Autophagy Induced by Oxygen-Glucose Deprivation Mediates the Injury to the Neurovascular Unit

Zhang, Xinyang; Fu, Chen; Chen, Baoxin; Xu, Zhen-Min; Zeng, Zixiu; He, Liyu; Lü, Yan; Chen, Zhigang; Liu, Xuemei

doi:10.12659/msm.915123

Cited by 10 publications

(12 citation statements)

References 36 publications

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“…However, two studies showed a reduction of viability (as detected by MTT) starting only at 6 hours of OGD in primary rat brain microvascular ECs [70, 71] and another study using bEnd.3 cells found decreased cell viability (as detected by MTT) and increased annexin A5/PI staining by 6 and 12 hours of OGD [72]. Other studies in primary mouse brain microvascular ECs and bEnd.3 cells detected the start of cell death (according to MTT and active caspase-3) even later, at 12 hours [73–75] or 16 hours after OGD onset [76].…”

Section: Systematic Review Of Ec Death In Strokementioning

confidence: 99%

The impact of endothelial cell death in the brain and its role after stroke: A systematic review

Zille

Ikhsan

Jiang

et al. 2019

CST

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The supply of oxygen and nutrients to the brain is vital for its function and requires a complex vascular network that, when disturbed, results in profound neurological dysfunction. As part of the pathology in stroke, endothelial cells die. As endothelial cell death affects the surrounding cellular environment and is a potential target for the treatment and prevention of neurological disorders, we have systematically reviewed important aspects of endothelial cell death with a particular focus on stroke. After screening 2876 publications published between January 1, 2010 and August 7, 2019, we identified 154 records to be included. We found that endothelial cell death occurs rapidly as well as later after the onset of stroke conditions. Among the different cell death mechanisms, apoptosis was the most widely investigated (92 records), followed by autophagy (20 records), while other, more recently defined mechanisms received less attention, such as lysosome-dependent cell death (2 records) and necroptosis (2 records). We also discuss the differential vulnerability of brain cells to injury after stroke and the role of endothelial cell death in the no-reflow phenomenon with a special focus on the microvasculature. Further investigation of the different cell death mechanisms using novel tools and biomarkers will greatly enhance our understanding of endothelial cell death. For this task, at least two markers/criteria are desirable to determine cell death subroutines according to the recommendations of the Nomenclature Committee on Cell Death.

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Section: Systematic Review Of Ec Death In Strokementioning

confidence: 99%

The impact of endothelial cell death in the brain and its role after stroke: A systematic review

Zille

Ikhsan

Jiang

et al. 2019

CST

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“…Ischemia/hypoxia increased the level of microtubule-associated protein 1 light chain 3 (LC3), as was found in undifferentiated (n = 9) (Lai et al 2020 ; Liu et al 2016 , 2021 ; Niu et al 2018 ; Shi et al 2012 ; Wang et al 2017 , 2019c ; Zhi et al 2020 ; Zhou et al 2019 ) and differentiated SH-SY5Y cells (n = 2) (Cheng et al 2019 ; Zhang et al 2019b ). Connexin32 (CX32) was found to inhibit the autophagic effect of nuclear receptor 4A1 (NUR77) during ischemia/hypoxia in one study using undifferentiated SH-SY5Y cells (Ping et al 2021 ).…”

Section: Resultsmentioning

confidence: 79%

Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

2023

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Translation of neuroprotective treatment effects from experimental animal models to patients with cerebral ischemia has been challenging. Since pathophysiological processes may vary across species, an experimental model to clarify human-specific neuronal pathomechanisms may help. We conducted a scoping review of the literature on human neuronal in vitro models that have been used to study neuronal responses to ischemia or hypoxia, the parts of the pathophysiological cascade that have been investigated in those models, and evidence on effects of interventions. We included 147 studies on four different human neuronal models. The majority of the studies (132/147) was conducted in SH-SY5Y cells, which is a cancerous cell line derived from a single neuroblastoma patient. Of these, 119/132 used undifferentiated SH-SY5Y cells, that lack many neuronal characteristics. Two studies used healthy human induced pluripotent stem cell derived neuronal networks. Most studies used microscopic measures and established hypoxia induced cell death, oxidative stress, or inflammation. Only one study investigated the effect of hypoxia on neuronal network functionality using micro-electrode arrays. Treatment targets included oxidative stress, inflammation, cell death, and neuronal network stimulation. We discuss (dis)advantages of the various model systems and propose future perspectives for research into human neuronal responses to ischemia or hypoxia. Graphical Abstract

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“…Ischemic stroke is caused by a sudden interruption of blood flow to the brain, resulting in brain cell death and neurological dysfunction ( 24 ). With increase in the aging population, the number of patients with stroke is also increasing and is predicted to reach 77 million by 2030 ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Ameliorates Cerebral Ischemic Injury by Inhibiting Ferroptosis

Dong

et al. 2021

Front. Neurol.

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Background: Our previous study found that electroacupuncture (EA) can promote the recovery of neurological functions, reduce the volume of cerebral infarction, and protect the neurovascular unit in middle cerebral artery occlusion (MCAO) rats. Some studies have shown that ferroptosis is closely related to ischemic stroke; however, whether EA plays a protective role by regulating ferroptosis is unknown.Objective: We aimed to investigate the inhibitory effects of EA on ferroptosis in MCAO rats.Methods: We used 36 adult male Sprague–Dawley rats in this study. MCAO rats were established according to the Zea method and treated with EA at a continuous wave of 2/100 Hz and ~2–4 V for 30 min for 7 consecutive days. We analyzed the coordinated motor deficit and volume of cerebral infarction in vivo through 9.4-tesla magnetic resonance imaging. Then, the ischemic brain tissue was isolated and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron were determined. Western blotting and real-time quantitative PCR were performed to evaluate the expression of glutathione peroxidase 4 (GPX4), transferrin (Tf), transferrin receptor 1 (TfR1), and ferritin heavy chain 1 (FTH1). To confirm the results, we used a transmission electron microscope to observe the mitochondrial morphology.Results: EA intervention significantly decreased the oxidative stress level and inhibited ferroptosis. EA significantly improved coordinated motor deficit (P < 0.01) and decreased cerebral infarct volume (P < 0.01) in the EA + MCAO group, compared with the MCAO group. EA downregulated the level of MDA (P < 0.01) and total iron (P < 0.01) and upregulated the level of SOD (P < 0.01) and GSH (P < 0.01) in the EA + MCAO group, compared with the MCAO group. EA increased the levels of GPX4 and GPX4 mRNA (P < 0.01) and FTH1 and FTH1 mRNA (P < 0.05, P < 0.01), whereas it decreased the levels of Tf and Tf mRNA (P < 0.05, P < 0.01) and TfR1 and TfR1 mRNA (P < 0.01) in the EA + MCAO group, compared with the MCAO group. EA also promoted the recovery of mitochondrial morphology according to the mitochondrial classification system for the ischemic cerebral tissue.Conclusion: Our results indicate that EA can inhibit ferroptosis by regulating oxidative stress and iron-related proteins, thus conferring protection against MCAO in a rat model.

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Autophagy Induced by Oxygen-Glucose Deprivation Mediates the Injury to the Neurovascular Unit

Cited by 10 publications

References 36 publications

The impact of endothelial cell death in the brain and its role after stroke: A systematic review

The impact of endothelial cell death in the brain and its role after stroke: A systematic review

Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

Electroacupuncture Ameliorates Cerebral Ischemic Injury by Inhibiting Ferroptosis

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