METABOLIC AND PERMEABILITY CHANGES CAUSED BY THIAMINE-DEFICIENCY IN IMMORTALIZED RAT-BRAIN MICROVESSEL ENDOTHELIAL-CELLS

The possible involvement of blood-brain barrier (BBB) breakdown in the pathogenesis of thiamine deficiency encephalopathy was investigated i n RBE4 cells, an immortalized rat brain endothelial cell line. The eff ects of thiamine deficiency produced by addition of pyrithiamine and b y reduction of thiamine in the culture medium, on the metabolism and p ermeability of the RBE4 monolayer was examined. Pyrithiamine treatment in low thiamine medium (M199) for 7 days caused cytotoxic effects on RBE4 cells at all concentrations (10-50 mu g/ml). Pyrithiamine caused a concentration- and time-dependent decrease in MTT reduction and a si gnificant increase in glucose consumption and lactate production compa red to controls. Pyrithiamine treatment for 3 days caused a significan t decrease in MIT reduction at 50 mu g/ml only. In contrast, increased glucose consumption and lactate production by the RBE4 cells was obse rved after treatment for 3 days with concentrations of 25 mu g/ml pyri thiamine and above. The permeability of RBE4 cell monolayers to [C-14] sucrose (M-w 342), but not FITC-dextran (M-w 4000) was significantly i ncreased by treatment with pyrithiamine concentrations of 25 mu g/ml a nd above for 3 days. These effects were not accompanied by detectable changes in F-actin distribution or content, although F-actin content w as significantly reduced by 7 days exposure to pyrithiamine. These res ults suggest that metabolic and permeability changes in thiamine-defic ient RBE4 cells may be important early events in thiamine-deficiency e ncephalopathy. The relative role of the BBB in the pathogenesis of thi amine deficiency is discussed.