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15 April 2017, Volume 12 Issue 4 Previous Issue    Next Issue

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Heterogeneous populations of neural stem cells contribute to myelin repair Rainer Akkermann, Felix Beyer, Patrick Küry 2017, 12 (4):  509-517.  doi: 10.4103/1673-5374.204999 Abstract ( 428 )   PDF (957KB) ( 714 )   Save be damage to this specialized lipid structure. Long-term loss of electrical insulation and of further supportive functions myelin provides to axons, as seen in demyelinating diseases such as multiple sclerosis (MS), leads to neurodegeneration and results in progressive disabilities. Multiple lines of evidence have demonstrated the increasing inability of oligodendrocyte precursor cells (OPCs) to replace lost oligodendrocytes (OLs) in order to restore lost myelin. Much research has been dedicated to reveal potential reasons for this regeneration deficit but despite promising approaches no remyelination-promoting drugs have successfully been developed yet. In addition to OPCs neural stem cells of the adult central nervous system also hold a high potential to generate myelinating OLs. There are at least two neural stem cell niches in the brain, the subventricular zone lining the lateral ventricles and the subgranular zone of the dentate gyrus, and an additional source of neural stem cells has been located in the central canal of the spinal cord. While a substantial body of literature has described their neurogenic capacity, still little is known about the oligodendrogenic potential of these cells, even if some animal studies have provided proof of their contribution to remyelination. In this review, we summarize and discuss these studies, taking into account the different niches, the heterogeneity within and between stem cell niches and present current strategies of how to promote stem cell-mediated myelin repair. Related Articles | Metrics

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Axon degeneration: make the Schwann cell great agai Keit Men Wong, Elisabetta Babetto, Bogdan Beirowski 2017, 12 (4):  518-524.  doi: 10.4103/1673-5374.205000 Abstract ( 438 )   PDF (994KB) ( 706 )   Save Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration (WD), which occurs after acute axonal injury. In the peripheral nervous system (PNS), WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system (CNS), WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well-documented that Schwann cells (SCs) have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs ‘sense’ axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro-degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent findings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss. Related Articles | Metrics

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RhoA as a target to promote neuronal survival and axon regeneration Jianli Hu, Michael E. Selzer 2017, 12 (4):  525-528.  doi: 10.4103/1673-5374.205080 Abstract ( 397 )   PDF (699KB) ( 419 )   Save Paralysis following spinal cord injury (SCI) is due to failure of axonal regeneration. It is believed that the capacities of neurons to regrow their axons are due partly to their intrinsic characteristics, which in turn are greatly influenced by several types of inhibitory molecules that are present, or even increased in the extracellular environment of the injured spinal cord. Many of these inhibitory molecules have been studied extensively in recent years. It has been suggested that the small GTPase RhoA is an intracellular convergence point for signaling by these extracellular inhibitory molecules, but due to the complexity of the central nervous system (CNS) in mammals, and the limitation of pharmacological tools, the specific roles of RhoA are unclear. By exploiting the anatomical and technical advantages of the lamprey CNS, we recently demonstrated that RhoA knockdown promotes true axon regeneration through the lesion site after SCI. In addition, we found that RhoA knockdown protects the large, identified reticulospinal neurons from apoptosis after their axons were axotomized in spinal cord. Therefore, manipulation of the RhoA signaling pathway may be an important approach in the development of treatments that are both neuroprotective and axon regeneration-promoting, to enhance functional recovery after SCI. Related Articles | Metrics

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The reasons for end-to-side coaptation: how does lateral axon sprouting work? Stefano Geuna, Igor Papalia, Giulia Ronchi, Francesco Stagno d’Alcontres, Konstantinos Natsis, Nikolaos A. Papadopulos, Michele R. Colonna 2017, 12 (4):  529-533.  doi: 10.4103/1673-5374.205081 Abstract ( 363 )   PDF (358KB) ( 676 )   Save Nerve fibers are attracted by sutureless end-to-side nerve coaptation into the recipient nerve. Opening a window in the epineurium enhances axon attraction and myelination. The authors analyze the features of nerve repair by end-to-side coaptation. They highlight the known mechanisms of axon sprouting and different hypotheses of start up signals (presence or absence of an epineurial window, role of Schwann cells, signaling from the distal trunk). The clinical literature is also presented and differences between experimental and clinical applications are pointed out. The authors propose their point of view and perspectives deriving from recent experimental and clinical experiences. Related Articles | Metrics

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Phosphatidylserine improves axonal transport by inhibition of HDAC and has potential in treatment of neurodegenerative diseases Shiran Naftelberg, Gil Ast, Eran Perlson 2017, 12 (4):  534-537.  doi: 10.4103/1673-5374.205082 Abstract ( 321 )   PDF (608KB) ( 588 )   Save Familial dysautonomia (FD) is a rare children neurodegenerative disease caused due to a point mutation in the IKBKAP gene that results in decreased IKK complex-associated protein (IKAP) protein production. The disease affects mostly the dorsal root ganglion (DRG) and the sympathetic ganglion. Recently, we found that the molecular mechanisms underlying neurodegeneration in FD patients are defects in axonal transport of nerve growth factors and microtubule stability in the DRG. Neurons are highly polarized cells with very long axons. In order to survive and maintain proper function, neurons depend on transport of proteins and other cellular components from the neuronal body along the axons. We further demonstrated that IKAP is necessary for axon maintenance and showed that phosphatidylserine acts as an HDAC6 inhibitor to rescue neuronal function in FD cells. In this review, we will highlight our latest research findings. Related Articles | Metrics

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The complexities underlying age-related macular degeneration: could amyloid beta play an important role? Savannah A. Lynn, Eloise Keeling, Rosie Munday, Gagandeep Gabha, Helen Griffiths, Andrew J. Lotery, J. Arjuna Ratnayaka 2017, 12 (4):  538-548.  doi: 10.4103/1673-5374.205083 Abstract ( 390 )   PDF (3378KB) ( 712 )   Save Age-related macular degeneration (AMD) causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer’s-linked amyloid beta (Aβ) group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer’s disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that Aβ fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of Aβ were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of Aβ accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of Aβ-mediated retinopathy. Furthermore, we discuss our findings revealing how Aβ behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose Aβ as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for late-stage AMD. Related Articles | Metrics

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Neurotrophic factors in Alzheimer’s and Parkinson’s diseases: implications for pathogenesis and therapy Tuane Bazanella Sampaio, Anne Suely Savall, Maria Eduarda Ziani Gutierrez, Simone Pinton 2017, 12 (4):  549-557.  doi: 10.4103/1673-5374.205084 Abstract ( 432 )   PDF (288KB) ( 621 )   Save Neurotrophic factors comprise essential secreted proteins that have several functions in neural and non-neural tissues, mediating the development, survival and maintenance of peripheral and central nervous system. Therefore, neurotrophic factor issue has been extensively investigated into the context of neurodegenerative diseases. Alzheimer’s disease and Parkinson’s disease show changes in the regulation of specific neurotrophic factors and their receptors, which appear to be critical for neuronal degeneration. Indeed, neurotrophic factors prevent cell death in degenerative processes and can enhance the growth and function of affected neurons in these disorders. Based on recent reports, this review discusses the main findings related to the neurotrophic factor support – mainly brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor – in the survival, proliferation and maturation of affected neurons in Alzheimer’s disease and Parkinson’s disease as well as their putative application as new therapeutic approach for these diseases management. Related Articles | Metrics

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Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhag Juan Pías-Peleteiro, Francisco Campos, José Castillo, Tomás Sobrino 2017, 12 (4):  558-561.  doi: 10.4103/1673-5374.205085 Abstract ( 332 )   PDF (386KB) ( 571 )   Save Intracerebral hemorrhage (ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells (EPCs) have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice. Related Articles | Metrics

