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Cerebral blood flow heterogeneity in preterm sheep: lack of physiologic support for vascular boundary zones in fetal cerebral white matter.

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.
AuthorsMelissa M McClure, Art Riddle, Mario Manese, Ning Ling Luo, Dawn A Rorvik, Katherine A Kelly, Clyde H Barlow, Jeffrey J Kelly, Kevin Vinecore, Colin T Roberts, A Roger Hohimer, Stephen A Back
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 28 Issue 5 Pg. 995-1008 (May 2008) ISSN: 0271-678X [Print] United States
PMID18091757 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Topics
  • Animals
  • Cerebral Cortex (blood supply, embryology, pathology)
  • Cerebrovascular Circulation (physiology)
  • Corpus Callosum (blood supply, embryology, pathology)
  • Electroencephalography
  • Epilepsy (pathology, physiopathology)
  • Female
  • Gestational Age
  • Hypoxia-Ischemia, Brain (pathology, physiopathology)
  • In Situ Nick-End Labeling
  • Microspheres
  • Nerve Fibers, Myelinated (pathology, physiology)
  • Oligodendroglia (pathology, physiology)
  • Predictive Value of Tests
  • Pregnancy
  • Reperfusion Injury (pathology, physiopathology)
  • Severity of Illness Index
  • Sheep

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