title: Neuronal apoptosis may not contribute to the long-term cognitive dysfunction induced by a brief exposure to 2% sevoflurane in developing rats.
abstract: BACKGROUND
  Sevoflurane is an inhaled anesthetic commonly used in the pediatric. Recent animal studies suggest that early exposure to high concentration of sevoflurane for a long duration can induce neuroapoptosis and later cognitive dysfunction. However, the neurodevelopmental impact induced by lower concentration and shorter exposure duration of sevoflurane is unclear. To investigate whether early exposure to 2% concentration of sevoflurane for a short duration (clinically relevant usage of sevoflurane) can also induce neuroapoptosis and later cognitive dysfunction.
  
  
  METHODS
  Rat pups were subjected to control group, 2% sevoflurane for 3h and 3% sevoflurane for 6h. TUNEL assay and apoptotic enzyme cleaved caspase-3 measured by western blot were used for detection of neuronal apoptosis in frontal cortex and CA1 region of hippocampus 24 after sevoflurane treatment. Long-term cognitive function was evaluated by Morris water maze and passive avoidance test as the rats grew up.
  
  
  RESULTS
  The apoptotic levels in frontal cortex and CA1 region were significantly increased after rats exposed to 3% sevoflurane for 6h (P<0.05), but not 2% sevoflurane for 3h (P>0.05). Exposure to both 2% sevoflurane for 3h and 3% sevoflurane for 6h could cause long-term cognitive dysfunction and animals exposed to 3% sevoflurane for 6h exhibited worse neurodevelopmental outcomes (P<0.05).
  
  
  CONCLUSIONS
  It was suggested that neuronal apoptosis might not contribute to long-term cognitive dysfunction induced by 2% concentration and short exposure time of sevoflurane. Our findings also suggested that the mechanisms of sevoflurane-induced neurodevelopmental impact might be various, depending on the concentration and exposure duration.
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China. Electronic address: dr_hongjiang@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China. Electronic address: mzkyanj@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects; D001784:Blood Gas Analysis; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D003071:Cognition / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D000077149:Sevoflurane
chemical_list: D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: Anesthesia; Apoptosis; Developing brain; Neurodevelopment; Neurotoxicity; Sevoflurane