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A tale of motor neurons and CD4+ T cells: moving forward by looking back Abhirami Kannan Iyer, Kathryn J. Jones 2017, 12 (4):  562-565.  doi: 10.4103/1673-5374.205086 Abstract ( 332 )   PDF (306KB) ( 560 )   Save Amyotrophic lateral sclerosis (ALS) is a fatal progressive disorder characterized by the selective degeneration of motor neurons (MN). The impact of peripheral immune status on disease progression and MN survival is becoming increasingly recognized in the ALS research field. In this review, we briefly discuss findings from mouse models of peripheral nerve injury and immunodeficiency to understand how the immune system regulates MN survival. We extend these observations to similar studies in the widely used superoxide dismutase 1 (SOD1) mouse model of ALS. Last, we present future hypotheses to identify potential causative factors that lead to immune dysregulation in ALS. The lessons from preceding work in this area offer new exciting directions to bridge the gap in our current understanding of immune-mediated neuroprotection in ALS. Related Articles | Metrics

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Analyzing the role of extracellular matrix during nervous system development to advance new regenerative strategies Teresa Caprile, Hernán Montecinos 2017, 12 (4):  566-567.  doi: 10.4103/1673-5374.205087 Abstract ( 302 )   PDF (545KB) ( 421 )   Save Related Articles | Metrics

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Nerves and hydrogen peroxide: how old enemies become new friend Francesca Meda, Alain Joliot, Sophie Vriz 2017, 12 (4):  568-569.  doi: 10.4103/1673-5374.205088 Abstract ( 468 )   PDF (658KB) ( 486 )   Save Related Articles | Metrics

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Ghosts in the shell: identification of microglia in the human central nervous system by P2Y12 receptor Alexander Mildner 2017, 12 (4):  570-571.  doi: 10.4103/1673-5374.205090 Abstract ( 322 )   PDF (146KB) ( 435 )   Save Related Articles | Metrics

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RhoA/ROCK activation in major pelvic ganglion mediates caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury Michael Bell, Nikolai A. Sopko, Hotaka Matsui, Johanna L. Hannan, Trinity J. Bivalacqua 2017, 12 (4):  572-573.  doi: 10.4103/1673-5374.205091 Abstract ( 344 )   PDF (132KB) ( 578 )   Save Related Articles | Metrics

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Why and how does light therapy offer neuroprotection in Parkinson’s disease? John Mitrofanis 2017, 12 (4):  574-575.  doi: 10.4103/1673-5374.205092 Abstract ( 370 )   PDF (137KB) ( 1158 )   Save Related Articles | Metrics

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Delivery of therapeutics to posterior eye segment: cell-encapsulating systems Francisca S.Y. Wong, Ken K. Tsang, Amy C.Y. Lo 2017, 12 (4):  576-577.  doi: 10.4103/1673-5374.205093 Abstract ( 297 )   PDF (151KB) ( 612 )   Save Related Articles | Metrics

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Role of the STRIPAK complex and the Hippo pathway in synaptic terminal formatio Chisako Sakuma, Takahiro Chihara 2017, 12 (4):  578-579.  doi: 10.4103/1673-5374.205089 Abstract ( 331 )   PDF (337KB) ( 615 )   Save Related Articles | Metrics

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Regulatory role of microRNA on inflammatory responses of diabetic retinopathy Eun-Ah Ye, Jena J. Steinle 2017, 12 (4):  580-581.  doi: 10.4103/1673-5374.205095 Abstract ( 371 )   PDF (139KB) ( 472 )   Save Related Articles | Metrics

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Food, polyphenols and neuroprotection Rui F.M. Silva, Lea Pogačnik 2017, 12 (4):  582-583.  doi: 10.4103/1673-5374.205096 Abstract ( 312 )   PDF (239KB) ( 661 )   Save Related Articles | Metrics

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Recent advances and future directions for the pharmacogenetic basis of anti-VEGF treatment response in neovascular age-related macular degeneration Moeen Riaz, Paul N. Baird 2017, 12 (4):  584-585.  doi: 10.4103/1673-5374.205094 Abstract ( 414 )   PDF (159KB) ( 433 )   Save Related Articles | Metrics

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Translational research in early neuroscience careers of high school students Zachary M. Diamandis, Nicholas S. Diaco, Cesar V. Borlongan 2017, 12 (4):  586-587.  doi: 10.4103/1673-5374.205097 Abstract ( 402 )   PDF (145KB) ( 486 )   Save Related Articles | Metrics

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Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice Teresa Neri-Gómez, Judith Espinosa-Raya, Sofía Díaz-Cintra, Julia Segura-Uribe, Sandra Orozco-Suárez, Juan Manuel Gallardo, Christian Guerra-Araiza 2017, 12 (4):  588-595.  doi: 10.4103/1673-5374.205098 Abstract ( 341 )   PDF (1201KB) ( 728 )   Save Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes. Related Articles | Metrics

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Aerobic exercise combined with huwentoxin-I mitigates chronic cerebral ischemia injury Hai-feng Mao, Jun Xie, Jia-qin Chen, Chang-fa Tang, Wei Chen, Bo-cun Zhou, Rui Chen, Hong-lin Qu, Chu-zu Wu 2017, 12 (4):  596-602.  doi: 10.4103/1673-5374.205099 Abstract ( 308 )   PDF (1046KB) ( 727 )   Save Ca2+ channel blockers have been shown to protect neurons from ischemia, and aerobic exercise has significant protective effects on a variety of chronic diseases. The present study injected huwentoxin-I (HWTX-I), a spider peptide toxin that blocks Ca2+ channels, into the caudal vein of a chronic cerebral ischemia mouse model, once every 2 days, for a total of 15 injections. During this time, a subgroup of mice was subjected to treadmill exercise for 5 weeks. Results showed amelioration of cortical injury and improved neurological function in mice with chronic cerebral ischemia in the HWTX-I + aerobic exercise group. The combined effects of HWTX-I and exercise were superior to HWTX-I or aerobic exercise alone. HWTX-I effectively activated the Notch signal transduction pathway in brain tissue. Aerobic exercise up-regulated synaptophysin mRNA expression. These results demonstrated that aerobic exercise, in combination with HWTX-I, effectively relieved neuronal injury induced by chronic cerebral ischemia via the Notch signaling pathway and promoting synaptic regeneration. Related Articles | Metrics

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Diffusion tensor imaging assesses white matter injury in neonates with hypoxic-ischemic encephalopathy Hong-xin Li, Xing Feng, Qian Wang, Xuan Dong, Min Yu, Wen-juan Tu 2017, 12 (4):  603-609.  doi: 10.4103/1673-5374.205102 Abstract ( 279 )   PDF (827KB) ( 423 )   Save With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy (14 moderate cases and 8 severe cases) underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy. Related Articles | Metrics

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Low frequency repetitive transcranial magnetic stimulation improves motor dysfunction after cerebral infarction Zhi-yong Meng, Wei-qun Song 2017, 12 (4):  610-613.  doi: 10.4103/1673-5374.205100 Abstract ( 466 )   PDF (218KB) ( 457 )   Save Low frequency (≤ 1 Hz) repetitive transcranial magnetic stimulation (rTMS) can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency rTMS group and a control group. The patients in the low frequency rTMS group were given 1-Hz rTMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores (National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment) improved significantly in the low frequency rTMS group, and the effects were better than that in the control group. We conclude that low frequency (1 Hz) rTMS for 14 days can help improve motor function after cerebral infarction. Related Articles | Metrics

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Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering Feng Fu, Zhe Qin, Chao Xu, Xu-yi Chen, Rui-xin Li, Li-na Wang, Ding-wei Peng, Hong-tao Sun, Yue Tu, Chong Chen, Sai Zhang, Ming-liang Zhao, Xiao-hong Li 2017, 12 (4):  614-622.  doi: 10.4103/1673-5374.205101 Abstract ( 306 )   PDF (2398KB) ( 674 )   Save Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer-aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine. Related Articles | Metrics

