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.
