Background:In response to inflammation and other stressors, tryptophan is catalyzed by
Tryptophan 2,3-Dioxygenase (TDO), which leads to activation of the kynurenine pathway. Sepsis is
a serious condition in which the body responds improperly to an infection, and the brain is the
inflammation target in this condition.Objective:This study aimed to determine if the induction of TDO contributes to the permeability of
the Blood-Brain Barrier (BBB), mortality, neuroinflammation, oxidative stress, and mitochondrial
dysfunction, besides long-term behavioral alterations in a preclinical model of sepsis.Methods:Male Wistar rats with two months of age were submitted to the sepsis model using Cecal
Ligation and Perforation (CLP). The rats received allopurinol (Allo, 20 mg/kg, gavage), a TDO
inhibitor, or a vehicle once a day for seven days.Results:Sepsis induction increased BBB permeability, IL-6 level, neutrophil infiltrate, nitric oxide
formation, and oxidative stress, resulting in energy impairment in 24h after CLP and Allo administration
restored these parameters. Regarding memory, Allo restored short-term memory impairment
and decreased depressive behavior. However, no change in survival rate was verified.Conclusion:In summary, TDO inhibition effectively prevented depressive behavior and memory
impairment 10 days after CLP by reducing acute BBB permeability, neuroinflammation, oxidative
stress, and mitochondrial alteration.