Brain selective nanocarriers loaded with triamcinolone prevented emocional sequelae and oxidative stress induced by traumatic brain injury

Abstract

Traumatic brain injury (TBI) causes a variety of neuropathologicalmanifestations including cognitive, emotional and physiological deficits, probably related to early neuroinflammatory processes. We have previously shown that TBI increases levels of protein (AOPP) and lipid (MDA) peroxidation, considered oxidative stress (OS) biomarkers that persisted over a week. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies did not report significant effects, probably because of the limited blood brain barrier permeability of clinically available anti-inflammatory drug formulations. Objective: to evaluate the effectiveness of brain selective nanocarriers, loadedwith the synthetic glucocorticoid triamcinolone (NA-TA), to prevent oxidative stress (OS) processes and to reduce the emotional sequelae induced by TBI. Materials and methods: TBI was induced in anesthetized adult male Wistar rats, which 15 min and 24 h later received a dose of NA-TA. Animals were sacrificed 1 or 7 days after treatment to measure AOPP and MDA levels in different brain areas. Other groups of animals were exposed to contextual fear conditioning 6 days after TBI and treatment. Twenty-four h (test 1) and 6 days (test 2, 12 days after TBI) after conditioning, fear memory expression was evaluated. Results: TBI induced a significant decrease in the % freezing only in test 2 compared to the controls (two-way ANOVA). Interestingly, preliminary data suggest that animals treated with NATA did not show changes in fear memory. Also, TA prevented increments in AOPP and MDA levels (one-way ANOVA). Conclusions: TBI induced neuroinflammatory mediators that could have detrimental actions on fear memory retention, probably through emotional processing alteration. NA-TA administration could be a therapeutic alternative for the early treatment of neuroinflammation mediated byTBI, that contribute to the emotional sequelae prevention.