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    31 August 2016, Volume 11 Issue 8 Previous Issue    Next Issue
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    Uncoupling protein 2 in the glial response to stress: implications for neuroprotection
    Daniel T. Hass, Colin J. Barnstable
    2016, 11 (8):  1197-1200.  doi: 10.4103/1673-5374.189159
    Abstract ( 340 )   PDF (353KB) ( 890 )   Save

    Reactive oxygen species (ROS) are free radicals thought to mediate the neurotoxic effects of several neurodegenerative disorders. In the central nervous system, ROS can also trigger a phenotypic switch in both astrocytes and microglia that further aggravates neurodegeneration, termed reactive gliosis. Negative regulators of ROS, such as mitochondrial uncoupling protein 2 (UCP2) are neuroprotective factors that decrease neuron loss in models of stroke, epilepsy, and parkinsonism. However, it is unclear whether UCP2 acts purely to prevent ROS production, or also to prevent gliosis. In this review article, we discuss published evidence supporting the hypothesis that UCP2 is a neuroprotective factor both through its direct effects in decreasing mitochondrial ROS and through its effects in astrocytes and microglia. A major effect of UCP2 activation in glia is a change in the spectrum of secreted cytokines towards a more anti-in?ammatory spectrum. There are multiple mechanisms that can control the level or activity of UCP2, including a variety of metabolites and microRNAs. Understanding these mechanisms will be key to exploitingthe protective effects of UCP2 in therapies for multiple neurodegenerative conditions.

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    Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?
    Erin A. Gutilla, Oswald Steward
    2016, 11 (8):  1201-1203.  doi: 10.4103/1673-5374.189160
    Abstract ( 358 )   PDF (239KB) ( 550 )   Save

    The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN) gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST) to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown of PTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a frst look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

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    TRPV1 may increase the effectiveness of estrogen therapy on neuroprotection and neuroregeneration
    Ricardo Ramírez-Barrantes, Ivanny Marchant, Pablo Olivero
    2016, 11 (8):  1204-1207.  doi: 10.4103/1673-5374.189162
    Abstract ( 357 )   PDF (571KB) ( 507 )   Save
    Aging induces physical deterioration, loss of the blood brain barrier, neuronal loss-induced mental and neurodegenerative diseases. Hypotalamus-hypophysis-gonad axis aging precedes symptoms of menopause or andropause and is a major determinant of sensory and cognitive integrated function. Sexual steroids support important functions, exert pleiotropic effects in different sensory cells, promote regeneration, plasticity and health of the nervous system. Their diminution is associated with impaired cognitive and mental health and increased risk of neurodegenerative diseases. Then, restoring neuroendocrine axes during aging can be key to enhance brain health through neuroprotection and neuroregeneration, depending on the modulation of plasticity mechanisms. Estrogen-dependent transient receptor potential cation channel, subfamily V, member 1 (TRPV1) expression induces neuroprotection, neurogenesis and regeneration on damaged tissues. Agonists of TRPV1 can modulate neuroprotection and repair of sensitive neurons, while modulators as other cognitive enhancers may improve the survival rate, differentiation and integration of neural stem cell progenitors in functional neural network. Menopause constitutes a relevant clinical model of steroidal production decline associated with progressive cognitive and mental impairment, which allows exploring the effects of hormone therapy in health outcomes such as dysfunction of CNS. Simulating the administration of hormone therapy to virtual menopausal individuals allows assessing its hypothetical impact and sensitivity to conditions that modify the effectiveness and effciency.
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    Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery
    Jennifer M. Colón, Jorge D. Miranda
    2016, 11 (8):  1208-1211.  doi: 10.4103/1673-5374.189164
    Abstract ( 357 )   PDF (827KB) ( 503 )   Save
    Spinal cord injury (SCI) is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, in?ammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the benefcial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-in?ammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the feld.
