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Phosphodiesterase 5 inhibition as a therapeutic target for ischemic stroke: A systematic review of preclinical studies

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  1. Cyclic nucleotide phosphodiesterases (PDEs) and endothelial function in ischaemic stroke. A review

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  2. A switch-variant model integrates the functions of an autoimmune variant of the phosphatase PTPN22

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  4. Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction

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  5. Proteome-wide mapping of the Drosophila acetylome demonstrates a high degree of conservation of lysine acetylation

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  1. A Qualitative Inquiry Into Patient Reported Factors That Influence Time From Stroke Symptom Onset to Hospitalization

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  2. Time trends in incidence, comorbidity, and mortality of ischemic stroke in Denmark, 1996-2016

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  3. Atypisk aura forårsaget af blodprop hos en 42-årig mand med migræne med aura.

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  4. How to identify fatigue in stroke patients: an investigation of the post-stroke fatigue case definition validity

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Phosphodiesterase 5 inhibitors (PDE5i), such as sildenafil (Viagra®) are widely used for erectile dysfunction and pulmonary hypertension. Preclinical studies suggest that PDE5i may improve functional outcome following ischemic stroke. In this systematic review we aimed to evaluate the effects of selective PDE5i in animal models of brain ischaemia. A systematic search in Medline, Embase, and The Cochrane Library was performed including studies in English assessing the effects of selective PDE5i. 32 publications were included describing outcome in 3646 animals. Neuroprotective effects of PDE5i were dependent on the NO-cGMP-PKG-pathway. These included reduced neuronal apoptosis (n=3 studies), oxidative stress (n=5), and neuroinflammation (n=2). PDE5i increased angiogenesis and elevated regional cerebral blood flow in the ischemic penumbra, and improved functional recovery. Some studies found that PDE5i treatment reduced lesion volume (n=9), others found no effect (n=9). Treatment was effective when administered within 24h post-ischemia, though treatment delayed to seven days improved outcome in one study. This review demonstrates both neuroprotective and neurorestorative effects of PDE5i in animal models of stroke, though the specific underlying signaling pathways relating to PDE5 inhibition and cGMP may remain serendipitous in some studies. There is currently limited evidence on the effects of selective PDE5i in human stroke patients, hence translation of preclinical results into clinical trials may be warranted.

Original languageEnglish
JournalCellular Signalling
Volume38
Pages (from-to)39-48
Number of pages10
ISSN0898-6568
DOIs
Publication statusPublished - Oct 2017

    Research areas

  • Animals, Apoptosis/drug effects, Brain Ischemia/drug therapy, Cerebrovascular Circulation/drug effects, Disease Models, Animal, Female, Humans, Inflammation/pathology, Male, Memory/drug effects, Models, Biological, Molecular Targeted Therapy, Neovascularization, Physiologic/drug effects, Neurogenesis/drug effects, Neuroprotection/drug effects, Oxidative Stress/drug effects, Phosphodiesterase 5 Inhibitors/pharmacology, Stroke/drug therapy, Synapses/drug effects, Treatment Outcome

ID: 54645612