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7. Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

Author

Alvites, Rui D., primary, Branquinho, Mariana V., additional, Sousa, Ana C., additional, Lopes, Bruna, additional, Sousa, Patrícia, additional, Prada, Justina, additional, Pires, Isabel, additional, Ronchi, Giulia, additional, Raimondo, Stefania, additional, Luís, Ana L., additional, Geuna, Stefano, additional, Varejão, Artur Severo P., additional, and Maurício, Ana Colette, additional

Published
2022
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13. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

Author

Porporato, Paolo E., Filigheddu, Nicoletta, Reano, Simone, Ferrara, Michele, Angelino, Elia, Gnocchi, Viola F., Prodam, Flavia, Ronchi, Giulia, Fagoonee, Sharmila, Fornaro, Michele, Chianale, Federica, Baldanzi, Gianluca, Surico, Nicola, Sinigaglia, Fabiola, Perroteau, Isabelle, Smith, Roy G., Sun, Yuxiang, Geuna, Stefano, and Graziani, Andrea

Subjects
Ghrelin -- Physiological aspects -- Genetic aspects -- Research, Cachexia -- Risk factors -- Genetic aspects -- Diagnosis -- Care and treatment -- Research, Atrophy, Muscular -- Risk factors -- Genetic aspects -- Diagnosis -- Care and treatment -- Research, Health care industry
Abstract

Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a-independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a-independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kβ-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a-mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner., Introduction Skeletal muscle atrophy involves massive loss of muscle structural proteins, which leads to muscle weight decrease and progressive loss of muscle function. Skeletal muscle atrophy is induced by muscle [...]

Published
2013
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19. Preclinical Validation of SilkBridgeTM for Peripheral Nerve Regeneration

Author

Fregnan, Federica, primary, Muratori, Luisa, additional, Bassani, Giulia A., additional, Crosio, Alessandro, additional, Biagiotti, Marco, additional, Vincoli, Valentina, additional, Carta, Giacomo, additional, Pierimarchi, Pasquale, additional, Geuna, Stefano, additional, Alessandrino, Antonio, additional, Freddi, Giuliano, additional, and Ronchi, Giulia, additional

Published
2020
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20. Fibroblasts Colonizing Nerve Conduits Express High Levels of Soluble Neuregulin1, a Factor Promoting Schwann Cell Dedifferentiation

Author

Fornasari, Benedetta E., primary, El Soury, Marwa, additional, Nato, Giulia, additional, Fucini, Alessia, additional, Carta, Giacomo, additional, Ronchi, Giulia, additional, Crosio, Alessandro, additional, Perroteau, Isabelle, additional, Geuna, Stefano, additional, Raimondo, Stefania, additional, and Gambarotta, Giovanna, additional

Published
2020
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23. The Use of a Hypoallergenic Dermal Matrix for Wrapping in Peripheral Nerve Lesions Regeneration: Functional and Quantitative Morphological Analysis in an Experimental Animal Model

Author

Colonna, Michele Rosario, primary, Fazio, Antonina, additional, Costa, Alfio Luca, additional, Galletti, Franco, additional, Lo Giudice, Roberto, additional, Galletti, Bruno, additional, Galletti, Cosimo, additional, Lo Giudice, Giorgio, additional, Dell’Aversana Orabona, Giovanni, additional, Papalia, Igor, additional, Ronchi, Giulia, additional, and Geuna, Stefano, additional

Published
2019
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30. REGULATION OF THE NRG1/ERBB SYSTEM IN CMT1A PERIPHERAL NERVES

Author

Gambarotta, Giovanna, Fornasari, BENEDETTA ELENA, Ronchi, Giulia, Pascal, Davide, Raimondo, Stefania, El Soury Marwa, Budau Claudia Alexandra, Visigalli, Davide, Nobbio, Lucilla, Schenone, Angelo, and Geuna, Stefano

Published
2016

31. Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides

Author

Stenberg, Lena, primary, Stößel, Maria, additional, Ronchi, Giulia, additional, Geuna, Stefano, additional, Yin, Yaobin, additional, Mommert, Susanne, additional, Mårtensson, Lisa, additional, Metzen, Jennifer, additional, Grothe, Claudia, additional, Dahlin, Lars B., additional, and Haastert-Talini, Kirsten, additional

Published
2017
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32. Two factor-based reprogramming of rodent and human fibroblasts into Schwann cells

Author

Mazzara, Pietro Giuseppe, primary, Massimino, Luca, additional, Pellegatta, Marta, additional, Ronchi, Giulia, additional, Ricca, Alessandra, additional, Iannielli, Angelo, additional, Giannelli, Serena Gea, additional, Cursi, Marco, additional, Cancellieri, Cinzia, additional, Sessa, Alessandro, additional, Del Carro, Ubaldo, additional, Quattrini, Angelo, additional, Geuna, Stefano, additional, Gritti, Angela, additional, Taveggia, Carla, additional, and Broccoli, Vania, additional

Published
2017
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35. Ghrelin: A novel neuromuscular recovery promoting factor?

