Neuroscience Letters, 78 (1987) 311-317 311 Elsevier Scientific Publishers Ireland Ltd. NSL 04703 Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia Henrik Hagberg 1, Peter Andersson l, Ingemar Kjellmer 2, Klara Thiringer 2 and Magnus Thordstein 3 / 2 3 Institute of Neurobiology, Department of Pediatrics and Physiology, University of GSteborg, G6teborg (Sweden) (Received 23 February 1987; Revised version received 26 March 1987; Accepted 27 March 1987) Key words." Ischemia; Hypoxia; Fetal lamb; Excitatory amino acid; Inhibitory amino acid 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 extraceUular amino acid levels. During extreme asphyxia, i.e. abolished evoked potentials and reduced cerebral blood flow, marked extracellular elevations of glutamate (3- to 1l-fold), aspartate (3- to 7-fold), y-aminobutyric acid (GABA) (3- to 5-fold) and taurine (3- to 18-fold) occurred, the higher values representing striatum. Exces- sive levels of excitatory amino acids may exert injurious effects on immature neurons during such hypoxic- ischemic states. Prolonged hypoxia-ischemia in neonates results in irreversible cell injuries loca- lized mainly in the brain hemispheres and to some degree in the brainstem and the cerebellum [16]. The cellular mechanisms involved in the development of ischemic damage in the immature brain are largely unknown. During complete ischemia in the adult brain glutamate and aspartate reach extracellular levels that may be toxic [1, 11]. Lesion of glutamatergic afferents to different hippocampal regions protect against ischemic cell death [7, 27]. In addition, glutamate receptor-antagonists, espe- cially those blocking the N-methyl-D-aspartate (NMDA) receptor type, prevent anoxic neuronal cell death in vitro [18] and reduce ischemic cell damage in vivo [24]. Some observations suggest a role of excitotoxins also in the genesis of ischemic inju- ries in the immature brain: there is a high density of glutamate receptors of the NMDA Correspondence." H. Hagberg, Institute of Neurobiology, University of Grteborg, P.O. Box 33031, S- 400 33 Grteborg, Sweden. 0304-3940/87/$ 03.50 O 1987 Elsevier Scientific Publishers Ireland Ltd.