Protective effects of combined treatment with mild hypothermia and edaravone against cerebral ischemia/reperfusion injury via oxidative stress and Nrf2 pathway regulation

Abstract

Mild hypothermia (MH) and edaravone (EDA) exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. However, whether MH and EDA exert synergistic effects against cerebral I/R injury remains unknown. The aim of the present study was to investigate the effects and mechanism of action of MH in combination with EDA in cerebral I/R injury. A rat cerebral I/R injury model was constructed by middle cerebral artery occlusion (MCAO) followed by reperfusion, and the mice were treated by MH, EDA or the inhibitor of the Nrf2 signaling pathway brusatol (Bru). It was observed that mice treated by MCAO had higher neurological deficit scores and oxidative stress levels, and low spatial learning and memory capacity; moreover, the CA1 region of the hippocampi of the mice exhibited reduced neuronal density and viability, and reduced mitochondrial dysfunction. However, MH in combination with EDA reversed the effects of MCAO, which were blocked by Bru injection. The levels of glutathione (GSH), GSH peroxidase, catalase and superoxide dismutase in rat ischemic hemisphere tissues were reduced by Bru. Western blotting demonstrated that the combined treatment with MH and EDA promoted the nuclear localization of Nrf2, and increased the levels of NAD(P)H quinone oxidoreductase and heme oxygenase (HO)-1. In conclusion, MH combined with EDA exerted synergistic neuroprotective effects against cerebral I/R injury involving changes in the Nrf2/HO-1 pathway.

Puerarin Attenuates Oxidative Stress and Ferroptosis via AMPK/PGC1α/Nrf2 Pathway after Subarachnoid Hemorrhage in Rats

“…The levels of malondialdehyde (MDA) (S0131), antioxidant enzyme superoxide dismutase (SOD) (S0101), and glutathione (GSH)/oxidized glutathione (GSSG) (S0053) were measured using ELISA assay kits according to the manufacturer’s instructions (Beyotime Biotechnology, Shanghai, China). Briefly, MDA detection was based on the chromogenic reaction between MDA and thiobarbituric acid, and measured at 535 nm light wave [ 33 ]. SOD analysis was performed according to the WST-8 method and detected at 450 nm light wave [ 34 , 35 ].…”

“…SOD analysis was performed according to the WST-8 method and detected at 450 nm light wave [ 34 , 35 ]. The GSH/GSSG assay was performed by glutathione reductase treatment and the concentration is detected at 412 nm light wave [ 33 ].…”

Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways

“…Western blotting was used to measure protein levels in cortical or cellular samples as discussed previously ( 24 ). Briefly, samples were lysed in RIPA buffer and centrifuged at 13,362 g for 15 min at 4°C.…”

The Protective Effect of Edaravone on TDP-43 Plus Oxidative Stress-Induced Neurotoxicity in Neuronal Cells: Analysis of Its Neuroprotective Mechanisms Using RNA Sequencing

“…The expression of genes involved in the Nrf2 pathway was upregulated following edaravone treatment in TDP-43-expressing 1464R cells in the presence of ethacrynic acid. It was previously shown that edaravone activates the Nrf2/HO-1 pathway, exerts neuroprotective effects (including a reduction of neurological and cognitive dysfunction), and protects against cell apoptosis in mouse and rat models of various neurological disorders [ 39 , 40 , 41 , 42 ]. In the Nrf2/G93A mouse model of ALS pathology, the expression of Nrf2 was accelerated in both spinal cord motor neurons and lower limb muscles during disease progression [ 43 ].…”