Stroke biomarkers: can they help us to guide stroke thrombolysis?

The use of blood biomarkers is getting increasingly popular in the field of cerebrovascular diseases, since biomarkers might aid physicians in several steps of stroke evaluation. We will discuss whether stroke diagnosis might be possible using some specific brain biomarkers and if this approach will permit rapid referral of stroke patients to hospitals with acute treatments such as tissue plasminogen activator (t-PA) available. Although thrombolytic therapy in acute stroke is effective since it accelerates clot lyses and earlier restoration of blood flow, up to 40-50% of treated patients do not recanalize or do it too late, and between 6 and 15% suffer hemorrhagic transformations with high death rates. In the context of the neurovascular unit, t-PA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema and hemorrhage. In humans, biomarkers such as matrix metalloproteinase-9 (MMP-9) or fibronectin, which might be used to select patients at higher risk of hemorrhagic transformation, and high plasminogen activator inhibitor-1 (PAI-1) interfering with tPA-induced recanalization, thus predicting clot-lyses resistance and poor outcome, have been recently identified. Moreover, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth in spite of thrombolytic therapy suggesting its ultra-early role in brain injury. Other biomarkers such as C-reactive protein may accurately predict stroke mortality following reperfusion therapies. Finally, we will also show that genetic background of stroke patients may condition plasma levels of some of these biomarkers and influence therapeutic response in t-PA-treated patients.