Hypoxia-ischemia produces focal disruption of glutamate receptors in developing brain.
We examined the impact of a perinatal hypoxic-ischemic insult on the distribution of glutamate receptors in developing brain. We used a well characterized rodent model for perinatal hypoxic-ischemic encephalopathy, unilateral carotid artery occlusion followed by exposure to 8% oxygen for 2.5 h in 7-day-old rat pups. This preparation results in focal neuronal damage in striatum, hippocampus, and cortex ipsilateral to ligation. Alterations in the regional distribution of glutamate binding in the first 24 h after the insult were assessed with quantitative in vitro [3H]glutamate autoradiography. In lesioned animals, we found progressive selective reductions in [3H]glutamate binding in forebrain ipsilateral to ligation in regions destined for neuronal damage. The earliest and most prominent unilateral reductions in binding were noted in the dentate gyrus of hippocampus (-45 +/- 9%, compared with contralateral hemisphere at 24 h). Acute reductions in specific glutamate binding appear to be a sensitive marker for hypoxic-ischemic neuronal damage in the immature brain. These observations suggest that neurons bearing glutamate receptors may be particularly susceptible to hypoxic-ischemic injury.
D000367:Age Factors; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid