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Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats
Andrea Tapia-Bustos1,2, Carolyne Lespay-Rebolledo1, Valentina Vío1
1Molecular & Clinical Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
Insights
Perinatal asphyxia (PA) impairs brain development and cell survival in rats. Mesenchymal stem cell (MSC) treatment protected against these effects, improving myelination and oligodendrocyte survival in the developing brain.
Area of Science:
- Neuroscience
- Developmental Biology
- Regenerative Medicine
Background:
- Perinatal asphyxia (PA) is a significant risk factor for neonatal brain injury.
- Oligodendrocytes (OLs) are crucial for brain development and myelination.
- Understanding the impact of PA on OLs and neuroinflammation is vital for developing effective treatments.
Purpose of the Study:
- To investigate the effects of PA on OLs, neuroinflammation, and cell viability in the rat telencephalon.
- To evaluate the therapeutic potential of mesenchymal stem cell (MSC) treatment in a rat model of PA.
Main Methods:
- A rat model of global PA was established by immersing fetuses in a water bath.
- Neonates received either vehicle or MSCs treatment via lateral ventricle injection.
- Assays included myelin-basic protein (MBP) levels, Olig-1/Olig-2, glial phenotype, neuroinflammation markers, and cell death.
Main Results:
- PA led to decreased MBP, increased Olig-1 mRNA, elevated IL-6 mRNA, and increased cell death, including OLs, at postnatal day 7.
- MSC treatment effectively prevented PA-induced deficits in myelination, OL number, and cell death.
- PA induced regional and developmental-dependent changes in myelination and OL maturation.
Conclusions:
- PA significantly impacts myelination and OL maturation in a region- and time-dependent manner.
- Neonatal MSC treatment offers a promising therapeutic strategy to improve OL survival and promote myelination following PA.
- This study highlights the neuroprotective potential of MSCs in mitigating PA-induced brain injury.
Abstract:
The effect of perinatal asphyxia (PA) on oligodendrocyte (OL), neuroinflammation, and cell viability was evaluated in telencephalon of rats at postnatal day (P)1, 7, and 14, a period characterized by a spur of neuronal networking, evaluating the effect of mesenchymal stem cell (MSCs)-treatment. The issue was investigated with a rat model of global PA, mimicking a clinical risk occurring under labor. PA was induced by immersing fetus-containing uterine horns into a water bath for 21 min (AS), using sibling-caesarean-delivered fetuses (CS) as controls. Two hours after delivery, AS and CS neonates were injected with either 5 μL of vehicle (10% plasma) or 5 × 104 MSCs into the lateral ventricle. Samples were assayed for myelin-basic protein (MBP) levels; Olig-1/Olig-2 transcriptional factors; Gglial phenotype; neuroinflammation, and delayed cell death. The main effects were observed at P7, including: (i) A decrease of MBP-immunoreactivity in external capsule, corpus callosum, cingulum, but not in fimbriae of hippocampus; (ii) an increase of Olig-1-mRNA levels; (iii) an increase of IL-6-mRNA, but not in protein levels; (iv) an increase in cell death, including OLs; and (v) MSCs treatment prevented the effect of PA on myelination, OLs number, and cell death. The present findings show that PA induces regional- and developmental-dependent changes on myelination and OLs maturation. Neonatal MSCs treatment improves survival of mature OLs and myelination in telencephalic white matter.
