Journal of Neuroscience, Vol 9, 798-805, Copyright © 1989 by Society for Neuroscience
Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia
E Westerberg, DT Monaghan, H Kalimo, CW Cotman and TW Wieloch
Laboratory for Experimental Brain Research, University of Lund, Lund Hospital, Sweden.
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)
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