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    Automatic counting of microglial cell activation and its applications
    Beatriz I. Gallego Collado, Pablo de Gracia
    2016, 11 (8):  1212-1215.  doi: 10.4103/1673-5374.189166
    Abstract ( 308 )   PDF (789KB) ( 600 )   Save
    Glaucoma is a multifactorial optic neuropathy characterized by the damage and death of the retinal ganglion cells. This disease results in vision loss and blindness. Any vision loss resulting from the disease cannot be restored and nowadays there is no available cure for glaucoma; however an early detection and treatment, could offer neuronal protection and avoid later serious damages to the visual function. A full understanding of the etiology of the disease will still require the contribution of many scientifc efforts. Glial activation has been observed in glaucoma, being microglial proliferation a hallmark in this neurodegenerative disease. A typical project studying these cellular changes involved in glaucoma often needs thousands of images - from several animals - covering different layers and regions of the retina. The gold standard to evaluate them is the manual count. This method requires a large amount of time from specialized personnel. It is a tedious process and prone to human error. We present here a new method to count microglial cells by using a computer algorithm. It counts in one hour the same number of images that a researcher counts in four weeks, with no loss of reliability.
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    Prospects for bone marrow cell therapy in amyotrophic lateral sclerosis: how far are we from a clinical treatment?
    Fernanda Gubert, Marcelo F. Satiago
    2016, 11 (8):  1216-1219.  doi: 10.4103/1673-5374.189167
    Abstract ( 206 )   PDF (345KB) ( 437 )   Save
    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive muscular atrophy and death within 3–5 years after its onset. Despite the signifcant advances in knowledge of ALS pathology, no effective treatment is available. Therefore, it is imperative to search for new alternatives to treat ALS. Cell therapy, especially using bone-marrow cells, has showed to be very useful to protect the neural tissue in different brain disease or traumatic lesions. In ALS, most published results show benefcial effects of the use bone marrow cells, especially mesenchymal stromal cells. However, until now, the best outcome extends animal’s lifespan by only a few weeks. It is essential to continue the search for a really effective therapy, testing different cells, routes and time-windows of administration. Studying the mechanisms that initiate and spread the degenerative process is also important to fnd out an effective therapy. Therefore, we discussed here some progresses that have been made using bone-marrow cell therapy as a therapeutic tool for ALS.
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    Volume transmission and receptor-receptor interactions in heteroreceptor complexes: understanding the role of new concepts for brain communication
    Kjell Fuxe, Dasiel O. Borroto-Escuela
    2016, 11 (8):  1220-1223.  doi: 10.4103/1673-5374.189168
    Abstract ( 301 )   PDF (526KB) ( 3879 )   Save
    The discovery of the central monoamine neurons not only demonstrated novel types of brain stem neurons forming global terminal networks all over the brain and the spinal cord, but also to a novel type of communication called volume transmission. It is a major mode of communication in the central nervous system that takes places in the extracellular ?uid and the cerebral spinal ?uid through diffusion and ?ow of molecules, like neurotransmitters and extracellular vesicles. The integration of synaptic and volume transmission takes place through allosteric receptor-receptor interactions in heteroreceptor complexes. These heterocomplexes represent major integrator centres in the plasma membrane and their protomers act as moonlighting proteins undergoing dynamic changes and their structure and function. In fact, we propose that the molecular bases of learning and memory can be based on the reorganization of multiples homo and heteroreceptor complexes into novel assembles in the post-junctional membranes of synapses.
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    Guiding the migration of grafted cells to promote axon regeneration
    Xiao-bing Yuan, Christopher Haas, Itzhak Fischer
    2016, 11 (8):  1224-1225.  doi: 10.4103/1673-5374.189169
    Abstract ( 188 )   PDF (530KB) ( 449 )   Save
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    Potassium channel blockers restore axonal conduction in CNS trauma and diseases
    Jessica C. Page, Riyi Shi
    2016, 11 (8):  1226-1227.  doi: 10.4103/1673-5374.189172
    Abstract ( 240 )   PDF (173KB) ( 484 )   Save
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    Ghrelin is the metabolic link connecting calorie restriction to neuroprotection
    Jacqueline A. Bayliss, Zane B. Andrews
    2016, 11 (8):  1228-1229.  doi: 10.4103/1673-5374.189171
    Abstract ( 380 )   PDF (282KB) ( 743 )   Save
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    Cell-specifc mineralocorticoid receptors: future therapeutic targets for stroke?
