Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/jcbfm.2010.149

Type

Journal article

Journal

J Cereb Blood Flow Metab

Publication Date

11/2010

Volume

30

Pages

1804 - 1816

Keywords

Animals, Arginine, Brain, Brain Ischemia, Cerebrovascular Circulation, Drug Interactions, Drug Stability, Fibrinolytic Agents, Humans, Isoenzymes, Neurotoxicity Syndromes, Neurotoxins, Nitric Oxide, Nitric Oxide Synthase, Receptors, LDL, Receptors, N-Methyl-D-Aspartate, Recombinant Proteins, Severity of Illness Index, Tissue Plasminogen Activator