title: Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?
abstract: Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns.
authors.affiliation: Department of Pediatrics, McGill University, Montreal, QC, Canada.
authors.forename: Henna
authors.initials: H
authors.lastname: Shaikh
authors.forename: Mirna
authors.initials: M
authors.lastname: Lechpammer
authors.forename: Frances E
authors.initials: FE
authors.lastname: Jensen
authors.forename: Simon K
authors.initials: SK
authors.lastname: Warfield
authors.forename: Anne H
authors.initials: AH
authors.lastname: Hansen
authors.forename: Bela
authors.initials: B
authors.lastname: Kosaras
authors.forename: Michael
authors.initials: M
authors.lastname: Shevell
authors.forename: Pia
authors.initials: P
authors.lastname: Wintermark
mesh_terms: D000818:Animals; D001238:Asphyxia Neonatorum / Q000150:complications* / Q000473:pathology* / Q000628:therapy; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology; D007231:Infant, Newborn; D009389:Neovascularization, Pathologic; D011446:Prospective Studies; D051381:Rats; D020318:Rats, Long-Evans