EARLY TREATMENT WITH TRIAMCINOLONE-LOADED NANOCARRIERS AMELIORATES COGNITIVE AND EMOTIONAL SEQUELAE INDUCED BY TRAUMATIC BRAIN INJURY AND MODULATES OXIDATIVE STRESS

MARCOTTI A; AGUSTIN MONTIVERO; MARÍA LINA FORMICA; SILVERO C, M. JAZMÍN; BECERRA MC; PONCE BETI MF; GASTON CALFA; SANTIAGO D PALMA; MARIELA F. PÉREZ.

Congreso; 3RD FALAN CONGRES; 2022

FALAN

Traumatic brain injury (TBI) causes a variety of neuropathological manifestations includingcognitive, emotional and physiological deficits, probably related to early neuroinflammatoryprocesses. 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 andneuroprotective treatments, most pre-clinical studies did not report significant effects, probablybecause of the limited blood brain barrier permeability of clinically available anti-inflammatorydrug formulations. Objective: to evaluate the effectiveness of nanocarriers loaded with thesynthetic glucocorticoid triamcinolone (NA-TA), to prevent oxidative stress (OS) processes andto reduce the cognitive and emotional sequelae induced by TBI. Materials and methods: TBIwas induced in anesthetized adult male Wistar rats, which 15 min and 24 h later received a doseof NA-TA. Animals were sacrificed 1 or 7 days after treatment to measure AOPP and MDA levelsin different brain areas. Additionally, a group of animals was submitted novel object recognition(NOR) test 7 days after TBI induction. Finally, other groups were exposed to contextual fearconditioning 6 days after TBI and treatment. Twenty-four h (test 1) and 6 days (test 2, 12 daysafter TBI) after conditioning, fear memory expression was evaluated. Results: TBI induced asignificant decrease in the discrimination index of a novel object 7 days after trauma (t-test) thatcould be prevented by early administration of NA-TA. On the other hand, TBI induced asignificant decrease in the % freezing only in test 2 compared to the controls (two-way ANOVA).Interestingly, preliminary data suggest that animals treated with NA-TA did not show changes infear memory. Also, TA prevented increments in AOPP and MDA levels (one-way ANOVA).Conclusions: TBI induced neuroinflammatory mediators that could have detrimental actions onrecognition memory and fear memory retention probably through cognitive and emotionalprocessing alteration. NA-TA administration could be a therapeutic alternative for the earlytreatment of neuroinflammation mediated by TBI, that contribute to the cognitive andemotional sequelae prevention.