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New insights on the standardization of peripheral nerve regeneration quantitative analysis

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Neural Regeneration Research 2015年第5期10卷 707-709页

作者： Giulia Ronchi stefania raimondo Stefano Geuna Giovanna Gambarotta Department of Clinical and Biological Sciences University of TorinoOrbassano (To)Italy Neuroscience Institute Cavalieri Ottolenghi (NICO) Orbassano (To)Italy Neuroscience Institute of Torino (NIT) Interdepartmental Centre of Advanced Studies in NeuroscienceUniversity of TorinoItaly

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, sen- sory and autonomic functions, thus inter... 详细信息

关键词： gene RNA New insights on the standardization of peripheral nerve regeneration quantitative analysis very

Role of inflammatory cytokines in peripheral nerve injury

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Neural Regeneration Research 2012年第29期7卷 2259-2266页

作者： Federica Fregnan Luisa Muratori Anabel Rodriguez Simǒes Maria Giuseppina Giacobini-Robecchi stefania raimondo Department of Clinical and Biological Sciences University of TurinOrbassano 10043 TurinItaly Neuroscience Institute of the "Cavalieri Ottolenghi" Foundation Orbassano 10043TurinItaly

Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.

关键词： pro-inflammatory cytokines anti-inflammatory cytokines inflammatory reaction peripheral nervoussystem nerve injury wallerian degeneration Schwann cells macrophage axonal regeneration myelin neural regeneration

Chitosan tubes enriched with fresh skeletal muscle fibers for delayed repair of peripheral nerve defects

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Neural Regeneration Research 2019年第6期14卷 1079-1084页

作者： AlessANDro Crosio Benedetta Elena Fornasari Giovanna Gambarotta Stefano Geuna stefania raimondo Bruno Battiston Pierluigi Tos Giulia Ronchi Department of Orthopedics and Traumatology II-Surgery for Hand and Upper Limb-AOU Città della Salute e della Scienza di Torino-CTO Hospital Department of Clinical and Biological Sciences University of Torino Neuroscience Institute Cavalieri Ottolenghi University of Torino UO Microchirurgia e Chirurgia della Mano Ospedale Gaetano Pini

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.

关键词： tubulization Schwann cells scaffold tissue engineering nerve reconstruction morphometrical analyses grasping test secondary repair median nerve nerve regeneration

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

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Neural Regeneration Research 2023年第6期18卷 1378-1385页

作者： Marwa El Soury óscar Darío García-García Isabella Tarulli Jesús Chato-Astrain Isabelle Perroteau Stefano Geuna stefania raimondo Giovanna Gambarotia Víctor Carriel Department of Clinical and Biological Sciences University of TorinoTorinoItaly Neuroscience Institute Cavalieri Ottolenghi University of TorinoTorinoItaly Department of Histology Tissue Engineering GroupUniversity of GranadaGranadaSpain Instituto de Investigacion Biosanitaria Ibs.GRANADAGranadaSpain

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 *** 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 *** 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 *** changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 ***,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 *** composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell *** 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.

关键词： adipose-derived stem cells chitosan conduit fibrin and collagen hydrogel nerve regeneration nerve repair neuregulin 1 peripheral nerve sciatic nerve

Use of hybrid chitosan membranes and human mesenchymal stem cells from the Wharton jelly of umbilical cord for promoting nerve regeneration in an axonotmesis rat model

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Neural Regeneration Research 2012年第29期7卷 2247-2258页

作者： Andrea Gärtner Tiago Pereira Maria Joāo Simōes Paulo AS Armada-da-Silva Miguel L França Rosa Sousa Simone Bompasso stefania raimondo Yuki Shirosaki Yuri Nakamura Satoshi Hayakawa Akiyoshi Osakah Beatriz Porto Ana Lúcia Luís Artur SP Varejāo Ana Colette Maurício Animal Science and Study Centre/Food and Agrarian Sciences and Technologies Institute Porto University4099-003 PortoPortugal Institute of Biomedical Sciences Abel Salazar Veterinary Clinics DepartmentPorto UniversityPorto 4099-003Portugal Faculty of Human Kinetics Technical University of LisbonCruz Quebrada-Dafundo1499-002Portugal Institute of Biomedical Sciences Abel Salazar Cytogenetic DepartmentPorto UniversityPorto 4099-003Portugal Neuroscience Institute of the Cavalieri Ottolenghi Foundation Orbassano 10043TurinItaly Department of Clinical and Biological Sciences University of TurinOrbassano 10010TurinItaly Graduate School of Natural Science and Technology Okayama UniversityOkayama 700-8530Japan Faculty of Engineering Okayama UniversityOkayama 700-8530Japan Department of Veterinary Sciences Research Centre in SportsHealth and Human DevelopmentUniversity of Trás-os-Montes and Alto DouroVila Real 5001-801Portugal

