Hypoxia-ischemia stimulates hippocampal glutamate efflux in perinatal rat brain: an in vivo microdialysis study.
We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on hippocampal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right hippocampus of postnatal d 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and animals were exposed to 8% oxygen for 2 h (n = 6, histologically verified). Ten 20-min dialysis fractions were collected from each animal: three sequential 20-min baseline samples, six samples during hypoxia, and a recovery sample in room air. Eight amino acids were detected in dialysates with a HPLC assay. There was marked intra- and interanimal variation in glutamate efflux; mean glutamate efflux increased from 17 pmol/min in baseline samples to 51 in the 2nd h of hypoxia (p = 0.002, Kruskal Wallis test). There was a concurrent decline in glutamine efflux (310 to 207 pmol/min, p = 0.0005). Alanine efflux doubled during hypoxia (p = 0.015). There were no changes in efflux of the other five amino acids analyzed. In this experimental model of perinatal stroke, during the acute evolution of hypoxic-ischemic brain injury, transient large increases in glutamate efflux and corresponding declines in glutamine efflux were detected. These data support the hypothesis that synaptic concentrations of the endogenous excitatory amino acid glutamate increase during the evolution of hippocampal ischemic injury.
Department of Pediatrics, University of Michigan, Ann Arbor 48109-0570.
F S
FS
Silverstein
B
B
Naik
J
J
Simpson
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001693:Biological Transport, Active; D002545:Brain Ischemia / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000378:metabolism; D003956:Dialysis; D004195:Disease Models, Animal; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000098:blood supply / Q000293:injuries / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D005971:Glutamates; D018698:Glutamic Acid