Abstract
OBJECTIVES:To investigate the molecular mechanism of edaravone (EDA) in improving the post-traumatic brain injury (TBI) dysfunction in learning and memory.METHODS:In vitro and in vivo TBI models were established using hydrogen peroxide (H2O2) treatment for hippocampal nerve stem cells (NSCs) and surgery for rats, followed by EDA treatment. WST 1 measurement, methylthiazol tetrazolium assay, and flow cytometry were performed to determine the activity, proliferation, and apoptosis of NSCs, and malondialdehyde (MDA), lactic dehydrogenase (LDH), and reactive oxygen species (ROS) detection kits were used to analyze the oxides in NSCs.RESULTS:Following EDA pretreatment, NSCs presented with promising resistance to H2O2-induced oxidative stress, whereas NSCs manifested significant increases in activity and proliferation and a decrease in apoptosis. Meanwhile, for NSCs, EDA pretreatment reduced the levels of MDA, LDH, and ROS, with a significant upregulation of Nrf2/antioxidant response element (ARE) signaling pathway, whereas for EDA-treated TBI rats, a significant reduction was observed in the trauma area and injury to the hippocampus, with improvement in memory and learning performance and upregulation of Nrf2/ARE signaling pathway.CONCLUSIONS:EDA, by regulating the activity of Nrf2/ARE signal pathway, can improve the TBI-induced injury to NSCs and learning and memory dysfunction in rats.
Highlights
Traumatic brain injury (TBI) has gained increasing attention in clinical research for its contribution to the death and disability of teenagers worldwide [1,2,3]
nerve stem cells (NSCs) were divided into three groups: the hydrogen peroxide (H2O2) group (NSCs were treated with 30% H2O2 for 4h), the EDA group (NSCs were treated with 30% H2O2 and 3 mg/mL EDA for 4h), and the control group (NSCs were treated with normal saline in similar volume)
As a result, compared with NSCs in a normal environment, H2O2 treatment resulted in a sharp decrease in the vitality of NSCs, whereas this change was partially reversed by EDA treatment (Figure 1A, *po0.05, **po0.01, ***po0.001)
Summary
Traumatic brain injury (TBI) has gained increasing attention in clinical research for its contribution to the death and disability of teenagers worldwide [1,2,3]. Dysfunction in learning and memory is a type of brain sequelae in the mechanism of TBI or secondary TBI, which is mainly induced by abnormal activity in the hippocampus. Current evidence has shown that post-TBI dysfunction in learning and memory involves significantly complicated pathologies, including neuronal death and dysfunction in the synapse, hippocampus, or brain network [4,5,6]. Received for publication on May 19, 2021. Accepted for publication on September 16, 2021
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