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Ketamine decreases immune gene expression in ovine fetal frontal cortex exposed to acute hypoxic hypoxia (887.5)
Author(s) -
Chang Eileen,
Rabaglino Maria,
Richards Elaine,
Wood Charles
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.887.5
Subject(s) - fetus , hypoxia (environmental) , biology , medicine , endocrinology , andrology , chemistry , genetics , pregnancy , organic chemistry , oxygen
Fetal hypoxic hypoxia (HH), a consequence of maternal hypoxia, stimulates glutamatergic neurotransmission. We hypothesize that excitotoxicity induced by HH can be reduced by pretreatment with ketamine (KET), an NMDA receptor antagonist. The objective was to evaluate the genomic response of fetal frontal cortex under HH with KET. KET (3 mg/kg) was administered intravenously to chronically catheterized ovine fetuses (n=3‐5/group; 123±3 d gestation) 10 min prior to 30 min HH. Fetal frontal cortex was collected 24 hrs post‐HH. mRNA was extracted, labeled, and hybridized to ovine Agilent 15.5k microarray. Significant differences in gene expression between control±KET and HH±KET groups were determined by F‐statistics using the limma package for R (P<0.05). Differentially up‐/down‐regulated genes were analyzed by gene ontology and network analysis, identifying statistically significant overrepresentation of biological processes (P<0.05). Significantly up‐/down‐regulated genes: HH: 244/470 and HH+KET: 556/246. There were 120 common genes up‐regulated by HH and down‐regulated by HH+KET. The enriched biological processes for the overlap genes were involved in regulation of immune system processes (TLR2, MYD88, NFKBIA, IL8, IL6R, IL6ST, CD5, CD14, ICAM1, CCL2, CCL4L1). In conclusion, acute HH increased genomic expression of immune pathways in fetal frontal cortex, and ketamine reduced the response suggesting potential therapy for attenuating neuronal hypoxic damage in fetuses and neonates.