Electroacupuncture exerts neuroprotective effects on ischemia/reperfusion injury in JNK knockout mice: the underlying mechanism

Abstract Background This study aimed to explore the role of miR-380-5p in cerebral ischemia/reperfusion (CIR) injury-induced neuronal cell death and the potential signaling pathway involved. Methodology Human neuroblastoma cell line SH-SY5Y cells were used in this study. Oxygen and glucose deprivation/reperfusion (OGD/R) model was used to mimic ischemia/reperfusion injury. CCK-8 assay and flow cytometry were used to examine cell survival. Quantitative real time PCR (RT-qPCR) assay and Western blotting were used to measure the change of RNA and protein expression, respectively. TargetScan and Luciferase assay was used to confirm the target of miR-380-5p. Malondialdehyde (MDA) superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) were measured using commercial kits. Results miR-380-5p was downregulated in SH-SY5Y cells after OGD/R. Cell viability was increased by miR-380-5p, while cell apoptosis was reduced by miR-380-5p mimics. MDA was reduced by miR-380-5p mimics, while SOD and GSHPx were increased by miR-380-5p. Results of TargetScan and luciferase assay have showed that BACH1 is the direct target of miR-380-5p. Expression of NRF2 was upregulated after OGD/R, but was not affected by miR-380-5p. mRNA expression of HO-1 and NQO1 and ARE activity were increased by miR-380-5p. Overexpression of BACH1 reversed the antioxidant and neuroprotective effects of miR-380-5p. Conclusion miR-380-5p inhibited cell death induced by CIR injury through target BACH1 which also facilitated the activation of NRF2, indicating the antioxidant and neuroprotective effects of miR-380-5p.

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Abstract 428: Pharmacologic and Activated Fibroblast-specific Gβγ-GRK2 Inhibition is Protective Following Ischemia Reperfusion Injury

Circulation Research ◽

10.1161/res.119.suppl_1.428 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Joshua G Travers ◽

Fadia A Kamal ◽

Michelle L Nieman ◽

Michelle A Sargent ◽

Jeffery D Molkentin ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Reperfusion Injury ◽

G Protein ◽

Knockout Mice ◽

Ischemia Reperfusion Injury ◽

Interstitial Fibrosis ◽

Myocardial Dysfunction ◽

Ischemia Reperfusion ◽

Ventricular Compliance

Heart failure is a devastating disease characterized by chamber remodeling, interstitial fibrosis and reduced ventricular compliance. Cardiac fibroblasts are responsible for extracellular matrix homeostasis, however upon injury or pathologic stimulation, these cells transform to a myofibroblast phenotype and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation induces excess signaling through G protein βγ subunits and ultimately the pathologic activation of G protein-coupled receptor kinase 2 (GRK2). We hypothesized that Gβγ-GRK2 inhibition plays an important role in the cardiac fibroblast to attenuate pathologic myofibroblast activation and cardiac remodeling. To investigate this hypothesis, mice were subjected to ischemia/reperfusion (I/R) injury and treated with the small molecule Gβγ-GRK2 inhibitor gallein. While animals receiving vehicle demonstrated a reduction in overall cardiac function as measured by echocardiography, mice treated with gallein exhibited nearly complete preservation of cardiac function and reduced fibrotic scar formation. We next sought to establish the cell specificity of this compound by treating inducible cardiomyocyte- and activated fibroblast-specific GRK2 knockout mice post-I/R. Although we observed modest restoration in cardiac function in cardiomyocyte-specific GRK2 null mice, treatment of these mice with gallein resulted in further protection against myocardial dysfunction following injury, suggesting a functional role in other cardiac cell types, including fibroblasts. Activated fibroblast-specific GRK2 knockout mice were also subjected to ischemia/reperfusion injury; these animals displayed preserved myocardial function and reduced collagen deposition compared to littermate controls following injury. Furthermore, systemic Gβγ-GRK2 inhibition by gallein did not appear to confer further protection over activated fibroblast-specific GRK2 ablation alone. In summary, these findings suggest a potential therapeutic role for Gβγ-GRK2 inhibition in limiting pathologic myofibroblast activation, interstitial fibrosis and heart failure progression.

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Synergistic neuroprotective effects of Danshensu and hydroxysafflor yellow A on cerebral ischemia-reperfusion injury in rats

Oncotarget ◽

10.18632/oncotarget.23272 ◽

2017 ◽

Vol 8 (70) ◽

pp. 115434-115443 ◽

Cited By ~ 10

Author(s):

Hang Xu ◽

WenXing Liu ◽

TianLong Liu ◽

Ning Su ◽

Chao Guo ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Hydroxysafflor Yellow A ◽

Neuroprotective Effects ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

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Neuroprotective Effects of Mitochondria-Targeted Plastoquinone and Thymoquinone in a Rat Model of Brain Ischemia/Reperfusion Injury

Molecules ◽

10.3390/molecules200814487 ◽

2015 ◽

Vol 20 (8) ◽

pp. 14487-14503 ◽

Cited By ~ 31

Author(s):

Denis Silachev ◽

Egor Plotnikov ◽

Ljubava Zorova ◽

Irina Pevzner ◽

Natalia Sumbatyan ◽

...

Keyword(s):

Reperfusion Injury ◽

Brain Ischemia ◽

Rat Model ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Neuroprotective Effects

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Neuroprotective effects of FK-506, l-carnitine and azathioprine on spinal cord ischemia-reperfusion injury

European Journal of Cardio-Thoracic Surgery ◽

10.1016/s1010-7940(03)00582-7 ◽

2004 ◽

Vol 25 (1) ◽

pp. 105-110 ◽

Cited By ~ 14

Author(s):

Serdar Akgun ◽

Atike Tekeli ◽

Ozlem Kurtkaya ◽

Ali Civelek ◽

Selim C Isbir ◽

...

Keyword(s):

Spinal Cord ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Spinal Cord Ischemia ◽

Neuroprotective Effects ◽

Fk 506

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The Mechanism of Gastrodin Participating in Improving the Cerebral Ischemia-Reperfusion Injury Through Notch 1 and NF-κB Signaling Pathways

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2543 ◽

2021 ◽

Vol 11 (2) ◽

pp. 271-275

Author(s):

Qing Hong ◽

Junqiang Ye ◽

Xijia Wang ◽

Chao Zhang

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Signaling Pathways ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Brain Area ◽

Notch 1 ◽

Neuroprotective Effects ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

Background: The purpose of this study was to investigate whether Gastrodin can activate the Notch 1 signaling pathway in the ischemic brain area to produce neuroprotective effects against cerebral ischemia-reperfusion injury, and to elucidate the role of Notch 1 and NF-κB signaling pathways in the Gastrodin-induced cerebral ischemic tolerance. Material and methods: The focal cerebral ischemia reperfusion model of middle cerebral artery embolism was established. TTC staining was applied to detect cerebral infarction. Tunel/NeuN immunofluorescence double labeling was employed to detect apoptosis. WB was used to detect the expressions of proteins related to the Notch 1 and NF-κB pathways. Results: Gastrodin can reduce neuron apoptosis in hippocampus after MCAO/R injury. After DAPT blocked Notch 1 signaling, the neuroprotective effects of Gastrodin improving neural function score, reducing cerebral infarction volume, and inhibiting neuronal apoptosis, were all reversed. Compared with the MCAO/R group, DAPT blocking Notch 1 signaling can also improve the neurological score of rats after MCAO/R injury, reduce cerebral infarct volume, and reduce neuronal apoptosis. Gastrodin can activate Notch 1 and NF-κB signaling pathways in cerebral ischemic areas and increase the expression of related proteins. After DAPT inhibited the Notch 1 signaling in the ipsilateral brain region, the phosphorylation level was significantly decreased, indicating that the activity of the NF-κB pathway was regulated by the Notch 1 signaling. Conclusion: Gastrodin-mediated protection against cerebral ischemia-reperfusion injury is related to the activation of Notch 1 signaling and the up-regulation of NF-κB signaling pathway activity in neurons of ischemic brain area.

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Nuclear Factor (Erythroid-Derived 2)-Like 2 (Nrf2) Contributes to the Neuroprotective Effects of Histone Deacetylase Inhibitors In Retinal Ischemia–Reperfusion Injury

Neuroscience ◽

10.1016/j.neuroscience.2019.08.027 ◽

2019 ◽

Vol 418 ◽

pp. 25-36 ◽

Cited By ~ 2

Author(s):

Chuandi Zhou ◽

Dawei Luo ◽

Wenwen Xia ◽

Chufeng Gu ◽

Tashi lahm ◽

...

Keyword(s):

Reperfusion Injury ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitors ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Retinal Ischemia ◽

Nuclear Factor ◽

Neuroprotective Effects

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Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1–Drp1 pathway

Cell Death Discovery ◽

10.1038/s41420-020-00338-3 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Shuai Yang ◽

Bin Hu ◽

Zongming Wang ◽

Changming Zhang ◽

Haosen Jiao ◽

...

Keyword(s):

Reperfusion Injury ◽

Brain Ischemia ◽

Receptor Agonist ◽

Ischemia Reperfusion Injury ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Mitochondrial Fission ◽

Cb1 Receptor ◽

Cannabinoid Cb1 Receptor ◽

Neuroprotective Effects

Abstract Activation of the cannabinoid CB1 receptor induces neuroprotection against brain ischemia/reperfusion injury (IRI); however, the mechanism is still unknown. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neuronal cells and middle cerebral artery occlusion (MCAO)-induced brain IRI in rats to mimic ischemic brain injury, and hypothesized that the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) would protect ischemic neurons by inhibiting mitochondrial fission via dynamin-related protein 1 (Drp1). We found that OGD/R injury reduced cell viability and mitochondrial function, increased lactate dehydrogenase (LDH) release, and increased cell apoptosis, and mitochondrial fission. Notably, ACEA significantly abolished the OGD/R-induced neuronal injuries described above. Similarly, ACEA significantly reversed MCAO-induced increases in brain infarct volume, neuronal apoptosis and mitochondrial fission, leading to the recovery of neurological functions. The neuroprotective effects of ACEA were obviously blocked by coadministration of the CB1 receptor antagonist AM251 or by the upregulation of Drp1 expression, indicating that ACEA alleviates brain IRI via the CB1–Drp1 pathway. Our findings suggest that the CB1 receptor links aberrant mitochondrial fission to brain IRI, providing a new therapeutic target for brain IRI treatment.

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