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Ca2+ involvement in activation of extracellular-signalregulated-kinase 1/2 and m-calpain after axotomy of the sciatic nerve Lisa B. Mårtensson, Charlotta Lindwall Blom, Lars B. Dahlin 2017, 12 (4):  623-628.  doi: 10.4103/1673-5374.205103 Abstract ( 310 )   PDF (824KB) ( 610 )   Save Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells (SCs), are poorly understood. Here, we investigated axotomy-induced activation of extracellular-signal-regulated kinase-1/2 (ERK1/2; important for proliferation) and m-calpain in vitro, and the relation to Ca2+ deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis(β-aminoethyl ether)-N,N,N’,N’-tetraacetic acid (EGTA). In some experiments, 5-bromo-2′-deoxyuridine (BrdU) was added during the last 24 hours to detect proliferating cells and propidium iodide (PI) was added at the last hour to detect dead and/or dying cells. Immunohistochemistry of sections of the cultured nerve segments was performed to label m-calpain and the phosphorylated and activated form of ERK1/2. The experiments revealed that immunoreactivity for p-ERK1/2 increased with time in organotypically cultured SCs. p-ERK1/2 and m-calpain were also observed in axons. A significant increase in the number of dead or dying SCs was observed in nerve segments cultured for 24 hours. When deprived of Ca2+, activation of axonal m-calpain was reduced, whereas p-ERK1/2 was increased in SCs. Ca2+ deprivation also significantly reduced the number of proliferating SCs, and instead increased the number of dead or dying SCs. Ca2+ seems to play an important role in activation of ERK1/2 in SCs and in SC survival and proliferation. In addition, extracellular Ca2+ levels are also required for m-calpain activation and up-regulation in axons. Thus, regulation of Ca2+ levels is likely to be a useful method to promote SC proliferation. Related Articles | Metrics

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Recombinant human fibroblast growth factor-2 promotes nerve regeneration and functional recovery after mental nerve crush injury Sung Ho Lee, Wei-Peng Jin, Na Ri Seo, Kang-Mi Pang, Bongju Kim, Soung-Min Kim, Jong-Ho Lee 2017, 12 (4):  629-636.  doi: 10.4103/1673-5374.205104 Abstract ( 297 )   PDF (1416KB) ( 942 )   Save Several studies have shown that fibroblast growth factor-2 (FGF2) can directly affect axon regeneration after peripheral nerve damage. In this study, we performed sensory tests and histological analyses to study the effect of recombinant human FGF-2 (rhFGF2) treatment on damaged mental nerves. The mental nerves of 6-week-old male Sprague-Dawley rats were crush-injured for 1 minute and then treated with 10 or 50 μg/mL rhFGF2 or PBS in crush injury area with a mini Osmotic pump. Sensory test using von Frey filaments at 1 week revealed the presence of sensory degeneration based on decreased gap score and increased difference score. However, at 2 weeks, the gap score and difference score were significantly rebounded in the mental nerve crush group treated with 10 μg/mL rhFGF2. Interestingly, treatment with 10 μg/mL rhFGF had a more obviously positive effect on the gap score than treatment with 50 μg/mL rhFGF2. In addition, retrograde neuronal tracing with Dil revealed a significant increase in nerve regeneration in the trigeminal ganglion at 2 and 4 weeks in the rhFGF2 groups (10 μg/mL and 50 μg/mL) than in the PBS group. The 10 μg/mL rhFGF2 group also showed an obviously robust regeneration in axon density in the mental nerve at 4 weeks. Our results demonstrate that 10 μg/mL rhFGF induces mental nerve regeneration and sensory recovery after mental nerve crush injury. Related Articles | Metrics

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Exenatide promotes regeneration of injured rat sciatic nerve Ersin Kuyucu, Bilal Gümüs, Oytun Erbas, Fatih Oltulu, Arslan Bora 2017, 12 (4):  637-643.  doi: 10.4103/1673-5374.205105 Abstract ( 373 )   PDF (666KB) ( 602 )   Save Damage to peripheral nerves results in partial or complete dysfunction. After peripheral nerve injuries, a full functional recovery usually cannot be achieved despite the standard surgical repairs. Neurotrophic factors and growth factors stimulate axonal growth and support the viability of nerve cells. The objective of this study is to investigate the neurotrophic effect of exenatide (glucagon like peptide-1 analog) in a rat sciatic nerve neurotmesis model. We injected 10 μg/d exenatide for 12 weeks in the experimental group (n = 12) and 0.1 mL/d saline for 12 weeks in the control group (n = 12). We evaluated nerve regeneration by conducting electrophysiological and motor functional tests. Histological changes were evaluated at weeks 1, 3, 6, and 9. Nerve regeneration was monitored using stereomicroscopy. The electrophysiological and motor functions in rats treated with exenatide were improved at 12 weeks after surgery. Histological examination revealed a significant increase in the number of axons in injured sciatic nerve following exenatide treatment confirmed by stereomicroscopy. In an experimentally induced neurotmesis model in rats, exenatide had a positive effect on nerve regeneration evidenced by electromyography, functional motor tests, histological and stereomicroscopic findings. Related Articles | Metrics

