Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Abstract

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

Keywords: anti-oxidants; edaravone; mitoquinone; oxidative stress; traumatic brain injury.

Figure 1

Oxidative stress in traumatic brain injury (TBI): (A) excitotoxicity; (B) Ca²⁺ sequestration and cyt c release; (C) lipid peroxidation; (D) oxidative stress pathways.

Figure 2

The proposed neurotherapeutic mechanisms of edaravone. (A) Suppression of oxidative stress by edaravone; (B) effects of edaravone in TBI. Molecular graphics of the superoxide dismutase (SOD) enzyme was visualized using the 3D Protein Imager online server [71].

Figure 3

The mediated therapeutic mechanisms of MitoQ targeting the mitochondria with its proposed implications on TBI. (A) Formation of MitoQ; (B) role of MitoQ in attenuation of neuronal apoptosis; (C) inhibitory role of MitoQ following TBI. Molecular graphics of the Superoxide Dismutase (SOD) enzyme, fission protein, Bax protein, Amyloid-ß plaques, and phosphorylated Tau were visualized using the 3D Protein Imager online server [71].