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

AGUSTIN MONTIVERO; MARISA GHERSI,; SILVERO MJ; EMILCE ARTUR DE LA VILLARMOIS; BECERRA MC; CLAUDIA B. HEREÑÚ; MARIELA F. PÉREZ

Congreso; Reunión Conjunta SAIC, SAI, SAFIS 2018. LXIII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

SAIC, SAI, SAFIS

Traumatic Brain Injury (TBI) is the major cause of morbidity andmortality in individuals under 40 years old. After the injury, neuroinflamationand oxidative stress (OS) are induced, leading to the developmentof many neurological deficits as well as reduction in thesurvival rate of critical trauma patients. Despite the efforts focusedto develop anti-inflamatory and neuroprotective treatments, manyof the pre-clinical studies failed to show significant effects, probablybecause the access to central nervous system of no steroidal anti-inflammatory drugs (NSAID) or steroids is limited. A therapeuticalternative of increasing clinical interest in the treatment of neurologicaldeficits, is the use of neurotrophic factors such as Insulin-likegrowth factor 1 (IGF1), since they are neuromodulators associatedwith neuroprotection and anti-inflamatory effects. To highlight thepathophysiological effects of OS in rats with TBI, specific biomarkershave 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 aimof the present investigation is to elucidate the temporal course ofOS related to neuroinflammation, and to test IGF1 therapy. For thispurpose, magnetic nanoparticles-adenoviral vectors complexes(over-expressing IGF1) were administrated 15 min after TBI, via CisternaMagna and magnetically redirected to TBI regions. The resultsshowed an increase of AOPP and MDA at 60 min, 24 h and 7 daysafter TBI in the motor cortex, the prefrontal cortex, and hippocampus.Gene therapy significantly reduced AOPP and MDA levels inthe studied brain areas, leading to similar values as control animals.In conclusion, IGF1 gene therapy associated with nanotechnologycould be a valuable therapeutic approach for neuroinflammatoryprocesses related to TBI. Further experiments will be performed inorder to determine a correlation between OS parameters and behavioraldeficits associated to TBI.