title: Propofol limits microglial activation after experimental brain trauma through inhibition of nicotinamide adenine dinucleotide phosphate oxidase.
abstract: BACKGROUND
  Microglial activation is implicated in delayed tissue damage after traumatic brain injury (TBI). Activation of microglia causes up-regulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, with the release of reactive oxygen species and cytotoxicity. Propofol appears to have antiinflammatory actions. The authors evaluated the neuroprotective effects of propofol after TBI and examined in vivo and in vitro whether such actions reflected modulation of NADPH oxidase.
  
  
  METHODS
  Adult male rats were subjected to moderate lateral fluid percussion TBI. Effect of propofol on brain microglial activation and functional recovery was assessed up to 28 days postinjury. By using primary microglial and BV2 cell cultures, the authors examined propofol modulation of lipopolysaccharide and interferon-γ-induced microglial reactivity and neurotoxicity.
  
  
  RESULTS
  Propofol improved cognitive recovery after TBI in novel object recognition test (48 ± 6% for propofol [n = 15] vs. 30 ± 4% for isoflurane [n = 14]; P = 0.005). The functional improvement with propofol was associated with limited microglial activation and decreased cortical lesion volume and neuronal loss. Propofol also attenuated lipopolysaccharide- and interferon-γ-induced microglial activation in vitro, with reduced expression of inducible nitric oxide synthase, nitric oxide, tumor necrosis factor-α, interlukin-1β, reactive oxygen species, and NADPH oxidase. Microglial-induced neurotoxicity in vitro was also markedly reduced by propofol. The protective effect of propofol was attenuated when the NADPH oxidase subunit p22 was knocked down by small interfering RNA. Moreover, propofol reduced the expression of p22 and gp91, two key components of NADPH oxidase, after TBI.
  
  
  CONCLUSIONS
  The neuroprotective effects of propofol after TBI appear to be mediated, in part, through the inhibition of NADPH oxidase.
authors.affiliation: * Postdoctoral Research Fellow, † Assistant Professor, ‡ Research Associate, § Postdoctoral Research Fellow, ‖ Research Assistant, # David S. Brown Professor and Director of the Center for Shock Trauma and Anesthesiology Research (STAR), Department of Anesthesiology and Center for STAR, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: Junfang
authors.initials: J
authors.lastname: Wu
authors.forename: Shruti V
authors.initials: SV
authors.lastname: Kabadi
authors.forename: Boris
authors.initials: B
authors.lastname: Sabirzhanov
authors.forename: Kelsey
authors.initials: K
authors.lastname: Guanciale
authors.forename: Marie
authors.initials: M
authors.lastname: Hanscom
authors.forename: Juliane
authors.initials: J
authors.lastname: Faden
authors.forename: Katherine
authors.initials: K
authors.lastname: Cardiff
authors.forename: Charles Jeremy
authors.initials: CJ
authors.lastname: Bengson
authors.forename: Alan I
authors.initials: AI
authors.lastname: Faden
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D002452:Cell Count; D002460:Cell Line; D002540:Cerebral Cortex / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D011134:Polysaccharides; D015742:Propofol / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D011134:Polysaccharides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D007371:Interferon-gamma; D019255:NADPH Oxidases; D015742:Propofol