Cerebral amino acid profiles after hypoxia-reoxygenation and N-acetylcysteine treatment in the newborn piglet

Lauren L. Jantzie, Po Yin Cheung, Scott T. Johnson, David L. Bigam, Kathryn G. Todd

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Neonatal hypoxia-ischemia (HI) is a common clinical occurrence. Recently, much evidence has been gathered to suggest that oxygen free radicals are implicated in the pathogenesis of hypoxia-reoxygenation injury through the initiation and propagation of toxic cascades including glutamate excitotoxicity and the manifestation of post-HI neurologic disorders. Following HI, excessive free radicals are formed and antioxidant defenses are diminished. N-acetylcysteine (NAC) is a clinically available antioxidant and has been previously shown to reduce oxidative stress and scavenge free radicals in multiple models of brain injury. Objectives: Using an acutely instrumented swine model of neonatal hypoxia-reoxygenation, the objective of the present study was to examine the neurochemical effects of NAC administration in 5 brain regions exquisitely vulnerable to severe hypoxia. Methods: In a blinded fashion, newborn piglets (1-4 d, 1.4-2.2 kg) were block randomized into surgical sham (SHAM), hypoxic control (HC) and NAC-treated (H-NAC) groups. Both HC and H-NAC piglets were subject to 2 h of alveolar hypoxia (paO2 = 20-40 mm Hg) and then resuscitated with 100% O2for 1 h followed by 21% for an additional 3 h. Results: Our results show that two hours of severe hypoxemia causes metabolic acidosis and significant changes in cerebral amino acids including glutamate, aspartate and alanine, in all brain regions investigated including the cortex, basal ganglia and thalamus. The administration of NAC 10 min into the reoxygenation period and subsequently continued as an infusion, maintains post-resuscitation amino acid neurochemistry at the levels observed in SHAM piglets. Conclusions: In newborn piglets that have sustained brain injury related to hypoxia/reoxygenation, the administration of NAC does not disrupt cerebral amino acid balance and maintains cerebral amino acid homeostasis.

Original languageEnglish (US)
Pages (from-to)195-203
Number of pages9
JournalNeonatology
Volume97
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Keywords

  • Amino acid neurotransmitters
  • Hypoxia-ischemia
  • Hypoxia-reoxygenation
  • N-acetylcysteine
  • Resuscitation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Biology

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