    Quynh N. Dinh, Grant R. Drummond, Christopher G. Sobey, Sophocles Chrissobolis
    2016, 11 (8):  1230-1231.  doi: 10.4103/1673-5374.189173
    Abstract ( 350 )   PDF (188KB) ( 440 )   Save
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    Lithium: from mood stabilizer to putative cognitive enhancer
    Adele Quartini, Angela Iannitelli, Giuseppe Bersani
    2016, 11 (8):  1234-1235.  doi: 10.4103/1673-5374.189175
    Abstract ( 361 )   PDF (311KB) ( 471 )   Save
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    Treating spinal cord injury via sustained drug delivery from calcium phosphate coatings
    Daniel J. Hellenbrand, Amgad Hanna
    2016, 11 (8):  1236-1237.  doi: 10.4103/1673-5374.189176
    Abstract ( 224 )   PDF (346KB) ( 467 )   Save
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    Beyond reproduction: the role of progesterone in neuropathic pain after spinal cord injury
    Susana Laura González, María Florencia Coronel
    2016, 11 (8):  1238-1240.  doi: 10.4103/1673-5374.189177
    Abstract ( 165 )   PDF (297KB) ( 501 )   Save
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    Differing roles for parvalbumin neurons after nerve injury
    Peter J. Shortland, David A. Mahns
    2016, 11 (8):  1241-1242.  doi: 10.4103/1673-5374.189179
    Abstract ( 317 )   PDF (447KB) ( 504 )   Save
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    Melanopsin expression is an indicator of the well-being of melanopsin-expressing retinal ganglion cells but not of their viability
    Marta Agudo-Barriuso, Francisco M. Nadal-Nicolás, María H. Madeira, Giuseppe Rovere, Beatriz Vidal-Villegas, Manuel Vidal-Sanz
    2016, 11 (8):  1243-1244.  doi: 10.4103/1673-5374.189182
    Abstract ( 348 )   PDF (1557KB) ( 477 )   Save
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    A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury: a molecular dynamics simulation study
    Anand Kumar Pandey, Swet Chand Shukla, Pallab Bhattacharya, Ranjana Patnaik
    2016, 11 (8):  1247-1253.  doi: 10.4103/1673-5374.189186
    Abstract ( 308 )   PDF (1771KB) ( 564 )   Save
    The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies. This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities. μ-Calpain, a calcium ion activated intracellular cysteine protease causes serious cellular insult, leading to cell death in various pathological conditions including hypoxia and ischemic stroke. Hence, it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury. As the inhibitory property of μ-calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with μ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the μ-calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quercetin with μ-calpain. Affnity binding of quercetin with μ-calpain had a value of –28.73 kJ/mol and a Ki value of 35.87 μM that may be a probable reason to lead to altered functioning of μ-calpain. Hence, quercetin was found to be an inhibitor of μ-calpain which might have a possible therapeutic role in hypoxic injury.
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    Glucose metabolism and neurogenesis in the gerbil hippocampus after transient forebrain ischemia
    Dae Young Yoo, Kwon Young Lee, Joon Ha Park, Hyo Young Jung, Jong Whi Kim, Yeo Sung Yoon, Moo-Ho Won, Jung Hoon Choi, In Koo Hwang
    2016, 11 (8):  1254-1259.  doi: 10.4103/1673-5374.189189
    Abstract ( 502 )   PDF (2945KB) ( 848 )   Save
    Recent evidence exists that glucose transporter 3 (GLUT3) plays an important role in the energy metabolism in the brain. Most previous studies have been conducted using focal or hypoxic ischemia models and have focused on changes in GLUT3 expression based on protein and mRNA levels rather than tissue levels. In the present study, we observed change in GLUT3 immunoreactivity in the adult gerbil hippocampus at various time points after 5 minutes of transient forebrain ischemia. In the sham-operated group, GLUT3 immunoreactivity in the hippocampal CA1 region was weak, in the pyramidal cells of the CA1 region increased in a time-dependent fashion 24 hours after ischemia, and in the hippocampal CA1 region decreased signifcantly between 2 and 5 days after ischemia, with high level of GLUT3 immunoreactivity observed in the CA1 region 10 days after ischemia. In a double immuno?uorescence study using GLUT3 and glial-fbrillary acidic protein (GFAP), we observed strong GLUT3 immunoreactivity in the astrocytes. GLUT3 immunoreactivity increased after ischemia and peaked 7 days in the dentate gyrus after ischemia/reperfusion. In a double immuno?uorescence study using GLUT3 and doublecortin (DCX), we observed low level of GLUT3 immunoreactivity in the differentiated neuroblasts of the subgranular zone of the dentate gyrus after ischemia. GLUT3 immunoreactivity in the sham-operated group was mainly detected in the subgranular zone of the dentate gyrus. These results suggest that the increase in GLUT3 immunoreactivity may be a compensatory mechanism to modulate glucose level in the hippocampal CA1 region and to promote adult neurogenesis in the dentate gyrus.
