Reperfusion Injury After Stroke Study

Background: stroke is a major cause of death and disability. Intravenous thrombolysis and mechanical thrombectomy are able to re-open occluded vessels and save the ischemic tissue from death. However, recanalization of the occluded vessel may trigger activation of detrimental molecular pathways and exacerbate blood brain barrier (BBB) disruption, eventually determining hemorrhagic transformation (HT) or cerebral edema (CE), causing the so-called "reperfusion injury". There is increasing evidence that a number of factors measurable as circulating biomarkers, particularly metalloproteinases (MMP), contribute to reperfusion brain injury. Preliminary data show that BBB disruption can be traced in vivo by Computed Tomography Perfusion (CTP) imaging. The aim of this study is to evaluate the effects of circulating and imaging biomarkers in relation to reperfusion injury. Methods: consecutive patients presenting with acute ischemic stroke in the anterior circulation territory, scoring≥7 on NIHSS, candidates to intravenous thrombolysis or to endovascular treatment, will be enrolled in one hospital centre. Circulating levels of pro-, anti-inflammatory, immunomodulatory factors, metalloproteinases and their inductors/inhibitors, factors of endothelial dysfunction and fibrin resistance to lysis will be measured in blood samples taken from each patients pre-thrombolysis and 24 hours after thrombolysis. Biomarker levels will be studied in relation to CTP measures of BBB permeability and in relation to imaging signs of reperfusion injury after acute interventions, such as hemorrhagic transformation and cerebral edema. Results: enrollment started on October 2015. As of January 2017, 70 patients have been included. Results are expected by the end of 2018 with an estimated sample size of 140 patients. Using a definite protocol, a prospective collection of data, and an adequate number of patients assuring statistically powered data, this study will integrate clinical information wit