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Ketamine (KET) decreases inflammatory and apoptotic gene expression in ovine fetal frontal cortex exposed to global acute hypoxic hypoxia (HH)
Author(s) -
Chang Eileen ILing,
Rabaglino Maria Belen,
Richards Elaine M.,
Wood Charles E.
Publication year - 2013
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.27.1_supplement.717.6
Subject(s) - fetus , apoptosis , inflammation , endocrinology , hypoxia (environmental) , medicine , chemistry , biology , biochemistry , pregnancy , genetics , organic chemistry , oxygen
HH activates fetal neuroendocrine stress responses, perhaps by excessive glutamatergic signaling, which could stimulate inflammation and apoptosis in fetal brain. We have shown that HH stimulates inflammation and apoptosis genomic response with ovine gene array. We propose that treatment with KET, an N‐ methyl‐D‐aspartate receptor antagonist, during HH will interrupt inflammatory and apoptotic signaling pathways in fetal frontal cortex. Fetal sheep (n=3–5/group) were chronically catheterized (125 d gestation). KET (3 mg/kg) was administered intravenously to the fetus 10 min prior to the induction of HH (30 min) stimulation or normoxic control (NC). Fetal frontal cortex was collected 24 hrs post‐HH, and cDNA was synthesized from mRNA using random primers. CASP8, MYD88, and NFKB mRNA expression were measured using real‐time PCR and normalized to β‐actin mRNA. At 24 hrs post‐HH, CASP8, MYD88, and NFKB mRNA expressions increased vs. NC, 2.01‐fold, 1.32‐fold, and 1.40‐fold, and KET treatment attenuated this increase to 0.98‐fold, 1.08‐fold, and 0.91‐fold, respectively (CASP8, P<0.05, one‐way ANOVA; MYD88, P<0.05, one‐way ANOVA; NFKB, P<0.05, t‐test 24 HH vs. 24 HH+KET). Fetal inflammatory (MYD88, NFKB) and apoptotic (CASP8) responses were activated with HH and reduced with KET. The results are consistent with our gene array analysis. Research supported by NIH grants HD033053, HD057561, and DK076541.