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    Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury
    Guo-zhu Sun, Fen-fei Gao, Zong-mao Zhao, Hai Sun, Wei Xu, Li-wei Wu, Yong-chang He
    2016, 11 (8):  1260-1266.  doi: 10.4103/1673-5374.189190
    Abstract ( 318 )   PDF (1236KB) ( 525 )   Save
    Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated, mitochondrial, and endoplasmic reticulum stress pathways. Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury, and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra. Here, we established rat models of ?uid percussion-induced traumatic brain injury and found that protein expression of caspase-12, caspase-3 and the endoplasmic reticulum stress marker 78 kDa glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours. Furthermore, numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury. These fndings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra, and may play an important role in the pathophysiology of secondary brain injury.
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    Safety of different acupuncture manipulations for posterior circulation ischemia with vertigo
    Yan Wen, Chao Zhang, Xiao-feng Zhao, Shi-zhe Deng, Si He, Ling-hui Huang, Guang Tian, Zhi-hong Meng
    2016, 11 (8):  1267-1273.  doi: 10.4103/1673-5374.189191
    Abstract ( 331 )   PDF (398KB) ( 515 )   Save
    Acupuncture at Fengchi (GB20) in the posterior neck improves vertigo. However, subarachnoid hemorrhage and spinal epidural hematoma have been reported to occur after acupuncture in the posterior neck. Therefore, in the present study, we assessed the safety of acupuncture at Fengchi. Laboratory tests and adverse event reports were used to evaluate the safety of different acupuncture manipulations for the treatment of posterior circulation ischemia with vertigo. A total of 136 patients were randomly assigned to four groups. Verum acupuncture was conducted with different needle insertion directions (contralateral paropia or prominentia laryngea) and different needle twisting frequencies (60 or 120 times/minute) at Fengchi and matching acupoints (for example, Zhongwan [CV12], Qihai [CV6], Zusanli [ST36], and Fenglong [ST40]). The patients received 14 treatments over 3–4 weeks. Routine blood analysis, hepatic and renal function tests, urine and feces tests and electrocardiography were performed before the frst treatment session and after the fnal session. Adverse events were recorded after every session. Of the 136 patients, 120 completed the study. There were no signifcant differences between pretreatment and posttreatment test results in any of the groups. Only fve patients suffered from minor adverse events (needling pain, slight hematoma and transient chest tightness). No serious adverse events were found. Our results indicate that a 14-session course of needling at Fengchi is relatively safe for treating posterior circulation ischemia with vertigo.
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    Difference in cortical activation during use of volar and dorsal hand splints: a functional magnetic resonance imaging study
    Sung Ho Jang, Woo Hyuk Jang
    2016, 11 (8):  1274-1277.  doi: 10.4103/1673-5374.189192
    Abstract ( 365 )   PDF (399KB) ( 460 )   Save
    There have been no studies reported on the difference in cortical activation during use of volar and dorsal hand splints. We attempted to investigate the difference in cortical activation in the somatosensory cortical area during use of volar and dorsal hand splints by functional magnetic resonance imaging (fMRI). We recruited eight healthy volunteers. fMRI was performed while subjects who were ftted with volar or dorsal hand splints performed grasp-release movements. Regions of interest were placed on the primary motor cortex (M1), primary somatosensory cortex (S1), posterior parietal cortex (PPC), and secondary somatosensory cortex (S2). Results of group analysis of fMRI data showed that the total numbers of activated voxels in all ROIs were significantly higher during use of volar hand splint (3,376) compared with that (1,416) during use of dorsal hand splint. In each ROI, use of volar hand splint induced greater activation in all ROIs (M1: 1,748, S1 :1,455, PPC: 23, and S2: 150) compared with use of dorsal hand splint (M1: 783, S1: 625, PPC: 0, and S2: 8). The peak activated value was also higher during use of volar hand splint (t-value: 17.29) compared with that during use of dorsal hand splint (t-value: 13.11). Taken together, use of volar hand splint induced greater cortical activation relevant to somatosensory function than use of dorsal hand splint. This result would be important for the physiatrist and therapist to apply appropriate somatosensory input in patients with brain injury.
