The Effects Of Sevoflurane To Neonatal Rat Nervous System An Experimental Study

Background: Every year millions of infants and young children around the world are treated with anesthetics and surgery, but the effects of these general anesthetics on the intelligences to these children with the developing nervous systems are not clear. Preclinical researches demonstrated that the prolonged anesthetics exposure to neonatal animals would lead to neuronal apoptosis, abnormal development of dendritic architecture, neurodegenaration of neurons and later impairment of neurological function in adult. The specific mechanism is unclear.Objectives: To investigate the effects of sevoflurane to rp S6 and other molecules in its related signal pathway to study the mechanisms of sevoflurane in general anesthesia.Methods: Establish a model of sevoflurane inhalation anesthesia to neonatal rats. The P8 SD rats were randomly divided into two groups: the anesthesia group and the oxygen control group. With 70% oxygen air mixture as the carrier gas, anesthesia group rats were sampled after giving sevoflurane anesthesia, respectively in 0.5 h, 1 h, 2 h, 4 h. the pups were taken to their mother’s side after 4 hour’s anesthesia and were sampled 0.5 h and 2 h after the ending of anesthesia respectively. Another group of oxygen control, direct use of 70% oxygen mixture inhaled air. And at the same time point sampling. The newborn rat hippocampus and cortex tissue were removed and westernblot experiments were performed on the protein of Caspase-3, rp S6, p- rp S6, AKT, p-AKT, m TOR, p- m TOR, ERK, p- ERK, JNK, p- JNK, P38, p- P38. Actin acted as the internal reference. On the other hand, the newborn rat were perfused by left ventricle and immunohistochemical experiment were conducted testing the expression distribution of Caspase-3 and p-rp S6. In addition, the samples of hippocampus and cortex from each group in 4h time point were directly extraction of RNA to compose the gene chip test.Results: Neonatal exposure to sevoflurane increase the expression of Caspase-3 in hippocampus and cortex after 4hour’s anesthesia; Neonatal Exposure to Sevoflurane Inhibited the phosphorylation of rp S6 in both cerebral cortex and hippocampus in time dependence pattern; Neonatal exposure to Sevoflurane Inhibited AKT phosphorylation and had no effect on m TOR activity in cerebral cortex and hippocampus; Neonatal exposure to sevoflurane had a paradoxical effect on ERK phosphorylation in cerebral cortex and hippocampus; Neonatal exposure to sevoflurane enhanced the phosphorylation of PP1 in cerebral cortex and hippocampus; The results of gene chip demonstrated that multiple genes expression were changed after 4hour’s sevoflurane anesthesia. A great deal of these genes are closely related to the nervous system development, cognitive memory.Conclusions: Our study establishes that neonatal sevoflurane anesthesia could really cause apoptosis of the central nervous system. The mechanism of the damage may be caused by the inhibition of phosphorylation of ribosomal protein S6 from sevoflurane and the inhibition effects were mediated by the inhibition of activity of AKT and enhance activity of PP1. Gene chip results suggested that sevoflurane on newborn animals are related to the development of the nervous system with a strong inhibition or activation of multiple genes, they can also be one of the reasons lead to cell degeneration.