IGF1 GENE THERAPY ASSOCIATED WITH NANOTECHNOLOGY REVERSED OXIDATIVE STRESS IN AN ANIMAL MODEL OF TRAUMATIC BRAIN INJURY

AGUSTÍN J. MONTIVERO; MARISA S. GHERSI; M. JAZMÍN SILVERO C.; EMILCE ARTUR DE LA VILLARMOIS; MARÍA FLORENCIA CONSTANTIN ; MARÍA CECILIA BECERRA; CLAUDIA HEREÑÚ; MARIELA F. PEREZ

Mar del Plata

Congreso; SAIC; 2018

Traumatic Brain Injury (TBI) is the major cause of morbidity and mortality in individuals under 40 years old. After the injury, neuroinflamation and oxidative stress (OS) are induced, leading to the development of many neurological deficits as well as reduction in the survival rate of critical trauma patients. Despite de efforts focused to develop anti-inflamatory and neuroprotective treatments, many of the pre-clinical studies failed to show significant effects, probably because the access to central nervous system of no steroidal anti-inflamatory drugs (NSAID) or steroids is limited. A therapeutic alternative of increasing clinical interest in the treatment of neurological deficits, is the use of neurotrophic factors such as insuline-like growth factor 1 (IGF1), since they are neuromodulators associated with neuroprotection and anti-inflamatory effects. To highlight the pathophysiological effects of OS in rats with TBI, specific biomarkers have been studied such as advanced oxidation protein products (AOPP)-to identify the protein oxidation damage and malondialdehyde (MDA) as a final product of lipid peroxidation. The aim of the present investigation is to elucidate the temporal course of OS related to neuroinflammation, and to test IGF1 therapy. For this purpose, magnetic nanoparticles-adenoviral vectors complexes (over-expressing IGF1) were administrated 15 min after TBI, via cisterna Magna and magnetically redirected to TBI regions. The results showed an increse of AOPP and MDA at 60 min, 24 h and 7 days after TBI in the motor cortex, the prefrontal cortex, and hippocampus. Gene therapy significantly reduced AOPP and MDA levels in the studied brain areas, leading to similar values as control animals. In conclusion, IGF1 therapy associated with nanotechnology could be a valuable therapeutic approach for neuroinflammatory processes related to TBI. Further experiments will be performed in order to determine a correlation between OS parameters and behavioral deficits associated to TBI.