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    30 November 2016, Volume 11 Issue 11 Previous Issue    Next Issue
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    Methods for the analysis of neuronal plasticity and brain connectivity during neurological recovery
    Eduardo H. Sanchez-Mendoza, Tayana Silva de Carvalho, Dirk M. Hermann
    2016, 11 (11):  1701-1703.  doi: 10.4103/1673-5374.194704
    Abstract ( 293 )   PDF (478KB) ( 434 )   Save
    The study of neuronal plasticity under pathological conditions is now a major point of focus on the feld of neurological recovery. Afer the repeated failure of acute neuroprotection strategies for stroke treatment, the design of studies aimed at promoting the reconstruction of neuronal networks has become essential. Methods for the delivery of therapeutic agents on a steady dosage, thus preventing pharmacological peaks or excessive manipulation of experimental animals, are thus required. Additionally, methods that allow the visualization of neurological remodeling processes are fundamental to the understanding of how a therapeutic agent exerts its function. Here we describe how the use of miniosmotic pumps for the steady delivery of such agents, together with tract tracer injections, can be combined to unveil important information on how the brain changes afer stroke and how therapeutic agents promote brain remodeling recovery.
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    Applicability of tooth derived stem cells in neural regeneration
    Ludovica Parisi, Edoardo Manfredi
    2016, 11 (11):  1704-1707.  doi: 10.4103/1673-5374.194705
    Abstract ( 355 )   PDF (413KB) ( 574 )   Save
    Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and ofen to the development of a scar which constitutes a mechanical barrier for the regeneration. Regarding these aspects, many e?orts have been done in the research of a cell component that combined with sca?olds and growth factors could be suitable for nervous regeneration in regenerative medicine approaches. Autologous mesenchymal stem cells represent nowadays the ideal candidate for this aim, thank to their multipotency and to their amount inside adult tissues. However, issues in their harvesting, through the use of invasive techniques, and problems involved in their ageing, require the research of new autologous sources. To this purpose, the recent discovery of a stem cells component in teeth, and which derive from neural crest cells, has came to the light the possibility of using dental stem cells in nervous system regeneration. In this work, in order to give guidelines on the use of dental stem cells for neural regeneration, we brie?y introduce the concepts of regeneration and regenerative medicine, we then focus the attention on odontogenesis, which involves the formation and the presence of a stem component in di?erent parts of teeth, and fnally we describe some experimental approaches which are exploiting dental stem cells for neural studies.
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    The status of Nrf2-based therapeutics: current perspectives and future prospects
    Irina G. Gazaryan, Bobby Tomas
    2016, 11 (11):  1708-1711.  doi: 10.4103/1673-5374.194706
    Abstract ( 345 )   PDF (542KB) ( 743 )   Save
    This mini-review presents the authors’ vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and in particular, via disruption of Nrf2-Keap1 interaction. Tere are two opposite “chemical” mechanisms underlying such activation: the frst one is a non-specifc covalent modifcation of Keap1 thiols, resulting in side e?ects of varied severity, and the second one is the shif of the Nrf2-Kelch-like ECH associated protein-1 (Keap1) binding equilibrium in the presence of a competitive and chemically benign displacement agent. At this point, no displacement activators exhibit sufcient biological activity in comparison with common Nrf2 activators working via Keap1 thiol modifcation. Hence, the hope in therapeutics is now linked to the FDA approved dimethylfumarate, whose derivative, monomethylfumarate, as we demonstrated recently, is much less toxic but equally biologically potent and an ideal candidate for clinical trials right now. A newly emerging player is a nuclear inhibitor of Nrf2, BTB domain and CNC homolog 1 (Bach1). Te commercially developed Bach1 inhibitors are currently under investigation in our laboratory showing promising results. In our viewpoint, the perfect future drug will present the combination of a displacement activator and Bach1 inhibitor to insure safety and efciency of Nrf2 activation.
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    Six psychotropics for pre-symptomatic & early Alzheimer’s (MCI), Parkinson’s, and Huntington’s disease modifcation
    Edward C. Lauterbach
    2016, 11 (11):  1712-1726.  doi: 10.4103/1673-5374.194708
    Abstract ( 393 )   PDF (1077KB) ( 511 )   Save
    The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modifcation in NDDs may be promising and can spare regulatory barriers. Te literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious fndings follow. Mild cognitive impairment (MCI) phase of AD: salutary human randomized controlled trial fndings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD: human epidemiological data indicate that lithium reduces AD risk. Animal model studies (AMS) reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD: valproate AMS fndings show promise. Pre-symptomatic PD: lithium and valproate AMS fndings are encouraging. Early HD: uncontrolled clinical data indicate non-progression with lithium, ?uoxetine, donepezil, and memantine. Pre-symptomatic HD: lithium and valproate are auspicious in AMS. Many other promising fndings awaiting replication (valproate in MCI; lithium, valproate, ?uoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, ?uoxetine in pre-symptomatic PD; donepezil in early HD; lithium, ?uoxetine, memantine in pre-symptomatic HD) are reviewed. Dose- and stage-dependent e?ects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.
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    Neuroin?ammation, neurodegeneration and regeneration in multiple sclerosis: intercorrelated manifestations of the immune response
    Tatiana Koudriavtseva, Caterina Mainero
