Edaravone attenuates traumatic brain injury through anti-inflammatory and anti-oxidative modulation.

Traumatic brain injury (TBI) is among the leading causes of irreversible neurological damage and death worldwide. The aim of the present study was to investigate whether edaravone (EDA) had a neuroprotective effect on TBI as well as to identify the potential mechanism. Results demonstrated that EDA suppressed inflammatory and oxidative responses in mice following TBI. This was evidenced by a reduction in glutathione peroxidase, interleukin 6, tumor necrosis factor-α and hydrogen peroxide levels, in addition to an increase in hemeoxygenase-1, quinone oxidoreductase 1 and superoxide dismutase levels, thereby mitigating neurofunctional deficits, cell apoptosis and structural damage. EDA prevented the transfer of NF-κB protein from the cytoplasm to the nucleus, whilst promoting the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) protein in mice following TBI. These results indicated that EDA exerted neuroprotective effects, including impeding neurofunctional deficits, cell apoptosis and structural damage, in mice with TBI, potentially via suppression of NF-κB-mediated inflammatory activation and promotion of the Nrf2 antioxidant pathway.

Correction to: Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury.

The original version of this article unfortunately contained a mistake. The Fluorescence Immunoassays text written in Materials and Methods section and Fig. 1i, j is incorrect. In Fig. 1j, the images corresponding to Sham and TBI + ILG are incorrect. In Fig. 1i the figure caption "TBI + EDA" are incorrect. The corrected text and Fig. 1i, j are given below.

Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2-/- mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2-/- mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.

Isoliquiritigenin protects against blood­brain barrier damage and inhibits the secretion of pro-inflammatory cytokines in mice after traumatic brain injury.

Traumatic brain injury (TBI) caused by an external mechanical force acting on the brain is a serious neurological condition. Inflammation plays an important role in prolonging secondary tissue injury after TBI, leading to neuronal cell death and dysfunction. Isoliquiritigenin (ILG) is a flavonoid monomer with anti-inflammatory characteristic. Thus, we had investigated the potential protective effects of ILG on TBI-induced injuries and identified the mechanisms underlying it. Here, we have demonstrated that ILG preserves blood brain barrier (BBB) integrity in vivo, suppresses the activation of microglia and inflammatory responses in mice after TBI, consequently leading to neurofunctional deficits, brain oedema, structural damage, and macrophage infiltration. In vitro, ILG exerts anti-inflammatory effect, and upregulates tight junction proteins 120­ß­catenin and occludin in SH­SY5Y cells under oxygen glucose deprivation/reoxygenation (OGD/D) condition. Additionally, we found that PI3K/AKT/GSK­3ß signalling pathway is involved in ILG treatment for TBI. To further confirm it, we had used SC79 (ethyl 2­amino­6­chloro­4­(1­cyano­2­ethoxy­2­oxoethyl)­4H­chromene­3­carboxylate), an Akt specific activator, to activate Akt, we found that SC79 partially reduces the protective effect of ILG for TBI. Overall, our current study reveals the neuroprotective role of ILG on TBI-induced BBB damage, downregulated tight junction proteins via PI3K/AKT/GSK­3ß signalling pathway. Furthermore, ILG suppresses the secretion of pro-inflammatory cytokines after TBI through inhibiting the PI3K/AKT/GSK­3ß/NF­κB signalling pathway. Our findings suggest that GSK­3ß is a key regulatory factor during TBI-induced secretion of inflammatory cytokines, neuronal apoptosis and destruction of BBB.