Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction

Isahaya, Kenji; Yamada, Koji; Yamatoku, Masato; Sakurai, Kenzo; Takaishi, Satoshi; Kato, Bunta; Hirayama, Toshikazu; Hasegawa, Yasuhiro

doi:10.1016/j.jstrokecerebrovasdis.2010.05.009

Cited by 31 publications

(19 citation statements)

References 35 publications

(24 reference statements)

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“…Improved outcomes have been reported after MMP-9 inhibition. [144][145][146][147][148][149][150] The beneficial effects of pharmaceutical MMP-9 inhibitors are probably most pronounced when they are administered early during reperfusion, but more research is needed to establish the clinical implications of their use. 151 Glibenclamide is being tested for safety in patients with severe ischaemic stroke in a phase II clinical trial.…”

Section: Therapeutic Targetsmentioning

confidence: 99%

Intramyocardial haemorrhage after acute myocardial infarction

et al. 2014

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In patients with acute myocardial infarction (AMI), the guideline-recommended treatment is mechanical revascularization by percutaneous coronary intervention (PCI), which is effective at reducing mortality. However, a substantial proportion of patients with AMI develop chronic cardiac failure owing to poor restoration of microvascular function and myocardial perfusion, despite restoration of epicardial vessel patency. This occurrence is called the 'no-reflow' phenomenon. Although pathological and clinical observations initially seemed to support the hypothesis that no-reflow was the result of microvascular obstruction, irreversible microvascular injury and subsequent intramyocardial haemorrhage are now also thought to be important factors in this process. Intramyocardial haemorrhage shares several pathophysiological features with the haemorrhagic transformation that occurs after ischaemic stroke. Understanding of the role of intramyocardial haemorrhage in the no-reflow phenomenon and myocardial injury is crucial to the development of new therapeutic strategies to treat AMI. In this Review, we provide a comprehensive overview of the pathogenesis and clinical relevance of intramyocardial haemorrhage, and discuss diagnostic options and future therapeutic strategies.

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Section: Therapeutic Targetsmentioning

confidence: 99%

Intramyocardial haemorrhage after acute myocardial infarction

et al. 2014

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“…Since 2001 in Japan, edaravone is an approved treatment of ischemic stroke when administered within the first 24 hours of onset. Human studies show that edaravone can significantly suppress MMP-9 serum level after ischemic stroke [167]. On the other hand, edaravone was found to increase the HT rate in case of cardiogenic embolism treated with heparin and rtPA, though this did not impact the clinical outcome, on the contrary, the group treated with edaravone showed a higher rate of good outcome among patients suffered HI-1 and HI-2.…”

