Document Detail

Role of instrumented fetal sheep preparations in defining the pathogenesis of human periventricular white-matter injury.
MedLine Citation:
PMID:  16970848     Owner:  NLM     Status:  MEDLINE    
Periventricular white-matter injury is the major form of brain injury associated with prematurity and the leading cause of cerebral palsy in survivors of premature birth. Progress in understanding the pathogenesis of periventricular white-matter injury requires the development of animal models that are relevant to the unique physiology of the preterm human brain and that replicate the major neuropathologic features of human injury. The sheep is the most extensively studied true fetal preparation. The neurodevelopment of the preterm sheep fetus (0.65 gestation) is comparable to that of the preterm human between approximately 24 and 28 weeks. The size of the fetal sheep permits chronic instrumentation so that well-defined insults can be studied with reliable measurements of blood flow and metabolism in cerebral white-matter. We review here recent developments in the understanding of the role of cerebral hypoxia-ischemia and vulnerable oligodendrocyte progenitors in the pathogenesis of periventricular white-matter injury in the immature sheep fetus. We focus on recent developments in high-resolution spatially defined cerebral blood flow measurements in utero. We determined ovine white-matter maturation between 90 and 120 days' gestation, as defined by immunohistochemical localization of oligodendrocyte lineage-specific antibodies. There was considerable spatial and temporal heterogeneity in oligodendrocyte maturation in the immature periventricular white-matter. Oligodendrocyte maturation in the 90- to 105-day fetal sheep closely coincided with that of the preterm human during the high-risk period for white-matter injury. Hence, the immature state of the 90- to 105-day fetal periventricular white-matter is an optimal and dynamic developmental window to study the role of cellular-maturational factors in the pathogenesis of white-matter injury. We conclude with a review of the significant advantages of the instrumented fetal sheep to accelerate progress in the translation of preventive therapies for periventricular white-matter injury and cerebral palsy.
Stephen A Back; Art Riddle; A Roger Hohimer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Journal of child neurology     Volume:  21     ISSN:  0883-0738     ISO Abbreviation:  J. Child Neurol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-09-14     Completed Date:  2006-11-21     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  8606714     Medline TA:  J Child Neurol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  582-9     Citation Subset:  IM    
Department of Pediatrics, Oregon Health & Science University, Portland 97239-3098, USA.
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MeSH Terms
Cerebrovascular Circulation / physiology
Disease Models, Animal*
Hypoxia-Ischemia, Brain / pathology
Infant, Newborn
Infant, Premature
Leukomalacia, Periventricular / etiology*,  pathology,  physiopathology
Oligodendroglia / physiology
Stem Cells / physiology
Grant Support
Comment In:
J Child Neurol. 2006 Jul;21(7):580-1   [PMID:  16970847 ]

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