H. Landolt et al., REPRODUCIBLE PERACUTE GLUTAMATE-INDUCED FOCAL LESIONS OF THE NORMAL RAT-BRAIN USING MICRODIALYSIS, Journal of clinical neuroscience, 5(2), 1998, pp. 193-202
The neurotoxic effect of the excitatory amino acid neurotransmitter gl
utamate was first demonstrated 20 years ago, but the recent developmen
t of potent glutamate antagonist drugs with effects against ischaemic
damage in vivo and their introduction in clinical studies has made 'ex
citotoxicity' a major focus of current interest. Despite this, the fac
tors influencing glutamate neurotoxicity in vivo are poorly understood
, and the role of glutamate as a neurotoxin in vivo is contested. By u
sing a microdialysis probe to deliver glutamate to the normal rat cort
ex, we have devised a reproducible model of peracute 'excitotoxic' dam
age. 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 c
ulture. The histological and ultrastructural features of the glutamate
lesion are very similar to those of acute ischaemia, although their d
evelopment is much more rapid after glutamate. True extracellular glut
amate 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. (C) Harcourt Brace
& Co. Ltd 1998.