Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia

Abstract

The changes in excitatory amino acid receptor ligand binding induced by transient cerebral ischemia were studied in the rat hippocampal subfields. Ten minutes of ischemia was induced by common carotid artery occlusion combined with hypotension, and the animals were allowed variable periods of recovery ranging from 1 day to 4 weeks. The binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to quisqualate receptors, 3H-kainic acid (KA) to kainate receptors, and 3H-glutamate to N-methyl-D-aspartate (NMDA) receptors as determined by quantitative autoradiography. One week following ischemia the CA1 region of the hippocampus displayed a severe (90%) dendrosomatic lesion with preservation of presynaptic terminals. This was associated with a 60% decrease in AMPA binding and a 25% decrease in glutamate binding to NMDA receptors. At 4 weeks postischemia, both AMPA and NMDA sites were greatly reduced. Although the dentate gyrus granule cells are resistant to an ischemic insult of this magnitude, this region showed marked changes in receptor binding. One week following ischemia, the AMPA and NMDA binding decreased by approximately 40 and 20%, respectively. Following 2 weeks of recovery, the NMDA binding was not significantly different from control level, while the AMPA binding remained depressed up to 4 weeks postischemia. The high density of KA binding sites in the inner molecular layer of the dentate gyrus was unaffected by the ischemic insult, despite an extensive degeneration of cells in the hilus of dentate gyrus which projects glutamatergic afferents to this area.(ABSTRACT TRUNCATED AT 250 WORDS)