    2016, 11 (11):  1727-1730.  doi: 10.4103/1673-5374.194804
    Abstract ( 291 )   PDF (327KB) ( 473 )   Save
    Multiple sclerosis (MS) is a chronic immune-mediated in?ammatory-demyelinating disorder of the central nervous system, with a strong neurodegenerative component. Te question whether neurodegeneration in MS is independent or related to neuroin?ammation has been long debated, but not yet fully clarifed. Furthermore, little is still known on how neuroin?ammation and neurodegeneration in MS are related to potential regenerative processes. In this perspective, we brie?y discuss main clinical, pathological and experimental evidence on the relationship between neuroin?ammation and neurodegeneration in MS, and on their connection with regeneration. We discuss that these processes in MS might represent intercorrelated manifestations of the immune response, especially of the innate immunity.
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    Targeting neuronal nitric oxide synthase as a valuable strategy for the therapy of neurological disorders
    Cristina Maccallini, Rosa Amoroso
    2016, 11 (11):  1731-1734.  doi: 10.4103/1673-5374.194707
    Abstract ( 245 )   PDF (373KB) ( 477 )   Save
    The management of neurological disorders have huge and increasing human and economic costs. Despite this, there is a scarcity of effective therapeutics, and there is an extreme urgency for new and real treatments. In this short review we analyze some promising advancements in the search of new bioactive molecules targeting neuronal nitric oxide synthase (nNOS), an enzyme deputed to the biosynthesis of nitric oxide (NO). In di?erent conditions of neuronal damages, this molecule is overproduced, contributing to the pathogenesis and progression of neuronal diseases. Two main approaches to modulate nNOS are discussed: a frst one consisting in the direct inhibition of the enzyme by means of small organic molecules, which can be also active against other di?erent targets involved in such diseases. A second section is dedicated to molecules able to prevent the formation of the ternary complex N-methyl-D-aspartate (NMDA)- type glutamate receptors, postsynaptic density-95 (PSD95) protein-nNOS, which is necessary to activate the latter for the biosynthesis of NO.
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    The Epigenome as a therapeutic target for Parkinson’s disease
    Shane V. Hegarty, Aideen M. Sullivan, Gerard W. O’Keeffe
    2016, 11 (11):  1735-1738.  doi: 10.4103/1673-5374.194803
    Abstract ( 292 )   PDF (398KB) ( 680 )   Save
    Parkinson’s disease (PD) is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their e?ectiveness wear o? over time and their prolonged use leads to disabling side-e?ects in PD patients. Tere is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. Tis article frst discusses the present evidence implicating global, and dopaminergic neuron-specifc, alterations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes that mediate this process are attractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective e?ects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential.
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    Anti-in?ammatory properties of the glial scar
    Tarsis F. Gesteira, Yvette M. Coulson-Tomas, Vivien J. Coulson-Tomas
    2016, 11 (11):  1742-1743.  doi: 10.4103/1673-5374.194710
    Abstract ( 245 )   PDF (143KB) ( 437 )   Save
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    Neuroprotection by salubrinal treatment in global cerebral ischemia
    Berta Anuncibay-Soto, María Santos-Galdiano, Arsenio Fernández-López
    2016, 11 (11):  1744-1745.  doi: 10.4103/1673-5374.194711
    Abstract ( 338 )   PDF (208KB) ( 466 )   Save
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    Adult neurogenesis and in vivo reprogramming: combining strategies for endogenous brain repair
    Kathryn S. Jones, Bronwen Connor
    2016, 11 (11):  1748-1749.  doi: 10.4103/1673-5374.194712
    Abstract ( 160 )   PDF (149KB) ( 405 )   Save
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    Pretreatment of ca?eine leads to partial neuroprotection in MPTP model of Parkinson’s disease
    Puneet Bagga, Anant B. Patel
    2016, 11 (11):  1750-1751.  doi: 10.4103/1673-5374.194716
    Abstract ( 270 )   PDF (149KB) ( 733 )   Save
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    Targeting lysophospholipid signaling as a therapeutic approach towards improved peripheral nerve regeneration
    Fabian Szepanowski, Bernd C. Kieseier
    2016, 11 (11):  1754-1755.  doi: 10.4103/1673-5374.194720
    Abstract ( 161 )   PDF (361KB) ( 529 )   Save
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    HSP70 cleavage-induced photoreceptor cell death caused by N-methyl-N-nitrosourea
    Yoshiki Koriyama, Ayako Furukawa
    2016, 11 (11):  1758-1759.  doi: 10.4103/1673-5374.194721
    Abstract ( 300 )   PDF (567KB) ( 649 )   Save
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    Chaperoning glucocerebrosidase: a therapeutic strategy for both Gaucher disease and Parkinsonism
    Benjamin McMahon, Elma Aflaki, Ellen Sidransky
    2016, 11 (11):  1760-1761.  doi: 10.4103/1673-5374.194717
    Abstract ( 508 )   PDF (141KB) ( 462 )   Save
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    Spinal cord injury: potential neuroprotective therapy based on neural-derived peptides
    Elisa García, José Mondragón-Caso, Antonio Ibarra
    2016, 11 (11):  1762-1763.  doi: 10.4103/1673-5374.194718
    Abstract ( 161 )   PDF (160KB) ( 874 )   Save
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    Electrospun fbers: a guiding sca?old for research and regeneration of the spinal cord
    Nicholas J. Schaub
    2016, 11 (11):  1764-1765.  doi: 10.4103/1673-5374.194719
    Abstract ( 193 )   PDF (140KB) ( 502 )   Save
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    Effects of professional rehabilitation training on the recovery of neurological function in young stroke patients
    Chao-jin-zi Li, Xiao-xia Du, Kun Yang, Lu-ping Song, Peng-kun Li, Qiang Wang, Rong Sun, Xiao-ling Lin, Hong-yu Lu, Tong Zhang
    2016, 11 (11):  1766-1772.  doi: 10.4103/1673-5374.194746
    Abstract ( 307 )   PDF (289KB) ( 482 )   Save

    Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-aged/older stroke patients hospitalized in the Department of Neurological Rehabilitation, China Rehabilitation Research Center, Capital Medical University, China from February 2014 to May 2015. Results demonstrated that hemorrhagic stroke (59.6%) was the primary stroke type found in the young group, while ischemic stroke (60.0%) was the main type detected in the middle-aged/older group. Compared with older stroke patients, education level and incidence of hyperhomocysteinemia were higher in younger stroke patients, whereas, incidences of hypertension, diabetes, and heart disease were lower. Te average length of hospital stay was longer in the young group than in the middle-aged/older group. Te main risk factors observed in the young stroke patients were hypertension, drinking, smoking, hyperlipidemia, hyperhomocysteinemia, diabetes, previous history of stroke, and heart disease. Te most accepted rehabilitation program consisted of physiotherapy, occupational therapy, speech therapy, acupuncture and moxibustion. Average rehabilitation training time was 2.5 hours/day. Barthel Index and modifed Rankin Scale scores were increased at discharge. Six months afer discharge, the degree of occupational and economic satisfaction declined, and there were no changes in family life satisfaction. Te degrees of other life satisfaction (such as friendship) improved. Te degree of disability and functional status improved signifcantly in young stroke patients afer professional rehabilitation, but the number of patients who returned to society within 6 months afer stroke was still small.

