Neurological sequel following episodes of thiamine deficiency (TD) are common and characterize a public health problem. Therapeutic strategies have been investigated to mitigate the deleterious effects of the disorder. This study aimed to evaluate the therapeutic potential of concomitant use of thiamine, antioxidant and anti-inflammatory agents in attenuating neurological effects in deficient mice, as well as to characterize the lesions and cellular mechanisms associated with TD. The dietary deficiency model in association with injections of thiamine antagonist, pyrithiamine, was used in the study. The mice were separated into twenty groups (n = 6): eight control groups and twelve deficient groups. The groups were divided into two TD protocols followed by recovery promotion: protocol A, with a single episode of TD induction for 9 days, followed by 7 day recovery period, and protocol B, with two consecutive cycles of TD induction (9 days) followed by recovery treatment periods with neuroprotective substances (7 days). After the periods of protocols A and B, the analyzes were performed. In induction, control groups received AIN-93M standard feed and deficient groups received AIN93TD deficient feed and pyrithiamine (Ptd groups, 0.5 mg/kg); on recovery, control e deficient groups received AIN-93M feed and i.p. saline injections (Cont group, 0.9% NaCl), thiamine (Tm and Ptd+Tm groups, 100 mg/kg), Trolox (Tr and Ptd+Tr groups, 1 mg/kg), dimethylsulfoxide (Dmso and Ptd+Dmso groups, 1 ml/kg) or combinations (Ptd+Tm+Tr and Ptd+Tm+Dmso groups). After the treatments, they were tested in Morris water maze (MWM), open field and rotarod and euthanized to assess cell viability in nervous tissue (TTC reduction test), modulation of MAPK pathways, and histopathology. Recovery treatments with neuroprotective substances partially alleviated behavioral changes. The associated administration of thiamine with Trolox or with DMSO, in recurrent deficiency, completely reversed the decrease in cell viability. The reduction in morphological lesions was more intense in the animals of the Ptd+Tm+Tr and Ptd+Tm+Dmso groups, with only rare vacuolated neurons and preservation of the neuronal population in the thalamus. In parallel, the recovery treatments promoted increased phosphorylation of ERK1/2 in the cerebral cortex and thalamus. The data suggest that the tested substances (DMSO and Trolox) have neuroprotective potential, as adjuvants to thiamine in the treatment of deficiency, decreasing the possibility of neurological sequelae through the modulation of important cellular metabolic pathways.
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