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Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats.

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.

SUBMITTER: Tapia-Bustos A

PROVIDER: S-EPMC8004671 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats.

Tapia-Bustos Andrea A Lespay-Rebolledo Carolyne C Vío Valentina V Pérez-Lobos Ronald R Casanova-Ortiz Emmanuel E Ezquer Fernando F Herrera-Marschitz Mario M Morales Paola P

International journal of molecular sciences 20210323 6

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), usi ...[more]

PMID: 33806988

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Project description:BackgroundPerinatal asphyxia (PA) occurs in about 2 to 10 per 1000 live full-term births. Although neonatal epileptic seizures are observed in up to 60% of cases, PA may mimic or subtend other conditions. Hypoxia related brain injury is particularly relevant, as it may have permanent effects on neuropsychomotor development. Antepartum obstetric conditions, may, in turn, lead to hypoxic-ischemic damage to the fetus and the newborn, often underlying PA. Herein, a case of PA that hid and triggered signs and symptoms of Glutaric Aciduria type I (GA-I), is reported.Case presentationR.F. was born at term after prolonged labour, by induced vaginal delivery with the Kristeller manoeuvre. He presented with severe asphyxia and asystoly. Immediate cardiopulmonary resuscitation promptly restored cardiorespiratory parameters, allowing for early extubation 30 min after. During the following hours, severe axial muscle hypotonia with an increased tone of the limb extensor muscles became evident. The absence of crying and archaic reflexes persisted and there was an onset of generalized tonic or clonic seizure. First level metabolic and inflammatory markers were within the normal range. An inherited metabolic disease was then suspected, due to the persistent clinical signs of severe neurological damage without any detectable septic parameter. GA-I was assessed and specific treatment started without any clinical improvement, although ensuring adequate growth and metabolic control. Thereafter, the baby developed a severe encephalopathy with drug resistant epileptic seizures. The progression of the neurological damage and a CVC-related sepsis led him to exitus at 2 years.ConclusionsTo the best of our knowledge, this is the first case of early post-natal onset of GA-I reported in literature to date, in the absence of expanded newborn screening (NBS) programme. As expanded NBS programmes for inborn errors of metabolism have not yet been internationally adopted, we are of the opinion that such diseases may well be hidden by misleading signs and symptoms imputable to other more frequent harmful clinical conditions. Moreover, it would be advisable that neonatologists be trained to include GA-I in the differential diagnosis of neurological damage secondary to PA.

Dataset Information

Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats.

Publications

Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats.

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