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    NADPH oxidase 2 does not contribute to early reperfusion-associated reactive oxygen species generation following transient focal cerebral ischemia
    Yuan Zhang, Ting Wang, Ke Yang, Ji Xu, Jian-ming Wu, Wen-lan Liu
    2016, 11 (11):  1773-1778.  doi: 10.4103/1673-5374.194747
    Abstract ( 258 )   PDF (493KB) ( 539 )   Save

    Excess production of reactive oxygen species (ROS) critically contributes to occurrence of reperfusion injury, the paradoxical response of ischemic brain tissue to restoration of cerebral blood ?ow. However, the enzymatic sources of ROS generation remain to be unclear. Tis study examined Nox2-containing NADPH oxidase (Nox2) expression and its activity in ischemic brain tissue following post-ischemic reperfusion to clarify the mechanism of enzymatic reaction of ROS. Male Sprague-Dawley rats were subjected to 90-minute middle cerebral artery occlusion, followed by 3 or 22.5 hours of reperfusion. Quantitative reverse transcriptase PCR and western blot assay were performed to measure mRNA and protein expression of Nox2. Lucigenin ?uorescence assays were performed to assess Nox activity. Our data showed that Nox2 mRNA and protein expression levels were signifcantly increased (3.7-fold for mRNA and 3.6-fold for protein) in ischemic brain tissue at 22.5 hours but not at 3 hours following post-ischemic reperfusion. Similar results were obtained for the changes of NADPH oxidase activity in ischemic cerebral tissue at the two reperfusion time points. Our results suggest that Nox2 may not contribute to the early burst of reperfusion-related ROS generation, but is rather an important source of ROS generation during prolonged reperfusion.

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    Protective effect of ginkgo proanthocyanidins against cerebral ischemia/reperfusion injury associated with its antioxidant effects
    Wang-li Cao, Hai-bo Huang, Ling Fang, Jiang-ning Hu, Zhu-ming Jin, Ru-wei Wang
    2016, 11 (11):  1779-1783.  doi: 10.4103/1673-5374.194722
    Abstract ( 247 )   PDF (894KB) ( 495 )   Save

    Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proanthocyanidins (20, 40, 80 mg/kg) were intraperitoneally administered 1, 24, 48 and 72 hours before reperfusion. Results showed that ginkgo proanthocyanidins could effectively mitigate neurological disorders, shorten infarct volume, increase superoxide dismutase activity, and decrease malondialdehyde and nitric oxide contents. Simultaneously, the study on grape seed proanthocyanidins (40 mg/kg) confrmed that different sources of proanthocyanidins have a similar effect. Te neurological outcomes of ginkgo proanthocyanidins were similar to that of nimodipine in the treatment of cerebral ischemia/reperfusion injury. Our results suggest that ginkgo proanthocyanidins can effectively lessen cerebral ischemia/reperfusion injury and protect ischemic brain tissue and these effects are associated with antioxidant properties.

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    Effect of ephrin-B2 on the expressions of angiopoietin-1 and -2 afer focal cerebral ischemia/reperfusion
    Hui Xiao, Qing Huang, Jia-qi Wang, Qing-qing Deng, Wen-ping Gu
    2016, 11 (11):  1784-1789.  doi: 10.4103/1673-5374.194723
    Abstract ( 362 )   PDF (1226KB) ( 531 )   Save

    Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of focal cerebral ischemia was prepared by focal middle cerebral artery occlusion, followed by 24-hour reperfusion. Ten, ephrin-B2 protein was administered intracerebroventricularly for 3 consecutive days via a micro-osmotic pump. Western blot assay and quantitative real-time reverse transcription PCR demonstrated the expression levels of angiopoietin-1 (Ang-1) mRNA and protein in the penumbra cortex of the ephrin-B2 treated group were decreased at day 4 afer reperfusion, and increased at day 28, while the expression levels of angiopoietin-2 (Ang-2) were highly up-regulated at all time points tested. Double immuno?uorescent staining indicated that Ang-1 and Ang-2 were both expressed in vascular endothelial cells positive for CD31. Tese fndings indicate that ephrin-B2 in?uences the expressions of Ang-1 and Ang-2 during angiogenesis following transient focal cerebral ischemia.

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    Apolipoprotein E polymorphisms increase the risk of post-stroke depression
    Xue-bin Li, Jie Wang, An-ding Xu, Jian-min Huang, Lan-qing Meng, Rui-ya Huang, Jun-li Wang
    2016, 11 (11):  1790-1796.  doi: 10.4103/1673-5374.194748
    Abstract ( 354 )   PDF (485KB) ( 513 )   Save

    Recent reports have shown that apolipoprotein E (APOE) polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study (including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction) to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our fndings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. Tese results suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function afer stoke. Indeed, these fndings provide clinical data for future post-stroke depression gene interventions.

