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| 1 | Role of neurotrophic factors in enhancing linear axonal growth of ganglionic sensory neurons in vitro显示文摘Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor in maintaining the survival of peripheral neurons remains poorly understood. In regenerative medicine, different modalities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. This study was to investigate the influence of nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor on the growth of neurites using two in vitro models of dorsal root ganglia explants and dorsal root ganglia-derived primary cell dissociated cultures. Quantitative data showed that the total neurite length and tortuosity were differently influenced by trophic factors. Nerve growth factor and, indirectly, brain-derived neurotrophic factor stimulate the tortuous growth of sensory fibers and the formation of cell clusters. Neurotrophin-3, however, enhances neurite growth in terms of length and linearity allowing for a more organized and directed axonal elongation towards a peripheral target compared to the other growth factors. These findings could be of considerable importance for any clinical application of neurotrophic factors in peripheral nerve regeneration. Ethical approval was obtained from the Regione Piemonte Animal Ethics Committee ASLTO1(file # 864/2016-PR) on September 14, 2016. | Michele Fornaro Alessia Giovannelli Angelica Foggetti Luisa Muratori Stefano Geuna Giorgia Novajra Isabelle Perroteau | 2020 | Neural Regeneration Research2020，15，9： | 3 |
| 2 | Chitosan tubes enriched with fresh skeletal muscle fibers for delayed repair of peripheral nerve defects显示文摘Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the 'gold standard' technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016. | AlessANDro Crosio Benedetta Elena Fornasari Giovanna Gambarotta Stefano Geuna Stefania Raimondo Bruno Battiston Pierluigi Tos Giulia Ronchi | 2019 | Neural Regeneration Research2019，14，6： | 2 |
| 3 | Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells显示文摘AIM: To study the therapeutic effect of three tubeguides with electrical conductivity associated to mesenchymal stem cells(MSCs) on neuro-muscular regeneration after neurotmesis.METHODS: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol(PVA), PVA-carbon nanotubes(CNTs) and MSCs, and PVA-polypyrrole(PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functionalindex(SSI), and by withdrawal reflex latency(WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs(P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group(P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the 'minimal Feret's diameter' respectively. Stereological analysis disclosed a significantly(P < 0.05) increased myelin thickness(M), ratio myelin thickness/axon diameter(M/d) and ratio axon diameter/fiber diameter(d/D; g-ratio) in PVA-CNT-MSCs group(P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible that might prevent the secondary neurogenic muscular atrophy by improving the reestablishment of the neuro-muscular junction. | Jorge Ribeiro Tiago Pereira Ana Rita Caseiro Paulo Armada-da-Silva Isabel Pires Justina Prada Irina Amorim Sandra Amado Miguel Franca Carolina Goncalves Maria Ascensao Lopes Jose Domingos Santos Dina Morais Silva Stefano Geuna Ana Lúcia Luís Ana Colette Maurício | 2015 | World Journal of Stem Cells2015，7，6： | 2 |
| 4 | Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus显示文摘 | Di Nicolantonio Federica Arena Sabrina Tabernero Josep Grosso Stefano Molinari Francesca Macarulla Teresa Russo Mariangela Cancelliere Carlotta Zecchin Davide Mazzucchelli Luca Sasazuki Takehiko Shirasawa Senji Geuna Massimo Frattini Milo Ba | 2010 | Journal of Clinical Investigation2010，，8： | 1 |
| 5 | The reasons for end-to-side coaptation:how does lateral axon sprouting work?显示文摘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. | Stefano Geuna Igor Papalia Giulia Ronchi Francesco Stagno d'Alcontres Konstantinos Natsis Nikolaos A. Papadopulos Michele R. Colonna | 2017 | Neural Regeneration Research2017，12，4： | 1 |
| 6 | Direct muscle neurotization after end-to-end and end-to-side neurorrhaphy An experimental study in the rat forelimb model显示文摘The need for the continuous research of new tools for improving motor function recovery after nerve injury is justified by the still often unsatisfactory clinical outcome in these patients. It has been previously shown that the combined use of two reconstructive techniques, namely end-to-side neurorrhaphy and direct muscle neurotization in the rat hindlimb model, can lead to good results in terms of skeletal muscle reinnervation. Here we show that, in the rat forelimb model, the combined use of direct muscle neurotization with either end-to-end or end-to-side neurorrhaphy to reinnervate the denervated flexor digitorum muscles, leads to muscle atrophy prevention over a long postoperative time lapse (10 months). By contrast, very little motor recovery (in case of end-to-end neurorrhaphy) and almost no motor recovery (in case of end-to-side neurorrhaphy) were observed in the grasping activity controlled by flexor digitorum muscles. It can thus be concluded that, at least in the rat, direct muscle neurotization after both end-to-end and end-to-side neurorrhaphy represents a good strategy for preventing denervation-related muscle atrophy but not for regaining the lost motor function. | Igor Papalia Giulia Ronchi Luisa Muratori Alessandra Mazzucco Ludovico Magaudda Stefano Geuna | 2012 | Neural Regeneration Research2012，7，29： | 1 |
