title: Chronic fetal hypoxia produces selective brain injury associated with altered nitric oxide synthases.
abstract: OBJECTIVE
  The purpose of this study was to investigate the impact of chronic hypoxia on the nitric oxide synthase isoenzymes in specific brain structures.
  
  
  METHODS
  Time-mated pregnant guinea pigs were exposed to 10.5% molecular oxygen for 14 days (animals with chronic fetal hypoxia; HPX) or room air (control animals; NMX); L-N6-(1-iminoethyl)-lysine (L-NIL; an inducible nitric oxide synthase inhibitor, 1 mg/kg/d) was administered to HPX group for 14 days (L-NIL + HPX). Fetal brains were harvested at term. Multilabeled immunofluorescence was used to generate a brain injury map. Laser capture microdissection and quantitative polymerase chain reaction were applied; cell injury markers, apoptosis activation, neuron loss, total nitric oxide, and the levels of individual nitric oxide synthase isoenzymes were quantified.
  
  
  RESULTS
  Chronic hypoxia causes selective fetal brain injury rather than global. Injury is associated with differentially affected nitric oxide synthases in both neurons and glial cells, with inducible macrophage-type nitric oxide synthase up-regulated at all injury sites. L-NIL attenuated the injury, despite continued hypoxia.
  
  
  CONCLUSIONS
  These studies demonstrate that chronic hypoxia selectively injures the fetal brain in part by the differential regulation of nitric oxide synthase isoenzymes in an anatomic- and cell-specific manner.
authors.affiliation: Department of Obstetrics and Gynecology, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Dong
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Josh
authors.initials: J
authors.lastname: Stites
authors.forename: Katherine
authors.initials: K
authors.lastname: Newell
authors.forename: Carl P
authors.initials: CP
authors.lastname: Weiner
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000201:enzymology* / Q000209:etiology; D002908:Chronic Disease; D005260:Female; D005311:Fetal Hypoxia / Q000150:complications / Q000201:enzymology*; D006168:Guinea Pigs; D007527:Isoenzymes / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications
chemical_list: D007527:Isoenzymes; D019001:Nitric Oxide Synthase