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    Dynamic expression of nerve growth factor and its receptor TrkA after subarachnoid hemorrhage in rat brain
    Jin-ning Song, Zun-wei Liu, Long Sui, Bin-fei Zhang, Yong-lin Zhao, Xu-dong Ma, Hua Gu
    2016, 11 (8):  1278-1284.  doi: 10.4103/1673-5374.189193
    Abstract ( 301 )   PDF (2163KB) ( 681 )   Save
    Delayed ischemic neurologic defcit after subarachnoid hemorrhage results from loss of neural cells. Nerve growth factor and its receptor TrkA may promote regeneration of neural cells, but their expression after subarachnoid hemorrhage remains unclear. In the present study, a rat model of subarachnoid hemorrhage was established using two injections of autologous blood into the cistern magna. Immunohistochemical staining suggested that the expression of nerve growth factor and TrkA in the cerebral cortex and brainstem increased at 6 hours, peaked at 12 hours and decreased 1 day after induction of subarachnoid hemorrhage, whereas the expression in the hippocampus increased at 6 hours, peaked on day 1, and decreased 3 days later. Compared with those for the rats in the sham and saline groups, neurobehavioral scores decreased signifcantly 12 hours and 3 days after subarachnoid hemorrhage (P < 0.05). These results suggest that the expression of nerve growth factor and its receptor TrkA is dynamically changed in the rat brain and may thus participate in neuronal survival and nerve regeneration after subarachnoid hemorrhage.
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    Protective mechanisms of microRNA-27a against oxygen-glucose deprivation-induced injuries in hippocampal neurons
    Qun Cai, Ting Wang, Wen-jie Yang, Xing Fen
    2016, 11 (8):  1285-1292.  doi: 10.4103/1673-5374.189194
    Abstract ( 285 )   PDF (841KB) ( 827 )   Save

    Hypoxic injuries during fetal distress have been shown to cause reduced expression of microRNA-27a (miR-27a), which regulates sensitivity of cortical neurons to apoptosis. We hypothesized that miR-27a overexpression attenuates hypoxia- and ischemia-induced neuronal apoptosis by regulating FOXO1, an important transcription factor for regulating the oxidative stress response. miR-27a mimic was transfected into hippocampal neurons to overexpress miR-27a. Results showed increased hippocampal neuronal viability and decreased caspase-3 expression. The luciferase reporter gene system demonstrated that miR-27a directly binded to FOXO1 3′UTR in hippocampal neurons and inhibited FOXO1 expression, suggesting that FOXO1 was the target gene for miR-27a. These fndings confrm that miR-27a protects hippocampal neurons against oxygen-glucose deprivation-induced injuries. The mechanism might be mediated by modulation of FOXO1 and apoptosis-related gene caspase-3 expression.

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    miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy
    Gang Li, Qing-shan Li, Wen-bin Li, Jian Wei, Wen-kai Chang, Zhi Chen, Hu-yun Qiao, Ying-wei Jia, Jiang-hua Tian, Bing-sheng Liang
    2016, 11 (8):  1293-1303.  doi: 10.4103/1673-5374.189195
    Abstract ( 369 )   PDF (4454KB) ( 920 )   Save
    Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle) and a typical fast muscle (tibialis anterior muscle) at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e) could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the fnal targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation). Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.
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    Curcumin upregulates S100 expression and improves regeneration of the sciatic nerve following its complete amputation in mice
    Guo-min Liu, Kun Xu, Juan Li, Yun-gang Luo
    2016, 11 (8):  1304-1311.  doi: 10.4103/1673-5374.189196
    Abstract ( 331 )   PDF (1884KB) ( 647 )   Save
    The repair of peripheral nerve injury after complete amputation is diffcult, and even with anastomosis, the rapid recovery of nerve function remains challenging. Curcumin, extracted from plants of the genus Curcuma, has been shown to have anti-oxidant and anti-in?ammatory properties and to improve sciatic nerve crush injury in rats. Here, we determined whether curcumin had neuroprotective effects following complete peripheral nerve amputation injury. BALB/c mice underwent complete sciatic nerve amputation, followed by an immediate epineurium anastomosis. Mice were intragastrically administered curcumin at doses of 40 (high), 20 (moderate), and 10 mg/kg/d (low) for 1 week. We found that myelin in the mice of the high- and moderate-dose curcumin groups appeared with regular shape, uniform thickness, clear boundary, and little hyperplasia surrounding the myelin. High and moderate doses of curcumin markedly improved both action potential amplitude of the sciatic nerves and the conduction velocity of the corresponding motor neurons, and upregulated mRNA and protein expression of S100, a marker for Schwann cell proliferation, in L4–6 spinal cord segments. These results suggest that curcumin is effective in promoting the repair of complete sciatic nerve amputation injury and that the underlying mechanism may be associated with upregulation of S100 expression.
