For how long is brain tissue salvageable? Thrombolysis-based evidence.

Area of Science:

• Neurology
• Cardiovascular Medicine
• Pharmacology

Background:

• Recombinant tissue plasminogen activator (t-PA) is approved for acute ischemic stroke treatment within 3 hours.
• European trials (ECASS I, II) did not show t-PA efficacy when initiated up to 6 hours.
• Prourokinase (PROACT I) showed insufficient data, leading to the larger PROACT II trial.

Purpose of the Study:

• To evaluate the efficacy of thrombolytic therapy for acute ischemic stroke.
• To determine the optimal time window for initiating thrombolytic treatment.
• To assess the potential for salvageable brain tissue in acute stroke patients.

Main Methods:

• Analysis of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA trial.
• Review of European Cooperative Acute Stroke Study (ECASS) I and II trials.
• Meta-analysis of thrombolytic trials, including t-PA and prourokinase (PROACT II).

Main Results:

• A meta-analysis suggests thrombolysis is effective up to 6 hours after stroke onset.
• Salvageable brain tissue may remain for at least 8 hours post-symptom onset.
• The PROACT II trial demonstrated significant outcome improvement with prourokinase initiated within 6 hours.

Conclusions:

• Thrombolytic therapy, including t-PA and prourokinase, can be effective for acute ischemic stroke.
• The therapeutic window for stroke treatment may extend to 8 hours.
• Neuroprotectant therapy during this extended window warrants further investigation.