scholarly journals Electroacupuncture Pre-treatment Exerts an Anti-apoptotic Effect in Cerebral Ischaemia and Reperfusion Injury in Rats

2021 ◽  
Author(s):  
Zhu Luwen ◽  
Ye Tao ◽  
Tang Qiang, ◽  
Yan Wang ◽  
Li Hongyu ◽  
...  
Keyword(s):  
Cerebral Ischaemia ◽  
Neurological Deficits ◽  
Tunel Staining ◽  
Caspase 9 ◽  
Brain Infarct ◽  
Severity Scores ◽  
Ischaemia And Reperfusion ◽  
Apoptotic Effect ◽  
Cyt C ◽  
Pre Treatment

Background: Electroacupuncture (EA) pre-treatment can play a significant neuroprotective role in rats with cerebral ischaemia and reperfusion (CIR) injury, but the specific mechanism needs to be further elucidated. <br><br>Objective: To investigate the effects of EA pre-treatment on apoptosis-related proteins Bax, Bcl-2, Cytochrome c (cyt c), cleaved caspase-9 and -3 in rats with CIR injury. Methods: CIR injury was induced using middle cerebral artery occlusion (MCAO) ischaemia-reperfusion. Thirty-six male Specific Pathogen Free (SPF) Sprague-Dawley rats were randomly divided into three groups: Sham (n=12), MCAO (n=12), and the EA+MCAO group (n=12). EA+MCAO group rats received electroacupuncture at DU20 for 2 consecutive weeks before MCAO model preparation. After 24 h of reperfusion, neurological deficits were evaluated by modified neurological severity scores. Brain infarct volumes were examined by 2,3,5-triphenyltetrazolium chloride staining. Expression of Bax, Bcl-2, cyt c, cleaved caspase-9 and -3 in the ischaemic penumbra were detected by Western blotting, and apoptosis evaluated by TUNEL staining. <br><br>Results: After perfusion for 24 h, compared with the MCAO group, the neurological deficit scores and brain infarct volumes in the EA+MCAO group were significantly decreased (P<0.05), as was the level of Bax (P<0.05) or the Bax/Bcl-2 ratio (P<0.05), levels of cyt c, cleaved caspase-9 and -3 also decreased (P<0.05), like the number of TUNEL-positive cells (P<0.05), in contrast, the level of Bcl-2 increased (P<0.05). <br><br>Conclusion: EA pre-treatment exerts an anti-apoptotic effect through Bax-to-Bcl-2 ratio downregulation, blockage of mitochondrial cyt c release to the cytosol, and reduction of caspase-9 and -3 expression in rats with CIR injury.

Hydroxysafflor Yellow A Reprograms TLR9 Signalling Pathway in Ischaemic Cortex after Cerebral Ischaemia and Reperfusion

2018 ◽  
Vol 17 (5) ◽  
pp. 370-382 ◽  
Author(s):  
Zhe Gong ◽  
Jingrui Pan ◽  
Xiangpen Li ◽  
Hongxuan Wang ◽  
Lei He ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Cerebral Ischaemia ◽  
Glucose Deprivation ◽  
Signalling Pathway ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Hydroxysafflor Yellow A ◽  
Ischaemia And Reperfusion ◽  
Anti Inflammatory ◽  
Acute Cerebral Ischaemia

Background and Objective: Hydroxysafflor yellow A (HSYA) was reported to suppress inflammation in ischaemic microglia. However, the mechanism through which HSYA inhibits inflammation caused by cerebral ischaemia and reperfusion injury remains unknown. Here, we have mimicked acute cerebral ischaemia and reperfusion injury by subjecting male Sprague-Dawley rats to transient middle cerebral artery occlusion for 90 minutes and have demonstrated that toll-like receptor 9 (TLR9) was upregulated from day 3 after reperfusion, accompanied by the persistent activation of the pro-inflammatory nuclear factor-κB (NF-κB) pathway from 6 hours to day 7. HSYA was injected intraperitoneally at a dose of 6 mg/kg per day, which activated TLR9 in microglia of ischaemic cortex at 6 hours after reperfusion and then obviously suppressed the NF-κB pathway from day 1 to day 7. Meanwhile, HSYA also activated the anti-inflammatory pathway through interferon regulatory factor 3 from day 1 to day 3. The anti-inflammatory effect of HSYA was partially reversed by TLR9-siRNA interference in primary microglia, which was stimulated by oxygen-glucose deprivation and reoxygenation treatment. The regulation of TLR9-mediated inflammation by HSYA was consistent with the recovery of neurological deficits in rats. Conclusion: Therefore, our findings support that HSYA exerts anti-inflammatory effects by reprogramming the TLR9 signalling pathway during treatment of acute cerebral ischaemia and reperfusion injury.