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Mitomycin C induces apoptosis in human epidural scar fibroblasts after surgical decompression for spinal cord injury Tao Sui, Da-wei Ge, Lei Yang, Jian Tang, Xiao-jian Cao, Ying-bin Ge 2017, 12 (4):  644-653.  doi: 10.4103/1673-5374.205106 Abstract ( 319 )   PDF (1846KB) ( 702 )   Save Numerous studies have shown that topical application of mitomycin C after surgical decompression effectively reduces scar adhesion. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of mitomycin C on the proliferation and apoptosis of human epidural scar fibroblasts. Human epidural scar fibroblasts were treated with various concentrations of mitomycin C (1, 5, 10, 20, 40 μg/mL) for 12, 24 and 48 hours. Mitomycin C suppressed the growth of these cells in a dose- and time-dependent manner. Mitomycin C upregulated the expression levels of Fas, DR4, DR5, cleaved caspase-8/9, Bax, Bim and cleaved caspase-3 proteins, and it downregulated Bcl-2 and Bcl-xL expression. In addition, inhibitors of caspase-8 and caspase-9 (Z-IETD-FMK and Z-LEHD-FMK, respectively) did not fully inhibit mitomycin C-induced apoptosis. Furthermore, mitomycin C induced endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78, CAAT/enhancer-binding protein homologous protein (CHOP) and caspase-4 in a dose-dependent manner. Salubrinal significantly inhibited the mitomycin C-induced cell viability loss and apoptosis, and these effects were accompanied by a reduction in CHOP expression. Our results support the hypothesis that mitomycin C induces human epidural scar fibroblast apoptosis, at least in part, via the endoplasmic reticulum stress pathway. Related Articles | Metrics

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Neuroprotective mechanism of Kai Xin San: upregulation of hippocampal insulin-degrading enzyme protein expression and acceleration of amyloid-beta degradation Na Wang, Yong-ming Jia, Bo Zhang, Di Xue, Maharjan Reeju, Yan Li, Shu-ming Huang, Xue-wei Liu 2017, 12 (4):  654-659.  doi: 10.4103/1673-5374.205107 Abstract ( 366 )   PDF (823KB) ( 724 )   Save Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β (Aβ)-induced cognitive dysfunction and is neuroprotective in vivo, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme (IDE), which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42 (200 μM, 5 μL) into the hippocampus and subsequently administered Kai Xin San (0.54 or 1.08 g/kg/d) intragastrically for 21 consecutive days. Hematoxylin-eosin and Nissl staining revealed that Kai Xin San protected neurons against Aβ-induced damage. Furthermore, enzyme-linked immunosorbent assay, western blot and polymerase chain reaction results showed that Kai Xin San decreased Aβ42 protein levels and increased expression of IDE protein, but not mRNA, in the hippocampus. Our findings reveal that Kai Xin San facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats. Related Articles | Metrics

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Effects of medicinal plants on Alzheimer’s disease and memory deficits Muhammad Akram, Allah Nawaz 2017, 12 (4):  660-670.  doi: 10.4103/1673-5374.205108 Abstract ( 289 )   PDF (315KB) ( 960 )   Save Alzheimer’s disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer’s disease. However, the proper treatment option is still not available. There is no cure for Alzheimer’s disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced worldwide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer’s disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer’s disease and memory deficits using conventional herbal therapy. Related Articles | Metrics

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Recovery of multiply injured ascending reticular activating systems in a stroke patient Sung Ho Jang, Han Do Lee 2017, 12 (4):  671-672.  doi: 10.4103/1673-5374.205109 Abstract ( 368 )   PDF (481KB) ( 713 )   Save Related Articles | Metrics