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    Neuroprotective potential of Indigofera oblongifolia leaf methanolic extract against lead acetate-induced neurotoxicity
    Saleh Al-Quraishy, Mohamed A. Dkhil, Shaimaa R. Ibrahim, Ahmed E. Abdel Moneim
    2016, 11 (11):  1797-1803.  doi: 10.4103/1673-5374.194749
    Abstract ( 255 )   PDF (1093KB) ( 801 )   Save
    Lead (Pb) is one of the most common environmental toxicants, exposure to which can cause signifcant neurotoxicity and an associated decline in brain function. Tis study investigated the possible neuroprotective role of Indigofera oblongifolia leaf methanolic extract (IOLME) against lead-induced neurotoxicity. Rats were intraperitoneally injected with lead acetate, with or without IOLME (intragastric administration for 5 days), and the neuroprotective effect of IOLME was assessed by measuring the lead concentration, redox status (lipid peroxidation, nitric oxide and glutathione), enzymatic antioxidant activities (superoxide dismutase, catalase, glutathione peroxidase and reductase), PCR assays of apoptosis markers (Bax and Bcl-2) and histopathology of the brain. Te increases in the lipid peroxidation, nitric oxide, and apoptosis, the decreases in the glutathione level and the activity of antioxidant enzymes, and the altered histology of the brain induced by lead acetate were mitigated in the brain of rats pre-treated with IOLME. Tese fndings indicate that IOLME has benefcial effects and it mitigates lead acetate-induced neurotoxicity via its antioxidant and anti-apoptotic activities.
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    Ankfy1 is dispensable for neural stem/precursor cell development
    Chao Weng, Man Ding, Lian-sheng Chang, Ming-xin Ren, Hong-feng Zhang, Zu-neng Lu, Hui Fu
    2016, 11 (11):  1804-1809.  doi: 10.4103/1673-5374.194750
    Abstract ( 285 )   PDF (912KB) ( 410 )   Save

    There are few studies on the membrane protein Ankfy1. We have found Ankfy1 is specifcally expressed in neural stem/precursor cells during early development in mice (murine). To further explore Ankfy1 function in neural development, we developed a gene knockout mouse with a mixed Balb/C and C57/BL6 genetic background. Using immuno?uorescence and in situ hybridization, neural defects were absent in mixed genetic Ankfy1 null mice during development and in adults up to 2 months old. However, Ankfy1 gene knockout mice with a pure genetic background were found to be lethal in the C57/BL6 inbred mice embryos, even afer seven generations of backcrossing. Polymerase chain reaction confrmed homozygotes were unattainable as early as embryonic day 11.5. We conclude that Ankfy1 protein is dispensable in neural stem/precursor cells, but could be critical for early embryonic murine development, depending on the genetic background.

