Small temperature variations alter edaravone-induced neuroprotection of cortical cultures exposed to prolonged hypoxic episodes

Shibuta, Satoshi; Varathan, Sriranganathan; Kamibayashi, Takahiko; Mashimo, Takashi

doi:10.1093/bja/aep320

Cited by 11 publications

(6 citation statements)

References 41 publications

(28 reference statements)

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“…Mild hypothermia treatment for 24 h after OGD markedly relieves neuronal hypoxic and sugar-deficient injury caused by OGD, whereas mild hypothermia treatment for 6 h did not have a significant protective effect. These results suggest that mild hypothermia treatment after OGD requires application for a long duration, which is in agreement with previously reported research results (34,36,37). Therefore, for ischemic and hypoxic cerebral injury, mild hypothermia treatment for 24 h is more effective.…”

Section: Discussionsupporting

confidence: 92%

Protective effect of mild hypothermia on oxygen-glucose deprivation injury in rat hippocampal neurons after hypoxia

Zhou

Jiang

Zhang

et al. 2013

Molecular Medicine Reports

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Abstract. The present study aimed to establish an oxygen-glucose deprivation (OGD) model of ischemic and hypoxic cerebral neurons to investigate the protective effect of mild hypothermia on neuronal OGD and its mechanisms. OGD injury was significantly mitigated in cells with 24 h of mild hypothermia compared with cells without mild hypothermia; cell morphology improved, the lactic acid dehydrogenase (LDH) release rate was decreased, cytoactivity was increased and the neuronal apoptotic rate was decreased. By contrast, no significant improvement in injury was observed after 6 h of mild hypothermia. This suggests that mild hypothermia treatment following OGD is effective only when implemented for 24 h. Additionally, the caspase-3 activity of neurons increased following OGD, which was positively associated with the neuronal apoptotic rate. However, the caspase-3 activity after 24 h of mild hypothermia was reduced. Simultaneously, the neuronal apoptotic rate was decreased, suggesting that mild hypothermia may inhibit neuronal apoptosis by reducing caspase-3 activity. Therefore, reducing caspase-3 activity potentially constitutes one of the protective mechanisms of mild hypothermia in neuronal OGD.

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Section: Discussionsupporting

confidence: 92%

Protective effect of mild hypothermia on oxygen-glucose deprivation injury in rat hippocampal neurons after hypoxia

Zhou

Jiang

Zhang

et al. 2013

Molecular Medicine Reports

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“…Edaravone, which has been used clinically in both ischemia and neurodegenerative diseases, confers neuroprotection in comparable concentrations to CeNPs in cell culture studies, but edaravone is not as potent an antioxidant. Neuroprotective effects in brain slices require 100–200 times higher concentrations of edaravone that CeNPs (5.8 μM CeNPs versus >500 μM edaravone) to achieve similar effects [83,84]. Based on the greater potency of CeNPs in these studies, CeNPs are an attractive candidate for further development as a therapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Enzyme-Mimetic Activity and Neuroprotective Effects of Cerium Oxide Nanoparticles Stabilized with Various Ratios of Citric Acid and EDTA

et al. 2019

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Cerium oxide (CeO2) nanoparticles (CeNPs) are potent antioxidants that are being explored as potential therapies for diseases in which oxidative stress plays an important pathological role. However, both beneficial and toxic effects of CeNPs have been reported, and the method of synthesis as well as physico-chemical, biological, and environmental factors can impact the ultimate biological effects of CeNPs. In the present study, we explored the effect of different ratios of citric acid (CA) and EDTA (CA/EDTA), which are used as stabilizers during synthesis of CeNPs, on the antioxidant enzyme-mimetic and biological activity of the CeNPs. We separated the CeNPs into supernatant and pellet fractions and used commercially available enzymatic assays to measure the catalase-, superoxide dismutase (SOD)-, and oxidase-mimetic activity of each fraction. We tested the effects of these CeNPs in a mouse hippocampal brain slice model of ischemia to induce oxidative stress where the fluorescence indicator SYTOX green was used to assess cell death. Our results demonstrate that CeNPs stabilized with various ratios of CA/EDTA display different enzyme-mimetic activities. CeNPs with intermediate CA/EDTA stabilization ratios demonstrated greater neuroprotection in ischemic mouse brain slices, and the neuroprotective activity resides in the pellet fraction of the CeNPs. The neuroprotective effects of CeNPs stabilized with equal proportions of CA/EDTA (50/50) were also demonstrated in two other models of ischemia/reperfusion in mice and rats. Thus, CeNPs merit further development as a neuroprotective therapy for use in diseases associated with oxidative stress in the nervous system.

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“…It has also been demonstrated that EDA protects neuronal cells from ischemic injury by inhibiting the translocation of 5-lipoxygenase to the nuclear membrane, thereby blocking the 5-lipoxygenase signaling pathway (12). Moreover, EDA combined with MH significantly improves neuroprotection in rats exposed to hypoxia (13).…”

Section: Introductionmentioning

confidence: 99%

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

Wang

et al. 2020

Int J Oncol

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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.

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Small temperature variations alter edaravone-induced neuroprotection of cortical cultures exposed to prolonged hypoxic episodes

Abstract: Temperature is a potential factor in determining whether edaravone confers a neuroprotective effect when applied during prolonged hypoxic insults.

Cited by 11 publications

References 41 publications

Protective effect of mild hypothermia on oxygen-glucose deprivation injury in rat hippocampal neurons after hypoxia

Protective effect of mild hypothermia on oxygen-glucose deprivation injury in rat hippocampal neurons after hypoxia

Antioxidant Enzyme-Mimetic Activity and Neuroprotective Effects of Cerium Oxide Nanoparticles Stabilized with Various Ratios of Citric Acid and EDTA

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

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