Oxycodone relieves permeability damage and apoptosis of oxygen-glucose deprivation/reoxygenation-induced brain microvascular endothelial cells through ras homolog family member A (RhoA)/ Rho-associated coiled-coil containing kinases (ROCK)/ myosin light chain 2 (MLC2) signal

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

ABSTRACT

Cerebrovascular disease, an important cause of acute ischemic stroke, has attracted worldwide attention. Oxycodone has been widely used to treat various painful disorders. This study was designed to explore the mechanism of oxycodone in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cell model. For the reliability of the results in the following experiments, the viability was firstly detected using CCK-8. With the application of LDH, TEER and TUNEL assays, the LDH expression, permeability and apoptosis of brain microvascular endothelial cells were detected, respectively. Besides, the mRNA and protein expressions of tight junction proteins and RhoA were measured using RT-qPCR and Western blot. Moreover, RT-qPCR was employed to evaluate the expressions of inflammatory cytokines. Western blot was adopted to measure the levels of RhoA, ROCK, MLC2 and apoptosis-related proteins. The results revealed that oxycodone attenuated permeability damage, inflammatory factor release and apoptosis of OGD/R-induced brain microvascular endothelial cells in a dose-dependent manner. It was also found that oxycodone could reduce the expressions of RhoA, ROCK and MLC2 in brain microvascular endothelial cells induced by OGD/R. More importantly, oxycodone exhibited desirable effects on OGD/R-induced brain microvascular endothelial cells through RhoA/ROCK/MLC2 signal. In conclusion, oxycodone relieved permeability damage and apoptosis of OGD/R-induced brain microvascular endothelial cells through RhoA/ROCK/MLC2 signal, suggesting that oxycodone might be an effective method for the improvement of cerebral ischemia-reperfusion injury.

Related collections

Most cited references 30

Record: found
Abstract: found
Article: not found

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.

(2002)

To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. Collaborative meta-analyses (systematic overviews). Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000. Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

0 comments Cited 501 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Cell biology of ischemia/reperfusion injury.

Theodore Kalogeris, Christopher P. Baines, Maike Krenz … (2012)

Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues. Copyright © 2012 Elsevier Inc. All rights reserved.

0 comments Cited 403 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

NXY-059 for the treatment of acute ischemic stroke.

Ashfaq Shuaib, Kennedy R Lees, Patrick Lyden … (2007)

The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. We sought confirmation of efficacy in a second, larger trial. We enrolled 3306 patients with acute ischemic stroke in a randomized, double-blind trial to receive a 72-hour infusion of intravenous NXY-059 or placebo within 6 hours after the onset of stroke symptoms. Our primary end point was the distribution of disability scores on the modified Rankin scale at 90 days. We examined scores on neurologic and activities-of-daily-living scales as secondary end points. We also tested the hypothesis that NXY-059 would reduce alteplase-related intracranial hemorrhages. The efficacy analysis was based on 3195 patients. Prognostic factors were well balanced between the treatment groups. Mortality was equal in the two groups, and adverse-event rates were similar. The distribution of scores on the modified Rankin scale did not differ between the group treated with NXY-059 (1588 patients) and the placebo group (1607 patients; P=0.33 by the Cochran-Mantel-Haenszel test; odds ratio for limiting disability, 0.94; 95% confidence interval [CI], 0.83 to 1.06). Analysis of categorized scores on the modified Rankin scale confirmed the lack of benefit: the odds ratio for trichotomization into modified Rankin scale scores of 0 to 1 versus 2 to 3 versus 4 to 6 was 0.92 (95% CI, 0.80 to 1.06). There was no evidence of efficacy for any of the secondary end points. Among patients treated with alteplase, there was no difference between the NXY-059 group and the placebo group in the frequency of symptomatic or asymptomatic hemorrhage. NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms. (ClinicalTrials.gov number, NCT00061022 [ClinicalTrials.gov].) Copyright 2007 Massachusetts Medical Society.

0 comments Cited 157 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Bioengineered

Journal ID (iso-abbrev): Bioengineered

Title: Bioengineered

Publisher: Taylor & Francis

ISSN (Print): 2165-5979

ISSN (Electronic): 2165-5987

Publication date (Electronic, pub): 16 February 2022

Publication date (Electronic, collection): 2022

Publication date PMC-release: 16 February 2022

Volume: 13

Issue: 3

Pages: 5205-5215

Affiliations

[0001]Department of Emergency, Affiliated Hospital of Jiangnan University; , Wuxi, Jiangsu, China

Author notes

CONTACT Wei Sun sunweisw07@ 123456163.com Department of Emergency, Affiliated Hospital of Jiangnan University; , No. 200 Huihe Road, Binhu District, Wuxi, Jiangsu 214000, China

Article

Publisher ID: 2037371

DOI: 10.1080/21655979.2022.2037371

PMC ID: 8982462

PubMed ID: 35170371

SO-VID: e51be82e-a44f-4e08-8c46-02e80ff5b10e

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oxycodone relieves permeability damage and apoptosis of oxygen-glucose deprivation/reoxygenation-induced brain microvascular endothelial cells through ras homolog family member A (RhoA)/ Rho-associated coiled-coil containing kinases (ROCK)/ myosin light chain 2 (MLC2) signal

Read this article at

ABSTRACT

Related collections

Journal of Disability Research

Most cited references 30

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.

Cell biology of ischemia/reperfusion injury.

NXY-059 for the treatment of acute ischemic stroke.

Author and article information

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 142

Cited by 2

Most referenced authors 344