{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:42:10Z","timestamp":1760035330103,"version":"build-2065373602"},"reference-count":136,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["P30EY14801","U01EY027257"],"award-info":[{"award-number":["P30EY14801","U01EY027257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Extracellular vesicles (EVs) are bilayer lipid membrane particles that are released by every cell type. These secretions are further classified as exosomes, ectosomes, and microvesicles. They contain biomolecules (RNAs, proteins, metabolites, and lipids) with the ability to modulate various biological processes and have been shown to play a role in intercellular communication and cellular rejuvenation. Various studies suggest exosomes and\/or microvesicles as a potential platform for drug delivery. EVs may deliver lipids and nucleotides directly to an injury site in an axon, promoting growth cone stabilization and membrane expansion as well as repair, thus positively modulating adult axon regeneration. In this review, we will provide a perspective on the metabolite composition of EVs in adult axonal regeneration relevant to the central nervous system (CNS), specifically that pertaining to the optic nerve. We will present an overview of the methods for isolation, enrichment, omics data analysis and quantification of extracellular vesicles with the goal of providing direction for future studies relevant to axon regeneration. We will also include current resources for multi-omics data integration relevant to extracellular vesicles from diverse cell types.<\/jats:p>","DOI":"10.3390\/metabo15070454","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T06:03:13Z","timestamp":1751868193000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicle Metabolomics Holds Promise for Adult Axon Regeneration"],"prefix":"10.3390","volume":"15","author":[{"given":"Maria D.","family":"Cabrera Gonzalez","sequence":"first","affiliation":[{"name":"Miami Integrative Metabolomics Research Center, Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackson","family":"Watson","sequence":"additional","affiliation":[{"name":"Miami Integrative Metabolomics Research Center, Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Leal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Universidade Positivo, Curitiba 81280-330, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Moceri","sequence":"additional","affiliation":[{"name":"Miami Integrative Metabolomics Research Center, Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Plummer","sequence":"additional","affiliation":[{"name":"Miami Integrative Metabolomics Research Center, Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biraj","family":"Mahato","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelrahman Y.","family":"Fouda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjoy K.","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Miami Integrative Metabolomics Research Center, Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8974","DOI":"10.7150\/thno.44912","article-title":"Mechanical stimulation of Schwann cells promote peripheral nerve regeneration via extracellular vesicle-mediated transfer of microRNA 23b-3p","volume":"10","author":"Xia","year":"2020","journal-title":"Theranostics"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Klimovich, P., Rubina, K., Sysoeva, V., and Semina, E. (2021). New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413380"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.2174\/1570159X19666210203161559","article-title":"Exosomes as a Promising Therapeutic Strategy for Peripheral Nerve Injury","volume":"19","author":"Yu","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.1523\/JNEUROSCI.4013-14.2015","article-title":"Effects of PTEN and Nogo Codeletion on Corticospinal Axon Sprouting and Regeneration in Mice","volume":"35","author":"Geoffroy","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s40135-017-0153-0","article-title":"Extracellular Vesicles: Biomarkers, Therapeutics, and Vehicles in the Visual System","volume":"5","author":"Steketee","year":"2017","journal-title":"Curr. Ophthalmol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6113","DOI":"10.2147\/IJN.S390378","article-title":"Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications","volume":"17","author":"Wu","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1081\/CNV-120023777","article-title":"Neuronal stem cells biology and plasticity","volume":"21","author":"Mondal","year":"2003","journal-title":"Cancer Invest."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/B978-0-12-819410-2.00001-1","article-title":"Defining neuroplasticity","volume":"184","author":"Innocenti","year":"2022","journal-title":"Handb. Clin. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev.neuro.051508.135600","article-title":"The glial nature of embryonic and adult neural stem cells","volume":"32","author":"Kriegstein","year":"2009","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8393","DOI":"10.1523\/JNEUROSCI.1131-22.2022","article-title":"Mechanisms of Axon Growth and Regeneration: Moving between Development and Disease","volume":"42","author":"Bradke","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neures.2014.07.005","article-title":"Proteomic identification of the molecular basis of mammalian CNS growth cones","volume":"88","author":"Igarashi","year":"2014","journal-title":"Neurosci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/scientificamerican0979-54","article-title":"The Neuron","volume":"241","author":"Stevens","year":"1979","journal-title":"Sci. Am."},{"key":"ref_14","unstructured":"Squire, L.R. (2009). Wallerian Degeneration. Encyclopedia of Neuroscience, Academic Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nrn3680","article-title":"Wallerian degeneration: An emerging axon death pathway linking injury and disease","volume":"15","author":"Conforti","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00401-015-1482-4","article-title":"Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury","volume":"130","author":"Chen","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.celrep.2016.03.028","article-title":"Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System","volume":"15","author":"Geoffroy","year":"2016","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.tins.2014.08.008","article-title":"Axon plasticity in the mammalian central nervous system after injury","volume":"37","author":"Chen","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2105586","DOI":"10.1002\/advs.202105586","article-title":"Exosomes-Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth","volume":"9","author":"Fan","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.21037\/atm-20-5351","article-title":"The basic science of optic nerve regeneration","volume":"9","author":"Fague","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Steele-Nicholson, L.J., and Andrews, M.R. (2022). Axon-Targeting Motifs: Mechanisms and Applications of Enhancing Axonal Localisation of Transmembrane Proteins. Cells, 11.","DOI":"10.3390\/cells11060937"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Huang, J., Zhang, G., Li, S., Li, J., Wang, W., Xue, J., Wang, Y., Fang, M., and Zhou, N. (2024). Correction: Endothelial cell-derived exosomes boost and maintain repair-related phenotypes of Schwann cells via miR199-5p to promote nerve regeneration. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-023-02289-0"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/01.LAB.0000056993.28149.BF","article-title":"Macrophage response to peripheral nerve injury: The quantitative contribution of resident and hematogenous macrophages","volume":"83","author":"Mueller","year":"2003","journal-title":"Lab. Invest."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1084\/jem.165.4.1218","article-title":"The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration","volume":"165","author":"Perry","year":"1987","journal-title":"J. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s004010050611","article-title":"The dynamics of macrophage recruitment after nerve transection","volume":"93","author":"Taskinen","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.expneurol.2009.12.032","article-title":"PTEN\/mTOR and axon regeneration","volume":"223","author":"Park","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1126\/science.1161566","article-title":"Promoting axon regeneration in the adult CNS by modulation of the PTEN\/mTOR pathway","volume":"322","author":"Park","year":"2008","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Poongodi, R., Chen, Y.L., Yang, T.H., Huang, Y.H., Yang, K.D., Lin, H.C., and Cheng, J.K. (2021). Bio-Scaffolds as Cell or Exosome Carriers for Nerve Injury Repair. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413347"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Thery","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s10571-015-0314-3","article-title":"Schwann Cell Exosomes Mediate Neuron-Glia Communication and Enhance Axonal Regeneration","volume":"36","author":"Court","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.jconrel.2023.10.012","article-title":"Schwann cell-derived extracellular vesicles as a potential therapy for retinal ganglion cell degeneration","volume":"363","author":"Zhu","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Massoumi, H., Amin, S., Soleimani, M., Momenaei, B., Ashraf, M.J., Guaiquil, V.H., Hematti, P., Rosenblatt, M.I., Djalilian, A.R., and Jalilian, E. (2023). Extracellular-Vesicle-Based Therapeutics in Neuro-Ophthalmic Disorders. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24109006"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"jcs239004","DOI":"10.1242\/jcs.239004","article-title":"Schwann cell reprogramming into repair cells increases miRNA-21 expression in exosomes promoting axonal growth","volume":"133","author":"Catalan","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Royo, F., Thery, C., Falcon-Perez, J.M., Nieuwland, R., and Witwer, K.W. (2020). Methods for Separation and Characterization of Extracellular Vesicles: Results of a Worldwide Survey Performed by the ISEV Rigor and Standardization Subcommittee. Cells, 9.","DOI":"10.3390\/cells9091955"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mex.2015.01.002","article-title":"Quick and reliable method for retina dissociation and separation of rod photoreceptor perikarya from adult mice","volume":"2","author":"Feodorova","year":"2015","journal-title":"MethodsX"},{"key":"ref_36","first-page":"55785","article-title":"Isolation of Primary Murine Retinal Ganglion Cells (RGCs) by Flow Cytometry","volume":"5","author":"Chintalapudi","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1039\/C6AN00892E","article-title":"Effective isolation of exosomes with polyethylene glycol from cell culture supernatant for in-depth proteome profiling","volume":"141","author":"Weng","year":"2016","journal-title":"Analyst"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/bs.pmbts.2018.03.001","article-title":"Gangliosides in Axon Stability and Regeneration","volume":"156","author":"Lopez","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Qazi, R.E.M., Sajid, Z., Zhao, C., Hussain, I., Iftikhar, F., Jameel, M., Rehman, F.U., and Mian, A.A. (2023). Lyophilization Based Isolation of Exosomes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310477"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Noboa-Velastegui, J., Leon, J.C., Castro, J., Fletes, A., Madrigal, P., Alvarez, I., and Navarro, R. (2025). Comparison of Methods for Isolating Exosomes from Plasma Subjects with Normal and High Fat Percentages. Life, 15.","DOI":"10.20944\/preprints202405.0665.v2"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Martins, T.S., Catita, J., Rosa, I.M., da Cruz e SilvaSilva, O.A.B., and Henriques, A.G. (2018). Exosome isolation from distinct biofluids using precipitation and column-based approaches. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198820"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e12128","DOI":"10.1002\/jev2.12128","article-title":"Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin","volume":"10","author":"Veerman","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, J., Li, P., Zhang, T., Xu, Z., Huang, X., Wang, R., and Du, L. (2021). Review on Strategies and Technologies for Exosome Isolation and Purification. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.811971"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108010","DOI":"10.1016\/j.diabres.2020.108010","article-title":"The profiles of microRNAs from urinary extracellular vesicles (EVs) prepared by various isolation methods and their correlation with serum EV microRNAs","volume":"160","author":"Park","year":"2020","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Peng, Y., Zhao, M., Hu, Y., Guo, H., Zhang, Y., Huang, Y., Zhao, L., Chai, Y., and Wang, Z. (2022). Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer. BMC Immunol., 23.","DOI":"10.1186\/s12865-022-00514-3"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Muraoka, S., Jedrychowski, M.P., Yanamandra, K., Ikezu, S., Gygi, S.P., and Ikezu, T. (2020). Proteomic Profiling of Extracellular Vesicles Derived from Cerebrospinal Fluid of Alzheimer\u2019s Disease Patients: A Pilot Study. Cells, 9.","DOI":"10.3390\/cells9091959"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Konoshenko, M.Y., Lekchnov, E.A., Vlassov, A.V., and Laktionov, P.P. (2018). Isolation of Extracellular Vesicles: General Methodologies and Latest Trends. Biomed Res. Int., 2018.","DOI":"10.1155\/2018\/8545347"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"32945","DOI":"10.3402\/jev.v5.32945","article-title":"Techniques used for the isolation and characterization of extracellular vesicles: Results of a worldwide survey","volume":"5","author":"Gardiner","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Livshits, M.A., Khomyakova, E., Evtushenko, E.G., Lazarev, V.N., Kulemin, N.A., Semina, S.E., Generozov, E.V., and Govorun, V.M. (2015). Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol. Sci. Rep., 5.","DOI":"10.1038\/srep17319"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1515\/hsz-2013-0141","article-title":"Current methods for the isolation of extracellular vesicles","volume":"394","author":"Balaj","year":"2013","journal-title":"Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jim.2008.07.007","article-title":"Discrimination between exosomes and HIV-1: Purification of both vesicles from cell-free supernatants","volume":"338","author":"Cantin","year":"2008","journal-title":"J. Immunol. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"23430","DOI":"10.3402\/jev.v3.23430","article-title":"Single-step isolation of extracellular vesicles by size-exclusion chromatography","volume":"3","author":"Boing","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"24858","DOI":"10.3402\/jev.v3.24858","article-title":"The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling","volume":"3","author":"Mestdagh","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-4939-2550-6_15","article-title":"A protocol for exosome isolation and characterization: Evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods","volume":"1295","author":"Greening","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E968","DOI":"10.1073\/pnas.1521230113","article-title":"Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes","volume":"113","author":"Kowal","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ymeth.2012.01.002","article-title":"Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes","volume":"56","author":"Tauro","year":"2012","journal-title":"Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1002\/elps.201800526","article-title":"Recent advances and challenges in the recovery and purification of cellular exosomes","volume":"40","year":"2019","journal-title":"Electrophoresis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ymeth.2015.05.028","article-title":"Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches","volume":"87","author":"Zarovni","year":"2015","journal-title":"Methods"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/elps.202100124","article-title":"Biological nanoparticles: Relevance as novel target drug delivery systems and leading chromatographic isolation approaches","volume":"43","year":"2022","journal-title":"Electrophoresis"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sidhom, K., Obi, P.O., and Saleem, A. (2020). A Review of Exosomal Isolation Methods: Is Size Exclusion Chromatography the Best Option?. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202007.0485.v2"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-1-4939-9769-5_4","article-title":"Exosomes Extraction and Identification","volume":"2054","author":"Wu","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1007\/s00018-018-2773-4","article-title":"Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins","volume":"75","author":"Karimi","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41556-018-0040-4","article-title":"Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation","volume":"20","author":"Zhang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/s41596-019-0126-x","article-title":"Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization","volume":"14","author":"Zhang","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14205","DOI":"10.1021\/acsnano.3c01117","article-title":"Microfluidic Devices: A Tool for Nanoparticle Synthesis and Performance Evaluation","volume":"17","author":"Gimondi","year":"2023","journal-title":"ACS Nano"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jim.2011.10.012","article-title":"Methodology for isolation, identification and characterization of microvesicles in peripheral blood","volume":"375","author":"Jayachandran","year":"2012","journal-title":"J. Immunol. Methods"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1186\/s13287-024-04005-7","article-title":"Different storage and freezing protocols for extracellular vesicles: A systematic review","volume":"15","author":"Ahmadian","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bosch, S., de Beaurepaire, L., Allard, M., Mosser, M., Heichette, C., Chretien, D., Jegou, D., and Bach, J.M. (2016). Trehalose prevents aggregation of exosomes and cryodamage. Sci. Rep., 6.","DOI":"10.1038\/srep36162"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e12238","DOI":"10.1002\/jev2.12238","article-title":"Identification of storage conditions stabilizing extracellular vesicles preparations","volume":"11","author":"Gorgens","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"26913","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles","volume":"3","author":"Lotvall","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/0471143030.cb0322s30","article-title":"Isolation and characterization of exosomes from cell culture supernatants and biological fluids","volume":"30","author":"Thery","year":"2006","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Jung, M.K., and Mun, J.Y. (2018). Sample Preparation and Imaging of Exosomes by Transmission Electron Microscopy. J. Vis. Exp., e56482.","DOI":"10.3791\/56482"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"109562","DOI":"10.1016\/j.exer.2023.109562","article-title":"Glaucomatous aqueous humor vesicles are smaller and differ in composition compared to controls","volume":"234","author":"Mueller","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Skliar, M., and Chernyshev, V.S. (2019). Imaging of Extracellular Vesicles by Atomic Force Microscopy. J. Vis. Exp., e59254.","DOI":"10.3791\/59254-v"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kowkabany, G., and Bao, Y. (2024). Nanoparticle Tracking Analysis: An Effective Tool to Characterize Extracellular Vesicles. Molecules, 29.","DOI":"10.3390\/molecules29194672"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1365-2567.2012.03569.x","article-title":"Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells","volume":"136","author":"Soo","year":"2012","journal-title":"Immunology"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kobayashi, H., Shiba, T., Yoshida, T., Bolidong, D., Kato, K., Sato, Y., Mochizuki, M., Seto, T., Kawashiri, S., and Hanayama, R. (2024). Precise analysis of single small extracellular vesicles using flow cytometry. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-57974-3"},{"key":"ref_78","first-page":"225","article-title":"AFM capabilities in characterization of particles and surfaces: From angstroms to microns","volume":"59","author":"Starostina","year":"2008","journal-title":"J. Cosmet. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"21494","DOI":"10.3402\/jev.v2i0.21494","article-title":"Cryo-electron microscopy of extracellular vesicles in fresh plasma","volume":"2","author":"Yuana","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1146\/annurev.biophys.050708.133634","article-title":"Advances in imaging secondary ion mass spectrometry for biological samples","volume":"38","author":"Boxer","year":"2009","journal-title":"Annu. Rev. Biophys."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Chamberlain, C.A., Hatch, M., and Garrett, T.J. (2021). Extracellular Vesicle Analysis by Paper Spray Ionization Mass Spectrometry. Metabolites, 11.","DOI":"10.3390\/metabo11050308"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19179","DOI":"10.3402\/jev.v1i0.19179","article-title":"Fast characterisation of cell-derived extracellular vesicles by nanoparticles tracking analysis, cryo-electron microscopy, and Raman tweezers microspectroscopy","volume":"1","author":"Tatischeff","year":"2012","journal-title":"J. Extracell. Vesicles"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.bbamem.2016.12.005","article-title":"Characterization of extracellular vesicles by IR spectroscopy: Fast and simple classification based on amide and CH stretching vibrations","volume":"1859","author":"Mihaly","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Willms, E., Johansson, H.J., Mager, I., Lee, Y., Blomberg, K.E., Sadik, M., Alaarg, A., Smith, C.I., Lehtio, J., and El Andaloussi, S. (2016). Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci. Rep., 6.","DOI":"10.1038\/srep22519"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Maekawa, M., and Mano, N. (2022). Cutting-edge LC-MS\/MS applications in clinical mass spectrometry: Focusing on analysis of drugs and metabolites. Biomed. Chromatogr., 36.","DOI":"10.1002\/bmc.5347"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Abyadeh, M., Mirshahvaladi, S., Kashani, S.A., Paulo, J.A., Amirkhani, A., Mehryab, F., Seydi, H., Moradpour, N., Jodeiryjabarzade, S., and Mirzaei, M. (2024). Proteomic profiling of mesenchymal stem cell-derived extracellular vesicles: Impact of isolation methods on protein cargo. J. Extracell. Biol., 3.","DOI":"10.1002\/jex2.159"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"O111-016717","DOI":"10.1074\/mcp.O111.016717","article-title":"Targeted data extraction of the MS\/MS spectra generated by data-independent acquisition: A new concept for consistent and accurate proteome analysis","volume":"11","author":"Gillet","year":"2012","journal-title":"Mol. Cell. Proteom."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1021\/acs.jproteome.0c00153","article-title":"Impact of the Identification Strategy on the Reproducibility of the DDA and DIA Results","volume":"19","author":"McClatchy","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12014-024-09489-2","article-title":"Proteomic profiling of extracellular vesicles derived from human serum for the discovery of biomarkers in Avascular necrosis","volume":"21","author":"Sung","year":"2024","journal-title":"Clin. Proteom."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jmb.2015.09.019","article-title":"ExoCarta: A Web-Based Compendium of Exosomal Cargo","volume":"428","author":"Keerthikumar","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.plipres.2017.03.001","article-title":"Lipids in exosomes: Current knowledge and the way forward","volume":"66","author":"Skotland","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kalra, H., Drummen, G.P., and Mathivanan, S. (2016). Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020170"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1021\/ac0262560","article-title":"Tandem mass tags: A novel quantification strategy for comparative analysis of complex protein mixtures by MS\/MS","volume":"75","author":"Thompson","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"W251","DOI":"10.1093\/nar\/gkv380","article-title":"MetaboAnalyst 3.0--making metabolomics more meaningful","volume":"43","author":"Xia","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Wang, T., Li, Y., Guo, M., Dong, X., Liao, M., Du, M., Wang, X., Yin, H., and Yan, H. (2021). Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy. Front. Cell. Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.659783"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.exer.2015.10.004","article-title":"Neuroprotective effect of 4-(Phenylsulfanyl)butan-2-one on optic nerve crush model in rats","volume":"143","author":"Chien","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10633-018-9663-9","article-title":"Flash visual evoked potentials (FVEP) in various stimulation conditions","volume":"138","author":"Maruszczyk","year":"2019","journal-title":"Doc. Ophthalmol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/gps.4117","article-title":"Using visual evoked potentials for the early detection of amnestic mild cognitive impairment: A pilot investigation","volume":"30","author":"Fix","year":"2015","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3727\/096368910X","article-title":"Mesenchymal stem cells","volume":"20","author":"Ding","year":"2011","journal-title":"Cell Transpl."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jchemneu.2019.01.006","article-title":"UMSC-derived exosomes promote retinal ganglion cells survival in a rat model of optic nerve crush","volume":"96","author":"Pan","year":"2019","journal-title":"J. Chem. Neuroanat."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1167\/iovs.08-3267","article-title":"Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in naive and optic nerve-injured retinas","volume":"50","author":"Agudo","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/sctm.16-0428","article-title":"Bone Marrow-Derived Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Retinal Ganglion Cells Through miRNA-Dependent Mechanisms","volume":"6","author":"Mead","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7544","DOI":"10.1167\/iovs.13-13045","article-title":"Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury","volume":"54","author":"Mead","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_106","first-page":"487","article-title":"The therapeutic effects of bone marrow mesenchymal stem cells after optic nerve damage in the adult rat","volume":"10","author":"Tan","year":"2015","journal-title":"Clin. Interv. Aging"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Mesentier-Louro, L.A., Zaverucha-do-Valle, C., da Silva-Junior, A.J., Nascimento-Dos-Santos, G., Gubert, F., de Figueiredo, A.B., Torres, A.L., Paredes, B.D., Teixeira, C., and Tovar-Moll, F. (2014). Distribution of mesenchymal stem cells and effects on neuronal survival and axon regeneration after optic nerve crush and cell therapy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110722"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e5008","DOI":"10.1002\/jms.5008","article-title":"Spatial neurolipidomics-MALDI mass spectrometry imaging of lipids in brain pathologies","volume":"59","author":"Jha","year":"2024","journal-title":"J. Mass Spectrom."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1167\/iovs.17-22509","article-title":"Optic Nerve Regeneration After Crush Remodels the Injury Site: Molecular Insights From Imaging Mass Spectrometry","volume":"59","author":"Stark","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1021\/jasms.0c00187","article-title":"MALDI Mass Spectrometry Imaging in a Primary Demyelination Model of Murine Spinal Cord","volume":"31","author":"Sekera","year":"2020","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"103950","DOI":"10.1016\/j.dib.2019.103950","article-title":"Comparative lipid profiling dataset of the inflammation-induced optic nerve regeneration","volume":"24","author":"Trzeciecka","year":"2019","journal-title":"Data Brief"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"108306","DOI":"10.1016\/j.dib.2022.108306","article-title":"Metabolomics dataset of mouse optogenetic axon regeneration after optic nerve crush","volume":"42","author":"Jauregui","year":"2022","journal-title":"Data Brief"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.cmet.2020.08.015","article-title":"Glial Metabolic Rewiring Promotes Axon Regeneration and Functional Recovery in the Central Nervous System","volume":"32","author":"Li","year":"2020","journal-title":"Cell Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-022-04884-x","article-title":"The gut metabolite indole-3 propionate promotes nerve regeneration and repair","volume":"607","author":"Serger","year":"2022","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"10125","DOI":"10.7150\/thno.62525","article-title":"Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT\/mTOR signaling","volume":"11","author":"Zhao","year":"2021","journal-title":"Theranostics"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0304-3940(96)12506-4","article-title":"The carbohydrate N-acetylglucosamine is involved in the guidance of neurites from chick ciliary ganglion neurons through the extracellular matrix of rat skeletal muscle fiber","volume":"207","author":"Iglesias","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5937","DOI":"10.1523\/JNEUROSCI.2570-09.2010","article-title":"N-acetylglucosamine 6-O-sulfotransferase-1-deficient mice show better functional recovery after spinal cord injury","volume":"30","author":"Ito","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_118","first-page":"53","article-title":"The effect of allantoin on cellular multiplication in degenerating and regenerating nerves","volume":"55","author":"Loots","year":"1979","journal-title":"S. Afr. Med. J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e55076","DOI":"10.15252\/embr.202255076","article-title":"Histidine