Non-N-methyl-D-aspartate glutamate receptors mediate oxygen--glucose deprivation-induced oligodendroglial injury

Brain Res. 2000 Jan 31;854(1-2):207-15. doi: 10.1016/s0006-8993(99)02359-8.

Abstract

Cells of oligodendroglial lineage are susceptible to oxygen and glucose deprivation. When oligodendrocyte-like cells differentiated from CG-4-immortalized rat O-2A progenitor cells were exposed to hypoxia alone or glucose deprivation alone for 48 h, release of lactate dehydrogenase (LDH) into the culture medium did not increase. However, when cells were deprived of both oxygen and glucose for 6 or 12 h preceding reoxygenation for 2 h, LDH release increased. Adding glucose to the medium protected against cell death and increased lactate production in a concentration-dependent manner. Cell damage induced by deprivation of oxygen and glucose was prevented by calcium-free medium or by non-N-methyl-D-aspartate glutamate receptor (GluR) antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione or LY293558, but not by the voltage-dependent calcium channel blocker, nimodipine, or by the N-methyl-D-aspartate GluR antagonist, MK-801. The glutamate concentration in the medium from cells exposed to oxygen-glucose deprivation for 12 h was 49.70+/-3.04 microM/l, which is sufficient to activate GluRs during deprivation of oxygen and glucose. Apoptotic cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) or Hoechst 33258 staining did not increase in cells exposed to oxygen-glucose deprivation for 12 h and subsequent reoxygenation for 2 h. No DNA laddering was detected by agarose gel electrophoresis from cells exposed to deprivation of oxygen and glucose. Neither acetyl-YVAD-CHO, an inhibitor of caspase-1-like proteases, nor acetyl-DEVD-CHO, an inhibitor of caspase-3-like proteases, prevented oxygen-glucose deprivation-induced injury. Thus, oxygen and glucose deprivation causes calcium-influx-induced necrotic cell damage in cells of oligodendroglial lineage via non-N-methyl-D-aspartate GluR channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / administration & dosage
  • Calcium / pharmacology
  • Cell Line
  • Culture Media / chemistry
  • Culture Media / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glucose / deficiency*
  • Glutamic Acid / analysis
  • Hypoxia / pathology*
  • Necrosis
  • Oligodendroglia / pathology*
  • Osmolar Concentration
  • Rats
  • Receptors, Glutamate / physiology*

Substances

  • Culture Media
  • Excitatory Amino Acid Antagonists
  • Receptors, Glutamate
  • Glutamic Acid
  • Glucose
  • Calcium