Intermittent Hypothermia Is Neuroprotective in an in vitro Model of Ischemic Stroke

Xu, Sui-Yi; Y, Hu; Wei-pin, LI; Wu, Yongming; Zhong, Jian; Wang, Shengnan; Li, Ké; Pan, Suyue

doi:10.7150/ijbs.8868

Cited by 19 publications

(7 citation statements)

References 39 publications

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“…MAP-2, a protein expressed primarily in neuronal dendrites, is critical for numerous microtubule-related processes, including microtubule assembly, stabilization and cross-linking (26). MAP-2 deficiency following ischemic stroke has been documented in previous studies (27,28). In the present study, decreased MAP-2 immunofluorescence activity was observed in MCAO model rats, indicating MAP-2 defect in ischemic stroke.…”

Section: Discussionsupporting

confidence: 72%

Carthamin yellow improves cerebral ischemia‑reperfusion injury by attenuating inflammation and ferroptosis in rats

et al. 2021

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Carthamin yellow (CY), a flavonoid compound extracted from safflower, has been reported to attenuate cardiac ischemia and reperfusion injury. However, whether CY could ameliorate ischemic stroke is not completely understood. In the present study, the preventive effects of CY on experimental ischemic stroke were investigated using middle cerebral artery occlusion (MCAO) model rats. Neurological scores, brain edema, infarct area and microtubule-associated protein 2 (MAP-2) immunoreactivity were assessed to evaluate the effects of CY on ischemic brain injury. The involvement of inflammation and ferroptosis were examined to investigate the mechanism underlying the effects of CY. The results demonstrated that 2-week CY treatment attenuated the neurological deficit score, brain water content and infarct area, and increased MAP-2 immunoreactivity in the cortex in MCAO model rats. CY administration also deactivated the cortex NF-κB/NLR family pyrin domain containing 3 inflammasome signaling pathway, and decreased serum TNF-α, IL-1β and IL-6 concentrations. Moreover, CY treatment inhibited Fe 2+ and reactive oxygen species accumulation, and reversed acyl-CoA synthetase long-chain family member 4, transferrin receptor 1, glutathione peroxidase 4 and ferritin heavy chain 1 protein expression levels in the brain. The levels of glutathione, superoxide dismutase and malondialdehyde in the serum were also reversed by CY treatment. Collectively, the results of the present study demonstrated that CY protected rats against ischemic stroke, which was associated with mitigation of inflammation and ferroptosis.

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Section: Discussionsupporting

confidence: 72%

Carthamin yellow improves cerebral ischemia‑reperfusion injury by attenuating inflammation and ferroptosis in rats

et al. 2021

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“…Amongst these, an increased expression of the protective GRP78 has been identified, and decreased expression of proapoptotic factor CHOP and, thereby, a reduction in apoptosis [ 19 , 20 ]. Furthermore, hypothermia is known to induce neuroprotection both in vivo [ 19 , 20 ] and in vitro [ 21 ]. Ero1-α has been identified as a CHOP target; however, contradictory evidence on signaling molecules leading to activation of the two isoforms Ero1-α/β exists [ 15 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

The Hypothermic Influence on CHOP and Ero1-α in an Endoplasmic Reticulum Stress Model of Cerebral Ischemia

et al. 2015

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Hypoxia induced endoplasmic reticulum stress causes accumulation of unfolded proteins in the endoplasmic reticulum and activates the unfolded protein response, resulting in apoptosis through CCAAT-enhancer-binding protein homologous protein (CHOP) activation. In an in vitro and in vivo model of ischemic stroke, we investigated whether hypothermia regulates the unfolded protein response of CHOP and Endoplasmic reticulum oxidoreductin-α (Ero1-α), because Ero1-α is suggested to be a downstream CHOP target. The gene expression of CHOP and Ero1-α was measured using Quantitative-PCR (Q-PCR) in rat hippocampi following global cerebral ischemia, and in hypoxic pheochromocytoma cells during normothermic (37 °C) and hypothermic (31 °C) conditions. As a result of ischemia, a significant increase in expression of CHOP and Ero1-α was observed after three, six and twelve hours of reperfusion following global ischemia. A stable increase in CHOP expression was observed throughout the time course (p < 0.01, p < 0.0001), whereas Ero1-α expression peaked at three to six hours (p < 0.0001). Induced hypothermia in hypoxia stressed PC12 cells resulted in a decreased expression of CHOP after three, six and twelve hours (p < 0.0001). On the contrary, the gene expression of Ero1-α increased as a result of hypothermia and peaked at twelve hours (p < 0.0001). Hypothermia attenuated the expression of CHOP, supporting that hypothermia suppress endoplasmic reticulum stress induced apoptosis in stroke. As hypothermia further induced up-regulation of Ero1-α, and since CHOP and Ero1-α showed differential regulation as a consequence of both disease (hypoxia) and treatment (hypothermia), we conclude that they are regulated independently.

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“…The primary neurons were cultured as previously described (16) with some modifications. Briefly, the cerebral cortex from rat no more than 7 d after birth was collected and cut into pieces as small as possible.…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Catalpol may improve axonal growth via regulating miR-124 regulated PI3K/AKT/mTOR pathway in neurons after ischemia

Zhu¹,

Wang²,

Shao³

et al. 2019

Ann. Transl. Med.

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Background: MicroRNA-124 (miR-124) is a brain-specific miRNA molecule, the highest expression in the cortex and is associated with neuronal protection after stroke. This study aimed to investigate whether catalpol could affect miR-124 to regulate PI3K/AKT/mTOR pathway, promoting axonal growth in stroke rats. Methods: Cells were divided into three groups: control group, miRNA124 agomir group, and miRNA124 antagomir group. To explore the mechanism, cells were divided into seven groups: control group, OGD group (OGD/R), miRNA124 agomir group, miRNA124 agomir plus catalpol group, miRNA124 antagomir group, miRNA124 antagomir plus catalpol group, and catalpol group. Before OGD/R, miRNA124 antagomir and microRNA124 agomir were transfected into neurons for 6 h by using ribo FECT nd Consumablesn/reper transfection kit. Cell survival and cell death were detected by MTT and LDH assay. Axonal growth was assessed by MAP-2 immunofluorescence staining. Western blotting and qPCR were used to detect the expression of molecules in the PI3K/AKT/mTOR pathway. Results: Inhibition of miR-124 activated PI3K/AKT/mTOR pathway and promoted neuronal survival and axonal growth. The expression of miR-124 increased after OGD/R, and catalpol could inhibit miR-124 to activate PI3K/AKT/mTOR pathway to further promote axonal growth. Conclusions: It is concluded that catalpol may inhibit miR-124 to activate PI3K/AKT/mTOR pathway, promoting axonal growth.

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Intermittent Hypothermia Is Neuroprotective in an in vitro Model of Ischemic Stroke

Cited by 19 publications

References 39 publications

Carthamin yellow improves cerebral ischemia‑reperfusion injury by attenuating inflammation and ferroptosis in rats

Carthamin yellow improves cerebral ischemia‑reperfusion injury by attenuating inflammation and ferroptosis in rats

The Hypothermic Influence on CHOP and Ero1-α in an Endoplasmic Reticulum Stress Model of Cerebral Ischemia

Catalpol may improve axonal growth via regulating miR-124 regulated PI3K/AKT/mTOR pathway in neurons after ischemia

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