Fluoxetine mitigating late-stage cognition and neurobehavior impairment induced by cerebral ischemia reperfusion injury through inhibiting ERS-mediated neurons apoptosis in the hippocampus

Xu, Feng; Zhang, Guixing; Yin, Jiangwen; Zhang, Qingtong; Ge, Ming; Li, Peng; Wang, Sheng; Li, Yan

doi:10.1016/j.bbr.2019.111952

Cited by 21 publications

(18 citation statements)

References 38 publications

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“…Although neurological deficit score evaluation and Barnes maze task test were performed, it may be a limitation that the TTC dying method was not used to assess the brain infarct area. The hippocampus is responsible for spatial learning and memory (24), which may be disturbed when the hippocampus sustains cerebral I/R injury (25). Therefore, the Barnes Maze task that helps evaluate spatial learning and memory ability was performed in the present study, and it was observed that EDA combined with MH could improve the spatial learning and memory ability of rats with cerebral I/R injury.…”

Section: Discussionmentioning

confidence: 85%

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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Section: Discussionmentioning

confidence: 85%

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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“…GRP 78 and GRP 94 are chaperone proteins for protein synthesis and termination in ERS. Previous studies show that Fluoxetine [ 14 ], sulforaphane [ 15 ], and Harpagide [ 16 ] protect neurons from hypoxia-reoxygenation-induced neuron apoptosis by reducing ERS. To investigate whether astragaloside IV could inhibit ERS to protect neuronal cells, we examined the expressions of ERS-related proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Endoplasmic reticulum (ER) is an important organelle folding cell surface and secreted protein in eukaryotic cells [ 12 ]. Imbalance of ER steady state leads to ERS [ 13 ] with the hall markers GRP 78 and GRP 94, which participates in nerve damage [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection Effect of Astragaloside IV from 2-DG-Induced Endoplasmic Reticulum Stress

Cai

et al. 2020

Oxidative Medicine and Cellular Longevity

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Objective. Astragaloside IV shows neuroprotective activity, but its mechanism remains unclear. To investigate whether astragaloside IV protects from endoplasmic reticulum stress (ERS), we focus on the regulation of glycogen synthase kinase-3β (GSK-3β) and mitochondrial permeability transition pore (mPTP) by astragaloside IV in neuronal cell PC12. Methods and Results. PC12 cells treated with different concentrations of ERS inductor 2-deoxyglucose (2-DG) (25-500 μM) showed a significant increase of glucose-regulated protein 78 (GRP 78) and GRP 94 expressions and a decrease of tetramethylrhodamine ethyl ester (TMRE) fluorescence intensity and mitochondrial membrane potential (∆Ψm), with the peak effect seen at 50 μM, indicating that 2-DG induces ERS and the mPTP opening. Similarly, 50 μM of astragaloside IV increased the GSK-3β phosphorylation at Ser9 most significantly. Next, we examined the neuroprotection of astragaloside IV by dividing the PC12 cells into control group, 2-DG treatment group, astragaloside IV plus 2-DG treatment group, and astragaloside IV only group. PC12 cells treated with 50 μM 2-DG for different time courses (0-36 hr) showed a significant increase of Cleaved-Caspase-3 with the peak at 6 hr. 2-DG significantly induced cell apoptosis and increased the green fluorescence intensity of Annexin V-FITC, and these effects were reversed by astragaloside IV. Such a result indicates that astragaloside IV protected neural cell survival from ERS. 2-DG treatment significantly increased the expressions of inositol-requiring ER-to-nucleus signal kinase 1 (IRE1), phosphor-protein kinase R-like ER kinase (p-PERK), but not affect the transcription factor 6 (ATF6) expression. 2-DG treatment significantly decreased the phosphorylation of GSK-3β and significantly reduced the TMRE fluorescence intensity and ∆Ψm, following mPTP open. Astragaloside IV significantly inhibited the above effects caused by 2-DG, except the upregulation of ATF6 protein. Taken together, astragaloside IV significantly inhibited the ERS caused by 2-DG. Conclusion. Our data suggested that astragaloside IV protects PC12 cells from ERS by inactivation of GSK-3β and preventing the mPTP opening. The GRP 78, GRP 94, IRE1, and PERK signaling pathways but not ATF6 are responsible for GSK-3β inactivation and neuroprotection by astragaloside IV.

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“…However, cerebral ischemic/reperfusion (I/R) injury caused by restoring blood flow after thrombolytic therapy aggravates neuronal apoptosis and exacerbates neuronal death (Liang et al, 2018). Most importantly, cerebral I/R injury further exacerbates cognitive impairment that is related with neurons apoptosis in hippocampus (Xu et al, 2019), which are more susceptible to cerebral I/R injury than the ones in other brain regions. Unfortunately, so far, effective drugs or strategies to fight cerebral I/R injury are unavailable due to its complex pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Icariside II, a PDE5 Inhibitor, Suppresses Oxygen-Glucose Deprivation/Reperfusion-Induced Primary Hippocampal Neuronal Death Through Activating the PKG/CREB/BDNF/TrkB Signaling Pathway

Deng

et al. 2020

Front. Pharmacol.

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Background: Ischemic stroke remains the leading cause of death and adult disability. Cerebral ischemic/reperfusion (I/R) injury is caused by ischemic stroke thereafter aggravates overwhelming neuronal apoptosis and even the death of neurons. Of note, hippocampus is more susceptive to cerebral I/R injury than the other brain region. This study was designed to explore the effects and mechanism of icariside II (ICS II), a pharmacologically active compound exists in herbal Epimedii with previous studyproved as a phosphodiesterase 5 (PDE5) inhibitor, on the oxygen glucose deprivation/ reoxygenation (OGD/R)-induced primary hippocampal neurons injury.

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Fluoxetine mitigating late-stage cognition and neurobehavior impairment induced by cerebral ischemia reperfusion injury through inhibiting ERS-mediated neurons apoptosis in the hippocampus

Cited by 21 publications

References 38 publications

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

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

Neuroprotection Effect of Astragaloside IV from 2-DG-Induced Endoplasmic Reticulum Stress

Icariside II, a PDE5 Inhibitor, Suppresses Oxygen-Glucose Deprivation/Reperfusion-Induced Primary Hippocampal Neuronal Death Through Activating the PKG/CREB/BDNF/TrkB Signaling Pathway

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