Reproducible peracute glutamate-induced focal lesions of the normal rat brain using microdialysis

Hans Landolt, Hiro Fujisawa, David I. Graham, William L. Maxwell, Ross Bullock

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The neurotoxic effect of the excitatory amino acid neurotransmitter glutamate was first demonstrated 20 years ago, but the recent development of potent glutamate antagonist drugs with effects against ischaemic damage in vivo and their introduction in clinical studies has made 'excitotoxicity' a major focus of current interest. Despite this, the factors influencing glutamate neurotoxicity in vivo are poorly understood, and the role of glutamate as a neurotoxin in vivo is contested. By using a micro dialysis probe to deliver glutamate to the normal rat cortex, we have devised a reproducible model of peracute 'excitotoxic' damage. We have demonstrated that concentrations of over 20 mM glutamate in the perfusate kill neurons in the intact brain in less than 90 min - 20 to 200 times more than that required for toxicity in mixed cell culture. The histological and ultrastructural features of the glutamate lesion are very similar to those of acute ischaemia, although their development is much more rapid after glutamate. True extracellular glutamate concentrations estimated from microdialysis studies (about 4 mM) are not far from our results. The reproducible quantifiable nature of the glutamate lesions in this model make it well suited to study the factors affecting the excitotoxic process in vivo.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalJournal of Clinical Neuroscience
Volume5
Issue number2
StatePublished - Dec 1 1998
Externally publishedYes

Fingerprint

Microdialysis
Glutamic Acid
Brain
Excitatory Amino Acid Antagonists
Excitatory Amino Acids
Neurotoxins
Neurotransmitter Agents
Dialysis
Ischemia
Cell Culture Techniques
Neurons

Keywords

  • Excitotoxicity
  • Focal lesion
  • Glutamate
  • Microdialysis
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology

Cite this

Landolt, H., Fujisawa, H., Graham, D. I., Maxwell, W. L., & Bullock, R. (1998). Reproducible peracute glutamate-induced focal lesions of the normal rat brain using microdialysis. Journal of Clinical Neuroscience, 5(2), 193-202.

Reproducible peracute glutamate-induced focal lesions of the normal rat brain using microdialysis. / Landolt, Hans; Fujisawa, Hiro; Graham, David I.; Maxwell, William L.; Bullock, Ross.

In: Journal of Clinical Neuroscience, Vol. 5, No. 2, 01.12.1998, p. 193-202.

Research output: Contribution to journalArticle

Landolt, H, Fujisawa, H, Graham, DI, Maxwell, WL & Bullock, R 1998, 'Reproducible peracute glutamate-induced focal lesions of the normal rat brain using microdialysis', Journal of Clinical Neuroscience, vol. 5, no. 2, pp. 193-202.
Landolt, Hans ; Fujisawa, Hiro ; Graham, David I. ; Maxwell, William L. ; Bullock, Ross. / Reproducible peracute glutamate-induced focal lesions of the normal rat brain using microdialysis. In: Journal of Clinical Neuroscience. 1998 ; Vol. 5, No. 2. pp. 193-202.
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