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The Neurovascular Research Laboratory from the Stroke Unit at the Vall d’Hebron Hospital, is one of the leading stroke translational research groups in Europe. In the ESN project, this group will work on adjunct therapies for thrombolysis.Our team is attending a large number of stroke patients (around 1600 per year) and the Stroke Unit that more patients has treated with t-PA in Spain. Most of those t-PA treated patients receive a multiparametric Magnetic Resonance Imaging and a continuous Transcranial-Doppler monitoring. We therefore are able to monitor brain tissue at risk and the exact moment of the brain artery reopening. This “human stroke model”, combined with the measurement of plasmatic biomarkers, permitted the Neurovascular Research Laboratory to identify relevant components of the cerebral ischemic cascade. We described for the first time in human stroke the involvement of MMP-9, MMP-13, TAFI and other related molecules. We have also identified several biomarkers that might be useful to predict thrombolysis safety and efficacy if measured before that treatment was initiated, such as MMP-9 for the dramatic hemorrhagic transformations that occurs in around 6-10% of t-PA treated patients or PAI-1 and TAFI for the lack of recanalization of the occluded brain artery.
We have recently extended biomarkers detection from ELISA techniques to other more sophisticated methods such as zymography detection of MMPs in the brain microdialysate (brain extracellular fluidsof several stroke areas i.e. infarct core and penumbra) in cases of malignant Middle Cerebral Artery infarction. Moreover we have also standardised Proteome arrays (multiplex microplate-based assays) using chemiluminiscent substrates (SearchLight system). Our work with human brain samples obtained from stroke necropsic studies combined with the use of the very new technology available at our lab (Laser Capture Microdissection) opens the possibility of microdissecting the Neurovascular Unit after stroke and identifying new powerful biomarkers in those tissues. Confirmatory studies may be conducted in well designed animal models since we are using rodent models resembling human stroke (permanent MCAO and embolic model).
The group has also identified the use of statins in the acute phase of ischemic stroke or the enhancement of t-PA induced-clot lyses by the use of continuous Doppler monitoring, as therapeutic advantages.
Project Staff
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