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These developments have opened new translational research avenues to explore the neuroprotective effects of platelet-extracellular vesicles (PEVs). Their potential in managing neurodegenerative conditions like traumatic brain injury (TBI) and Parkinson\u2019s disease (PD) warrants further exploration. We aimed here to characterize the composition of a PEV preparation isolated from platelet concentrate (PC)\u00a0supernatant, and determine its neuroprotective potential and neurorestorative effects in cellular and animal models of TBI and PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We isolated PEVs from the supernatant of clinical-grade PC collected from healthy blood donors utilizing high-speed centrifugation. PEVs were characterized by biophysical, biochemical, microscopic, and LC\u2013MS\/MS proteomics methods to unveil biological functions. Their functionality was assessed in vitro using SH-SY5Y neuronal cells, LUHMES dopaminergic neurons, and BV-2 microglial cells, and in vivo by intranasal administration in a controlled cortical impact (CCI)-TBI model using 8-weeks-old male C57\/BL6 mice, and in a PD model induced by MPTP in 5-month-old male C57\/BL6 mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PEVs varied in size from 50 to 350\u00a0nm, predominantly around 200\u00a0nm, with concentrations ranging between 10\n                      <jats:sup>10<\/jats:sup>\n                      and 10\n                      <jats:sup>11<\/jats:sup>\n                      \/mL. They expressed specific platelet membrane markers, exhibited a lipid bilayer by cryo-electron microscopy and, importantly, showed low\u00a0expression of pro-coagulant phosphatidylserine. LC\u2013MS\/MS indicated a rich composition of trophic factors, including neurotrophins, anti-inflammatory agents, neurotransmitters, and antioxidants, unveiling their multifaceted biological functions. PEVs aided in the restoration of neuronal functions in SH-SY5Y cells and demonstrated remarkable neuroprotective capabilities against erastin-induced ferroptosis in dopaminergic neurons. In microglial cells, they promoted anti-inflammatory responses, particularly under inflammatory conditions. In vivo\n                      <jats:italic>,<\/jats:italic>\n                      intranasally delivered PEVs showed strong anti-inflammatory effects in a TBI mouse model and conserved tyrosine hydroxylase expression of dopaminergic neurons of the substantia nigra in a PD model, leading to improved motor function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The potential of PEV-based therapies in neuroprotection opens new therapeutic avenues for neurodegenerative disorders. The study advocates for clinical trials to establish the efficacy of PEV-based biotherapies in neuroregenerative medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-024-01072-z","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T03:03:13Z","timestamp":1725505393000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson\u2019s disease models"],"prefix":"10.1186","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-3489","authenticated-orcid":false,"given":"Liling","family":"Delila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6802-4215","authenticated-orcid":false,"given":"Ouada","family":"Nebie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9540-8564","authenticated-orcid":false,"given":"Nhi Thao Ngoc","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Timmerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng-Yao","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7636-0393","authenticated-orcid":false,"given":"Yu-Wen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-5332","authenticated-orcid":false,"given":"Ming-Li","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-4230","authenticated-orcid":false,"given":"Luc","family":"Bu\u00e9e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4387-749X","authenticated-orcid":false,"given":"Szu-Yi","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-431X","authenticated-orcid":false,"given":"David","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2417-799X","authenticated-orcid":false,"given":"David","family":"Devos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-9243","authenticated-orcid":false,"given":"Thierry","family":"Burnouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"issue":"7","key":"1072_CR1","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s00018-022-04397-w","volume":"79","author":"O Nebie","year":"2022","unstructured":"Nebie O, et al. 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