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to assess the effect on nerve regeneration, associating a hybrid chitosan membrane with non-differentiated human mesenchymal stem cells isolated from Wharton＇s jelly of umbilical cord, in peripheral nerve reconstruction after crush injury. Chromosome analysis on human mesenchymal stem cell line from Wharton＇s jelly was carried out and no structural alterations were found in metaphase. Chitosan membranes were previously tested in vitro, to assess their ability in supporting human mesenchymal stem cell survival, expansion, and differentiation. For the in vivo testing, Sasco Sprague adult rats were divided in 4 groups of 6 or 7 animals each： Group 1, sciatic axonotmesis injury without any other intervention （Group 1-Crush）; Group 2, the axonotmesis lesion of 3 mm was infiltrated with a suspension of 1 250 -1 500 human mesenchymal stem cells （total volume of 50 pL）（Group 2-CrushCell）; Group 3, axonotmesis lesion of 3 mm was enwrapped with a chitosan type Ill membrane covered with a monolayer of non-differentiated human mesenchymal stem cells （Group 3-CrushChitlllCell） and Group 4, axonotmesis lesion of 3 mm was enwrapped with a chitosan type III membrane （Group 4-CrushChiUll）. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index, static sciatic index, extensor postural thrust, and withdrawal reflex latency. Stereological analysis was carded out on regenerated nerve fibers. Results showed that infiltration of human mesenchymal stem cells, or the combination of chitosan membrane enwrapment and human mesenchymal stem cell enrichment after nerve crush injury provide a slight advantage to post-traumatic nerve regeneration. Results obtained with chitosan type III membrane alone confirmed that they significantly improve post-traumatic axonal regrowth and may represent

关键词： stem cells mesenchymal stem cells Wharton jelly umbilical cord biomaterials chitosan axonotmesis functional analysis rat karyotype analysis stereological analysis

Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

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Neural Regeneration Research 2025年第7期20卷 2008-2010页

作者： Elena Ambrosini Angela Lanciotti Maria stefania Brignone Department of Neuroscience Istituto Superiore di SanitàRomeItaly

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult *** maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

关键词： alterations modulator maintain

Novel perspectives for neurodegeneration prevention: effects of bioactive polyphenols

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Neural Regeneration Research 2021年第7期16卷 1411-1412页

作者： stefania Crispi stefania Filosa Institute of Biosciences and Bioresources National Research Councilvia P.CastellinoNaplesItaly Department of Marine Biotechnology Stazione Zoologica Anton DohrnNapoliItaly Istituto di Ricovero e Cura a Carattere Scientifico Neuromed PozzilliItaly

Neurodegenerative diseases are becoming a big challenge for modern *** disorders strongly impact on patient and their ***, since the population is becoming older, these pathologies will deeply influence medical and socio-economic conditions in the next ***, efforts are needed to find new strategies devoted to define new protocols and identify novel substances able to prevent neurodegeneration or to improve the quality of life of people affected by neurodegenerative diseases(Alzheimer's Disease International, 2019).

关键词： prevention diseases neurodegeneration

Polyphenols-gut microbiota interplay and brain neuromodulation

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Neural Regeneration Research 2018年第12期13卷 2055-2059页

作者： stefania Filosa Francesco Di Meo stefania Crispi Institute of Biosciences and Bioresources National Research Council National Research Council via P. Castellino Naples Italy Istituto di Ricovero e Cura a Carattere Scientifico Neuromed Pozzilli Italy

Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.

关键词： polyphenols gut-microbiota gut-brain axis metagenomic neurodegeneration neurotransmitters prebiotics probiotics

Increased population density reduces body growth and female investment in a simultaneous hermaphrodite

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Current Zoology 2017年第2期63卷 151-157页

作者： Elio CANNARSA stefania MECONCELLI Department of Life Sciences and Systems Biology Universita di Torino Via Accademia Albertina 13 10123 Torino Italy.

Sex allocation theory applied to hermaphrodites assumes that there is a trade off between the alloca- tion of resources to male and female functions, within a fixed reproductive resource budget. Charnov＇s classic resource allocation model predicts a more female-biased sex allocation when competition among different sperm donors is low due to diminishing fitness returns for male investment. By manipulating the social group size, one automatically changes the population density at which individ- uals live. Increasing population density may affect reproductive allocation, leading to resource compe- tition and/or to increased concentration of harmful metabolites. This could lead to an over- or under- estimation of the individual adjustment of sex allocation responses to mating opportunities. In this article, we tested the effects of density and social group size separately on female investment and body growth （considered as proxy of the overall energy budget） in the simultaneously hermaphroditic polychaete worm Ophryotrocha diadema. We manipulated social group size （i.e., monogamous and promiscuous regimes） and density （i.e., 4 levels） using a full-factorial design, to identify the underlying factor affecting female allocation （in terms of egg production） and body growth. In contrast to findings of previous experiments, we found that an increase in population density reduced body growth and egg production of hermaphrodites irrespective of social group size. We advance the hypothesis that the increase of catabolites and oxygen consumption in high-density conditions reduces the overall resource budget and this could obscure group size effects on female fecundity.

关键词： body growth female fecundity mating group size Ophryotrocha diadema resource budget.