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 th e effect of pyrithiamine-induced thiamine deficiency on the levels of amino acids in the brain. Studies were carried out on (a) presymptomat ic animals immediately before the development of behavioral changes an d (b) acute symptomatic animals within 6 h following loss of righting reflexes. This latter stage precedes the appearance of histological le sions. The results were compared with pair-fed controls. Dialysis prob es were implanted in one vulnerable structure [ventral posterior media l thalamus (VPMT)] and one nonvulnerable area [frontal parietal cortex (FPC)] on the contralateral side. In VPMT of acute symptomatic animal s, the glutamate concentration was significantly increased (3.37 +/- 0 .64 muM; p < 0.005) compared with control values (0.93 +/- 0.09 muM), whereas in FPC no change in glutamate content was evident. These resul ts 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-m ediated excitotoxic mechanism may be responsible for the selective cer ebral vulnerability in thiamine deficiency.