Traumatic Brain Injury (TBI), is one of the most common causes of neurological damage in young populations. It is widely considered as a risk factor for neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s (PD) disease. These diseases are characterized in part by the accumulation of disease-specific misfolded proteins and share common pathological features, such as neuronal death, as well as inflammatory and oxidative damage. Nano formulation of Pomegranate seed oil [Nano-PSO (Granagard ^TM)] has been shown to target its active ingredient to the brain and thereafter inhibit memory decline and neuronal death in mice models of AD and genetic Creutzfeldt Jacob disease. In this study, we show that administration of Nano-PSO to mice before or after TBI application prevents cognitive and behavioral decline. In addition, immuno-histochemical staining of the brain indicates that preventive Nano-PSO treatment significantly decreased neuronal death, reduced gliosis and prevented mitochondrial damage in the affected cells. Finally, we examined levels of Sirtuin1 (SIRT1) and Synaptophysin (SYP) in the cortex using Western blotting. Nano-PSO consumption led to higher levels of SIRT1 and SYP protein postinjury. Taken together, our results indicate that Nano-PSO, as a natural brain-targeted antioxidant, can prevent part of TBI-induced damage.

Oxidative stress contributes to the pathophysiology of diverse neurodegenerative diseases and acute brain injuries. Pomegranate Seed Oil (PSO) is rich in punicic acid (PA), an omega-5 fatty acid with reported antioxidant and anti-inflammatory properties. However, conventional PSO and standard antioxidants show limited clinical success due to poor solubility, rapid degradation, low bioavailability, and limited delivery cross the blood-brain barrier (BBB). To address these limitations, GranaGard^® (Nano-PSO), a self-emulsifying nanoformulation, was developed to improve the bioavailability and CNS delivery of PSO-derived compounds. Nano-PSO significantly increases systemic absorption and brain accumulation of its bioactive metabolite, neuroprotective conjugated linoleic acid (CLA). In a transgenic mouse model of Creutzfeldt-Jakob Disease (CJD), continuous Nano-PSO administration was reported to delayed disease onset, prolong survival, reduce lipid oxidation, preserve neuronal viability, and increase neurogenesis. Beyond CJD, Nano-PSO showed potential neuroprotective effects in various neurological diseases and brain injury models, although the magnitude and consistency of these effects varied across models. In a small preliminary clinical study in Multiple Sclerosis (MS), Nano-PSO treatment was associated with improved verbal learning in a within-group analysis, although large controlled studies are needed. By improving pharmacokinetic barriers, Nano-PSO may offer a promising, potent strategy for mitigating neurodegeneration associated with oxidative stress. These preliminary findings warrant further investigation, including independent replication and controlled clinical studies to establish the reproducibility and clinical relevance of Nano-PSO.