MK801 decreases glutamate release and oxidative metabolism during hypoglycemic coma in piglets

Rebecca N. Ichord, Michael V. Johnston, Richard J. Traystman

Research output: Contribution to journalArticle

Abstract

Hypoglycemic coma increases extracellular excitatory amino acids, which mediate hypoglycemic neuronal degeneration. Cerebral oxygen consumption increases during hypoglycemic coma in piglets. We tested the hypothesis that the NMDA-receptor antagonist dizocilpine (MK801) attenuates the increase in cerebral oxygen consumption during hypoglycemia. We measured EEG, cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2) and cortical microdialysate levels of glutamate, aspartate and glycine in pentobarbital-anesthetized piglets during 60 min of insulin-induced hypoglycemic coma. NMDA-receptor distribution was measured by autoradiography. MK801 (0.75 mg/kg i.v.) was given within 5 min after onset of isoelectric EEG. Saline- and MK801-treated normoglycemic control animals were also studied. Brain temperature was maintained at 38.5±0.5°C. MK801 prevented the 5-10-fold increase in glutamate and aspartate occurring in saline-treated hypoglycemic animals, and attenuated the increase in CMRO2. Increases in CBF of 200-400% during hypoglycemic coma were not affected by MK801. MK801 did not alter CBF, CMRO2 or microdialysate amino acid levels in normoglycemic control animals. Parietal cortex corresponding to microdialysis sites was highly enriched in NMDA receptors, and the density and distribution overall of NMDA receptor binding sites were comparable to that reported in other species. We conclude that NMDA receptor activation plays a central role in hypoglycemia-induced glutamate release, and contributes to increased cerebral oxygen consumption. Neuroprotective effects of MK801 during hypoglycemia in piglets may involve inhibitory effects on glutamate release and oxidative metabolism.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalDevelopmental Brain Research
Volume128
Issue number2
DOIs
StatePublished - Jun 29 2001

Keywords

  • Cerebral blood flow
  • Cerebral oxygen consumption
  • Electroencephalogram
  • Excitotoxicity
  • Glucose
  • Piglet

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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