Abstract

Thrombolytic therapy with tissue plasminogen activator (tPA) remains the most effective treatment for acute ischemic stroke, but can cause vascular damage leading to edema formation and hemorrhagic transformation (HT). In this review, we discuss how tPA contributes to the pathogenesis of vascular damage and highlight evidence to support combination therapy of tPA with pharmacological agents that are vascular protective. There is an unmet need to develop therapeutic interventions which target the underlying mechanisms of vascular damage after acute ischemic stroke in order to prevent HT and improve the safety and impact of tPA.

Keywords: Ischemic stroke, vascular protection, tissue plasminogen activator (tPA), matrix metalloproteinases (MMPs), hemorrhagic transformation (HT), thrombolysis, blood–brain barrier, edema formation, vascular damage, clinical trials.