title: The effects of hypoxia on growth cones in the ovine fetal brain.
abstract: OBJECTIVE
  This study was designed to investigate the effects of hypoxia on neural process proliferation by studying its effects on growth cone tubulin and insulin-like growth factor (IGF)-I receptor content.
  
  
  METHODS
  Six fetal lambs were catheterized in the brachial artery and vein. Maternal oxygenation was reduced in steps from a fractional inspired oxygen concentration (FiO2) of 20% to 6% by addition of nitrogen to the inhaled gas mixture for a period of 4 h of reduced oxygen intake. Fetal arterial blood was sampled after the maternal FiO2 and oxygen were stable for >5 min at maternal FiO2 of 20% to 6%. Controls were obtained from normoxic fetuses whose ewes had similar surgery and were kept at an FiO2 of 20% throughout the experiment. Growth cones were isolated from the fetal cerebrum and cerebellum. alpha-tubulin and IGF-I receptors were quantified by immunoblotting. Tubulin and IGF-I receptor mRNA expressions were quantified by real-time polymerase chain reaction.
  
  
  RESULTS
  Maternal nitrogen breathing reduced fetal arterial pH from 7.32+/-0.06 to 6.99+/-0.02 (p<0.001). Hypoxia increased IGF-I receptors from 143+/-10 to 327+/-14 (p<0.001) and from 272+/-26 to 396+/-34 (p<0.001) fluorescence units/microg protein in the cerebrum and cerebellum, respectively. It also increased alpha-tubulin from 713+/-30 to 1873+/-126 (p<0.001) and from 780+/-34 to 2362+/-79 (p<0.001) fluorescence units/microg protein in the cerebrum and cerebellum, respectively. Expression of IGF-I receptor mRNA increased significantly in the hypoxic animals both in the cerebrum and the cerebellum, but there was no change in expression of alpha-tubulin mRNA.
  
  
  CONCLUSIONS
  This increase in IGF-I receptor expression and growth cone content may be an adaptive response to hypoxia to maintain neurite growth by facilitating binding of IGF-I. Hypoxia also increased the growth cone level of alpha-tubulin but did not increase its mRNA expression, which may indicate an inability to polymerize tubulin and build microtubules.
authors.affiliation: Division of Maternal-Fetal, Department of Obstetrics and Gynecology, UCLA Medical Center, Torrance, CA 90509, USA.
authors.forename: B L G
authors.initials: BL
authors.lastname: Morgan
authors.forename: C R
authors.initials: CR
authors.lastname: Chao
mesh_terms: D000818:Animals; D005260:Female; D005311:Fetal Hypoxia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism* / Q000473:pathology; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009584:Nitrogen; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012756:Sheep; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D017526:Receptor, IGF Type 1; D009584:Nitrogen