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

Melissa M. McClure, Art Riddle, Mario Manese, Ning Ling Luo, Dawn A. Rorvik, Katherine A. Kelly, Clyde H. Barlow, Jeffrey J. Kelly, Kevin Vinecore, Colin Roberts, Alan (Roger) Hohimer, Stephen Back

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)995-1008
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume28
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Cerebrovascular Circulation
Blood Vessels
Sheep
Ischemia
Wounds and Injuries
Reperfusion
White Matter
DNA Nucleotidylexotransferase
Regional Blood Flow
In Situ Nick-End Labeling

Keywords

  • Blood flow
  • Hypoxia ischemia
  • Microspheres
  • Oligodendrocyte
  • Sheep
  • Whitematter

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Cerebral blood flow heterogeneity in preterm sheep : Lack of physiologic support for vascular boundary zones in fetal cerebral white matter. / McClure, Melissa M.; Riddle, Art; Manese, Mario; Luo, Ning Ling; Rorvik, Dawn A.; Kelly, Katherine A.; Barlow, Clyde H.; Kelly, Jeffrey J.; Vinecore, Kevin; Roberts, Colin; Hohimer, Alan (Roger); Back, Stephen.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 28, No. 5, 05.2008, p. 995-1008.

Research output: Contribution to journalArticle

McClure, Melissa M. ; Riddle, Art ; Manese, Mario ; Luo, Ning Ling ; Rorvik, Dawn A. ; Kelly, Katherine A. ; Barlow, Clyde H. ; Kelly, Jeffrey J. ; Vinecore, Kevin ; Roberts, Colin ; Hohimer, Alan (Roger) ; Back, Stephen. / Cerebral blood flow heterogeneity in preterm sheep : Lack of physiologic support for vascular boundary zones in fetal cerebral white matter. In: Journal of Cerebral Blood Flow and Metabolism. 2008 ; Vol. 28, No. 5. pp. 995-1008.
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