scholarly journals Xuan Bi Tong Yu Fang Promotes Angiogenesis via VEGF-Notch1/Dll4 Pathway in Myocardial Ischemic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Shuangdi Li ◽  
Jingrong Dong ◽  
Guang Ta ◽  
Yinghui Liu ◽  
Junfeng Cui ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Sprague Dawley ◽  
Caspase 9 ◽  
Mitochondrial Structure ◽  
Transmission Electron ◽  
Sprague Dawley Rats ◽  
Cyt C ◽  
Endothelial Growth Factor

Objective. To investigate the effect of Xuan Bi Tong Yu Fang (XBTYF) on angiogenesis via the vascular endothelial growth factor- (VEGF-) Notch1/delta-like 4 (Dll4) pathway. Materials and Methods. Sixty Sprague-Dawley rats were randomly divided into six groups: control, sham-operated, myocardial ischemia model, and XBTYF treatment at 3.2, 1.6, and 0.8 g/kg. Electrocardiography was performed to evaluate the successful establishment of the model. Hematoxylin-eosin staining and transmission electron microscopy were carried out to observe the morphology and mitochondrial structure in myocardial cells, respectively. TUNEL staining was performed to assess the degree of cell apoptosis. The expression of VEGF-A, Notch1, Dll4, Bcl2, Bax, caspase 3, caspase 9, and cytochrome-c (Cyt-c) was observed by western blot. Results. XBTYF inhibited changes to the morphology and mitochondrial structure in cardiomyocyte and reduced cell apoptosis. Compared with the model group, XBTYF at all doses (3.2, 1.6, and 0.8 g/kg) reduced the expression of Notch1, Dll4, Bax, caspase 3, caspase 9, and Cyt-c, whereas expression of VEGF-A and Bcl2 was increased. Conclusion. XBTYF attenuated mitochondrial damage and cell apoptosis while promoting the angiogenesis of cardiomyocyte. The associated mechanism may be related to the VEGF-Notch1/Dll4 pathway.

Amiloride Alleviates Neurological Deficits Following Transient Global Ischemia and Engagement of Central IL-6 and TNF-α Signal

2019 ◽  
Vol 19 (8) ◽  
pp. 597-604
Author(s):  
Li Pang ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Caspase 3 ◽  
Global Ischemia ◽  
Neurological Deficits ◽  
Global Cerebral Ischemia ◽  
Caspase 9 ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Transient Global Ischemia

Background: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the Central Nervous System can alleviate neurological deficits after the induction of CA and further examine the participation of PIC signal in the hippocampus for the effects of amiloride. Methods: CA was induced by asphyxia and then cardiopulmonary resuscitation was performed in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As noted, it is unlikely that this procedure is clinically used although amiloride and other pharmacological agents were given into the brain in this study. Results: CA increased ASIC1 in the hippocampus of rats in comparison with control animals. This was associated with the increase in IL-1β, IL-6 and TNF-α together with Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1 in the hippocampus of CA rats. Conclusion: Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the Central Nervous System plays a neuroprotective role in the process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked global cerebral ischemia.

scholarly journals Effects of sodium alendronate on osteoporosis and apoptosis-related factors Cyt C, Apaf-1 and caspase-9

