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Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures.

Publication ,  Journal Article
Kudo, M; Aono, M; Lee, Y; Massey, G; Pearlstein, RD; Warner, DS
Published in: Anesthesiology
September 2001

BACKGROUND: Volatile anesthetics are known to ameliorate experimental ischemic brain injury. A possible mechanism is inhibition of excitotoxic cascades induced by excessive glutamatergic stimulation. This study examined interactions between volatile anesthetics and excitotoxic stress. METHODS: Primary cortical neuronal-glial cultures were exposed to N-methyl-D-aspartate (NMDA) or glutamate and isoflurane (0.1-3.3 mM), sevoflurane (0.1-2.9 mM), halothane (0.1-2.9 mM), or 10 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801). Lactate dehydrogenase release was measured 24 h later. In other cultures, effects of volatile anesthetics on Ca++ uptake and mitochondrial membrane potential were determined in the presence or absence of NMDA (0-200 microM). RESULTS: Volatile anesthetics reduced excitotoxin induced lactate dehydrogenase release by up to 52% in a dose-dependent manner. At higher concentrations, this protection was reversed. When corrected for olive oil solubility, the three anesthetics offered equivalent protection. MK-801 provided near-complete protection. Ca++ uptake was proportionally reduced with increasing concentrations of anesthetic but did not account for reversal of protection at higher anesthetic concentrations. Given equivalent NMDA-induced Ca++ loads, cells treated with volatile anesthetic had greater lactate dehydrogenase release than those left untreated. At protective concentrations, volatile anesthetics partially inhibited NMDA-induced mitochondrial membrane depolarization. At higher concentrations, volatile anesthetics alone were sufficient to induce mitochondrial depolarization. CONCLUSIONS: Volatile anesthetics offer similar protection against excitotoxicity, but this protection is substantially less than that provided by selective NMDA receptor antagonism. Peak effects of NMDA receptor antagonism were observed at volatile anesthetic concentrations substantially greater than those used clinically.

Duke Scholars

Published In

Anesthesiology

DOI

ISSN

0003-3022

Publication Date

September 2001

Volume

95

Issue

3

Start / End Page

756 / 765

Location

United States

Related Subject Headings

  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Neuroprotective Agents
  • Neuroglia
  • N-Methylaspartate
  • Mitochondria
  • Membrane Potentials
  • Glutamic Acid
  • Dose-Response Relationship, Drug
 

Citation

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Kudo, M., Aono, M., Lee, Y., Massey, G., Pearlstein, R. D., & Warner, D. S. (2001). Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures. Anesthesiology, 95(3), 756–765. https://doi.org/10.1097/00000542-200109000-00031
Kudo, M., M. Aono, Y. Lee, G. Massey, R. D. Pearlstein, and D. S. Warner. “Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures.Anesthesiology 95, no. 3 (September 2001): 756–65. https://doi.org/10.1097/00000542-200109000-00031.
Kudo M, Aono M, Lee Y, Massey G, Pearlstein RD, Warner DS. Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures. Anesthesiology. 2001 Sep;95(3):756–65.
Kudo, M., et al. “Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures.Anesthesiology, vol. 95, no. 3, Sept. 2001, pp. 756–65. Pubmed, doi:10.1097/00000542-200109000-00031.
Kudo M, Aono M, Lee Y, Massey G, Pearlstein RD, Warner DS. Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures. Anesthesiology. 2001 Sep;95(3):756–765.

Published In

Anesthesiology

DOI

ISSN

0003-3022

Publication Date

September 2001

Volume

95

Issue

3

Start / End Page

756 / 765

Location

United States

Related Subject Headings

  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Neuroprotective Agents
  • Neuroglia
  • N-Methylaspartate
  • Mitochondria
  • Membrane Potentials
  • Glutamic Acid
  • Dose-Response Relationship, Drug