Section: Edaravonementioning

confidence: 94%

Hemorrhagic transformation of ischemic stroke

J¹,

Hortobágyi²

2017

Vascul Dis Ther

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The better understanding of the diverse mechanisms leading to the hemorrhagic transformation of an ischemic stroke is the crucial point in the prevention of this altogether common phenomenon. The different individual risk factors include the anatomical variability of collateral blood supply, age, genetics, body weight, etiology of the occlusion, side of the occluded vessel, renal status, stroke severity, history of high serum glucose or hypertension and hypertension or hyperglycemia at the onset of the stroke, ferritin level, INR, antiplatelet usage or the platelet count etc. All these might contribute to the process of hemorrhagic transformation. These risk factors have been identified by retrospective epidemiological studies and are useful to identify patients who are at high risk for hemorrhagic conversion and help the decision between conservative, thrombolytic or more advanced treatments such as thrombectomy. The modulations of potential molecular targets participating in the process seem to be promising in animal models, but human trials are lacking the breakthrough success so far, both in extending the time frame of the thrombolysis and in replacing the recombinant tissue plasminogen activator (rtPA) as thrombolytic agent.So far, the careful preselection of patients eligible for thrombolytic therapy is the best way to prevent hemorrhagic transformation. The intensive research in the field revealing small but important molecular details are continuously contributing to the better understanding of hemorrhagic transformation with the intention of finding new agents that co-administrated to the rtPA or completely replacing that could decrease the risk of secondary bleeding.The aim of this review is to give comprehensive insight into the process of hemorrhagic transformation of ischemic stroke, starting with basic overview of the penumbra concept and the collateral supply followed by discussion of the recanalisation-reperfusion-hemorrhagic transformation process after vessel occlusion also highlighting the importance of timing and ratio of recanalisation spontaneously and in case of thrombolytic agent administration. We overview the risk factors of hemorrhagic transformation, which may be helpful to physicians to identify high risk patients before rtPA administration. The last part of the work is dealing with future therapeutic possibilities based on the so far revealed molecular mechanisms of hemorrhagic transformation. With the aim to assess the rate and influencing factors on the recanalisation and reperfusion rate 381 patients with large-vessel occlusion was investigated. The patient group involved ones treated with rtPA or treated conservatively. Partial or complete recanalisation was achieved in 121 out of 210 (58%) patients after intravenous rtPA administration. The recanalisation success was more likely if the patient had atrial fibrillation [4] -maybe because cardioembolic clots consists more fibrin and are more likely to reopen by plasmin proteolysis than thrombosis of an atherosclerotic plaq...

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“…38 The use of edaravone in acute stroke was approved in Japan in 2001, and it has been associated with lower serum levels of MMP-9 when it is given within 12 to 36 hours of stroke onset. 39 In combination with rtPA, 1 study reported a lower incidence of brain edema and white matter tissue injury in edaravone-treated patients. 40 Additional studies are required to verify whether edaravone improves the benefits of rtPA, but an ongoing Phase IIa clinical trial of this agent has specifically excluded these patients.…”

Section: Edaravone and Thrombolysis In Combinationmentioning

confidence: 99%

Translational Stroke Research of the Combination of Thrombolysis and Antioxidant Therapy

Amaro

2011

Stroke

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Abstract-Stroke is an enormous public health problem with an imperative need for more effective therapy. Recombinant tissue plasminogen activator is the only licensed drug for acute stroke, but its efficacy may be limited by the toxicity of the compound and by reperfusion injury. The coadministration of neuroprotective drugs could augment the value of thrombolytic therapy, but the evidence in support of this approach is scarce. The use of the free radical trapping NXY-059, either with or without recombinant tissue plasminogen activator, was not successful in Phase III studies. However, these results could reflect its weak antioxidant capacity, poor blood-brain barrier penetration, and lack of synergism with recombinant tissue plasminogen activator as well as the overly broad treatment window used in the reported trials. This article contends that further translational research should explore newer antioxidant drugs in combination with thrombolytic agents, but only if the combination yields additive or synergistic effects in preclinical thromboembolic models or in biomarker-assisted Phase II studies. Edaravone and novel nitrones endowed with a better pharmacokinetic profile or multitarget and thrombolytic activity are discussed as well as the latest research data on uric acid, a strong endogenous antioxidant in blood that is early consumed after acute stroke. The coadministration of uric acid and recombinant tissue plasminogen activator has shown to provide synergistic neuroprotection in experimental thromboembolic models and to lessen several biomarkers of oxidative stress in patients with acute stroke. The clinical efficacy of uric acid is currently under investigation in a Phase III trial that follows current recommendations of also evaluating surrogate biomarkers of treatment effects. (Stroke. 2011;42:1495-1499.)

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Effects of Edaravone, a Free Radical Scavenger, on Serum Levels of Inflammatory Biomarkers in Acute Brain Infarction

Cited by 31 publications

References 35 publications

Intramyocardial haemorrhage after acute myocardial infarction

Intramyocardial haemorrhage after acute myocardial infarction

Hemorrhagic transformation of ischemic stroke

Translational Stroke Research of the Combination of Thrombolysis and Antioxidant Therapy

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