title: N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia.
abstract: Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs.
  
  
  
  To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-κB in the prefrontal cortex of neonatal pigs.
  
  
  
  Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed.
  
  
  
  Cortex: there was no significant difference in mRNA expression between the intervention groups regarding IL-1β, IL6, TNFα, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1β than pigs treated with saline (placebo controls), i.e. 8.8 ± 3.9 versus 16.8 ± 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-κB (measured as the fold-change of phosphorylated p65Ser 536), was reduced in the NACA-pigs when compared to the placebo controls (5.2 ± 4.3 vs. 16.0 ± 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma: the NACA-pigs had a stronger reduction of TNFα in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01).
  
  
  
  The reduced levels of the pivotal inflammatory markers IL-1β and TNFα and the transcription factor NF-κB may indicate that NACA has possible neuroprotective effects after perinatal asphyxia.
authors: Department of Pediatric Research, University of Oslo, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors: Torkil
authors: T
authors: Benterud
authors: Martin B
authors: MB
authors: Ystgaard
authors: Sophia
authors: S
authors: Manueldas
authors: Leonid
authors: L
authors: Pankratov
authors: Clara
authors: C
authors: Alfaro-Cervello
authors: Geir
authors: G
authors: Florholmen
authors: Muhammad Shakil
authors: MS
authors: Ahmed
authors: Leiv
authors: L
authors: Sandvik
authors: Svante
authors: S
authors: Norgren
authors: Magnar
authors: M
authors: Bjørås
authors: Lars O
authors: LO
authors: Baumbusch
authors: Ronnaug
authors: R
authors: Solberg
authors: Ola Didrik
authors: OD
authors: Saugstad
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects; D005260:Female; D000860:Hypoxia / Q000628:therapy*; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000097:blood; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage*; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; C487056:N-Acetylcysteinamide; D010100:Oxygen; D000111:Acetylcysteine