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    Development of a 3D matrix for modeling mammalian spinal cord injury in vitro
    Juan Felipe Diaz Quiroz, Yuping Li, Conrado Aparicio, Karen Echeverri
    2016, 11 (11):  1810-1815.  doi: 10.4103/1673-5374.194751
    Abstract ( 216 )   PDF (821KB) ( 530 )   Save
    Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difculty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells afer exposure to drugs.
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    Methylprednisolone promotes recovery of neurological function afer spinal cord injury: association with Wnt/β-catenin signaling pathway activation
    Gong-biao Lu, Fu-wen Niu, Ying-chun Zhang, Lin Du, Zhi-yuan Liang, Yuan Gao, Ting-zhen Yan, Zhi-kui Nie, Kai Gao
    2016, 11 (11):  1816-1823.  doi: 10.4103/1673-5374.194753
    Abstract ( 432 )   PDF (1994KB) ( 770 )   Save
    Some studies have indicated that the Wnt/β-catenin signaling pathway is activated following spinal cord injury, and expression levels of specifc proteins, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β, are signifcantly altered. We hypothesized that methylprednisolone treatment contributes to functional recovery afer spinal cord injury by inhibiting apoptosis and activating the Wnt/β-catenin signaling pathway. In the current study, 30 mg/kg methylprednisolone was injected into rats with spinal cord injury immediately post-injury and at 1 and 2 days post-injury. Basso, Beattie, and Bresnahan scores showed that methylprednisolone treatment signifcantly promoted locomotor functional recovery between 2 and 6 weeks post-injury. Te number of surviving motor neurons increased, whereas the lesion size signifcantly decreased following methylprednisolone treatment at 7 days post-injury. Additionally, caspase-3, caspase-9, and Bax protein expression levels and the number of apoptotic cells were reduced at 3 and 7 days post-injury, while Bcl-2 levels at 7 days post-injury were higher in methylprednisolone-treated rats compared with saline-treated rats. At 3 and 7 days post-injury, methylprednisolone up-regulated expression and activation of the Wnt/β-catenin signaling pathway, including low-density lipoprotein receptor related protein-6 phosphorylation, β-catenin, and glycogen synthase kinase-3β phosphorylation. Tese results indicate that methylprednisolone-induced neuroprotection may correlate with activation of the Wnt/β-catenin signaling pathway.
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    Key genes expressed in different stages of spinal cord ischemia/reperfusion injury
    Jian-an Li, Chun-fang Zan, Peng Xia, Chang-jun Zheng, Zhi-ping Qi, Chun-xu Li, Zhi-gang Liu, Ting-ting Hou, Xiao-yu Yang
    2016, 11 (11):  1824-1829.  doi: 10.4103/1673-5374.194754
    Abstract ( 281 )   PDF (1485KB) ( 811 )   Save
    The temporal expression of microRNA afer spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. Te damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24- hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplifcation, labeling, and hybridization were used to obtain the microRNA expression profles of each group. Bioinformatics analysis confrmed four differentially expressed microRNAs (miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p) and their common target genes (Tmem69 and Cxcl10). Compared with the sham group, miR- 22-3p was continuously upregulated in all three ischemia groups but was highest in the group with no reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identifed the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.
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    Rab27a/Slp2-a complex is involved in Schwann cell myelination
    Wen-feng Su, Yun Gu, Zhong-ya Wei, Yun-tian Shen, Zi-han Jin, Ying Yuan, Xiao-song Gu, Gang Chen
    2016, 11 (11):  1830-1838.  doi: 10.4103/1673-5374.194755
    Abstract ( 238 )   PDF (2230KB) ( 870 )   Save
    Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafcking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafcking in Schwann cells. In this present study, we established a dorsal root ganglion (DRG) neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression signifcantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our fndings suggest that the Rab27a/ Slp2-a complex affects Schwann cell myelination in vitro.
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    HLA class II alleles and risk for peripheral neuropathy in type 2 diabetes patients
    Ahmad Marzban, Javad Kiani, Mehrdad Hajilooi, Hamzeh Rezaei, Zohreh Kahramfar, Ghasem Solgi
    2016, 11 (11):  1839-1844.  doi: 10.4103/1673-5374.194756
    Abstract ( 238 )   PDF (284KB) ( 510 )   Save
    The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. Tis study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. Te distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our fndings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Terefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.
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    Tissue-engineered rhesus monkey nerve grafs for the repair of long ulnar nerve defects: similar outcomes to autologous nerve grafs
    Chang-qing Jiang, Jun Hu, Jian-ping Xiang, Jia-kai Zhu, Xiao-lin Liu, Peng Luo
    2016, 11 (11):  1845-1850.  doi: 10.4103/1673-5374.194757
    Abstract ( 275 )   PDF (666KB) ( 666 )   Save
    Acellular nerve allografs can help preserve normal nerve structure and extracellular matrix composition. Tese allografs have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograf. Te graf was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry fndings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. Tere were no signifcant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neuroflaments between the experimental and control groups. However, outcome was signifcantly better in the experimental group than in the blank group. Tese fndings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. Te outcomes are similar to those obtained with autologous nerve graf.
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    Nerve growth factor protects against palmitic acid-induced injury in retinal ganglion cells
    Pan-shi Yan, Shu Tang, Hai-feng Zhang, Yuan-yuan Guo, Zhi-wen Zeng, Qiang Wen
    2016, 11 (11):  1851-1856.  doi: 10.4103/1673-5374.194758
    Abstract ( 256 )   PDF (998KB) ( 701 )   Save
    Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid (PA), a metabolic factor implicated in the development of diabetes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF signifcantly attenuated the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 (PI3K inhibitor), Akt VIII inhibitor, and PD98059 (ERK1/2 inhibitor). Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. Tese results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.
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    Cortical spreading depression-induced preconditioning in the brain
    Ping-ping Shen, Shuai Hou, Di Ma, Ming-ming Zhao, Ming-qin Zhu, Jing-dian Zhang, Liang-shu Feng, Li Cui, Jia-chun Feng
    2016, 11 (11):  1857-1864.  doi: 10.4103/1673-5374.194759
    Abstract ( 501 )   PDF (267KB) ( 566 )   Save
    Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cortical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, in?ammation, neurotropic factors, and cellular stress response. Specifcally, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the feld of neural regeneration and clinical application in the future.
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