Role of excitatory amino acid transporter 1 in neonatal rat neuronal damage induced by hypoxia-ischemia

The role of excitatory amino acid transporter 1 in neonatal rat neuronal da mage was studied following hypoxia-ischemia. To induce hypoxia-ischemia inj ury, rats on postnatal day 7 were exposed to 8% oxygen For 2h following uni lateral common carotid artery ligation. According to brain damage scoring b ased on Cresyl Violet staining, the neuronal damage time-dependently change d in the ischemic regions following hypoxia-ischemia. Immunohistochemical s tudies showed that excitatory amino acid transporter 1 expression was mainl y observed in the cerebral cortex ipsilateral to common carotid artery liga tion and markedly increased at 24 h and 48 h following hypoxia-ischemia. Co mbined with confocal laser scanning microscopic analysis, double staining s howed that excitatory amino acid transporter 1 positive staining appeared i n neurons as well 35 astrocytes after hypoxia-ischemia. Most excitatory ami no acid transporter 1 positive staining cells exhibited regular morphologic al characteristics and only a few were double-stained by terminal deoxynucl eotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling. Do wn-regulation of excitatory amino acid transporter 1 expression by intraven tricular administration of specific antisense oligonucleotide exacerbated n euronal damage in hypoxia-ischemia brain. These results suggest that the increase of excitatory amino acid transporte r 1 expression may be involved in a patho-physiological process of hypoxia- ischemia blain damage and may reflect a self-compensative mechanism for pro tecting neurons from further injury. (C) 2001 IBRO. Published by Elsevier S cience Ltd. All rights reserved.