title: Prophylactic maternal N-acetylcysteine in rats prevents maternal inflammation-induced offspring cerebral injury shown on magnetic resonance imaging.
abstract: OBJECTIVE
  Maternal infection or inflammation may induce fetal inflammatory responses associated with fetal injury and cerebral palsy. We sought to assess the inflammation-associated neuroprotective potential of prophylactic N-acetyl-cysteine (NAC). We examined the effect of NAC on prevention of maternal lipopolysaccharide (LPS)-induced neonatal brain injury using magnetic resonance imaging.
  
  
  METHODS
  Pregnant Sprague Dawley dams (n = 5-8) at embryonic day 18 received intraperitoneal injection of LPS or saline at time 0. Animals were randomized to receive 2 intravenous injections of NAC or saline (time -30 and 120 minutes). Pups were delivered spontaneously and allowed to mature until postnatal day 25. Female offspring were examined by magnetic resonance brain imaging and analyzed using voxel-based analysis after spatial normalization. T2 relaxation time was used to assess white matter injury and diffusion tensor imaging for apparent diffusion coefficient (ADC) to assess white and gray matter injury.
  
  
  RESULTS
  Offspring of LPS-treated dams exhibited significantly increased T2 levels and increased ADC levels in white and gray matter (eg, hypothalamus, motor cortex, corpus callosum, thalamus, hippocampus), consistent with diffuse cerebral injury. In contrast, offspring of NAC-treated LPS dams demonstrated similar T2 and ADC levels as control in both white and gray matter.
  
  
  CONCLUSIONS
  Maternal NAC treatment significantly reduced evidence of neonatal brain injury associated with maternal LPS. These studies suggest that maternal NAC therapy may be effective in human deliveries associated with maternal/fetal inflammation.
authors: Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, Israel. tomor2304@yahoo.com
authors: Ron
authors: R
authors: Beloosesky
authors: Yuval
authors: Y
authors: Ginsberg
authors: Nizar
authors: N
authors: Khatib
authors: Nir
authors: N
authors: Maravi
authors: Michael G
authors: MG
authors: Ross
authors: Joseph
authors: J
authors: Itskovitz-Eldor
authors: Zeev
authors: Z
authors: Weiner
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D018445:Infectious Disease Transmission, Vertical; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides; D008279:Magnetic Resonance Imaging; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides; D000111:Acetylcysteine