorganization in cerebellar cultures after injury
    Fredrick J. Seil
    2015, 10 (7):  1045-1046.  doi: 10.4103/1673-5374.160073
    Abstract ( 163 )   PDF (418KB) ( 487 )   Save
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    Novel rodent models of penetrating traumatic brain injury
    Stefan Plantman
    2015, 10 (7):  1047-1049.  doi: 10.4103/1673-5374.160074
    Abstract ( 227 )   PDF (530KB) ( 726 )   Save
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    Gene therapy in Parkinson’s disease: targeting the endplasmic reticulum proteostasis network
    Valentina Castillo, Gabriela Mercado, Claudio Hetz
    2015, 10 (7):  1053-1054.  doi: 10.4103/1673-5374.160077
    Abstract ( 189 )   PDF (417KB) ( 576 )   Save
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    Provision of nutrients after acute spinal cord injury: the implications of feast and famine
    Sarah Garber, Gregory Hawryluk
    2015, 10 (7):  1061-1062.  doi: 10.4103/1673-5374.160081
    Abstract ( 186 )   PDF (249KB) ( 590 )   Save
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    Potential of the use of an antioxidant compound to promote peripheral nerve regeneration after injury
    Sergio A. Gerhke, Jamil A. Shibli, Marcos B. Salles
    2015, 10 (7):  1063-1064.  doi: 10.4103/1673-5374.160082
    Abstract ( 164 )   PDF (413KB) ( 472 )   Save
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    Metallic nanoparticles for peripheral nerve regeneration: is it a feasible approach?
    Chiara Paviolo, Paul R. Stoddart
    2015, 10 (7):  1065-1066.  doi: 10.4103/1673-5374.160083
    Abstract ( 237 )   PDF (247KB) ( 597 )   Save
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    Lysophospholipids in retinal axon guidance: roles and cell signaling
    Eric Birgbauer
    2015, 10 (7):  1067-1068.  doi: 10.4103/1673-5374.160091
    Abstract ( 211 )   PDF (208KB) ( 513 )   Save
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    Electroacupuncture preconditioning attenuates ischemic brain injury by activation of the adenosine monophosphate-activated protein kinase signaling pathway
    Qiang-qiang Ran, Huai-long Chen, Yan-li Liu, Hai-xia Yu, Fei Shi, Ming-shan Wang
    2015, 10 (7):  1069-1075.  doi: 10.4103/1673-5374.160095
    Abstract ( 233 )   PDF (1829KB) ( 807 )   Save

    Electroacupuncture has therapeutic effects on ischemic brain injury, but its mechanism is still poorly understood. In this study, mice were stimulated by electroacupuncture at the Baihui (GV20) acupoint for 30 minutes at 1 mA and 2/15 Hz for 5 consecutive days. A cerebral ischemia model was established by ligating the bilateral common carotid artery for 15 minutes. At 72 hours after injury, neuronal injury in the mouse hippocampus had lessened, and the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive cells reduced after electroacupuncture treatment. Moreover, expression of adenosine monophosphate-activated protein kinase α (AMPKα) and phosphorylated AMPKα was up-regulated. Intraperitoneal injection of the AMPK antagonist, compound C, suppressed this phenomenon. Our findings suggest that electroacupuncture preconditioning alleviates ischemic brain injury via AMPK activation.

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    Progesterone is neuroprotective by inhibiting cerebral edema after ischemia
    Yuan-zheng Zhao, Min Zhang, Heng-fang Liu, Jian-ping Wang
    2015, 10 (7):  1076-1081.  doi: 10.4103/1673-5374.160097
    Abstract ( 320 )   PDF (707KB) ( 794 )   Save

    Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent studies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, progesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-regulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.

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    Aquaporin-4 gene silencing protects injured neurons after early cerebral infarction
    Zhan-ping He, Hong Lu
    2015, 10 (7):  1082-1087.  doi: 10.4103/1673-5374.160099
    Abstract ( 264 )   PDF (2465KB) ( 530 )   Save

    Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging (DWI). We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and siRNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging (T2WI) and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema.

