Chronic fetal hypoxia produces selective brain injury associated with altered nitric oxide synthases Journal Article


Authors: Dong, Yafeng; Yu, Zhiyong; Sun, Yan; Zhou, Hui; Stites, Josh; Newell, Katherine; Weiner, Carl P
Article Title: Chronic fetal hypoxia produces selective brain injury associated with altered nitric oxide synthases
Alternate Title: American journal of obstetrics and gynecology
Keywords: Female; Animals; Pregnancy; Chronic Disease; Guinea Pigs; Isoenzymes; Pregnancy Complications; Nitric Oxide Synthase; Fetal Hypoxia; Brain Injuries
Journal Title: American journal of obstetrics and gynecology
Volume: 204
Issue: 3
ISSN: 1097-6868
Publisher: Elsevier  
Date Published: 2011
Start Page: 254.e16
End Page: 28
DOI/URL:
Notes: OBJECTIVE The purpose of this study was to investigate the impact of chronic hypoxia on the nitric oxide synthase isoenzymes in specific brain structures. STUDY DESIGN 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. CONCLUSION 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.
KUMC Authors
  1. Carl Weiner
    208 Weiner
  2. Yafeng Dong
    20 Dong