Cerebral Blood Flow Heterogeneity in Preterm Sheep: Lack of Physiologic Support for Vascular Boundary Zones in Fetal Cerebral White Matter
Open Access
- 19 December 2007
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 28 (5), 995-1008
- https://doi.org/10.1038/sj.jcbfm.9600597
Abstract
Periventricular white matter (PVWM) injury is the leading cause of neurologic disability in survivors of prematurity. To address the role of ischemia in PVWM and cerebral cortical injury, we hypothesized that immaturity of spatially distal vascular ‘end zones’ or ‘border zones’ predisposes PVWM to greater decreases in cerebral blood flow (CBF) than more proximal structures. We quantified regional CBF with fluorescently labeled microspheres in 0.65 gestation fetal sheep in histopathologically defined three-dimensional regions by post hoc digital dissection and coregistration algorithms. Basal flow in PVWM was significantly lower than in gyral white matter and cortex, but was equivalent in superficial, middle, and deep PVWM. Absolute and relative CBF (expressed as percentage of basal) did not differ significantly during ischemia or reperfusion between PVWM, gyral white matter, or cortex. Moreover, CBF during ischemia-reperfusion was equivalent in three adjacent PVWM levels and was not consistent with the magnitude of severity of PVWM injury, defined by TUNEL (terminal deoxynucleotidyltransferase-mediated dUPT nick end labeling) staining. However, the magnitude of ischemia was predicted by the severity of discrete cortical lesions. Hence, unlike cerebral cortex, unique CBF disturbances did not account for the distribution of PVWM injury. Previously defined cellular maturational factors, thus, appear to have a greater influence on PVWM vulnerability to ischemic injury than the presence of immature vascular boundary zones.Keywords
This publication has 51 references indexed in Scilit:
- Topical Review: Role of Instrumented Fetal Sheep Preparations in Defining the Pathogenesis of Human Periventricular White-Matter InjuryJournal of Child Neurology, 2006
- Perinatal white matter injury: The changing spectrum of pathology and emerging insights into pathogenetic mechanismsMental Retardation and Developmental Disabilities Research Reviews, 2006
- Early Brain Injury in Premature Newborns Detected with Magnetic Resonance Imaging is Associated with Adverse Early Neurodevelopmental OutcomeThe Journal of Pediatrics, 2005
- Selective vulnerability of preterm white matter to oxidative damage defined by F2‐isoprostanesAnnals of Neurology, 2005
- Developmental changes in cerebral autoregulatory capacity in the fetal sheep parietal cortexThe Journal of Physiology, 2002
- The Structure of Blood Vessels in the Germinal Matrix and the Autoregulation of Cerebral Blood Flow in Premature InfantsPediatrics, 2001
- Regional blood flow measurements from fluorescent microsphere images using an Imaging CryoMicrotomeReview of Scientific Instruments, 2000
- Role of the Cerebrovascular and Metabolic Responses in the Delayed Phases of Injury After Transient Cerebral Ischemia in Fetal SheepStroke, 1999
- Fetal Cerebral Blood Flow and Metabolism during Oligemia and Early Postoligemic ReperfusionJournal of Cerebral Blood Flow & Metabolism, 1991
- The early embryonic pattern of internal vascularization of the mammalian cerebral cortexJournal of Comparative Neurology, 1964