title: Brain Injury and Inflammatory Response to Umbilical Cord Occlusions Is Limited With Worsening Acidosis in the Near-Term Ovine Fetus.
abstract: We hypothesized that repetitive umbilical cord occlusions (UCOs) with worsening fetal acidemia will lead to an inflammatory response within the brain and thereby brain injury which will be exacerbated by chronic hypoxemia and low-grade infection. Chronically instrumented fetal sheep served as controls (N = 10) or underwent repeated UCOs for up to 4 hours or until arterial pH was <7.00. Normoxic-UCO (N = 9) and hypoxic-UCO (N = 5) fetuses had arterial O2 saturation pre-UCOs of >55% and <55%, respectively, whereas lipopolysaccharide (LPS) UCO fetuses (N = 6) received LPS intra-amniotic (2 mg/h) starting 1 hour pre-UCOs. Animals were euthanized at 48 hours of recovery with fetal brains processed for assessment of inflammation (microglia and mast cell counts) and injury (necrosis-hematoxylin and eosin-and apoptosis-cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]). Repetitive UCOs resulted in severe acidemia in most animals with pH approaching 7.00 for all 3 UCO groups. However, there was no significant effect on measures of brain inflammation or injury, except in the LPS-UCO animals where TUNEL-positive cells were increased in the hippocampus, although small animal numbers in the hypoxic-UCO group may have limited the ability to detect significance in their TUNEL cell findings. We were therefore unable to confirm our working hypothesis since the near-term ovine fetal brain showed remarkable tolerance for these cord occlusion insults and likely involving protective metabolic mechanisms, despite the severe acidemia noted.
authors.affiliation: Department of Obstetrics and Gynecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Brad
authors.initials: B
authors.lastname: Matushewski
authors.affiliation: Biotron Experimental Climate Change Research Centre, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Nygard
authors.affiliation: Department of Pathology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Hammond
authors.affiliation: Department of Obstetrics and Gynaecology and Department of Neurosciences, CHU Ste-Justine Research Center, Université de Montréal, Montreal, Québec, Canada Centre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Québec, Canada.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Frasch
authors.affiliation: Department of Obstetrics and Gynecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada brichar1@uwo.ca.
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Richardson
mesh_terms: D000138:Acidosis / Q000209:etiology / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005311:Fetal Hypoxia / Q000209:etiology / Q000378:metabolism*; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D034561:Sheep, Domestic; D014470:Umbilical Cord / Q000098:blood supply* / Q000503:physiopathology*
keywords: brain apoptosis; brain necrosis; fetal hypoxia; microglia