Roles of autophagy and endoplasmic reticulum stress in intracerebral hemorrhage‐induced secondary brain injury in rats

Duan, Xuanchu; Wang, Wei; Feng, Dongxia; Yin, Jia; Zuo, Gang; Chen, Dongdong; Chen, Zhouqing; Li, Haiying; Zhong, Wei

doi:10.1111/cns.12703

Cited by 59 publications

(50 citation statements)

References 49 publications

(86 reference statements)

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“…As autophagy plays a critical role in the secondary injury mechanism of SCI, we examined whether the beneficial action of EPO on SCI was mediated by autophagy in our model system. Knowing that the conversion from LC3‐I to LC3‐II and expression of Beclin 1 are indispensable for the formation and expansion of autophagosomes, we detected these autophagic markers at 1, 3, and 7 days after injury to examine the temporal pattern of autophagic activity.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, autophagy has been demonstrated to be an important therapeutic mechanism for injuries of CNS such as SCI and several CNS degeneration diseases such as Alzheimer's disease. Accumulating evidence has shown that autophagy is induced after SCI, and the impairment of autophagy has been addressed to aggravate the secondary injury. The AMP‐activated protein kinase (AMPK) acts as an energy sensor responding to stress conditions such as oxidative stress and deprivation of nutrition, which also acts as a key player in autophagy.…”

Section: Introductionmentioning

confidence: 99%

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AMP‐activated protein kinase‐dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats

Wang

Xie

et al. 2018

CNS Neurosci Ther

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

AMP‐activated protein kinase‐dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats

Wang

Xie

et al. 2018

CNS Neurosci Ther

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“…As a lysosomal degradative pathway, autophagy is essential for survival and maintaining cellular homeostasis. In addition, autophagy is involved in diverse diseases and injuries (Jiang et al, 2015), including the pathological processes during ICH (Duan et al, 2017;Li et al, 2018c). Moreover, recent studies have demonstrated that oxidative stress contributes to autophagy (Duan et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Luteolin Exerts Neuroprotection via Modulation of the p62/Keap1/Nrf2 Pathway in Intracerebral Hemorrhage

Tan

et al. 2020

Front. Pharmacol.

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Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch-like enoyl-coenzyme A hydratase (ECH)-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

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“…It has been reported that autophagy pathway activation was detected in neurons after ICH [6]. Increasing evidence has indicated that the role of autophagy in ICH pathology is crucial [23]. MST4 plays multiple roles Representative western blot bands for MST4, pAKT, AKT, and LC3 expression in sham and ICH mice 12 h following ICH.…”

Section: Discussionmentioning

confidence: 98%

MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in Intracerebral Hemorrhage Mice

et al. 2020

Behavioural Neurology

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Background. The aim of this study was to explore the role of hesperadin in intracerebral hemorrhage (ICH) mice, with the involvement of the mammalian ste20-like kinase 4 (MST4)/AKT signaling pathway. Methods. All mice were divided into four groups: sham group, sham+hesperidin group, ICH group, and ICH+hesperadin group. The effects of hesperadin were assessed on the basis of brain edema and neurobehavioral function. Furthermore, we observed MST4, AKT, phosphorylation of AKT (pAKT), and microtubule-associated protein light chain 3 (LC3) by western blotting. Protein localization of MST4 and LC3 was determined by immunofluorescence. Results. The expression of MST4 was upregulated at 12 h and 24 h after ICH. Brain edema was significantly decreased and neurological function was improved in the hesperadin treatment group compared to the ICH group (P<0.05). Hesperadin decreases the expressions of MST and increases pAKT after ICH. Autophagy significantly increased in the ICH group, while hesperadin reduced this increase. Conclusion. Hesperadin provides neuroprotection against ICH by inhibiting the MST4/AKT signaling pathway.

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Roles of autophagy and endoplasmic reticulum stress in intracerebral hemorrhage‐induced secondary brain injury in rats

Abstract: At 6 hours after ICH, excessive autophagy may participate in ER stress-induced brain injury; at 7 days after ICH, autophagy could enhance the protection of ER stress inhibitor possibly via clearing up the cell rubbish generated due to the early-stage damaged autophagic flux.

Cited by 59 publications

References 49 publications

AMP‐activated protein kinase‐dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats

AMP‐activated protein kinase‐dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats

Luteolin Exerts Neuroprotection via Modulation of the p62/Keap1/Nrf2 Pathway in Intracerebral Hemorrhage

MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in Intracerebral Hemorrhage Mice

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