Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia

Extracellular levels of excitatory and inhibitory amino acids were measured in the cortex and striatum of asphyxiated fetal lambs. The fetus was exteriorized from the anesthetized ewe and dialysis probes were placed in the parietal cortex and caudate nucleus. Cerebral blood flow was measured with Xe-clearance. Cortical somatosensory-evoked potentials and electroencephalogram (EEG) were continuously recorded. Asphyxia was induced by clamping the umbilical cord or by graded compression of the maternal aorta. Asphyxia accompanied by elevated cerebral blood flow resulted in a moderate rise in extracellular amino acid levels. During extreme asphyxia, i.e. abolished evoked potentials and reduced cerebral blood flow, marked extracellular elevations of glutamate (3- to 11-fold), aspartate (3- to 7-fold), gamma-aminobutyric acid (GABA) (3- to 5-fold) and taurine (3- to 18-fold) occurred, the higher values representing striatum. Excessive levels of excitatory amino acids may exert injurious effects on immature neurons during such hypoxic-ischemic states.

[1]  M. Johnston,et al.  Perinatal Hypoxia‐Ischemia Disrupts Striatal High‐Affinity [3H]Glutamate Uptake into Synaptosomes , 1986, Journal of neurochemistry.

[2]  J. Coyle Biochemical aspects of neurotransmission in the developing brain. , 1977, International review of neurobiology.

[3]  J. Olney Excitatory transmitters and epilepsy-related brain damage. , 1985, International review of neurobiology.

[4]  F. Gage,et al.  Evidence for amelioration of ischaemic neuronal damage in the hippocampal formation by lesions of the perforant path. , 1985, Neurological research.

[5]  P. Roberts,et al.  Neurotoxicity of L‐Glutamate and DL‐Threo‐3‐Hydroxyaspartate in the Rat Striatum , 1985, Journal of neurochemistry.

[6]  J. Garthwaite,et al.  Amino acid neurotoxicity: Relationship to neuronal depolarization in rat cerebellar slices , 1986, Neuroscience.

[7]  Peter Lindroth,et al.  High performance liquid chromatographic determination of subpicomole amounts of amino acids by precolumn fluorescence derivatization with o-phthaldialdehyde , 1979 .

[8]  B. Meldrum,et al.  Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. , 1984, Science.

[9]  A. Hamberger,et al.  In vivo regulation of extracellular taurine and other neuroactive amino acids in the rabbit hippocampus. , 1985, Progress in clinical and biological research.

[10]  S. Butcher,et al.  Extracellular Overflow of Neuroactive Amino Acids During Severe Insulin‐Induced Hypoglycemia: In Vivo Dialysis of the Rat Hippocampus , 1986, Journal of neurochemistry.

[11]  N. Diemer,et al.  Ischemic CA-1 pyramidal cell loss is prevented by preischemic colchicine destruction of dentate gyrus granule cells , 1986, Brain Research.

[12]  H. Benveniste,et al.  Elevation of the Extracellular Concentrations of Glutamate and Aspartate in Rat Hippocampus During Transient Cerebral Ischemia Monitored by Intracerebral Microdialysis , 1984, Journal of neurochemistry.

[13]  Y. Nakamura,et al.  HYPOXIC‐ISCHEMIC BRAIN LESIONS FOUND IN ASPHYXIATING NEONATES , 1986, Acta pathologica japonica.

[14]  M. Johnston,et al.  The glutamate analogue quisqualic acid is neurotoxic in striatum and hippocampus of immature rat brain , 1986, Neuroscience Letters.

[15]  P. Gluckman,et al.  Stereotaxic method and atlas for the ovine fetal forebrain. , 1983, Journal of developmental physiology.

[16]  I. Kjellmer,et al.  Cerebral arterio-venous difference for hypoxanthine and lactate during graded asphyxia in the fetal lamb , 1982, Brain Research.

[17]  S. Rothman Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  H. Benveniste,et al.  Cellular Origin of Ischemia‐Induced Glutamate Release from Brain Tissue In Vivo and In Vitro , 1985, Journal of neurochemistry.

[19]  P. Campochiaro,et al.  Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[20]  T. Olsson,et al.  Cerebral Reactions during Intrauterine Asphyxia in the Sheep. I. Circulation and Oxygen Consumption in the Fetal Brain , 1974, Pediatric Research.

[21]  D. Choi,et al.  Glutamate neurotoxicity in cortical cell culture is calcium dependent , 1985, Neuroscience Letters.

[22]  M. Cynader,et al.  The laminar distributions and postnatal development of neurotransmitter and neuromodulator receptors in cat visual cortex , 1986, Brain Research Bulletin.

[23]  A. Hamberger,et al.  Ischemia-Induced Shift of Inhibitory and Excitatory Amino Acids from Intra- to Extracellular Compartments , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  R. Schwarcz,et al.  On the excitotoxic properties of quinolinic acid, 2,3-piperidine dicarboxylic acids and structurally related compounds , 1983, Neuropharmacology.