title: Comparison of neurodegeneration and cognitive impairment in neonatal mice exposed to propofol or isoflurane.
abstract: BACKGROUND
  While previous studies have demonstrated neuronal apoptosis and associated cognitive impairment after isoflurane or propofol exposure in neonatal rodents, the effects of these two anesthetics have not been directly compared. Here, we compare and contrast the effectiveness of isoflurane and propofol to cause neurodegeneration in the developing brain and associated cognitive dysfunction.
  
  
  METHODS
  Seven-day-old mice were used. Mice in the isoflurane treatment group received 6 h of 1.5% isoflurane, while mice in propofol treatment group received one peritoneal injection (150 mg/kg), which produced persistent anesthesia with loss of righting for at least 6 h. Mice in control groups received carrying gas or a peritoneal injection of vehicle (intralipid). At 6 h after anesthetic treatment, a subset of each group was sacrificed and examined for evidence of neurodegeneration, using plasma levels of S100β, and apoptosis using caspase-3 immunohistochemistry in the cerebral cortex and hippocampus and Western blot assays of the cortex. In addition, biomarkers for inflammation (interleukin-1, interleukin-6, and tumor necrosis factor alpha) were examined with Western blot analyses of the cortex. In another subset of mice, learning and memory were assessed 32 days after the anesthetic exposures using the Morris water maze.
  
  
  RESULTS
  Isoflurane significantly increased plasma S100β levels compared to controls and propofol. Both isoflurane and propofol significantly increased caspase-3 levels in the cortex and hippocampus, though isoflurane was significantly more potent than propofol. However, there were no significant differences in the inflammatory biomarkers in the cortex or in subsequent learning and memory between the experimental groups.
  
  
  CONCLUSIONS
  Both isoflurane and propofol caused significant apoptosis in the mouse developing brain, with isoflurane being more potent. Isoflurane significantly increased levels of the plasma neurodegenerative biomarker, S100β. However, these neurodegenerative effects of isoflurane and propofol in the developing brain were not associated with effects on inflammation or with cognitive dysfunction in later life.
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Anesthesiology, Shanghai First People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ge
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Soorena
authors.initials: S
authors.lastname: Khojasteh
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Neurology, Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Wenqiong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Donald
authors.initials: D
authors.lastname: Joseph
authors.affiliation: Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wei
mesh_terms: D000280:Administration, Inhalation; D000777:Anesthetics / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001925:Brain Damage, Chronic / Q000139:chemically induced; D053148:Caspase 3 / Q000032:analysis; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003072:Cognition Disorders / Q000139:chemically induced*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007249:Inflammation; D007274:Injections, Intraperitoneal; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity*; D007859:Learning Disabilities / Q000139:chemically induced; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced*; D015742:Propofol / Q000008:administration & dosage / Q000633:toxicity*; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood
chemical_list: D000777:Anesthetics; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; D007530:Isoflurane; C505409:Casp3 protein, mouse; D053148:Caspase 3; D015742:Propofol