Author

Raimondo, Stefania, Ronchi, Giulia, Geuna, Stefano, Pascal, Davide, Reano, Simone, Filigheddu, Nicoletta, GRAZIANI, ANDREA, Raimondo, S, Ronchi, G, Geuna, S, Pascal, D, Reano, S, Filigheddu, N, Graziani, A, Perroteau, I, Tos, P, Battiston, B, Raimondo, Stefania, Ronchi, Giulia, Geuna, Stefano, Pascal, Davide, Reano, Simone, Filigheddu, Nicoletta, and Graziani, Andrea

Subjects
Animal, Ghrelin, Injury, Peripheral nerve, Regeneration, Skeletal muscle, Animals, Axons, Humans, Nerve Regeneration, Neuromuscular Agents, Peripheral Nerve Injuries, Recovery of Function, Neurology (clinical), Cellular and Molecular Neuroscience, Peripheral Nerve Injurie, Axon, Human, Neuromuscular Agent
Abstract

Promoting neuromuscular recovery after neural injury is a major clinical issue. While techniques for nerve reconstruction are continuously improving and most peripheral nerve lesions can be repaired today, recovery of the lost function is usually unsatisfactory. This evidence claims for innovative nonsurgical therapeutic strategies that can implement the outcome after neural repair.Although no pharmacological approach for improving posttraumatic neuromuscular recovery has still entered clinical practice, various molecules are explored in experimental models of neural repair. One of such molecules is the circulating peptide hormone ghrelin. This hormone has proved to have a positive effect on neural repair after central nervous system lesion, and very recently its effectiveness has also been demonstrated in preventing posttraumatic skeletal muscle atrophy. By contrast, no information is still available about its effectiveness on peripheral nerve regeneration although preliminary data from our laboratory suggest that this molecule can have an effect also in promoting axonal regeneration after nerve injury and repair.Should this be confirmed, ghrelin might represent an ideal candidate as a therapeutic agent for improving posttraumatic neuromuscular recovery because of its putative effects at all the various structural levels involved in this regeneration process, namely, the central nervous system, the peripheral nerve, and the target skeletal muscle. © 2013 Elsevier Inc.

Published
2013

37. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury

Author

Muratori, Luisa, Ronchi, Giulia, Raimondo, Stefania, Geuna, Stefano, Giacobini-Robecchi, Maria Giuseppina, and Fornaro, Michele

Subjects
Pathology, medicine.medical_specialty, Article Subject, Sensory Receptor Cells, Neurogenesis, Cell Count, Sensory system, Biology, lcsh:RC321-571, Lesion, Dorsal root ganglion, Peripheral Nerve Injuries, Ganglia, Spinal, medicine, Animals, Rats, Wistar, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Nestin, Nerve injury, medicine.disease, Rats, medicine.anatomical_structure, Neurology, nervous system, Crush injury, Female, Neurology (clinical), medicine.symptom, Neuroscience, Research Article
Abstract

The evidence of neurons generatedex novoin sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage.

Published
2015

39. Experimental model for the study of the effects of platelet-rich plasma on the early phases of muscle healing

Author

Paolo, Borrione, Loredana, Grasso, Chierto, Elena, Geuna, Stefano, Racca, Silvia Anna, Abbadessa, Giuliana, Ronchi, Giulia, Fabio, Faiola, Alessia Di Gianfrancesco, and Fabio, Pigozzi

Subjects
Male, Wound Healing, Myositis, Platelet-Rich Plasma, Neovascularization, Physiologic, Reproducibility of Results, Rats, Up-Regulation, Chemotaxis, Leukocyte, Gene Expression Regulation, Antigens, CD, Blood Component Removal, Leukocytes, Animals, Rats, Wistar, Muscle, Skeletal, Blood Components and Regenerative Medicine
Abstract

There is abundant evidence suggesting that growth factors may play a key role in the healing process, especially in the early stages of inflammation. Despite the reported clinical successes with the use of growth factors there is still a lack of knowledge on the biological mechanism underlying the activity of platelet-rich plasma during the process of muscle healing. The aim of this study was to analyse the early effects of platelet- rich plasma in an easily reproducible animal model.Wistar male adult rats (n=102) were used in this study. The muscle lesion was created with a scalpel in the flexor sublimis muscles. Platelet-rich plasma was applied immediately after surgery. Treated, untreated and contralateral muscles were analysed by morphological evaluation and western blot assay.Leucocyte infiltration was significantly greater in muscles treated with platelet-rich plasma than in both untreated and contralateral muscles. The latter showed greater leucocyte infiltration when compared to the untreated muscles. Platelet-rich plasma treatment also modified the cellular composition of the leucocyte infiltration leading to increased expression of CD3, CD8, CD19 and CD68 and to decreased CD4 antigen expression in both platelet-rich plasma treated and contralateral muscles. Blood vessel density and blood vessel diameters were not statistically significantly different between the three groups analysed.The results of this study showed that treatment with platelet-rich plasma magnified the physiological early inflammatory response following a muscle injury, modifying the pattern of cellular recruitment. Local platelet-rich plasma treatment may exert a direct or, more plausibly, indirect systemic effect on healing processes, at least in the earliest inflammatory phase.

