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


OBJECTIVE
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 (paO(2) = 20-40 mm Hg) and then resuscitated with 100% O(2 )for 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.
Jantzie
Lauren L
LL
Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2R7, Canada.
Cheung
Po-Yin
PY
Johnson
Scott T
ST
Bigam
David L
DL
Todd
Kathryn G
KG
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001238:Asphyxia Neonatorum / Q000188:drug therapy / Q000378:metabolism; D054022:Cerebrum / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000534:rehabilitation; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism; D007231:Infant, Newborn; D055442:Metabolome / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism; D012151:Resuscitation; D013552:Swine
D000596:Amino Acids; D000975:Antioxidants; D016166:Free Radical Scavengers; D010100:Oxygen; D000111:Acetylcysteine