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 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.

scholarly journals Methane Saline Ameliorates Traumatic Brain Injury through Anti-Inflammatory, Antiapoptotic, and Antioxidative Effects by Activating the Wnt Signalling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Meng Li ◽  
Weiman Gao ◽  
Le Ji ◽  
Jia Li ◽  
Wanting Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Wnt Pathway ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Sprague Dawley ◽  
Wnt Signalling Pathway ◽  
Sprague Dawley Rats ◽  
Antioxidative Effects ◽  
Anti Inflammatory

Objective. Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved. Methods. Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and β-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway. Results. Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired. Conclusion. Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.

scholarly journals Sailuotong Capsule Prevents the Cerebral Ischaemia-Induced Neuroinflammation and Impairment of Recognition Memory through Inhibition of LCN2 Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yehao Zhang ◽  
Jianxun Liu ◽  
Mingjiang Yao ◽  
WenTing Song ◽  
Yongqiu Zheng ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Cerebral Ischaemia ◽  
Glucose Deprivation ◽  
Lipocalin 2 ◽  
Sprague Dawley ◽  
Male Adult ◽  
Induced Expression ◽  
Memory Recovery ◽  
Ischaemic Brain

Background. Astrogliosis can result in astrocytes with hypertrophic morphology after injury, indicated by extended processes and swollen cell bodies. Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily, has been reported to play a detrimental role in ischaemic brains and neurodegenerative diseases. Sailuotong (SLT) capsule is a standardized three-herb preparation composed of ginseng, ginkgo, and saffron for the treatment of vascular dementia. Although recent clinical trials have demonstrated the beneficial effect of SLT on vascular dementia, its potential cellular mechanism has not been fully explored. Methods. Male adult Sprague-Dawley (SD) rats were subjected to microsphere-embolized cerebral ischaemia. Immunostaining and Western blotting were performed to assess astrocytic reaction. Human astrocytes exposed to oxygen-glucose deprivation (OGD) were used to elucidate the effects of SLT-induced inflammation and astrocytic reaction. Results. A memory recovery effect was found to be associated with the cerebral ischaemia-induced expression of inflammatory proteins and the suppression of LCN2 expression in the brain. Additionally, SLT reduced the astrocytic reaction, LCN2 expression, and the phosphorylation of STAT3 and JAK2. For in vitro experiments, OGD-induced expression of inflammation and LCN2 was also decreased in human astrocyte by the SLT treatment. Moreover, LCN2 overexpression significantly enhanced the above effects. SLT downregulated these effects that were enhanced by LCN2 overexpression. Conclusions. SLT mediates neuroinflammation, thereby protecting against ischaemic brain injury by inhibiting astrogliosis and suppressing neuroinflammation via the LCN2-JAK2/STAT3 pathway, providing a new idea for the treatment strategy of ischaemic stroke.

scholarly journals Cardiovascular drugs attenuated myocardial resistance against ischaemia-induced and reperfusion-induced injury in a rat model of repetitive occlusion

Open Heart ◽  
2018 ◽  
Vol 5 (2) ◽  
pp. e000889 ◽  
Author(s):  
Nora Gatzke ◽  
Nadija Güc ◽  
Philipp Hillmeister ◽  
André Dülsner ◽  
Ferdinand Le Noble ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Rat Model ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Infarcted Myocardium ◽  
Ischaemia And Reperfusion ◽  
St Elevation ◽  
The Impact

ObjectiveWe investigated the impact of cardioprotective drugs on ST-elevation, arrhythmias and infarct size in a rat model of repetitive coronary artery occlusion.MethodsSeventy Sprague-Dawley rats were randomised to two control and five treatment groups. Placebo was either implantation of a pneumatic occluder onto the left anterior descending coronary artery (LAD) without starting repetitive occlusion (SHAM) or subsequent RO of the LAD over 10 days without medication (ROP). Treatment groups underwent RO and additionally received nitroglycerin (NTG), metoprolol, verapamil (VER), ranolazine (RAN) or candesartan (CAN). Two weeks after the intervention, rats underwent a single, sustained LAD occlusion followed by reperfusion. To evaluate differences in cardiac resistance against myocardial ischaemia and reperfusion injury, cardiac surrogate parameters including maximal ST-elevation, arrhythmias and infarct size were assessed.ResultsCompared with sham, RO alone and RO plus nitroglycerin were associated with significantly lower maximal ST-elevation and percentage of infarcted myocardium (SHAM 0.12 mV, ROP 0.06 mV (p=0.004), NTG 0.05 mV (p=0.005); SHAM 16.2%, ROP 6.6% (p=0.008), NTG 5.9% (p=0.006). Compared with RO alone, RO plus RAN was accompanied by increased ST-elevation (0.13 mV, p=0.018) and RO plusVER or CAN by more infarcted myocardium (14.2%, p=0.004% and 15.5%, p=0.003, respectively). Rats treated with VER, RAN or CAN tended to severe arrhythmias more frequently than those of the control groups.ConclusionsRO led to an increased myocardial resistance against ischaemia and reperfusion injury. Concomitant administration of nitroglycerin did not affect the efficacy of RO. Cardiovascular channel or receptor blockers reduced the efficacy of RO.

scholarly journals Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Suryamin Liman ◽  
Chi Wai Cheung ◽  
Kar Lok Wong ◽  
Wai Tai ◽  
Qiu Qiu ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Pain Syndrome ◽  
Preventive Treatment ◽  
Sprague Dawley ◽  
Ischaemia Reperfusion Injury ◽  
Cold Allodynia ◽  
Analgesic Effects ◽  
Ischaemia Reperfusion ◽  
Anti Inflammatory ◽  
Lower Temperature

Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS). Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti-inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP) model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia) in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56%) rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant). Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline (P<0.01) and methylprednisolone (P<0.05) groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (P<0.05). Proinflammatory cytokines TNF-αand IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (allP<0.05). In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain.

scholarly journals Mechanisms of the anti-inflammatory effects of the natural secosteroids physalins in a model of intestinal ischaemia and reperfusion injury

2005 ◽  
Vol 146 (2) ◽  
pp. 244-251 ◽  
Author(s):  
Angélica T Vieira ◽  
Vanessa Pinho ◽  
Lucilia B Lepsch ◽  
Cristóforo Scavone ◽  
Ivone M Ribeiro ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Intestinal Ischaemia ◽  
Ischaemia And Reperfusion ◽  
Anti Inflammatory

Hydroxysafflor Yellow A Attenuates Renal Ischemia- Reperfusion Injury in a Rat Model

2012 ◽  
Vol 9 (10) ◽  
pp. 967-972
Author(s):  
Weiran Chai ◽  
Wenhui Zhang ◽  
Zhu Jin ◽  
Yanqian Zheng ◽  
Peiyao Jin ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Rat Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Hydroxysafflor Yellow A ◽  
Renal Ischemia Reperfusion Injury
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