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    Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces
    Yun-peng Lin, Rong-cai Jiang, Jian-ning Zhang
    2015, 10 (7):  1088-1094.  doi: 10.4103/1673-5374.160100
    Abstract ( 121 )   PDF (943KB) ( 839 )   Save

    Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm (101.32 ± 11.16 kPa), 2.6 ± 0.16 atm (263.44 ± 16.21 kPa), and 3.6 ± 0.16 atm (364.77 ± 16.21 kPa), respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

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    Neurotoxicity of prenatal alcohol exposure on medullary pre-Bötzinger complex neurons in neonatal rats
    Ming-li Ji, Yun-hong Wu, Zhi-bin Qian
    2015, 10 (7):  1095-1100.  doi: 10.4103/1673-5374.160101
    Abstract ( 228 )   PDF (1051KB) ( 498 )   Save

    Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor (5-HT2AR) is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10% (v/v) throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2AR protein and mRNA levels in the pre-Bötzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2AR protein and mRNA levels.

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    Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain
    Ho-Sung Lee, Dai-In Kang, Seung Zhoo Yoon, Yeon Hee Ryu, Inhyung Lee, Hoon-Gi Kim, Byung-Cheon Lee, Ki Bog Lee
    2015, 10 (7):  1101-1106.  doi: 10.4103/1673-5374.160103
    Abstract ( 189 )   PDF (1622KB) ( 992 )   Save

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. 

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    Planning for selective amygdalohippocampectomy involving less neuronal fiber damage based on brain connectivity using tractography
    Seung-Hak Lee, Mansu Kim, Hyunjin Park
    2015, 10 (7):  1107-1112.  doi: 10.4103/1673-5374.160104
    Abstract ( 258 )   PDF (628KB) ( 984 )   Save

    Temporal lobe resection is an important treatment option for epilepsy that involves removal of potentially essential brain regions. Selective amygdalohippocampectomy is a widely performed temporal lobe surgery. We suggest starting the incision for selective amygdalohippocampectomy at the inferior temporal gyrus based on diffusion magnetic resonance imaging (MRI) tractography. Diffusion MRI data from 20 normal participants were obtained from Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org). A tractography algorithm was applied to extract neuronal fiber information for the temporal lobe, hippocampus, and amygdala. Fiber information was analyzed in terms of the number of fibers and betweenness centrality. Distances between starting incisions and surgical target regions were also considered to explore the length of the surgical path. Middle temporal and superior temporal gyrus regions have higher connectivity values than the inferior temporal gyrus and thus are not good candidates for starting the incision. The distances between inferior temporal gyrus and surgical target regions were shorter than those between middle temporal gyrus and target regions. Thus, the inferior temporal gyrus is a good candidate for starting the incision. Starting the incision from the inferior temporal gyrus would spare the important (in terms of betweenness centrality values) middle region and shorten the distance to the target regions of the hippocampus and amygdala.

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    The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein
    Tae-Beom Ahn, Beom S. Jeon
    2015, 10 (7):  1113-1119.  doi: 10.4103/1673-5374.160106
    Abstract ( 278 )   PDF (653KB) ( 788 )   Save

    Both genetic and environmental factors are important in the pathogenesis of Parkinson’s disease. As α-synuclein is a major constituent of Lewy bodies, a pathologic hallmark of Parkinson’s disease, genetic aspects of α-synuclein is widely studied. However, the influence of dietary factors such as quercetin on α-synuclein was rarely studied. Herein we aimed to study the neuroprotective role of quercetin against various toxins affecting apoptosis, autophagy and aggresome, and the role of quercetin on α-synuclein expression. PC12 cells were pre-treated with quercetin (100, 500, 1,000 μM) and then together with various drugs such as 1-methyl-4-phenylpyridinium (MPP+; a free radical generator), 6-hydroxydopamine (6-OHDA; a free radical generator), ammonium chloride (an autophagy inhibitor), and nocodazole (an aggresome inhibitor). Cell viability was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltertazolium bromide (MTT) assay. Apoptosis was detected by annexin V-fluorescein isothiocyanate and propidium iodide through the use of fluorescence activated cell sorter. α-Synuclein expression was detected by western blot assay and immunohistochemistry. The role of α-synuclein was further studied by knocking out α-synuclein using RNA interference. Cell viability increased at lower concentrations (100 and 500 μM) of quercetin but decreased at higher concentration (1,000 μM). Quercetin exerted neuroprotective effect against MPP+, ammonium chloride and nocodazole at 100 μM. MPP+ induced apoptosis was decreased by 100 μM quercetin. Quercetin treatment increased α-synuclein expression. However, knocking out α-synuclein exerted no significant effect on cell survival. In conclusion, quercetin is neuroprotective against toxic agents via affecting various mechanisms such as apoptosis, autophagy and aggresome. Because α-synuclein expression is increased by quercetin, the role of quercetin as an environmental factor in Parkinson’s disease pathogenesis needs further investigation.

