{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:31:05Z","timestamp":1782397865569,"version":"3.54.5"},"reference-count":106,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1190562"],"award-info":[{"award-number":["1190562"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1180042"],"award-info":[{"award-number":["1180042"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1200287"],"award-info":[{"award-number":["1200287"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal Asphyxia (PA) is a leading cause of motor and neuropsychiatric disability associated with sustained oxidative stress, neuroinflammation, and cell death, affecting brain development. Based on a rat model of global PA, we investigated the neuroprotective effect of intranasally administered secretome, derived from human adipose mesenchymal stem cells (MSC-S), preconditioned with either deferoxamine (an hypoxia-mimetic) or TNF-\u03b1+IFN-\u03b3 (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 \u00b0C for 21 min. Thereafter, 16 \u03bcL of MSC-S (containing 6 \u03bcg of protein derived from 2 \u00d7 105 preconditioned-MSC), or vehicle, were intranasally administered 2 h after birth to asphyxia-exposed and control rats, evaluated at postnatal day (P) 7. Alternatively, pups received a dose of either preconditioned MSC-S or vehicle, both at 2 h and P7, and were evaluated at P14, P30, and P60. The preconditioned MSC-S treatment (i) reversed asphyxia-induced oxidative stress in the hippocampus (oxidized\/reduced glutathione); (ii) increased antioxidative Nuclear Erythroid 2-Related Factor 2 (NRF2) translocation; (iii) increased NQO1 antioxidant protein; (iv) reduced neuroinflammation (decreasing nuclearNF-\u03baB\/p65 levels and microglial reactivity); (v) decreased cleaved-caspase-3 cell-death; (vi) improved righting reflex, negative geotaxis, cliff aversion, locomotor activity, anxiety, motor coordination, and recognition memory. Overall, the study demonstrates that intranasal administration of preconditioned MSC-S is a novel therapeutic strategy that prevents the long-term effects of perinatal asphyxia.<\/jats:p>","DOI":"10.3390\/ijms21207800","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T10:14:22Z","timestamp":1603275262000},"page":"7800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Intranasal Administration of Mesenchymal Stem Cell Secretome Reduces Hippocampal Oxidative Stress, Neuroinflammation and Cell Death, Improving the Behavioral Outcome Following Perinatal Asphyxia"],"prefix":"10.3390","volume":"21","author":[{"given":"Nancy","family":"Farf\u00e1n","sequence":"first","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Carril","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Redel","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zamorano","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Araya","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estephania","family":"Monz\u00f3n","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norton","family":"Contreras","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tapia-Bustos","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Universidad Andres Bello, Santiago 8370149, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Elena","family":"Quintanilla","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7696-4215","authenticated-orcid":false,"given":"Fernando","family":"Ezquer","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine-Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7710162, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Vald\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3468-7966","authenticated-orcid":false,"given":"Yedy","family":"Israel","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Herrera-Marschitz","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-2977","authenticated-orcid":false,"given":"Paola","family":"Morales","sequence":"additional","affiliation":[{"name":"Molecular &amp; Clinical Pharmacology Program, ICBM, Faculty of Medicine University of Chile, Santiago 8380453, Chile"},{"name":"Department of Neuroscience, Faculty of Medicine, University of Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1001\/jamapediatrics.2014.3269","article-title":"Hypoxic-Ischemic Encephalopathy","volume":"169","author":"Weiss","year":"2015","journal-title":"JAMA Pediatr."},{"key":"ref_2","first-page":"e030269","article-title":"Perinatal asphyxia in the term newborn","volume":"3","author":"Antonucci","year":"2014","journal-title":"J. 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