| 7 | Neurogenesis in the adult peripheral nervous system显示文摘Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence ofinsult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system. | Krzysztof Czaja Michele Fornaro Stefano Geuna | 2012 | Neural Regeneration Research2012，7，14： | 1 |
| 8 | Neuregulin 1 isoforms could be an effective therapeutic candidate to promote peripheral nerve regeneration显示文摘Traumatic injuries of peripheral nerves represent common casualties and their social impact is considerably high.Although peripheral nerves retain a good regeneration potential,the clinical outcome after nerve lesion is far from being satisfactory and functional recovery is almost never complete,especially in the case of large nerve defects,that result in loss or diminished sensitivity and/or motor activity of the innervated target organs.Therefore,to improve the outcome | Giovanna Gambarotta Giulia Ronchi Stefano Geuna Isabelle Perroteau | 2014 | Neural Regeneration Research2014，9，12： | 0 |
| 9 | Chitosan conduits enriched with fibrin-collagen hydrogel with or without adipose-derived mesenchymal stem cells for the repair of 15-mm-long sciatic nerve defect显示文摘Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3. | Marwa El Soury óscar Darío García-García Isabella Tarulli Jesús Chato-Astrain Isabelle Perroteau Stefano Geuna Stefania Raimondo Giovanna Gambarotia Víctor Carriel | 2023 | Neural Regeneration Research2023，18，6： | 0 |
| 10 | New insights on the standardization of peripheral nerve regeneration quantitative analysis显示文摘Peripheral nerves form a complex network connecting the central nervous system and the body.Injuries to peripheral nerves often lead to partial or complete loss of motor,sensory and autonomic functions,thus interfering with many aspects of an individual’s life.Despite the spontaneous ability of the peripheral nerve to regenerate,the technical surgical progresses and the significant advances in basic science,the study of | Giulia Ronchi Stefania Raimondo Stefano Geuna Giovanna Gambarotta | 2015 | Neural Regeneration Research2015，10，5： | 0 |
| 11 | Can we promote neural regeneration through microbiota-targeted strategies? Introducing the new concept of neurobiotics显示文摘The human body is populated by a large number of microbial colonies,with an estimated 10-100 trillion microbes.The total genome size of human microbial colonies by far overwhelms the size of the host’s genome.This heterogenous group of microbial colonies(primarily bacteria,but also archaea,eukaryotes and viruses)is referred to with the term microbiota,and although most of them populate the gut,microbes are also detectable in many other organs of the body,especially in the distal tracts of the genitourinary system and the skin.Over the last years,an increasing amount of evidence has been accumulated on how the microbiota exerts a significant influence on the development and physiology of the human body. | Celia Herrera-Rincon Julia Murciano-Brea Stefano Geuna | 2022 | Neural Regeneration Research2022，17，9： | 0 |
| 12 | Peripheral nerve regeneration research Why is it getting so “cool”?显示文摘More than twenty years ago, when I first started working on plasticity and regeneration in the peripheral nervous system, I had the feeling of being part of a little, though lively, scientific community that was rarther isolated in the world of neuroscience which appeared to me as almost only focused on central nervous system. Since then, things have progressively changed very much and, | Stefano Geuna | 2012 | Neural Regeneration Research2012，7，29： | 0 |
| 13 | Emerging issues in peripheral nerve repair显示文摘It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that, to further improve clinical outcome, the involvement of different scientific disciplines is required. This evolving reconstructive/regenerative approach is based on the interdisciplinary and integrated pillars of tissue engineering such as reconstructive microsurgery, transplantation and biomaterials. In this paper, some of the most promising innovations for the tissue engineering of nerves, emerging from basic science investigation, are critically overviewed with special focus on those approaches that appear today to be more suitable for clinical translation. | Stefano Geuna Pierluigi Tos Bruno Battiston | 2012 | Neural Regeneration Research2012，7，29： | 0 |
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