Myelin expression is altered in the brains of neonatal rats reared in a fluctuating oxygen atmosphere

Kofi Sedowofia, David Giles, Jean Wade, Steve Cunningham, Janet R McColm, Robert Minns, Neil McIntosh

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Preterm infants receiving supplemental oxygen therapy experience frequent fluctuations in their blood oxygen levels, the magnitude of which has been associated with the incidence and severity of retinopathy of prematurity in such infants. Objective: Our objective was to investigate in a relevant animal model whether the immature brain with its poorly vascularised white matter might also be susceptible to injury when exposed to such fluctuations in blood oxygen. Methods: Newborn rats were reared in an atmosphere in which a computer reproduced the oxygen fluctuations derived from the transcutaneous oxygen levels of a 24-week preterm infant who had developed severe retinopathy. Following 14 days of exposure, we measured the expression of active caspase-3, myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in the brains comparing with rat pups raised in room air. Results: Compared to room air controls, at day 14, the expression of active caspase-3 was increased by up to 162% (significant increase in 7 of 9 regions), MBP decreased by up to 70% (significant in the hypothalamus only) and GFAP increased by up to 103% (significant in 6 of 7 regions. On day 21, following 7 days of reparative recovery, GFAP levels in most areas of oxygen-exposed brains had returned to near control levels. There were no longer significant differences in caspase-3 levels apart from the cerebral cortex, cerebellum and striatum. In contrast, MBP expression was now much higher in most regions of the treated brains compared to controls. Conclusion: We conclude that fluctuations in blood oxygen, observed in preterm survivors, may constitute a source of injury to the white matter and corpus striatum of the developing brain and contribute to the neurological sequelae in extremely premature infants.
Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalNeonatology
Volume94
Issue number2
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Brain
  • Caspase 3
  • Cell Count
  • Disease Models, Animal
  • Fluorescent Antibody Technique, Direct
  • Glial Fibrillary Acidic Protein
  • Hyperoxia
  • Immunoenzyme Techniques
  • Myelin Basic Protein
  • Nerve Fibers, Myelinated
  • Oxygen
  • Rats
  • Rats, Sprague-Dawley

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