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    Antioxidative mechanism of Lycium barbarum polysaccharides promotes repair and regeneration following cavernous nerve injury
    Zhan-kui Zhao, Hong-lian Yu, Bo Liu, Hui Wang, Qiong Luo, Xie-gang Ding
    2016, 11 (8):  1312-1321.  doi: 10.4103/1673-5374.189197
    Abstract ( 412 )   PDF (2244KB) ( 792 )   Save
    Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties. We hypothesized that these polysaccharides resist oxidative stress-induced neuronal damage following cavernous nerve injury. In this study, rat models were intragastrically administered Lycium barbarum polysaccharides for 2 weeks at 1, 7, and 14 days after cavernous nerve injury. Serum superoxide dismutase and glutathione peroxidase activities signifcantly increased at 1 and 2 weeks post-injury. Serum malondialdehyde levels decreased at 2 and 4 weeks. At 12 weeks, peak intracavernous pressure, the number of myelinated axons and nicotinamide adenine dinucleotide phosphate-diaphorase-positive nerve fbers, levels of phospho-endothelial nitric oxide synthase protein and 3-nitrotyrosine were higher in rats administered at 1 day post-injury compared with rats administered at 7 and 14 days post-injury. These fndings suggest that application of Lycium barbarum polysaccharides following cavernous nerve crush injury effectively promotes nerve regeneration and erectile functional recovery. This neuroregenerative effect was most effective in rats orally administered Lycium barbarum polysaccharides at 1 day after cavernous nerve crush injury.
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    Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models
    Ya-jun Li, Bao-lin Zhao, Hao-ze Lv, Zhi-gang Qin, Min Luo
    2016, 11 (8):  1322-1326.  doi: 10.4103/1673-5374.189198
    Abstract ( 297 )   PDF (790KB) ( 555 )   Save

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These fndings confrm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

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    Rebuilding motor function of the spinal cord based on functional electrical stimulation
    Xiao-yan Shen, Wei Du, Wei Huang, Yi Chen
    2016, 11 (8):  1327-1332.  doi: 10.4103/1673-5374.189199
    Abstract ( 336 )   PDF (1480KB) ( 627 )   Save
    Rebuilding the damaged motor function caused by spinal cord injury is one of the most serious challenges in clinical neuroscience. The function of the neural pathway under the damaged sites can be rebuilt using functional electrical stimulation technology. In this study, the locations of motor function sites in the lumbosacral spinal cord were determined with functional electrical stimulation technology. A three-dimensional map of the lumbosacral spinal cord comprising the relationship between the motor function sites and the corresponding muscle was drawn. Based on the individual experimental parameters and normalized coordinates of the motor function sites, the motor function sites that control a certain muscle were calculated. Phasing pulse sequences were delivered to the determined motor function sites in the spinal cord and hip extension, hip ?exion, ankle plantar?exion, and ankle dorsi?exion movements were successfully achieved. The results show that the map of the spinal cord motor function sites was valid. This map can provide guidance for the selection of electrical stimulation sites during the rebuilding of motor function after spinal cord injury.
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    Association between chromosomal aberration of COX8C and tethered spinal cord syndrome: array-based comparative genomic hybridization analysis
    Qiu-jiong Zhao, Shao-cong Bai, Cheng Cheng, Ben-zhang Tao, Le-kai Wang, Shuang Liang, Ling Yin, Xing-yi Hang, Ai-jia Shang
    2016, 11 (8):  1333-1338.  doi: 10.4103/1673-5374.189200
    Abstract ( 313 )   PDF (1327KB) ( 555 )   Save
    Copy number variations have been found in patients with neural tube abnormalities. In this study, we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents. Of eight copy number variations, four were non-polymorphic. These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes, and microcephaly. Gene function enrichment analysis revealed that COX8C, a gene associated with metabolic disorders of the nervous system, was located in the copy number variation region of Patient 1. Our results indicate that array-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome. Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease.
