title: The fetal brainstem is relatively spared from injury following intrauterine hypoxemia.
abstract: Our aim was to test the hypothesis that the fetal brainstem is relatively spared, compared to other brain regions, from hypoxia-induced damage. We have used established experimental models of acute and chronic intrauterine compromise in sheep to mimic conditions that can arise in human pregnancy. The acute insult was 12 h of placental insufficiency induced by restricted utero-placental blood flow at 90 days of gestation (term approximately 147 days). Five weeks after this insult (n=7 fetuses) there was no overt damage to the brainstem nor were there alterations to the blood vessel morphology, volume of the medulla or of medullary nuclei compared to controls (n=8). This regimen is known to have significant effects on the forebrain and cerebellum. The chronic insult was induced in five fetuses via embolisation of the umbilico-placental circulation from 120 to 140 days of gestation. An additional three fetuses were found to be spontaneously hypoxemic (SH) immediately after surgery. At 140 days, in brainstems of all chronically hypoxemic fetuses compared to controls (n=8), there was an increase (P<0.05) in the percentage of neuropil occupied by blood vessels and abnormal myelin in the most severely SH fetus but no other morphological or neurochemical alterations. This regimen is known to cause marked damage to the cerebral hemispheres and to a lesser extent to the cerebellum. We suggest that the absence of marked structural or neurochemical alterations in the brainstem is most likely due to the maintenance of oxygen delivery to the brainstem during fetal hypoxemia.
authors.affiliation: Department of Anatomy and Cell Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Tolcos
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
authors.forename: Michelle
authors.initials: M
authors.lastname: Loeliger
authors.forename: Sibilah
authors.initials: S
authors.lastname: Breen
authors.forename: Megan
authors.initials: M
authors.lastname: Cock
authors.forename: Jhodie
authors.initials: J
authors.lastname: Duncan
authors.forename: Sandra
authors.initials: S
authors.lastname: Rees
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000196:embryology / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000860:Hypoxia / Q000196:embryology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism / Q000648:ultrastructure; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011247:Pregnancy; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012756:Sheep; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D016708:Synaptophysin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I