title: Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment.
abstract: BACKGROUND
  : Recent population studies have suggested that children with multiple exposures to anesthesia and surgery at an early age are at an increased risk of cognitive impairment. The authors therefore have established an animal model with single versus multiple exposures of anesthetic(s) in young versus adult mice, aiming to distinguish the role of different types of anesthesia in cognitive impairment.
  
  
  METHODS
  : Six- and 60-day-old mice were exposed to various anesthesia regimens. The authors then determined the effects of the anesthesia on learning and memory function, levels of proinflammatory cytokine interleukin-6 and tumor necrosis factor-α in brain tissues, and the amount of ionized calcium-binding adaptor molecule 1-positive cells, the marker of microglia activation, in the hippocampus.
  
  
  RESULTS
  : In this article, the authors show that anesthesia with 3% sevoflurane for 2 h daily for 3 days induced cognitive impairment and neuroinflammation (e.g., increased interleukin-6 levels, 151 ± 2.3% [mean ± SD] vs. 100 ± 9.0%, P = 0.035, n = 6) in young but not in adult mice. Anesthesia with 3% sevoflurane for 2 h daily for 1 day and 9% desflurane for 2 h daily for 3 days induced neither cognitive impairment nor neuroinflammation. Finally, an enriched environment and antiinflammatory treatment (ketorolac) ameliorated the sevoflurane-induced cognitive impairment.
  
  
  CONCLUSIONS
  : Anesthesia-induced cognitive impairment may depend on developmental stage, anesthetic agent, and number of exposures. These findings also suggest the cellular basis and the potential prevention and treatment strategies for anesthesia-induced cognitive impairment, which may ultimately lead to safer anesthesia care and better postoperative outcomes for children.
authors: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129-2060, USA.
authors: Xia
authors: X
authors: Shen
authors: Yuanlin
authors: Y
authors: Dong
authors: Zhipeng
authors: Z
authors: Xu
authors: Hui
authors: H
authors: Wang
authors: Changhong
authors: C
authors: Miao
authors: Sulpicio G
authors: SG
authors: Soriano
authors: Dandan
authors: D
authors: Sun
authors: Mark G
authors: MG
authors: Baxter
authors: Yiying
authors: Y
authors: Zhang
authors: Zhongcong
authors: Z
authors: Xie
mesh_terms: D000367:Age Factors; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism*; D000077335:Desflurane; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000008:administration & dosage / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D018836:Inflammation Mediators; D008738:Methyl Ethers; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane