Early Ischemic Blood Brain Barrier Damage: A Potential Indicator for Hemorrhagic Transformation FollowingTissue Plasminogen Activator (tPA) Thrombolysis?
Xinchun Jin, Jie Liu and Wenlan LiuAffiliation:
The Central Laboratory of Shenzhen Second People's Hospital Shenzhen University First Affiliated Hospital Shenzhen, China, 518035
AbstractTissue plasminogen activator (tPA) thrombolysis, remains the only United States Food and Drug Administration(FDA) approvedtreatmentfor acute ischemia stroke. However, the use of tPA has been profoundly constraineddue to its narrow therapeutic time window and the increased risk of potentially deadly hemorrhagic complications. TPA-associated hemorrhagic transformation (HT) often occurs as a result of catastrophic failure of theblood brain barrier (BBB), wherein the affected cerebral capillaries can no longer hold blood constituents.Due to its direct contribution to edema and HT, reperfusion-associated BBB damage has been extensively studied, whileBBB damage that occurs within the thrombolytic time window is largely neglected. Of note, ischemia-induced BBB damage in the early stroke stages isincreasingly appreciated to negatively impact the safety and efficacy profiles of thrombolytic therapy for ischemic stroke. In this review, we discussed therecent findings of spatio-temporal evolution of BBB injury in the early stages of cerebral ischemia and its association with intracerebral hemorrhage following tPA thrombolysis. The increased understanding of early ischemic BBB damage and its close link to tPA-associated HT is of particular importance for developing new preventive and therapeutic strategies to reduce the hemorrhagic complications in stroke thrombolysis
Blood brain barrier, hemorrhage transformation, ischemia stroke, matrix metalloproteinase, thrombolysis, tight junction proteins, tissue plasminogen activator
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