The effects of gamma glutamyl cysteinyl ethyl ester in traumatically brain injured rats post incident: insight into the role of glutathione elevation in oxidative stress

Traumatic brain injury (TBI) is a spontaneous event in which the brain sustains primary and secondary injuries. There are more than 2.3 million traumatic brain injuries occurring annually in the United States and exponentially more worldwide. These injuries may be mild, moderate, or severe based on intensity of impact. The damage caused by TBI results not only from the initial injury, but also from secondary damage due to DNA damage, protein oxidation, and oxidative stress which can impact overall brain function. Oxidative stress is the phenomenon in which there is an increase in the level of reactive oxygen and nitrogen species. A decrease in overall antioxidant capacity, which can lead to a loss of protein function is observed. Antioxidant therapies have been evaluated as potential treatments for traumatic brain injury. Glutathione, a potent antioxidant is depleted in traumatic brain injury. Gamma-glutamyl cysteinyl ethyl ester (GCEE), a glutathione mimetic, has been used as an antioxidant to alleviate oxidative stress. Currently, there are no approved treatments for TBI to prevent secondary injury post incident, but immediate medical attention is recommended as a delay in treatment as elevations in secondary consequences are exhibited. This study aims to determine if GCEE is neuroprotective against moderate TBI at an extended time point, 90 min as positive outcomes in reduction of oxidative stress markers were observed at lower time point (15, 30, and 60 min). Results from this work will provide insight into the alleviation of oxidative stress markers via antioxidant treatment of moderate traumatic brain injury at an expanded time point.