Thiamine deficiency and recovery: impact of recurrent episodes and beneficial effect of treatment with Trolox and dimethyl sulfoxide.

ABSTRACT

At present, thiamine deficiency (TD) is managed with administration of high doses of thiamine. Even so, severe and permanent neurological disorders can occur in recurrent episodes of TD. In this study, we used a murine model to assess the efficacy of TD recovery treatments using thiamine with or without additional administration of the antioxidant Trolox or the anti-inflammatory dimethyl sulfoxide (DMSO) after a single or recurrent episode of TD. TD was induced for 9 days with deficient chow and pyrithiamine, and the recovery period was 7 days with standard amounts of chow and thiamine, Trolox, and/or DMSO. After these periods, we evaluated behavior, histopathology, and ERK1/2 modulation in the brain. Deficient animals showed reductions in locomotor activity, motor coordination, and spatial memory. Morphologically, after a single episode of TD and recovery, deficient mice showed neuronal vacuolization in the dorsal thalamus and, after two episodes, a reduction in neuronal cell number. These effects were attenuated or reversed by the recovery treatments, mainly in the treatments with thiamine associated with Trolox or DMSO. Deficient animals showed a strong increase in ERK1/2 phosphorylation in the thalamus, hippocampus, and cerebral cortex after one deficiency episode and recovery. Interestingly, after recurrent TD and recovery, ERK1/2 phosphorylation remained high only in the deficient mice treated with thiamine and/or Trolox or thiamine with DMSO. Our data suggest that a protocol for TD treatment with thiamine in conjunction with Trolox or DMSO enhances the recovery of animals and possibly minimizes the late neurological sequelae.