Introduction
Use of biomarkers in clinical practice is getting popular among physicians to aid making diagnostic and prognostic decisions. Recently there has been a great interest for their use in neurovascular diseases to help physicians in various stages of the evaluation of stroke, from predicting the risk of suffering a stroke among healthy individuals to getting the biochemical diagnosis of stroke or using biomarkers as tools for outcome prediction.
We are conducting this research in large cohorts of well phenotyped stroke patients at the Stroke Unit of Valld’Hebron Hospital and also using experimental models that offer a great opportunity to study these biomarkers potential as therapeutic targets. The Neurovascular Research Laboratory has large experience on stroke biomarkerstranslational research and we have recently participated in the description of the proteomes of brain tissue and microdialysates after human ischemic stroke and of the transcriptome of human intracranial hemorrhage, which has allowed the identification of new promising candidate biomarkers and in neuroprotection.
1 .- To establish the systematic study of universal knowledge of “Biomarkers & stroke” through http://stroke-biomarkers.com website that attempts to provide a data compilation of published candidate biomarkers in the context of stroke (risk, diagnosis, subtype, etiology and prognosis), to offer updated protocols and to connect research groups with interest in the field.
2 .- “Stroke biomarker discovery” through the use of new experimental approaches in cerebral ischemia
- To describe the pattern of protein release by human brain endothelial cells subjected to hypoxia by means of SILAC (stable isotope labeling by amino acids in cell culture).
- Mapping the proteins of the core and peri-infarct rat brain subjected to cerebral ischemia by MALDI imaging mass spectrometry.
- To define the “integroma” for the first time in the area of brain ischemia in different animal models of stroke, by combining expression arrays and proteomic techniques.
- To study the differential gene expression and protein components of the neurovascular unit (neurons, astrocytes and endothelium), microdissected from ischemic brain parenchyma.
3 .- To replicate and validate candidate biomarkers in large populations and multinational multicenter stroke trials.
4 .- To implement technological improvements to evaluate candidate biomarkers in the laboratory with robotics and multiplexing and outside the lab, through point-of-care biosensors.
5 .- To transfer to hospitals and healthcare professionals the results of the above objectives as a final step of the process.
6.-“BiotargetS”. Is a project to evaluate the therapeutic value of some of the biomarkers identified by our lab so far using experimental models of stroke and to use some of those biomarkers in the monitoring of neuroprotection therapies (such as the acute use of statins following stroke).
- Joan Montaner Villalonga; MD, PhD.
- Teresa García Berrocoso; PhD.
- Alejandro Bustamante Rangel; Neurologist, PhD student.
- Victor Llombart Sebastià; PhD student.
- Alba Simats Oriol; PhD student.
- Anna Penalba Morenilla; Technician.
- Cristina Boada Llamas; Technician.
- Geneva, Jean-Charles Sanchez
- Berlin, Andreas Meissel
- Caen, Denis Vivien
- Boston, Xiaoing Wang, Klaus van Leyen, MM Ning
Lemarchant S, Dunghana H, Pomeshchik Y, Leinonen H, Kolosowska N, Korhonen P,
Kanninen KM, García-Berrocoso T, Montaner J, Malm T, Koistinaho J.
Anti-inflammatory effects of ADAMTS-4 in a mouse model of ischemic stroke. Glia.
2016 Jun 15. doi: 10.1002/glia.23017. [Epub ahead of print] PubMed PMID:
27301579.
Bustamante A, Díaz-Fernández B, Giralt D, Boned S, Pagola J, Molina CA,
García-Berrocoso T, Kanse SM, Montaner J. Factor seven activating protease (FSAP)
predicts response to intravenous thrombolysis in acute ischemic stroke. Int J
Stroke. 2016 Apr 12. pii: 1747493016641949. [Epub ahead of print] PubMed PMID:
27073188.
Gallego-Fabrega C, Carrera C, Reny JL, Fontana P, Slowik A, Pera J, Pezzini A,
Serrano-Heras G, Segura T, Martí-Fàbregas J, Muiño E, Cullell N, Montaner J,
Krupinski J, Fernandez-Cadenas I. TRAF3 Epigenetic Regulation Is Associated With
Vascular Recurrence in Patients With Ischemic Stroke. Stroke. 2016
May;47(5):1180-6. doi: 10.1161/STROKEAHA.115.012237. Epub 2016 Mar 29. PubMed
PMID: 27026631.
