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Transcriptomics Responses to Hypoxia and Ketamine in Ovine Fetal Hippocampus

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 hippocampus 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 17±1 to 10±1 mm Hg, or normoxia (PaO2 17±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 hippocampus was removed and mRNA extracted for transcriptomics and systems biology analysis. Hypoxia stimulated a transcriptomics response consistent with a an increase in inflammation (e.g., cytokine binding and response to LPS). Ketamine pretreatment reduced 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 hippocampal tissue that ketamine significantly reduced. We conclude that transient hypoxia produces inflammation of the fetal hippocampus and that ketamine, in a standard clinical dose, reduces the inflammation response.

ORGANISM(S): Ovis aries

PROVIDER: GSE97916 | GEO | 2017/08/31

SECONDARY ACCESSION(S): PRJNA383314

REPOSITORIES: GEO

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Transcriptomics Responses to Hypoxia and Ketamine in Ovine Fetal Cerebral Cortex

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Ovis aries

Project description:Transcriptomics Responses to Hypoxia and Ketamine in Ovine Fetal Hippocampus

| PRJNA383314 | ENA

The Genomics of the Fetal Hypothalamic Cellular Response to Transient Hypoxia: Endocrine, Immune, and Metabolic Responses

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