The Neuroprotective Effects of Edaravone in an Experimental Mouse Model of Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a form of acquired brain injury that poses a significant threat to public health. Mild to severe TBI is rapidly being classified as a chronic disease, given that evidence indicates that complications associated with TBI can persist for many years postinjury. At present, there is no effective pharmacological treatment that has been approved for the treatment of TBI. Edaravone (EDA) is a neuroprotective repurposed drug used to slow down motor neurons in Amyotrophic Lateral Sclerosis (ALS) patients. As a free radical scavenger, EDA has been shown to inhibit oxidative stress and improve memory and learning performances in various animal models of neurodegeneration. Previously, it has been demonstrated that EDA exerts anti-inflammatory effects in animal models of transient focal ischemia. In this study, we tested an experimental model of open-head controlled cortical impact (CCI) mouse model to evaluate the molecular mechanisms of the neuroprotective role of EDA at a chronic 30-day timepoint post-injury. A battery of behavioral tests were conducted to investigate the effect of EDA on behavioral outcomes. On the molecular level, immunofluorescence staining was performed to assess neuroinflammation, neuronal apoptosis, and axonal integrity. Previous studies state that the protective effect of EDA is mainly mediated through the nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element (ARE) signaling pathway. Therefore, RT-qPCR was done to study the expression levels of Nrf2 and its downstream antioxidant genes. In summary, we demonstrated that EDA indeed exerted neuroprotective effects on TBI-induced oxidative stress and neuroinflammation; this finding was mainly correlated with the Nrf2 pathway at a 30-day timepoint.