Triamcinolone-loaded nanocarriers: novel strategy to prevent cognitive and emotional sequelae induced by traumatic brain injurythrough modulation of the oxidative stress machinery

Abstract

TBI is known to cause cognitive and emotional deficits likely linked to early neuroinflammatory processes. We have shown that TBI increases levels of protein (AOPP) and lipid (MDA) peroxidation, which persisted over a week. Despite the efforts to develop neuroprotective treatments, most pre-clinical studies did not report significant effects. To evaluate the effectiveness of NT in cognitive and emotional sequelae by TBI, we induced it in anesthetized adult male Wistar rats and administered NT at 15 minutes and 24h post-injury. Brain tissue homogenates were assayed for MDA, AOPP and two antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT) 7 days after TBI. Animals were submitted to novel object recognition test (NOR) 7 days postTBI and fear memory evaluation 24 h (test 1) and 6 days (test 2) after conditioning. Our data showed that NT prevented increments in AOPP, MDA and CAT levels at 7 days after TBI. Additionally, TBI induced a significant decrease in the discrimination index of NOR at day 7 that could be prevented by NT administration. On the other hand, TBI induced a significant decrease in the % freezing only in test 2 which was prevented in animals treated with NT. We concluded that TBI induced neuroinflammatory mediators that could have detrimental actions on recognition memory and fear memory retention, likely through alteration of cognitive and emotional processing. NT administration could be a therapeutic alternative for the early treatment of neuroinflammation mediated by TBI, contributing to the prevention of cognitive and emotional sequelae by modulating OS machinery.