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

L. K. Friedman, M. D. Ginsberg, L. Belayev, R. Busto, O. F. Alonso, B. Lin, M. T. Globus

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Abstract

Hypothermia may afford histological neuroprotection induced by ischemia by preventing aberrant Ca 2+ influx through NMDA (N-methyl-D-aspartic acid) or Ca 2+-permeable AMPA (α-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°C). At 1 day, normothermic 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 three 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, postischemic hypothermia postponed neurodegeneration but only partially rescued the expression of AMPA and NR1 mRNAs at 7 days and not at 1 day after the insult. Therefore, hippocampal AMPA receptor mRNAs decline at a relatively similar rate after normothermic global ischemia and cellular neuroprotection by intraischemic hypothermia occurred independently of altered subunit composition of AMPA receptors. Since decreases persist within resistant neurons under the postischemic condition, AMPA receptor-mediated Ca 2+ currents probably do not contribute to selective vulnerability.

Original languageEnglish (US)
Pages (from-to)34-47
Number of pages14
JournalMolecular Brain Research
Volume86
Issue number1-2
DOIs
StatePublished - Jan 31 2001

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Keywords

  • AMPA receptor
  • Delayed neurodegeneration
  • Intraischemic hypothermia
  • NR1 receptor
  • Postischemic hypothermia
  • Selective vulnerability

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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