The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

Stephen Back, Art Riddle, Justin Dean, Alan (Roger) Hohimer

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Despite advances in neonatal intensive care, survivors of premature birth remain highly susceptible to unique patterns of developmental brain injury that manifest as cerebral palsy and cognitive-learning disabilities. The developing brain is particularly susceptible to cerebral white matter injury related to hypoxia-ischemia. Cerebral white matter development in fetal sheep shares many anatomical and physiological similarities with humans. Thus, the fetal sheep has provided unique experimental access to the complex pathophysiological processes that contribute to injury to the human brain during successive periods in development. Recent refinements have resulted in models that replicate major features of acute and chronic human cerebral injury and have provided access to complex clinically relevant studies of cerebral blood flow and neuroimaging that are not feasible in smaller laboratory animals. Here, we focus on emerging insights and methodologies from studies in fetal sheep that have begun to define cellular and vascular factors that contribute to white matter injury. Recent advances include spatially defined measurements of cerebral blood flow in utero, the definition of cellular maturational factors that define the topography of injury and the application of high-field magnetic resonance imaging to define novel neuroimaging signatures for specific types of chronic white matter injury. Despite the higher costs and technical challenges of instrumented preterm fetal sheep models, they provide powerful access to clinically relevant studies that provide a more integrated analysis of the spectrum of insults that appear to contribute to cerebral injury in human preterm infants.

Original languageEnglish (US)
Pages (from-to)359-370
Number of pages12
JournalNeurotherapeutics
Volume9
Issue number2
DOIs
StatePublished - Apr 2012

Fingerprint

Premature Infants
Sheep
Wounds and Injuries
Cerebrovascular Circulation
Neuroimaging
Neonatal Intensive Care
Learning Disorders
Premature Birth
Brain
Laboratory Animals
Cerebral Palsy
Fetal Development
White Matter
Brain Injuries
Survivors
Spectrum Analysis
Ischemia
Magnetic Resonance Imaging
Costs and Cost Analysis

Keywords

  • Cerebral blood flow
  • Cerebral palsy
  • Hypoxia-ischemia
  • MRI
  • Myelin
  • Oligodendrocyte
  • Ovine
  • White matter

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Clinical Neurology
  • Pharmacology

Cite this

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant. / Back, Stephen; Riddle, Art; Dean, Justin; Hohimer, Alan (Roger).

In: Neurotherapeutics, Vol. 9, No. 2, 04.2012, p. 359-370.

Research output: Contribution to journalArticle

Back, Stephen ; Riddle, Art ; Dean, Justin ; Hohimer, Alan (Roger). / The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant. In: Neurotherapeutics. 2012 ; Vol. 9, No. 2. pp. 359-370.
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