Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation

Chamorro, Ángel; Dirnagl, Ulrich; Urra, Xabier; Planas, Anna M.

doi:10.1016/s1474-4422(16)00114-9

Cited by 864 publications

(663 citation statements)

References 109 publications

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“…28 Multiple pathological processes that take place in ischemia are an overproduction of oxidants, inactivation of detoxification systems, excitotoxicity, inflammation and disruption of membranes. 29 The imbalance between the production of free radicals and body's counter mechanisms to eliminate those results in oxidative stress. 30 Various experimental studies strongly support the association between oxidative stress and ischemic damage.…”

Section: Discussionmentioning

confidence: 99%

Effect of Dalechampia indica Wight Extract Fractions on Behavioral and Biochemical Abnormalities following Ischemia-Reperfusion Insult in Rats

Srinivasula¹,

Maram²

2017

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Objective: To evaluate the cerebro protective effect of Dalechampia indica (DI) ethanolic (EDI) and chloroform (CDI) extract fractions against cerebral ischemia-reperfusion insult in rats. Method: The rats were treated with different doses (200 and 400 mg/kg) of EDI and CDI orally once daily for 30 days. After completion of pre-treatment, ischemia was induced by blocking bilateral common carotid arteries (BCCAO) for 30 mins followed by reperfusion and ferric chloride induced thrombosis. The post treatment was continued for another week after surgery. The behavioral parameters were assessed and finally, rats were sacrificed to isolate the brains to estimate biochemical parameters. Results: Combination of global (BCCAO) and focal (Thrombosis) ischemic model along with reperfusion has induced prominent ischemic insult indicated by antioxidant enzymes depletion and elevation of lipid peroxidation. Pre-treatment with different doses of EDI and CDI significantly improved the levels of superoxide dismutase (SOD), glutathione enzymes (GPx, GSH, GST, GR), catalase (CAT) and decreased the lipid peroxidation. Conclusion: Results established Cerebro protective role of Ethanolic extract fraction of DI in cerebrovascular insufficiency states and cerebral ischemic-reperfusion injury produced by bilateral common carotid artery ligation along with reperfusion and thrombosis which may attribute to presence of alkaloids,flavonoids, and phenolic compounds.

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Section: Discussionmentioning

confidence: 99%

Effect of Dalechampia indica Wight Extract Fractions on Behavioral and Biochemical Abnormalities following Ischemia-Reperfusion Insult in Rats

Srinivasula¹,

Maram²

2017

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“…Recently, randomized trials for acute stroke and neuroprotection have included growth factors, hypothermia, minocycline, natalizumab, fingolimod, and uric acid. 11 Common pathways targeted for neuroprotection include free radical scavengers, excitotoxicity, immune modulation, and more.…”

Section: Clinically Assessed Neuroprotective Therapiesmentioning

confidence: 99%

Experimental neuroprotection in ischemic stroke: a concise review

Rajah

Ding

2017

FOC

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Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. To date, intravenous tissue plasminogen activator and mechanical thrombectomy have been standards of care for AIS. There have been many advances in diagnostic imaging and endovascular devices for AIS; however, most neuroprotective therapies seem to remain largely in the preclinical phase. While many neuroprotective therapies have been identified in experimental models, none are currently used routinely to treat stroke patients. This review seeks to summarize clinical studies pertaining to neuroprotection, as well as the different preclinical neuroprotective therapies, their presumed mechanisms of action, and their future applications in stroke patients.

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“…[27][28][29] Counterintuitively, in view of the lack of efficacy of the same drugs in clinical trials, this may serve as a further indicator for the good prediction of rodent models of stroke! 30 we looked at the time window of major recent neuroprotection trials and found a median targeted inclusion time window of 16 hours. In animal models of stroke robust protection is usually observed only with the first 1 to 2 hours after occlusion of the artery.…”

Section: August 2016mentioning

confidence: 99%

Thomas Willis Lecture

Dirnagl

2016

Stroke

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Abstract-Based on research, mainly in rodents, tremendous progress has been made in our basic understanding of the pathophysiology of stroke. After many failures, however, few scientists today deny that bench-to-bedside translation in stroke has a disappointing track record. I here summarize many measures to improve the predictiveness of preclinical stroke research, some of which are currently in various stages of implementation: We must reduce preventable (detrimental) attrition. Key measures for this revolve around improving preclinical study design. Internal validity must be improved by reducing bias; external validity will improve by including aged, comorbid rodents of both sexes in our modeling. False-positives and inflated effect sizes can be reduced by increasing statistical power, which necessitates increasing group sizes. Compliance to reporting guidelines and checklists needs to be enforced by journals and funders. Customizing study designs to exploratory and confirmatory studies will leverage the complementary strengths of both modes of investigation. All studies should publish their full data sets. On the other hand, we should embrace inevitable NULL results. This entails planning experiments in such a way that they produce high-quality evidence when NULL results are obtained and making these available to the community. A collaborative effort is needed to implement some of these recommendations. Just as in clinical medicine, multicenter approaches help to obtain sufficient group sizes and robust results. Translational stroke research is not broken, but its engine needs an overhauling to render more predictive results.

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Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation

Cited by 864 publications

References 109 publications

Effect of Dalechampia indica Wight Extract Fractions on Behavioral and Biochemical Abnormalities following Ischemia-Reperfusion Insult in Rats

Effect of Dalechampia indica Wight Extract Fractions on Behavioral and Biochemical Abnormalities following Ischemia-Reperfusion Insult in Rats

Experimental neuroprotection in ischemic stroke: a concise review

Thomas Willis Lecture

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