{"doi":"10.7150/ijbs.73747","title":"Mesenchymal stromal cell-derived extracellular vesicles afford neuroprotection by modulating PI3K/AKT pathway and calcium oscillations","abstract":"Mesenchymal stromal cells (MSC) are widely recognized as potential effectors in neuroprotective therapy. The protective properties of MSC were considered to be associated with the secretion of extracellular vesicles (MSC-EV). We explored the effects of MSC-EV in vivo on models of traumatic and hypoxia-ischemia (HI) brain injury. Neuroprotective mechanisms triggered by MSC-EV were also studied in vitro using a primary neuroglial culture. Intranasal administration of MSC-EV reduced the volume of traumatic brain damage, correlating with a recovery of sensorimotor functions. Neonatal HI-induced brain damage was mitigated by the MSC-EV administration. This therapy also promoted the recovery of sensorimotor functions, implying enhanced neuroplasticity, and MSC-EV-induced growth of neurites in vitro supports this. In the in vitro ischemic model, MSC-EV prevented cell calcium (Ca 2+ ) overload and subsequent cell death. In mixed neuroglial culture, MSC-EV induced inositol trisphosphate (IP3) receptor-related Ca 2+ oscillations in astrocytes were associated with resistance to calcium overload not only in astrocytes but also in co-cultured neurons, demonstrating intercellular positive crosstalk between neural cells. This implies that phosphatidylinositol 3-Kinase/AKT signaling is one of the main pathways in MSC-EV-mediated protection of neural cells exposed to ischemic challenge. Components of this pathway were identified among the most enriched categories in the MSC-EV proteome.","journal":"International Journal of Biological Sciences","year":2022,"id":238370,"datarank":1.5369519197120418,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":0.9331491661017693,"self_endowment_contribution":0.6038027536102726,"citer_contribution":0.9331491661017693,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":44,"citers_with_citation_signal":35,"citers_with_endowment":35,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":862640,"name":"Victoria V. Golovicheva","orcid":null,"position":1,"is_corresponding":false},{"id":862071,"name":"Е. Г. Варламова","orcid":"0009-0000-9013-9855","position":2,"is_corresponding":false},{"id":862641,"name":"T. I. Danilina","orcid":null,"position":3,"is_corresponding":false},{"id":862072,"name":"Кirill Goryunov","orcid":"0000-0002-8776-7196","position":4,"is_corresponding":false},{"id":862642,"name":"Yulia A. Shevtsova","orcid":null,"position":5,"is_corresponding":false},{"id":862073,"name":"Irina B. Pevzner","orcid":"0000-0001-5048-1234","position":6,"is_corresponding":false},{"id":862074,"name":"Ljubava D. Zorova","orcid":"0000-0001-9046-712X","position":7,"is_corresponding":false},{"id":862643,"name":"Valentina A. Babenko","orcid":null,"position":8,"is_corresponding":false},{"id":862075,"name":"Ekaterina A. Evtushenko","orcid":"0000-0002-0679-6818","position":9,"is_corresponding":false},{"id":39626,"name":"A. A. Zharikova","orcid":"0000-0003-0723-0493","position":10,"is_corresponding":false},{"id":862076,"name":"Anastasia A. Khutornenko","orcid":"0000-0002-1573-9903","position":11,"is_corresponding":false},{"id":634005,"name":"Sergey I. Kovalchuk","orcid":"0000-0001-5273-3431","position":12,"is_corresponding":false},{"id":862077,"name":"Egor Y. Plotnikov","orcid":"0000-0003-2838-3704","position":13,"is_corresponding":false},{"id":471092,"name":"Dmitry B. Zorov","orcid":"0000-0003-0863-8490","position":14,"is_corresponding":false},{"id":745704,"name":"Г. Т. Сухих","orcid":"0000-0002-7712-1260","position":15,"is_corresponding":false},{"id":862078,"name":"Д. Н. Силачев","orcid":"0000-0003-0581-9755","position":16,"is_corresponding":false},{"id":277635,"name":"Egor A. Turovsky","orcid":"0000-0002-2528-8798","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:26.932537Z","pmid":"36147480","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}