Intraischemic but not postischemic hypothermia prevents non-selective hippocampal downregulation of AMPA and NMDA receptor gene expression after global ischemia

Hypothermia may afford histological neuroprotection induced by ischemia by preventing aberrant Ca2+ influx through NMDA (N-methyl-D-aspartic acid) or Ca2+-permeable AMPA (alpha -amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors. Expression of hippocampal GluR1(A), GluR2(B), GluR3(C) and NMDAR1 (NR1) subunits was investigated by in situ hybridization at 1 and 7 days after 10-min transient global ischemia in the presence and absence of intraischemic or postischemic brain hypothermia (30 degreesC). At 1 day, n ormothermic ischemia markedly suppressed the expression of GluR1(A), GluR2( B), and GluR3(C) receptor mRNAs to a similar degree in the vulnerable CA1. Less vulnerable CA3a-c subregions were also acutely downregulated. NR1 mRNA expression was reduced in CA1 but to a lesser extent than AMPA mRNAs. At 7 days after normothermic ischemia, a time of marked CA1 cell loss, all thre e AMPA transcripts were nearly absent in CA1 while a percentage (33.9+/-7.2 %) of NR1 mRNA remained. Intraischemic hypothermia fully blocked the damage and non-selective mRNA downregulations at 1 and 7 days. By contrast, posti schemic hypothermia postponed neurodegeneration but only partially rescued the expression of AMPA and NR1 mRNAs at 7 days and not at 1 day after the i nsult. Therefore, hippocampal AMPA receptor mRNAs decline at a relatively s imilar rate after normothermic global ischemia and cellular neuroprotection by intraischemic hypothermia occurred independently of altered subunit com position of AMPA receptors. Since decreases persist within resistant neuron s under the postischemic condition, AMPA receptor-mediated Ca2+ currents pr obably do not contribute to selective vulnerability. (C) 2001 Elsevier Scie nce B.V. All rights reserved.