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    Necrostatin-1 protection of dopaminergic neurons
    Jing-ru Wu, Jie Wang, Sheng-kui Zhou, Long Yang, Jia-le Yin, Jun-ping Cao, Yan-bo Cheng
    2015, 10 (7):  1120-1124.  doi: 10.4103/1673-5374.160108
    Abstract ( 368 )   PDF (985KB) ( 912 )   Save

    Necroptosis is characterized by programmed necrotic cell death and autophagic activation and might be involved in the death process of dopaminergic neurons in Parkinson’s disease. We hypothesized that necrostatin-1 could block necroptosis and give protection to dopaminergic neurons. There is likely to be crosstalk between necroptosis and other cell death pathways, such as apoptosis and autophagy. PC12 cells were pretreated with necroststin-1 1 hour before exposure to 6-hydroxydopamine. We examined cell viability, mitochondrial membrane potential and expression patterns of apoptotic and necroptotic death signaling proteins. The results showed that the autophagy/lysosomal pathway is involved in the 6-hydroxydopamine-induced death process of PC12 cells. Mitochondrial disability induced overactive autophagy, increased cathepsin B expression, and diminished Bcl-2 expression. Necrostatin-1 within a certain concentration range (5–30 μM) elevated the viability of PC12 cells, stabilized mitochondrial membrane potential, inhibited excessive autophagy, reduced the expression of LC3-II and cathepsin B, and increased Bcl-2 expression. These findings suggest that necrostatin-1 exerted a protective effect against injury on dopaminergic neurons. Necrostatin-1 interacts with the apoptosis signaling pathway during this process. This pathway could be a new neuroprotective and therapeutic target in Parkinson’s disease.

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    Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects
    Zhen Zhang, Tao Sun, Jian-guo Niu, Zhen-quan He, Yang Liu, Feng Wang
    2015, 10 (7):  1125-1133.  doi: 10.4103/1673-5374.160109
    Abstract ( 343 )   PDF (2074KB) ( 921 )   Save

    Amentoflavone is a natural biflavone compound with many biological properties, including anti-inflammatory, antioxidative, and neuroprotective effects. We presumed that amentoflavone exerts a neuroprotective effect in epilepsy models. Prior to model establishment, mice were intragastrically administered 25 mg/kg amentoflavone for 3 consecutive days. Amentoflavone effectively prevented pilocarpine-induced epilepsy in a mouse kindling model, suppressed nuclear factor-κB activation and expression, inhibited excessive discharge of hippocampal neurons resulting in a reduction in epileptic seizures, shortened attack time, and diminished loss and apoptosis of hippocampal neurons. Results suggested that amentoflavone protected hippocampal neurons in epilepsy mice via anti-inflammation, antioxidation, and antiapoptosis, and then effectively prevented the occurrence of seizures.

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    Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation
    Zhong-jun Zhang1, Ya-jun Li2, Xiao-guang Liu1, Feng-xiao Huang1, Tie-jun Liu1, Dong-mei Jiang1, Xue-man Lv3, Min Luo4
    2015, 10 (7):  1134-1138.  doi: 10.4103/1673-5374.160110
    Abstract ( 269 )   PDF (796KB) ( 751 )   Save

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

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    Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration difficulties after unilateral lumbar spinal cord injury
    Wan-shu Peng, Chao Qi, Hong Zhang, Mei-ling Gao, Hong Wang, Fei Ren, Xia-qing Li
    2015, 10 (7):  1139-1146.  doi: 10.4103/1673-5374.160111
    Abstract ( 189 )   PDF (1744KB) ( 744 )   Save

    Paired immunoglobulin-like receptor B (PirB) is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of PirB on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of PirB (via immunofluorescence) in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for PirB increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, PirB was mainly distributed along neuronal and axonal membranes. PirB was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for PirB was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of PirB immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that PirB may suppress repair after injury.

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    Loss of microRNA-124 expression in neurons in the peri-lesion area in mice with spinal cord injury
    Yu Zhao, Hui Zhang, Dan Zhang, Cai-yong Yu, Xiang-hui Zhao, Fang-fang Liu, Gan-lan Bian, Gong Ju, Jian Wang
    2015, 10 (7):  1147-1152.  doi: 10.4103/1673-5374.156983
    Abstract ( 372 )   PDF (1642KB) ( 1027 )   Save

    MicroRNA-124 (miR-124) is abundantly expressed in neurons in the mammalian central nervous system, and plays critical roles in the regulation of gene expression during embryonic neurogenesis and postnatal neural differentiation. However, the expression profile of miR-124 after spinal cord injury and the underlying regulatory mechanisms are not well understood. In the present study, we examined the expression of miR-124 in mouse brain and spinal cord after spinal cord injury using in situ hybridization. Furthermore, the expression of miR-124 was examined with quantitative RT-PCR at 1, 3 and 7 days after spinal cord injury. The miR-124 expression in neurons at the site of injury was evaluated by in situ hybridization combined with NeuN immunohistochemical staining. The miR-124 was mainly expressed in neurons throughout the brain and spinal cord. The expression of miR-124 in neurons significantly decreased within 7 days after spinal cord injury. Some of the neurons in the peri-lesion area were NeuN+/miR-124−. Moreover, the neurons distal to the peri-lesion site were NeuN+/miR-124+. These findings indicate that miR-124 expression in neurons is reduced after spinal cord injury, and may reflect the severity of spinal cord injury.

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    Outcomes of bowel program in spinal cord injury patients with neurogenic bowel dysfunction
    Zuhal Ozisler, Kurtulus Koklu, Sumru Ozel, Sibel Unsal-Delialioglu
    2015, 10 (7):  1153-1158.  doi: 10.4103/1673-5374.160112
    Abstract ( 241 )   PDF (235KB) ( 930 )   Save

    In this study, we aimed to determine gastrointestinal problems associated with neurogenic bowel dysfunction in spinal cord injury patients and to assess the efficacy of bowel program on gastrointestinal problems and the severity of neurogenic bowel dysfunction. Fifty-five spinal cord injury patients were included in this study. A bowel program according to the characteristics of neurogenic bowel dysfunction was performed for each patient. Before and after bowel program, gastrointestinal problems (constipation, difficult intestinal evacuation, incontinence, abdominal pain, abdominal distension, loss of appetite, hemorrhoids, rectal bleeding and gastrointestinal induced autonomic dysreflexia) and bowel evacuation methods (digital stimulation, oral medication, suppositories, abdominal massage, Valsalva maneuver and manual evacuation) were determined. Neurogenic bowel dysfunction score was used to assess the severity of neurogenic bowel dysfunction. At least one gastrointestinal problem was identified in 44 (80%) of the 55 patients before bowel program. Constipation (56%, 31/55) and incontinence (42%, 23/55) were the most common gastrointestinal problems. Digital rectal stimulation was the most common method for bowel evacuation, both before (76%, 42/55) and after (73%, 40/55) bowel program. Oral medication, enema and manual evacuation application rates were significantly decreased and constipation, difficult intestinal evacuation, abdominal distention, and abdominal pain rates were significantly reduced after bowel program. In addition, mean neurogenic bowel dysfunction score was decreased after bowel program. An effective bowel program decreases the severity of neurogenic bowel dysfunction and reduces associated gastrointestinal problems in patients with spinal cord injury.

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    Beta-nerve growth factor promotes neurogenesis and angiogenesis during the repair of bone defects
    Wei-hui Chen, Chuan-qing Mao, Li-li Zhuo, Joo L. Ong
    2015, 10 (7):  1159-1165.  doi: 10.4103/1673-5374.160114
    Abstract ( 208 )   PDF (4966KB) ( 850 )   Save

