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Updated: Aug 7, 2026

A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
Magnesium sulfate neither potentiates nor inhibits tissue plasminogen activator-induced thrombolysis
D Stewart1, V J Marder, S Starkman
1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Background:
Increasing circulating magnesium concentrations to 2-fold over normal baseline may afford a neuroprotective effect in patients with acute cerebral ischemia.
Objectives:
As patients receiving magnesium sulfate (MgSO(4)) in human clinical trials may also be candidates for subsequent thrombolytic therapy with tissue plasminogen activator (t-PA), preclinical assessment of possible inhibition or potentiation of fibrinolytic activity by MgSO(4) has important clinical relevance.
Methods:
We utilized an in vitro system, in which D-dimer release served as a reflection of t-PA-induced clot lysis, to measure the effect of magnesium at the target concentration being tested in human stroke clinical trials, and at 2- and 3-fold higher levels. Clots from normal volunteers were exposed to t-PA at concentrations that correspond to therapeutic or endogenous plasma t-PA levels.
Results:
MgSO(4) had no effect on t-PA-induced clot lysis at up to 3-fold target magnesium concentration (6x normal serum concentration).
Conclusions:
MgSO(4) concentrations well above the targeted level in therapeutic stroke trials does not affect t-PA-induced fibrinolytic activity, and therefore is a suitable agent for trials of combined neuroprotective and thrombolytic therapy in patients with acute ischemic stroke.
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