Chronic exposure of gestation rat to sevoflurane impairs offspring brain development

• Published in: Neurological sciences Vol. 33; no. 3; pp. 535 - 544
• Main Authors: Wang, Yuheng, Cheng, Yongxia, Liu, Guibo, Tian, Xiaodan, Tu, Xuefeng, Wang, Junke
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.06.2012; Springer Nature B.V
• Subjects: Age Factors; Anesthetics, Inhalation - toxicity; Animals; Apoptosis; Apoptosis - drug effects; Blood Gas Analysis; Brain; Brain - drug effects; Brain - growth & development; Brain - pathology; Chronic exposure; Drugs; Female; Fos protein; GAP-43 Protein - genetics; GAP-43 Protein - metabolism; Gene Expression Regulation, Developmental - drug effects; Gestation; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Hippocampus; Immunochemistry; MAP Kinase Signaling System - drug effects; Medicine; Medicine & Public Health; Methyl Ethers - toxicity; Microscopy, Electron, Transmission; Myelin P0 protein; N-Methyl-D-aspartic acid receptors; Neurodegeneration; Neurology; Neurons - drug effects; Neurons - pathology; Neurons - ultrastructure; Neuroradiology; Neurosciences; Neurosurgery; Neurotoxicity; Nitric Oxide Synthase Type I - genetics; Nitric Oxide Synthase Type I - metabolism; Oncogene Proteins v-fos - genetics; Oncogene Proteins v-fos - metabolism; Original Article; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - pathology; Progeny; Protein kinase C; Protein Kinase C-alpha - genetics; Protein Kinase C-alpha - metabolism; Psychiatry; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Sevoflurane; Western blotting; Sevoflurane; Developing brain; Neurotoxicity; Rat; Apoptosis
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-011-0762-6

Recently it was demonstrated that the exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors can trigger widespread apoptotic neurodegeneration. Sevoflurane is a new inhalation anesthetic agent commonly used in the clinic. Here we address whether sevoflurane could induce neurotoxicity in the developing brain. Sevoflurane was administered to rats before pregnancy and pregnant rats on embryonic days E6, E10, E14, and E18 1MAC for 6 h, and we employed histopathological, immunochemistry, semiquantitative RT-PCR, and Western blot to investigate the effect of the exposure of pregestation and gestation rats to sevoflurane on the offspring brain development. The results showed that the exposure of gestation but not pregestation rats to sevoflurane-induced extensive apoptotic neurodegeneration in the hippocampus of offspring at P0, P7, and P14, accompanied by altered expression of casepase-3, GAP-43, nNOS, NMDAR1, NMDAR2A, and NMDAR2B. Furthermore, upregulation of PKCα and p-JNK and downregulation of p-ERK and FOS protein levels were observed in the hippocampus of offspring at P0, P7, and P14 from rats exposed to sevoflurane at gestation, but not pregestation. In summary, our data suggest that sevoflurane induces developmental neurotoxicity in rats and this may be attributed to the upregulation of PKCα and p-JNK and downregulation of p-ERK and FOS protein in the hippocampus.