    We previously showed that the repair of bone defects is regulated by neural and vascular signals. In the present study, we examined the effect of topically applied β-nerve growth factor (β-NGF) on neurogenesis and angiogenesis in critical-sized bone defects filled with collagen bone substitute. We created two symmetrical defects, 2.5 mm in diameter, on either side of the parietal bone of the skull, and filled them with bone substitute. Subcutaneously implanted osmotic pumps were used to infuse 10 μg β-NGF in PBS (β-NGF + PBS) into the right-hand side defect, and PBS into the left (control) defect, over the 7 days following surgery. Immunohistochemical staining and hematoxylin-eosin staining were carried out at 3, 7, 14, 21 and 28 days postoperatively. On day 7, expression of β III-tubulin was lower on the β-NGF + PBS side than on the control side, and that of neurofilament 160 was greater. On day 14, β III-tubulin and protein gene product 9.5 were greater on the β-NGF + PBS side than on the control side. Vascular endothelial growth factor expression was greater on the experimental side than the control side at 7 days, and vascular endothelial growth factor receptor 2 expression was elevated on days 14 and 21, but lower than control levels on day 28. However, no difference in the number of blood vessels was observed between sides. Our results indicate that topical application of β-NGF promoted neurogenesis, and may modulate angiogenesis by promoting nerve regeneration in collagen bone substitute-filled defects.

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    Fibrin glue repair leads to enhanced axonal elongation during early peripheral nerve regeneration in an in vivo mouse model
    Georgios Koulaxouzidis, Gernot Reim, Christian Witzel
    2015, 10 (7):  1166-1171.  doi: 10.4103/1673-5374.156992
    Abstract ( 418 )   PDF (544KB) ( 674 )   Save

    Microsurgical suturing is the gold standard of nerve coaptation. Although literature on the usefulness of fibrin glue as an alternative is becoming increasingly available, it remains contradictory. Furthermore, no data exist on how both repair methods might influence the morphological aspects (arborization; branching) of early peripheral nerve regeneration. We used the sciatic nerve transplantation model in thy-1 yellow fluorescent protein mice (YFP; n = 10). Pieces of nerve (1cm) were grafted from YFP-negative mice (n = 10) into those expressing YFP. We performed microsuture coaptations on one side and used fibrin glue for repair on the contralateral side. Seven days after grafting, the regeneration distance, the percentage of regenerating and arborizing axons, the number of branches per axon, the coaptation failure rate, the gap size at the repair site and the time needed for surgical repair were all investigated. Fibrin glue repair resulted in regenerating axons travelling further into the distal nerve. It also increased the percentage of arborizing axons. No coaptation failure was detected. Gap sizes were comparable in both groups. Fibrin glue significantly reduced surgical repair time. The increase in regeneration distance, even after the short period of time, is in line with the results of others that showed faster axonal regeneration after fibrin glue repair. The increase in arborizing axons could be another explanation for better functional and electrophysiological results after fibrin glue repair. Fibrin glue nerve coaptation seems to be a promising alternative to microsuture repair.

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    Does the ratio of the carpal tunnel inlet and outlet cross-sectional areas in the median nerve reflect carpal tunnel syndrome severity?
    Li Zhang, Aierken Rehemutula, Feng Peng, Cong Yu, Tian-bin Wang, Lin Chen
    2015, 10 (7):  1172-1176.  doi: :10.4103/1673-5374.160117
    Abstract ( 184 )   PDF (737KB) ( 775 )   Save

    Although ultrasound measurements have been used in previous studies on carpal tunnel syndrome to visualize injury to the median nerve, whether such ultrasound data can indicate the severity of carpal tunnel syndrome remains controversial. The cross-sectional areas of the median nerve at the tunnel inlet and outlet can show swelling and compression of the nerve at the carpal. We hypothesized that the ratio of the cross-sectional areas of the median nerve at the carpal tunnel inlet to outlet accurately reflects the severity of carpal tunnel syndrome. To test this, high-resolution ultrasound with a linear array transducer at 5–17 MHz was used to assess 77 patients with carpal tunnel syndrome. The results showed that the cut-off point for the inlet-to-outlet ratio was 1.14. Significant differences in the inlet-to-outlet ratio were found among patients with mild, moderate, and severe carpal tunnel syndrome. The cut-off point in the ratio of cross-sectional areas of the median nerve was 1.29 between mild and more severe (moderate and severe) carpal tunnel syndrome patients with 64.7% sensitivity and 72.7% specificity. The cut-off point in the ratio of cross-sectional areas of the median nerve was 1.52 between the moderate and severe carpal tunnel syndrome patients with 80.0% sensitivity and 64.7% specificity. These results suggest that the inlet-to-outlet ratio reflected the severity of carpal tunnel syndrome.

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