Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adultsunder 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidativestress (OS) are triggered, contributing to the development of many TBI-inducedneurological deficits, and reducing the probability of critical trauma patients ́ survival.Regardless the research investment on the development of anti-inflammatory andneuroprotective treatments, most pre-clinical studies have failed to report significanteffects, probably because of the limited blood brain barrier permeability of no-steroidalor steroidal anti-inflammatory drugs. Lately, neurotrophic factors, such as the insulin-likegrowth factor 1 (IGF-1), are considered attractive therapeutic alternatives for diverseneurological pathologies, as they are neuromodulators linked to neuroprotection and anti-inflammatory effects. Considering this background, the aim of the present investigation isto test early IGF-1 gene therapy in both OS markers and cognitive deficits induced by TBI.Male Wistar rats were injectedviaCisterna Magna with recombinant adenoviral vectorscontaining the IGF-1 gene cDNA 15 min post-TBI. Animals were sacrificed after 60 min,24 h or 7 days to study the advanced oxidation protein products (AOPP) andmalondialdehyde (MDA) levels, to recognize the protein oxidation damage and lipidperoxidation respectively, in the TBI neighboring brain areas. Cognitive deficits wereassessed by evaluating working memory 7 days after TBI. The results reportedsignificant increases of AOPP and MDA levels at 60 min, 24 h, and 7 days after TBI inthe prefrontal cortex, motor cortex andhippocampus. In addition, at day 7, TBI alsoreduced working memory performance. Interestingly, AOPP, and MDA levels in the studiedbrain areas were significantly reduced after IGF-1 gene therapy that in turn preventedcognitive deficits, restoring TBI-animals working memory performance to similar valuesregarding control. In conclusion, early IGF-1 gene therapy could be considered a noveltherapeutic approach to targeting neuroinflammation as well as to preventing somebehavioral deficits related to TBI.