Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke

Kadir, Rais Reskiawan A.; Bayraktutan, Ulvi

Abstract

Stroke continues to be one of the leading causes of mortality and morbidity worldwide. Restoration of cerebral blood flow by recombinant plasminogen activator (rtPA) with or without mechanical thrombectomy is considered the most effective therapy for rescuing brain tissue from ischaemic damage, but this requires advanced facilities and highly skilled professionals, entailing high costs, thus in resource-limited contexts urokinase plasminogen activator (uPA) is commonly used as an alternative. This literature review summarises the existing studies relating to the potential clinical application of uPA in ischaemic stroke patients. In translational studies of ischaemic stroke, uPA has been shown to promote nerve regeneration and reduce infarct volume and neurological deficits. Clinical trials employing uPA as a thrombolytic agent have replicated these favourable outcomes and reported consistent increases in recanalisation, functional improvement and cerebral haemorrhage rates, similar to those observed with rtPA. Single-chain zymogen pro-urokinase (pro-uPA) and rtPA appear to be complementary and synergistic in their action, suggesting that their co-administration may improve the efficacy of thrombolysis without affecting the overall risk of haemorrhage. Large clinical trials examining the efficacy of uPA or the combination of pro-uPA and rtPA are desperately required to unravel whether either therapeutic approach may be a safe first-line treatment option for patients with ischaemic stroke. In light of the existing limited data, thrombolysis with uPA appears to be a potential alternative to rtPA-mediated reperfusive treatment due to its beneficial effects on the promotion of revascularisation and nerve regeneration.

Citation

Kadir, R. R. A., & Bayraktutan, U. (2019). Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke. Cellular and Molecular Neurobiology, 40, 347-355. https://doi.org/10.1007/s10571-019-00737-w

• Journal Article Type: Article
• Acceptance Date: Sep 12, 2019
• Online Publication Date: Sep 24, 2019
• Publication Date: Sep 24, 2019
• Deposit Date: Nov 6, 2019
• Publicly Available Date: Sep 25, 2020
• Journal: Cellular and Molecular Neurobiology
• Print ISSN: 0272-4340
• Electronic ISSN: 1573-6830
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 40
• Pages: 347-355
• DOI: https://doi.org/10.1007/s10571-019-00737-w
• Keywords: Cell Biology; Cellular and Molecular Neuroscience; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/3070361
• Publisher URL: https://link.springer.com/article/10.1007%2Fs10571-019-00737-w
• Additional Information: This is a post-peer-review, pre-copyedit version of an article published in Cellular and Molecular Neurobiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10571-019-00737-w