Intranasal Administration of Mesenchymal Stem Cell Secretome Reduces Hippocampal Oxidative Stress, Neuroinflammation and Cell Death, Improving the Behavioral Outcome Following Perinatal Asphyxia

Autor: Maureen Araya, Estephania Monzón, Paola Morales, José Luis Valdés, Mario Herrera-Marschitz, Raúl Alvarado, Martina Redel, Norton Contreras, Andrea Tapia-Bustos, Fernando Ezquer, Nancy Farfán, Jaime Carril, María Elena Quintanilla, Marta Zamorano, Yedy Israel
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
hippocampus
Pharmacology
medicine.disease_cause
Hippocampus
neuroinflammation
memory
lcsh:Chemistry
chemistry.chemical_compound
Neuroinflammation
Pregnancy
Medicine
Hippocampus (mythology)
oxidative stress
lcsh:QH301-705.5
Spectroscopy
Neurons
Asphyxia Neonatorum
Behavior
Animal
Mesenchymal stem cell secretome (MSC-S)
General Medicine
Neuroprotection
Computer Science Applications
Neuroprotective Agents
cell death
Behavioral development
Female
neuroprotection
Cell death
Programmed cell death
NF-E2-Related Factor 2
Neonatal hypoxia
behavioral development
Article
Catalysis
intranasal administration
Inorganic Chemistry
Memory
Intranasal administration
Animals
Humans
Rats
Wistar
Physical and Theoretical Chemistry
Molecular Biology
Administration
Intranasal
Inflammation
business.industry
mesenchymal stem cell secretome (MSC-S)
Organic Chemistry
Mesenchymal stem cell
Mesenchymal Stem Cells
Glutathione
medicine.disease
Perinatal asphyxia
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Oxidative stress
Apgar Score
business
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 7800, p 7800 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 20
ISSN: 1661-6596
1422-0067
Popis: 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-&alpha
+IFN-&gamma
(pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 °
C for 21 min. Thereafter, 16 &mu
L of MSC-S (containing 6 &mu
g 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-&kappa
B/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.
Databáze: OpenAIRE
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