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.authorFarfán, Nancy
dc.contributor.authorCarril, Jaime
dc.contributor.authorRedel, Martina
dc.contributor.authorZamorano, Marta
dc.contributor.authorAraya, Maureen
dc.contributor.authorMonzón, Estephania
dc.contributor.authorAlvarado, Raúl
dc.contributor.authorContreras, Norton
dc.contributor.authorTapia-Bustos, Andrea
dc.contributor.authorQuintanilla, María Elena
dc.contributor.authorEzquer, Fernando
dc.contributor.authorValdés, José Luis
dc.contributor.authorIsrael, Yedy
dc.contributor.authorHerrera-Marschitz, Mario
dc.contributor.authorMorales, Paola
dc.date.accessioned2021-07-14T14:43:00Z
dc.date.available2021-07-14T14:43:00Z
dc.date.issued2020
dc.description.abstractPerinatal 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-α+IFN-γ (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 °C for 21 min. Thereafter, 16 μL of MSC-S (containing 6 μg of protein derived from 2 × 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-κB/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.es
dc.format.extent27 p.es
dc.identifier.citationInternational Journal of Molecular Sciences . 2020 Oct 21;21(20):7800es
dc.identifier.urihttps://doi.org/10.3390/ijms21207800es
dc.identifier.urihttp://hdl.handle.net/11447/4174
dc.language.isoenes
dc.subjectNeonatal hypoxiaes
dc.subjectBehavioral developmentes
dc.subjectCell deathes
dc.subjectHippocampuses
dc.subjectIntranasal administrationes
dc.subjectMemoryes
dc.subjectMesenchymal stem cell secretome (MSC-S)es
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.typeArticlees

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