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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Fecha
2020-10
Profesor/a Guía
Facultad/escuela
Idioma
en
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Editor
MDPI AG
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Licencia CC
Attribution 4.0 International (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/
Resumen
PerinatalAsphyxia (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.
Notas
Indexación: Scopus.
Palabras clave
Behavioral development, Cell death, Hippocampus, Intranasal administration, Memory, Mesenchymal stem cell secretome (MSC-S), Neonatal hypoxia, Neuroinflammation, Neuroprotection, Oxidative stress
Citación
International Journal of Molecular SciencesOpen AccessVolume 21, Issue 20, Pages 1 - 272 October 2020 Article number 7800
DOI
10.3390/ijms21207800