Excitatory amino acid release and electrocortical brain activity after hypoxemia in near-term lambs.
BACKGROUND
Energy failure due to insufficient cerebral O(2)-supply leads to excess accumulation of calcium ions in presynaptic neurons, followed by excess release of excitatory amino acids (EAAs), which are potent neurotoxins, into the synaptic cleft.


OBJECTIVE
The aim of the present study was to determine whether extracellular EAAs release after prolonged hypoxemia affects electrocortical brain activity (ECBA), as a measure of brain cell function, in near-term born lambs.


METHODS
Ten near-term lambs (term: 147 days) were delivered at 131 days of gestation. After a stabilization period, prolonged hypoxemia (FiO(2): 0.10; duration 2.5h) was induced. Mean values of physiologic variables, including ECBA, were calculated over the last 3 min of normoxemia as well as of hypoxemia. Cerebral arterial and venous blood gases were determined at the end of the normoxemic and hypoxemic periods. Cerebrospinal fluid (CSF) was obtained at the end of the hypoxemic period. CSF from six normoxemic sibs was used for comparison. HPLC was used to measure EAAs in the CSF.


RESULTS
During hypoxemia, aspartate and glutamate concentration increased significantly (4.8 and 6.0 times, respectively), while asparagine and glutamine did not. ECBA decreased to 30% of the normoxemic value. Glutamate was significantly higher in lambs with a flat cerebral function monitor (CFM) tracing than in lambs with a burst-suppression pattern.


CONCLUSIONS
After prolonged hypoxemia aspartate and glutamate accumulated excessively in the CSF of near-term born lambs. Especially glutamate concentrations in CSF were related to the decline in brain cell function.
van Os
Sandra
S
Division of Neonatology, Department of Pediatrics 435, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Ruitenbeek
Wim
W
Hopman
Jeroen
J
van de Bor
Margot
M
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000134:cerebrospinal fluid*; D001786:Blood Glucose; D001921:Brain / Q000503:physiopathology; D004569:Electroencephalography; D005260:Female; D005865:Gestational Age; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D000860:Hypoxia / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000503:physiopathology*; D019344:Lactic Acid / Q000097:blood; D011247:Pregnancy; D012756:Sheep
D001786:Blood Glucose; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid