Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptomics Responses to Hypoxia and Ketamine in Ovine Fetal Cerebral Cortex

ABSTRACT: Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. The chemoreceptor reflex that is responsible for this physiological response is dependent on glutamatergic neurotransmission which, in times of vigorous activity, could produce cell death secondary to calcium uptake. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist of NMDA receptors, reduces the damage. Late-gestation, chronically catheterized fetal sheep were subjected to a 30 min period of ventilatory hypoxia that decreased fetal PaO2 from 17Â±1 to 10Â±1 mm Hg, or normoxia (PaO2 17Â±1 mm Hg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, iv). One day (24 h) after hypoxia/normoxia, fetal cerebral cortex was removed and mRNA extracted for transcriptomics and systems biology analysis. Hypoxia stimulated a transcriptomics response consistent with a reduction in cellular metabolism and an increase in inflammation. Ketamine pretreatment reduced both of these responses. The inflammation response modeled with transcriptomic system biology was validated by immunohistochemistry and showed increased abundance of microglia/macrophages after hypoxia in the cerebral cortical tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal cerebral cortex and that ketamine, in a standard clinical dose, reduces the inflammation response. 4 groups: hypoxia, hypoxia plus ketamine, normoxia, normoxia plus ketamine. Hypoxia produced by low PO2 in maternal inspired gas for 30 min, followed by normoxia recovery for 23.5 hours. Control fetuses maintained at normoxia for 30 min, followed by another 23.5 h of normoxia. Fetal frontal cerebral cortex collected for mRNA at end of 23.5 h recovery period.

ORGANISM(S): Ovis aries

SUBMITTER: Charles Wood

PROVIDER: E-GEOD-76110 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex.

Chang Eileen I EI Zárate Miguel A MA Rabaglino Maria B MB Richards Elaine M EM Arndt Thomas J TJ Keller-Wood Maureen M Wood Charles E CE

Physiological reports 20160331 6

Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist ofNMDAreceptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreas ...[more]

PMID: 27033443

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