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.
Highlights
Introduction iationsPerinatal asphyxia (PA), a prototype of obstetric complication, is the result of impaired gas exchange during labor or delivery, a major cause of death, neuropsychiatric dysfunctions, and learning disorders, short and long term, in affected newborns [1], increasing the costs associated with the acute treatment, and comorbidities in the life of the individuals
No differences were observed in the number of DAPI (TUNEL-DAPI+) or OL-specific (TUNEL-myelin basic protein (MBP)-DAPI+) cell death, in vehicle- compared to mesenchymal stem cell (MSCs)-treated caesarean-delivered fetuses (CS) neonates, except in cingulum, where no oligodendroglial death could be detected in the MSCs-treated CS
This study is on the effect of perinatal asphyxia (PA) in rats, focusing on myelination and glial cell response, and on the potential of MSC treatment to ameliorate these effects
Summary
MBP-positive pixels were, decreased in the external capsule (by ~50%), corpus callosum (by ~60%) and cingulum (by ~70%) in AS compared to CS animals; no differences were observed in the fimbriae of hippocampus.
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