Intravenous Thrombolytics for Ischemic Stroke

“…The intravenous thrombolytics (IVT) : The IVT treatment paradigm was originally developed to treat coronary thrombolysis but was found to be effective in treating stroke patients. The efficiency of thrombolytic drugs depends on factors including the age of the clot, the specificity of the thrombolytic agent for fibrin and the presence and half-life of neutralizing antibodies [ 123 ]. The drugs used in IVT treatment aim to promote fibrinolysin formation, which catalyzes the dissolution of the clot blocking the cerebral vessel.…”

Section: Prevention and Treatment Strategies For Strokementioning

confidence: 99%

Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives

Kuriakose

Xiao

2020

IJMS

700

388

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Stroke is the second leading cause of death and a major contributor to disability worldwide. The prevalence of stroke is highest in developing countries, with ischemic stroke being the most common type. Considerable progress has been made in our understanding of the pathophysiology of stroke and the underlying mechanisms leading to ischemic insult. Stroke therapy primarily focuses on restoring blood flow to the brain and treating stroke-induced neurological damage. Lack of success in recent clinical trials has led to significant refinement of animal models, focus-driven study design and use of new technologies in stroke research. Simultaneously, despite progress in stroke management, post-stroke care exerts a substantial impact on families, the healthcare system and the economy. Improvements in pre-clinical and clinical care are likely to underpin successful stroke treatment, recovery, rehabilitation and prevention. In this review, we focus on the pathophysiology of stroke, major advances in the identification of therapeutic targets and recent trends in stroke research.

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“…Ischemic and hemorrhagic stroke remain leading causes of death and disability worldwide (Sahni and Weinberger, 2007;Barreto, 2011). Current treatment strategies are primarily focused on the control of bleeding (Sahni and Weinberger, 2007), restoration of blood flow by thrombolytic therapies (Barreto, 2011), or lowering of intracranial pressure (Sahni and Weinberger, 2007) but are limited in success as they are aimed at the acute phase of brain damage and neglect that a significant amount of neuronal tissue damage develops progressively in the penumbra after the initial insult.…”

Section: Introductionmentioning

confidence: 99%

“…Current treatment strategies are primarily focused on the control of bleeding (Sahni and Weinberger, 2007), restoration of blood flow by thrombolytic therapies (Barreto, 2011), or lowering of intracranial pressure (Sahni and Weinberger, 2007) but are limited in success as they are aimed at the acute phase of brain damage and neglect that a significant amount of neuronal tissue damage develops progressively in the penumbra after the initial insult. Crucial molecular changes in penumbral tissue potentiate secondary brain injury, especially when ATP supply is insufficient to maintain ion homeostasis (White et al, 2000;Stankowski and Gupta, 2011).…”

Section: Introductionmentioning

confidence: 99%

Carbimazole Is an Inhibitor of Protein Synthesis and Protects from Neuronal Hypoxic Damage In Vitro

Lehane

Guelzow

Zenker

et al. 2013

J Pharmacol Exp Ther

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Oxygen deprivation during ischemic or hemorrhagic stroke results in ATP depletion, loss of ion homeostasis, membrane depolarization, and excitotoxicity. Pharmacologic restoration of cellular energy supply may offer a promising concept to reduce hypoxic cell injury. In this study, we investigated whether carbimazole, a thionamide used to treat hyperthyroidism, reduces neuronal cell damage in oxygen-deprived human SK-N-SH cells or primary cortical neurons. Our results revealed that carbimazole induces an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) that was associated with a marked inhibition of global protein synthesis. Translational inhibition resulted in significant bioenergetic savings, preserving intracellular ATP content in oxygen-deprived neuronal cells and diminishing hypoxic cellular damage. Phosphorylation of eEF2 was mediated by AMP-activated protein kinase and eEF2 kinase. Carbimazole also induced a moderate calcium influx and a transient cAMP increase. To test whether translational inhibition generally diminishes hypoxic cell damage when ATP availability is limiting, the translational repressors cycloheximide and anisomycin were used. Cycloheximide and anisomycin also preserved ATP content in hypoxic SK-N-SH cells and significantly reduced hypoxic neuronal cell damage. Taken together, these data support a causal relation between the pharmacologic inhibition of global protein synthesis and efficient protection of neurons from ischemic damage by preservation of high-energy metabolites in oxygen-deprived cells. Furthermore, our results indicate that carbimazole or other translational inhibitors may be interesting candidates for the development of new organprotective compounds. Their chemical structure may be used for computer-assisted drug design or screening of compounds to find new agents with the potential to diminish neuronal damage under ATP-limited conditions.

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Intravenous Thrombolytics for Ischemic Stroke

Abstract: For many decades, intravenous

Cited by 51 publications

References 73 publications

Outcomes of endovascular thrombectomy with and without bridging thrombolysis for acute large vessel occlusion ischaemic stroke

Outcomes of endovascular thrombectomy with and without bridging thrombolysis for acute large vessel occlusion ischaemic stroke

Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives

Carbimazole Is an Inhibitor of Protein Synthesis and Protects from Neuronal Hypoxic Damage In Vitro

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