Intranasal administration of mesenchymal stem cell secretome reduces hippocampal oxidative stress, neuroinflammation and cell death, improving the behavioral outcome following perinatal asphyxia

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dc.contributor.authorFarfan, N.
dc.contributor.authorCarril, J.
dc.contributor.authorRedel, M.
dc.contributor.authorZamorano, M.
dc.contributor.authorAraya, M.
dc.contributor.authorMonzón, E.
dc.contributor.authorAlvarado, R.
dc.contributor.authorContreras, N.
dc.contributor.authorTapia-Bustos, A.
dc.contributor.authorQuintanilla, M.E.
dc.contributor.authorEzquer, F.
dc.contributor.authorValdes, J.L.
dc.contributor.authorIsrael, Y.
dc.contributor.authorHerrera-Marschitz, M.
dc.contributor.authorMorales, P.
dc.date.accessioned2021-07-18T01:03:05Z
dc.date.available2021-07-18T01:03:05Z
dc.date.issued2020-10
dc.descriptionIndexación: Scopus.es
dc.description.abstractPerinatalAsphyxia (PA) is a leading cause ofmotor 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-ff+IFN- (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 ffC for 21 min. Thereafter, 16 ffL of MSC-S (containing 6 ffg of protein derived from 2 ff 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-ffB/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. © 2020 by the authors.es
dc.description.urihttps://www.mdpi.com/1422-0067/21/20/7800
dc.identifier.citationInternational Journal of Molecular SciencesOpen AccessVolume 21, Issue 20, Pages 1 - 272 October 2020 Article number 7800es
dc.identifier.doi10.3390/ijms21207800
dc.identifier.issn1661-6596
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/19423
dc.language.isoenes
dc.publisherMDPI AGes
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBehavioral developmentes
dc.subjectCell deathes
dc.subjectHippocampuses
dc.subjectIntranasal administrationes
dc.subjectMemoryes
dc.subjectMesenchymal stem cell secretome (MSC-S)es
dc.subjectNeonatal hypoxiaes
dc.subjectNeuroinflammationes
dc.subjectNeuroprotectiones
dc.subjectOxidative stresses
dc.titleIntranasal administration of mesenchymal stem cell secretome reduces hippocampal oxidative stress, neuroinflammation and cell death, improving the behavioral outcome following perinatal asphyxiaes
dc.typeArtículoes
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