dephosphorylation of the Gbeta protein GPB-1 promotes axon regeneration in C. elegans","volume":"23","author":"Sakai","year":"2022","journal-title":"EMBO Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1523\/JNEUROSCI.21-13-04649.2001","article-title":"MIP-1alpha, MCP-1, GM-CSF, and TNF-alpha control the immune cell response that mediates rapid phagocytosis of myelin from the adult mouse spinal cord","volume":"21","author":"Ousman","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1055\/s-0039-1683409","article-title":"Lysophosphatidylcholine is a Major Component of Platelet Microvesicles Promoting Platelet Activation and Reporting Atherosclerotic Plaque Instability","volume":"119","author":"Diehl","year":"2019","journal-title":"Thromb. Haemost."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bbrc.2020.11.119","article-title":"Structurally different lysophosphatidylethanolamine species stimulate neurite outgrowth in cultured cortical neurons via distinct G-protein-coupled receptors and signaling cascades","volume":"534","author":"Hisano","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41467-017-02533-w","article-title":"Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures","volume":"9","author":"Miranda","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Mersman, B., Zaidi, W., Syed, N.I., and Xu, F. (2020). Taurine Promotes Neurite Outgrowth and Synapse Development of Both Vertebrate and Invertebrate Central Neurons. Front. Synaptic. Neurosci., 12.","DOI":"10.3389\/fnsyn.2020.00029"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1089\/neu.2019.6604","article-title":"Taurine Promotes Axonal Regeneration after a Complete Spinal Cord Injury in Lampreys","volume":"37","author":"Pereiro","year":"2020","journal-title":"J. Neurotrauma"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/BF01318859","article-title":"Taurine, glutamate and GABA modulate the outgrowth from goldfish retinal explants and its concentrations are affected by the crush of the optic nerve","volume":"15","author":"Lima","year":"1998","journal-title":"Amino Acids"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wu, J.Y., and Prentice, H. (2010). Role of taurine in the central nervous system. J. Biomed. Sci., 17.","DOI":"10.1186\/1423-0127-17-S1-S1"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Kronman, H., Singh, A., Azam, S., Guzman, A.S., Zelli, D., Lau, T., Dobbin, J., Bigio, B., and Nasca, C. (2025). Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles. Biol. Psychiatry Glob. Open Sci., 5.","DOI":"10.1016\/j.bpsgos.2024.100401"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1007\/s11064-023-03911-1","article-title":"The Effect of Acetyl-L-Carnitine (ALCAR) on Peripheral Nerve Regeneration in Animal Models: A Systematic Review","volume":"48","author":"Pourshahidi","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.lfs.2018.10.043","article-title":"Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats","volume":"215","author":"Mirzakhani","year":"2018","journal-title":"Life Sci."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Sugihara, Y., Onoue, S., Tashiro, K., Sato, M., Hasegawa, T., and Katakura, Y. (2019). Carnosine induces intestinal cells to secrete exosomes that activate neuronal cells. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217394"},{"key":"ref_132","first-page":"e22305","article-title":"The metabolomic profiling identifies N, N-dimethylglycine as a facilitator of dorsal root ganglia neuron axon regeneration after injury","volume":"36","author":"Zhang","year":"2022","journal-title":"FASEB J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1194\/jlr.M003657","article-title":"Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins","volume":"51","author":"Subra","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1083\/jcb.126.3.801","article-title":"Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho","volume":"126","author":"Jalink","year":"1994","journal-title":"J. Cell Biol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Chatterjee, A., and Singh, R. (2023). Extracellular vesicles: An emerging player in retinal homeostasis. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1059141"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"102002","DOI":"10.1016\/j.jchemneu.2021.102002","article-title":"Allantoin, a purine metabolite, enhances peripheral nerve regeneration following sciatic nerve injury in rats: A stereological and immunohistochemical study","volume":"117","author":"Delibas","year":"2021","journal-title":"J. Chem. Neuroanat."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:04:31Z","timestamp":1760033071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/7\/454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":136,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["metabo15070454"],"URL":"https:\/\/doi.org\/10.3390\/metabo15070454","relation":{},"ISSN":["2218-1989"],"issn-type":[{"type":"electronic","value":"2218-1989"}],"subject":[],"published":{"date-parts":[[2025,7,4]]}}}