Cerebral vulnerability is associated with selective increase in extracellular glutamate concentration in experimental thiamine deficiency.
Microdialysis in the awake, freely moving rat was used to determine the effect of pyrithiamine-induced thiamine deficiency on the levels of amino acids in the brain. Studies were carried out on (a) presymptomatic animals immediately before the development of behavioral changes and (b) acute symptomatic animals within 6 h following loss of righting reflexes. This latter stage precedes the appearance of histological lesions. The results were compared with pair-fed controls. Dialysis probes were implanted in one vulnerable structure [ventral posterior medial thalamus (VPMT)] and one nonvulnerable area [frontal parietal cortex (FPC)] on the contralateral side. In VPMT of acute symptomatic animals, the glutamate concentration was significantly increased (3.37 +/- 0.64 microM; p < 0.005) compared with control values (0.93 +/- 0.09 microM), whereas in FPC no change in glutamate content was evident. These results suggest that glutamate plays a significant role in the development of central thiamine deficiency lesions. The absence of any increase in glutamate levels in the nonvulnerable FPC suggests that a glutamate-mediated excitotoxic mechanism may be responsible for the selective cerebral vulnerability in thiamine deficiency.
Hazell
A S
AS
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.
Butterworth
R F
RF
Hakim
A M
AM
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003956:Dialysis; D005110:Extracellular Space / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D008297:Male; D009994:Osmolar Concentration; D010296:Parietal Lobe / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000378:metabolism; D013832:Thiamine Deficiency / Q000378:metabolism*
D000596:Amino Acids; D005971:Glutamates; D018698:Glutamic Acid