Briens A, Gauberti M, Parcq J, Montaner J, Vivien D, Martinez de Lizarrondo S.
Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic
Activity of Cell-Derived Microparticles. Theranostics. 2016 Mar 2;6(5):610-26.
doi: 10.7150/thno.13757. eCollection 2016. PubMed PMID: 27022410; PubMed Central
PMCID: PMC4805657.
Ma F, Martínez-San Segundo P, Barceló V, Morancho A, Gabriel-Salazar M, Giralt
D, Montaner J, Rosell A. Matrix metalloproteinase-13 participates in
neuroprotection and neurorepair after cerebral ischemia in mice. Neurobiol Dis.
2016 Jul;91:236-46. doi: 10.1016/j.nbd.2016.03.016. Epub 2016 Mar 19. PubMed
PMID: 27001146.
Sambola A, García Del Blanco B, Ruiz-Meana M, Francisco J, Barrabés JA,
Figueras J, Bañeras J, Otaegui I, Rojas A, Vilardosa Ú, Montaner J, García-Dorado
D. Increased von Willebrand factor, P-selectin and fibrin content in occlusive
thrombus resistant to lytic therapy. Thromb Haemost. 2016 Jun 2;115(6):1129-37.
doi: 10.1160/TH15-12-0985. Epub 2016 Mar 10. PubMed PMID: 26962963.
Merino-Zamorano C, Delgado P, Fernández de Retana S, Fernández-Cadenas I,
Rodríguez-Luna D, Montaner J, Hernández-Guillamon M. Identification of Plasma
Biomarkers of Human Intracerebral Hemorrhage Subtypes through Microarray
Technology. J Stroke Cerebrovasc Dis. 2016 Mar;25(3):665-71. doi:
10.1016/j.jstrokecerebrovasdis.2015.11.032. Epub 2015 Dec 29. PubMed PMID:
26738811.
Bustamante A, García-Berrocoso T, Rodriguez N, Llombart V, Ribó M, Molina C,
Montaner J. Ischemic stroke outcome: A review of the influence of post-stroke
complications within the different scenarios of stroke care. Eur J Intern Med.
2016 Apr;29:9-21. doi: 10.1016/j.ejim.2015.11.030. Epub 2015 Dec 23. Review.
PubMed PMID: 26723523.
Llombart V, García-Berrocoso T, Bech-Serra JJ, Simats A, Bustamante A, Giralt
D, Reverter-Branchat G, Canals F, Hernández-Guillamon M, Montaner J.
Characterization of secretomes from a human blood brain barrier endothelial cells
in-vitro model after ischemia by stable isotope labeling with aminoacids in cell
culture (SILAC). J Proteomics. 2016 Feb 5;133:100-12. doi:
10.1016/j.jprot.2015.12.011. Epub 2015 Dec 21. PubMed PMID: 26718731.
Llombart V, García-Berrocoso T, Bustamante A, Giralt D, Rodriguez-Luna D,
Muchada M, Penalba A, Boada C, Hernández-Guillamon M, Montaner J. Plasmatic
retinol-binding protein 4 and glial fibrillary acidic protein as biomarkers to
differentiate ischemic stroke and intracerebral hemorrhage. J Neurochem. 2016
Jan;136(2):416-24. doi: 10.1111/jnc.13419. Epub 2015 Dec 17. PubMed PMID:
26526443.
González A, Moniche F, Cayuela A, García-Lozano JR, Torrecillas F,
Escudero-Martínez I, Gonzalez-Marcos JR, Mayol A, Montaner J. Effect of CYP2C19
Polymorphisms on the Platelet Response to Clopidogrel and Influence on the Effect
of High Versus Standard Dose Clopidogrel in Carotid Artery Stenting. Eur J Vasc
Endovasc Surg. 2016 Feb;51(2):175-86. doi: 10.1016/j.ejvs.2015.09.020. Epub 2015
Oct 31. PubMed PMID: 26526111.
Simats A, García-Berrocoso T, Montaner J. Neuroinflammatory biomarkers: From
stroke diagnosis and prognosis to therapy. Biochim Biophys Acta. 2016
Mar;1862(3):411-24. doi: 10.1016/j.bbadis.2015.10.025. Epub 2015 Oct 30. PubMed
PMID: 26524637.