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    No synergism between bis(propyl)-cognitin and rasagiline on protecting dopaminergic neurons in Parkinson’s disease mice
    Cheng-you Zheng, Bao-jian Guo, Wei Cai, Wei Cui, Shing-hung Mak, Yu-qiang Wang, Simon Ming-yuen Lee, Yi-fan Han, Zai-jun Zhang
    2016, 11 (8):  1339-1346.  doi: 10.4103/1673-5374.189201
    Abstract ( 309 )   PDF (1158KB) ( 471 )   Save
    Rasagiline, a monoamine oxidase-B inhibitor, and bis(propyl)-cognitin (B3C), a novel dimer are reported to be neuroprotective. Herein, the synergistical neuroprotection produced by rasagiline and B3C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice of Parkinsonism. By using neurobehavioural tests, high-performance liquid chromatography and western blot assay, we showed that B3C at 0.3 mg/kg, rasagiline at 0.02 mg/kg, as well as co-treatment with B3C and rasagiline prevented MPTP-induced behavioural abnormities, increased the concentrations of dopamine and its metabolites in the striatum, and up-regulated the expression of tyrosine hydroxylase in the substantia nigra. However, the neuroprotective effects of co-treatment were not signifcantly improved when compared with those of B3C or rasagiline alone. Collectively, we have demonstrated that B3C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.
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    Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy: a meta-analysis of 16 randomized controlled trials
    Bing Pang, Tian-yu Zhao, Lin-hua Zhao, Fang Wan, Ru Ye, Qiang Zhou, Feng Tian, Xiao-lin Tong
    2016, 11 (8):  1347-1358.  doi: 10.4103/1673-5374.189202
    Abstract ( 407 )   PDF (2884KB) ( 895 )   Save
    OBJECTIVE: This meta-analysis was performed to systematically assess the effcacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction (HGWWD) for treating diabetic peripheral neuropathy. DATA SOURCES: Six electronic databases, including the Cochrane Library, MEDLINE database, Chinese Biomedical Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journals Database, and the Wanfang Database, were search ed on the internet for randomized controlled trials published up until 1 December 2015. The search terms included “Chinese herbal medicine”, “diabetic peripheral neuropathy” and “randomized controlled trials” in Chinese and in English. DATA SELECTION: We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group, without restriction for the control group. We assessed literature quality in accordance with the Cochrane Review Handbook. A random or a fxed effects model was used to analyze outcomes using RevMan 5.2 software. OUTCOME MEASURES: The primary outcomes were changes in symptoms and nerve conduction velocities. The secondary outcomes were fasting blood glucose and hemorheological indexes. RESULTS: Sixteen randomized controlled trials, with a total of 1,173 patients, were included. Meta-analysis revealed that the effcacy of HGWWD for diabetic peripheral neuropathy was signifcantly superior compared with the control treatment (i.e., control group) (risk ratio = 0.36, 95% confdence interval (CI): 0.29–0.46, Z =8.33, P < 0.00001) Compared with the control group, there was an increase in median motor nerve conduction velocity (mean difference (MD) = 3.46, 95%CI: 1.88–5.04, Z = 4.30, P < 0.01) and median sensory nerve conduction velocity (MD = 3.30, 95%CI: 2.04–4.56, Z = 5.14, P < 0.01). There was also an increase in peroneal motor nerve conduction velocity (MD = 3.22, 95%CI: 2.45–3.98, Z = 8.21, P < 0.01) and peroneal sensory nerve conduction velocity (MD = 3.05, 95%CI: 2.01–4.09, Z = 5.75, P < 0.01) in the treatment groups. No signifcant difference in fasting blood glucose was found between the treatment groups and the control groups (MD = ?0.12, 95%CI: ?0.42–0.19, Z = 0.76, P = 0.45). Plasma viscosity was signifcantly decreased after treatment (MD = ?0.11, 95%CI: ?0.21 to ?0.02, Z = 2.30, P = 0.02). No signifcant difference in fbrinogen was detectable (MD = ?0.53, 95%CI: ?1.28– 0.22, Z = 1.38, P = 0.17). Four trials reported that treatment groups experienced no adverse reactions. Adverse events were not mentioned in the other 12 trials. No trial reported the incidence of complications, quality of life outcomes, or health economics. CONCLUSION: HGWWD treatment improves diabetic neurologic symptoms and ameliorates nerve conduction velocities. Our study suggests that HGWWD may have signifcant therapeutic effcacy for the treatment of diabetic peripheral neuropathy. However, the methodological quality of the randomized controlled trials was generally low. Larger and better-designed randomized controlled trials are required to more reliably assess the clinical effectiveness of HGWWD.
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