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The contribution of L-arginine to the neurotoxicity of recombinant tissue plasminogen activator following cerebral ischemia: a review of rtPA neurotoxicity

Citation

Harston, GWJ and Sutherland, BA and Kennedy, J and Buchan, AM, The contribution of L-arginine to the neurotoxicity of recombinant tissue plasminogen activator following cerebral ischemia: a review of rtPA neurotoxicity, Journal of Cerebral Blood Flow and Metabolism, 30, (11) pp. 1804-1816. ISSN 0271-678X (2010) [Refereed Article]


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DOI: doi:10.1038/jcbfm.2010.149

Abstract

Alteplase is the only drug licensed for acute ischemic stroke, and in this formulation, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) is stabilized in a solution of L-arginine. Improved functional outcomes after alteplase administration have been shown in clinical trials, along with improved histological and behavioral measures in experimental models of embolic stroke. However, in animal models of mechanically induced ischemia, alteplase can exacerbate ischemic damage. We have systematically reviewed the literature of both rtPA and L-arginine administration in mechanical focal ischemia. The rtPA worsens ischemic damage under certain conditions, whereas L-arginine can have both beneficial and deleterious effects dependent on the time of administration. The interaction between rtPA and L-arginine may be leading to the production of nitric oxide, which can cause direct neurotoxicity, altered cerebral blood flow, and disruption of the neurovascular unit. We suggest that alternative formulations of rtPA, in the absence of L-arginine, would provide new insight into rtPA neurotoxicity, and have the potential to offer more efficacious thrombolytic therapy for ischemic stroke patients.

Item Details

Item Type:Refereed Article
Keywords:cerebral ischemia, L-arginine, neurotoxicity, stroke, tissue plasminogen activator
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
Author:Sutherland, BA (Dr Brad Sutherland)
ID Code:115307
Year Published:2010
Web of Science® Times Cited:27
Deposited By:Office of the School of Medicine
Deposited On:2017-03-15
Last Modified:2017-03-15
Downloads:0

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