Published
2014

40. Epineurial Window Is More Efficient in Attracting Axons than Simple Coaptation in a Sutureless (Cyanoacrylate-Bound) Model of End-to-Side Nerve Repair in the Rat Upper Limb: Functional and Morphometric Evidences and Review of the Literature

Author

Papalia, Igor, primary, Magaudda, Ludovico, additional, Righi, Maria, additional, Ronchi, Giulia, additional, Viano, Nicoletta, additional, Geuna, Stefano, additional, and Colonna, Michele Rosario, additional

Published
2016
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41. Modulation of the Neuregulin 1/ ErbB system after skeletal muscle denervation and reinnervation.

Author

Morano, Michela, Ronchi, Giulia, Nicolò, Valentina, Fornasari, Benedetta Elena, Crosio, Alessandro, Perroteau, Isabelle, Geuna, Stefano, Gambarotta, Giovanna, and Raimondo, Stefania

Subjects
NEUREGULINS, SKELETAL muscle, PERIPHERAL nervous system, HOMEOSTASIS, NERVE tissue
Abstract

Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/ reinnervation processes. Here, we performed a detailed time-course expression analysis of several NRG1 isoforms and ErbB receptors in the rat superficial digitorum flexor muscle after three types of median nerve injuries of different severities. We found that ErbB receptor expression was correlated with the innervated state of the muscle, with upregulation of ErbB2 clearly associated with the denervation state. Interestingly, the NRG1 isoforms were differently regulated depending on the nerve injury type, leading to the hypothesis that both the NRG1α and NRG1β isoforms play a key role in the muscle reaction to injury. Indeed, in vitro experiments with C2C12 atrophic myotubes revealed that both NRG1α and NRG1β treatment influences the best-known atrophic pathways, suggesting that NRG1 might play an anti-atrophic role. [ABSTRACT FROM AUTHOR]

Published
2018
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46. Pig decellularized peripheral nerve supports fiber regeneration.

Author

Raimondo, Stefania, Muratori, Luisa, Ronchi, Giulia, Crosio, Alessandro, and Lovati, Arianna

Abstract

The article focuses on the development of a new decellularization protocol for pig nerves that preserves the nerve extracellular matrix (ECM) and its subsequent use in repairing rat median nerves, demonstrating its potential for treating severe nerve injuries.

Published
2023

48. The Mouse Median Nerve Experimental Model in Regenerative Research.

Author

Jager, Sara Buskbjerg, Ronchi, Giulia, Vaegter, Christian Bjerggaard, and Geuna, Stefano

Abstract

Sciatic nerve crush injury in rat animal model is one of the most common experimental models used in regenerative research. However, the availability of transgenic mouse for nerve regeneration studies is constantly increasing and, therefore, the shift from rat model to mouse model is, in some cases, necessary. Moreover, since most of the human nerve lesions occur in the upper limb, it is also advantageous to shift from sciatic nerve to median nerve. In this study we described an experimental model which involves lesions of the median nerve in the mouse. Data showed that the finger flexor muscle contraction strength, assessed to evaluate the motor function recovery, and reached values not different from the control already 20 days after injury. The degree of nerve regeneration evaluated with stereological methods in light microscopy showed that, 25 days after injury, the number of regenerated myelinated fibers was comparable to the control, but they were smaller with a thinner myelin thickness. Stereological analysis made in electron microscopy confirmed these results, although the total number of fibers quantified was significantly higher compared to light microscopy analysis, due to the very small size of some fibers that can be detected only in electron microscopy. [ABSTRACT FROM AUTHOR]

Published
2014
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50. Reconstruction of Critical Nerve Defects Using Allogenic Nerve Tissue: A Review of Current Approaches.

Author

Kornfeld, Tim, Borger, Anton, Radtke, Christine, and Ronchi, Giulia

Subjects
NERVE tissue, NERVE grafting, NEUROSURGERY, NERVES, AUTOTRANSPLANTATION
Abstract

Regardless of the nerve defect length, nerve injury is a debilitating condition for the affected patient that results in loss of sensory and motor function. These functional impairments can have a profound impact on the patient's quality of life. Surgical approaches for the treatment of short segment nerve defects are well-established. Autologous nerve transplantation, considered the gold standard, and the use of artificial nerve grafts are safe and successful procedures for short segment nerve defect reconstruction. Long segment nerve defects which extend 3.0 cm or more are more problematic for repair. Methods for reconstruction of long defects are limited. Artificial nerve grafts often fail to regenerate and autologous nerve grafts are limited in length and number. Cadaveric processed/unprocessed nerve allografts are a promising alternative in nerve surgery. This review gives a systematic overview on pre-clinical and clinical approaches in nerve allograft transplantation. [ABSTRACT FROM AUTHOR]

Published
2021
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