title: N-acetylcysteine reduces lipopolysaccharide-sensitized hypoxic-ischemic brain injury.
abstract: OBJECTIVE
  Maternal inflammation/infection alone or in combination with birth asphyxia increases the risk for perinatal brain injury. Free radicals are implicated as major mediators of inflammation and hypoxia-ischemia (HI)-induced perinatal brain injury. This study evaluated the neuroprotective efficacy of a scavenging agent, N-acetylcysteine (NAC), in a clinically relevant model.
  
  
  METHODS
  Lipopolysaccharide (LPS)-sensitized HI brain injury was induced in 8-day-old neonatal rats. NAC was administered in multiple doses, and brain injury was evaluated at 7 days after HI.
  
  
  RESULTS
  NAC (200mg/kg) provided marked neuroprotection with up to 78% reduction of brain injury in the pre+post-HI treatment group and 41% in the early (0 hour) post-HI treatment group, which was much more pronounced protection than another free radical scavenger, melatonin. Protection by NAC was associated with the following factors: (1) reduced isoprostane activation and nitrotyrosine formation; (2) increased levels of the antioxidants glutathione, thioredoxin-2, and (3) inhibition of caspase-3, calpain, and caspase-1 activation.
  
  
  CONCLUSIONS
  NAC provides substantial neuroprotection against brain injury in a model that combines infection/inflammation and HI. Protection by NAC was associated with improvement of the redox state and inhibition of apoptosis, suggesting that these events play critical roles in the development of lipopolysaccharide-sensitized HI brain injury.
authors.affiliation: Perinatal Center, Department of Physiology, Göteborg University, Göteborg, Sweden. xiaoyang.wang@fysiologi.gu.se
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Pernilla
authors.initials: P
authors.lastname: Svedin
authors.forename: Chunxia
authors.initials: C
authors.lastname: Nie
authors.forename: Risto
authors.initials: R
authors.lastname: Lapatto
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
authors.forename: Malin
authors.initials: M
authors.lastname: Gustavsson
authors.forename: Mats
authors.initials: M
authors.lastname: Sandberg
authors.forename: Jan-Olof
authors.initials: JO
authors.lastname: Karlsson
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002154:Calpain / Q000187:drug effects; D020169:Caspases / Q000187:drug effects; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects; D020925:Hypoxia-Ischemia, Brain / Q000139:chemically induced / Q000517:prevention & control*; D028421:Isoprostanes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008565:Membrane Proteins / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013879:Thioredoxins / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects
chemical_list: D028421:Isoprostanes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018696:Neuroprotective Agents; C516113:Txn2 protein, rat; C002744:3-nitrotyrosine; D014443:Tyrosine; D003553:Cystine; D013879:Thioredoxins; D002154:Calpain; D020169:Caspases; D005978:Glutathione; C030905:N-monoacetylcystine