2018 ◽  
Vol 29 (3) ◽  
Author(s):  
Hong Li ◽  
Chunde Li ◽  
Xiaodong Yi ◽  
Hong Liu ◽  
Yu Wang
Keyword(s):  
Caspase 9 ◽  
Related Factors ◽  
Cyt C

Abstract P125: A Novel Role for Survivin in Insulin-induced Inhibition of Myocardial Apoptosis in Ischemic/reperfused Heart

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rui Si ◽  
Qiujun Yu ◽  
Ning Zhou ◽  
Ling Tao ◽  
Wenyi Guo ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Survivin Expression ◽  
Fold Increase ◽  
Tunel Staining ◽  
Sprague Dawley ◽  
Signaling Mechanism ◽  
Akt Phosphorylation ◽  
Apoptotic Effect

Objectives: Insulin reduces post-ischemic myocardial apoptotic death, but the mechanism remains unclear. Survivin, an anti-apoptotic protein has recently found participating in vascular repair. This study aimed to test the hypothesis that the up-regulation of survivin by insulin may play a role in the antiapoptotic and cardioprotective effects in the ischemic/reperfused (I/R) heart, and further investigate the signaling mechanism involved. Methods : Isolated adult Sprague-Dawley rat hearts were subjected to 30 min regional ischemia and 3 h of reperfusion. The hearts were randomized to receive insulin, insulin plus LY294002 (specific inhibitor of PI3K), or insulin plus rapamycin (specific inhibitor of mTOR) at the start of reperfusion. To further confirm the correlation between survivin and myocardial survival in vitro, cardiomyocytes were infected with adenovirus encoding survivin or transfected with siRNA targeting survivin. Phosphorylation of Akt, mTOR, p70S6K and the expression of protein survivin were determined and infarct size was assessed using TTC staining, cardiomyocytes apoptosis were evaluated after reperfusion by TUNEL staining and DNA laddering. Results: I/R increased myocardial survivin expression. Insulin reperfusion (10 −7 mol/L) resulted in a 4.2-fold increase in survivin expression (P<0.01 vs. I/R alone), which was almost completely blocked by LY294002. Both of the mTOR phosphorylation and survivin expression were inhibited in the group of insulin reperfusion plus LY294002. Rapamycin reperfusion did not change Akt phosphorylation but partially inhibited survivin expression (16.7±1.2 vs. 9.8±1.6, P<0.01 vs. I/R+Ins), which indicated a cardioprotective effect of survivin and a possible PI3K/Akt/mTOR/SVV signaling pathway during I/R. Moreover, over-expressed survivin provides protection against stimulated ischemia reperfusion induced cardiomyocyte apoptosis, while targeting survivin blunted the anti-apoptotic effect of insulin. Conclusion: This study demonstrates that insulin up-regulates myocardial survivin expression, partly at least, via PI3-kinase-mTOR mechanism, which contributes to the anti-apoptotic effect of insulin in the I/R heart.

Real-Time In Situ Sequential Fluorescence Activation Imaging of Cyt c and Caspase-9 with a Gold–Selenium-Bonded Nanoprobe

2021 ◽  
Author(s):  
Bo Liu ◽  
Jingjing Li ◽  
Ping Zhou ◽  
Wei Pan ◽  
Na Li ◽  
...  
Keyword(s):  
Real Time ◽  
Caspase 9 ◽  
Cyt C

Abstract TP269: Lncrna-u90926 Aggravates Ischemic Brain Injury via Promoting Neutrophils Infiltration After Experimental Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Jian Chen ◽  
Yun Xu
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Expression Level ◽  
Neurological Deficits ◽  
Neurological Injury ◽  
Experimental Stroke ◽  
Ischemic Brain Injury ◽  
Triphenyltetrazolium Chloride ◽  
Ischemic Brain ◽  
Severity Scores

