Effects of isoflurane on expression of GFAP and EAAT2 in neonatal rats brian / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of prolonged exposure to isoflurane on the expression of glial fibrillary acidic protein (GFAP) and excitatory amino acid transporter-2 (EAAT2) in cortex of frontal lobe and hippocampus of neonatal rats. METHODS: Forty Wistar rats at postnatal day 7 were randomly divided into isoflurane group and control group according to the random number table method (n=20). Isoflurane group were exposed to 1.1% isoflurane (equivalent to 0.5 MAC for neonatal rats) for 6 h, the others were exposed to the gas mixture of 30% of the oxygen and nitrogen for 6 h in the control group. Five neonatal rats were sacrificed 12, 24 h, 3 and 7 d after exposure in each group. The brain were frozen and sliced, brain sections were double-stained with GFAP and EAAT2 markers. The fluorescence intensity of GFAP and EAAT2 double-labeled immunofluorescence was quantified in cortex of frontal lobe and hippocampus at 12, 24 h, 3 and 7 d after exposure by the Image J programme. RESULTS: Compared with the control group, the immunofluorescence intensity of GFAP in cortex of frontal lobe after exposure 12, 24 h in isoflurane group was significantly decreased(P < 0.01), whereas there was no significant difference after exposure 3, 7 d. The immunofluorescence intensity of GFAP in hippocampus after exposure 12, 24 h and 3 d in isoflurane group decreased compared with control group(P < 0.01), except 7 d after exposure. Double-labeled immunofluorescence showed lowered expression of GFAP and EAAT2 co-stained region in cortex of frontal lobe and hippocampus at 12, 24 h, 3 and 7 d after exposure in isoflurane group when compared with control group(P < 0.01). CONCLUSION: The 1.1% isoflurane prolonged exposure transiently reduces the expression of GFAP in the cortex and hippocampus, and delays the development of cytoskeleton. Whereas inhibiting the expression EAAT2 of astrocytes is prolonged, that may be one of the mechanisms for isoflurane-induced neurotoxicity.