Sevoflurane causes neuronal apoptosis and adaptability changes of neonatal rats

• Published in: Acta anaesthesiologica Scandinavica 2013-10, Vol.57 (9), p.1167-1174
• Main Authors: ZHENG, S. Q., AN, L. X., CHENG, X., WANG, Y. J.
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - drug effects; Anesthetics, Inhalation - toxicity; Animal memory; Animals; Animals, Newborn - physiology; Apoptosis; Apoptosis - drug effects; Behavior, Animal - drug effects; Blood Gas Analysis; Blotting, Western; Cerebral Cortex - pathology; Hippocampus - pathology; Immunohistochemistry; Maze Learning - drug effects; Memory - drug effects; Methyl Ethers - toxicity; Nerve Degeneration - chemically induced; Nerve Degeneration - pathology; Neurodegeneration; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - metabolism; Rats; Rats, Wistar; Respiratory Mechanics - drug effects; Rodents; Sample Size
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/aas.12163

Background Neonatal exposure to sevoflurane can induce neurodegeneration and learning deficits in developing brain. We hypothesised that with the increase in the concentration and duration of sevoflurane, neurodegeneration of neonatal rats aggravates and causes behaviour changes as the rats grow. Methods Twenty‐one post‐natal day (P)7 Wistar rats were randomly divided into seven groups. Blood analysis was performed after anaesthesia. According to the results, 120 P7 Wistar rats were randomly divided into five groups: Con sham anaesthesia; Sevo 1%‐2 h: exposed to 1% sevoflurane for 2 h; Sevo 1%‐4 h, Sevo 2%‐2 h and Sevo 2%‐4 h. Caspase‐3 positive cells in brain were detected by immunohistochemistry at 6 h after the end of anaesthesia. The cleaved poly(ADP‐ribose) polymerase (c‐PARP‐1) in cortex and hippocampus was detected by Western blot analysis. Behavioural tests such as Morris water maze and Open‐field Test were performed when the rats were 5‐week old, 8‐week old, and 14‐week old. Results Three per cent sevoflurane induced carbon dioxide accumulation. The level of c‐PARP‐1 in hippocampus area was significantly increased in Group 2%‐4h. The number of caspase‐3 positive cells in Group Sevo 1%‐2h, Group Sevo 2%‐2h and Group Sevo 2%‐4h was greater than that in Group Con. Rats exposed to sevoflurane had longer travel distance and time in open field when they were 5 weeks old. Animals from different groups had similar performance in Morris water maze. Conclusion Exposure to 2% sevoflurane causes neuronal apoptosis of neonatal rats, and long‐time exposure aggravates that. The adaptability in new environment is transiently decreased when the anaesthesia rats are 5 weeks old.