Background: Long non-coding RNAs (LncRNAs) are expressed at high levels in the brain in a variety of neuropathologic conditions, including stroke. However, the potential role of LncRNAs in ischemic stroke-associated microglial biological function and neurological injury remains largely unknown. Methods: Oxygen-glucose deprivation and transient middle cerebral artery occlusion (MCAO) in C57BL/6 mice were used as in vitro and in vivo ischemic stroke models. Microarray analysis was performed to explore the overall expression level changes of LncRNAs. Real-time polymerase chain reaction (RT-qPCR) was used to detect expression level of LncU90926 in brain, plasma and microglia. ShRNA-LncU90926 in lentivirus and microglia specific Adeno-associated virus (AAV) were used to knockdown LncU90926 in vitro and in vivo separately. Infarct volumes and neurological impairments were assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, Neurological Severity Scores (NSS), rotarod test and grip strength respectively. Immunofluorescence staining and flow cytometry were performed to detect the number of neutrophils recruited to brain. RT-qPCR was used to detect the level of chemokines (CXCL, CCL2) and inflammatory mediators associated with neutrophils (MPO, MMP3 and TIMP1). Results: (1). LncU90926 was markedly up-regulated in the infarcted brain and plasma after MCAO. Both MCAO and OGD treatment induced remarkable up-regulation of LncU90926 in microglia. (2). LncU90926 knockdown definitely attenuated brain infarct size and neurological deficits after ischemic stroke. (3). LncU90926 knockdown in microglia reduced the number of neutrophils recruited to brain, and CXCL1 and CCL2 were down-regulated in both MCAO and OGD models. LncU90926 knockdown also induced reduction of MPO, MMP3 and TIMP1 in the infarcted brain. Conclusions: LncU90926 was up-regulated in microglia after experimental stroke, and aggravates ischemic brain injury through facilitating neutrophils infiltration via up-regulating microglial chemokine.

scholarly journals Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Xiao Hu ◽  
Shirong Li ◽  
Desislava Met Doycheva ◽  
Lei Huang ◽  
Cameron Lenahan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Neuronal Degeneration ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
Tunel Staining ◽  
Artery Ligation ◽  
Neuroprotective Effects

Oxidative stress (OS) and neuronal apoptosis are major pathological processes after hypoxic-ischemic encephalopathy (HIE). Colony stimulating factor 1 (CSF1), binding to CSF1 receptor (CSF1R), has been shown to reduce neuronal loss after hypoxic-ischemia- (HI-) induced brain injury. In the present study, we hypothesized that CSF1 could alleviate OS-induced neuronal degeneration and apoptosis through the CSF1R/PLCG2/PKA/UCP2 signaling pathway in a rat model of HI. A total of 127 ten-day old Sprague Dawley rat pups were used. HI was induced by right common carotid artery ligation with subsequent exposure to hypoxia for 2.5 h. Exogenous recombinant human CSF1 (rh-CSF1) was administered intranasally at 1 h and 24 h after HI. The CSF1R inhibitor, BLZ945, or phospholipase C-gamma 2 (PLCG2) inhibitor, U73122, was injected intraperitoneally at 1 h before HI induction. Brain infarct volume measurement, cliff avoidance test, righting reflex test, double immunofluorescence staining, western blot assessment, 8-OHdG and MitoSOX staining, Fluoro-Jade C staining, and TUNEL staining were used. Our results indicated that the expressions of endogenous CSF1, CSF1R, p-CSF1R, p-PLCG2, p-PKA, and uncoupling protein2 (UCP2) were increased after HI. CSF1 and CSF1R were expressed in neurons and astrocytes. Rh-CSF1 treatment significantly attenuated neurological deficits, infarct volume, OS, neuronal apoptosis, and degeneration at 48 h after HI. Moreover, activation of CSF1R by rh-CSF1 significantly increased the brain tissue expressions of p-PLCG2, p-PKA, UCP2, and Bcl2/Bax ratio, but reduced the expression of cleaved caspase-3. The neuroprotective effects of rh-CSF1 were abolished by BLZ945 or U73122. These results suggested that rh-CSF1 treatment attenuated OS-induced neuronal degeneration and apoptosis after HI, at least in part, through the CSF1R/PLCG2/PKA/UCP2 signaling pathway. Rh-CSF1 may serve as therapeutic strategy against brain damage in patients with HIE.

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