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 damage was studied following hypoxia-ischemia. To induce hypoxia-ischemia injury, rats on postnatal day 7 were exposed to 8 % oxygen for 2 h following unilateral common carotid artery ligation. According to brain damage scoring based on Cresyl Violet staining, the neuronal damage time-dependently changed in the ischemic regions following hypoxia-ischemia. Immunohistochemical studies showed that excitatory amino acid transporter 1 expression was mainly observed in the cerebral cortex ipsilateral to common carotid artery ligation and markedly increased at 24 h and 48 h following hypoxia-ischemia. Combined with confocal laser scanning microscopic analysis, double staining showed that excitatory amino acid transporter 1 positive staining appeared in neurons as well as astrocytes after hypoxia-ischemia. Most excitatory amino acid transporter 1 positive staining cells exhibited regular morphological characteristics and only a few were double-stained by terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling. Down-regulation of excitatory amino acid transporter 1 expression by intraventricular administration of specific antisense oligonucleotide exacerbated neuronal damage in hypoxia-ischemia brain. These results suggest that the increase of excitatory amino acid transporter 1 expression may be involved in a pathophysiological process of hypoxia-ischemia brain damage and may reflect a self-compensative mechanism for protecting neurons from further injury.
National Key Laboratory of Medical Neurobiology, Medical Center of Fudan University, 200032, Shanghai, People's Republic of China.
F
F
Tao
S D
SD
Lu
L M
LM
Zhang
Y L
YL
Huang
F Y
FY
Sun
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D000831:Animals, Newborn; D048588:Benzoxazines; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D007839:Functional Laterality; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007700:Kinetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010078:Oxazines; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D048588:Benzoxazines; D010078:Oxazines; C028911:cresyl violet; D010751:Phosphopyruvate Hydratase