The use of plasma biomarkers is becoming increasingly popular in several fields of medicine. In fact, decision-making processes using biomarkers is widely accepted in medical situations such as initiating lipid lowering therapies (LDL), diagnosing acute myocardial infarction (troponins), and ruling out pulmonary embolism suspicions (D-dimer), among others.
Therefore we really believe that biochemical markers of stroke, will really open “a window to the brain…”. In fact, in this research line we aim to answer relevant clinical questions through the use of biomarkers.
Our main Objectives using mainly plasma proteins are:
1.- To predict stroke risk
2.- To make stroke diagnosis
3.- To differentiate stroke subtypes
4.- To establish evolution and prognosis
5.- To use Biomarkers as treatment end-points
Some of our findings might have therapeutic implications since biological markers described by the group such as MMP-9 are well associated with Blood Brain Barrier disruption. In this direction, we have described MMP-9 predicting haemorrhagic complications among stroke patients receiving thrombolytic treatment. These approaches might contribute to increase safety of reperfusion treatments. The impact of this research line is clear, since articles like this (Circulation 2003) have been cited more than 180 times since its publication.
The study of these molecules will also have diagnostic implications because we have proposed the biochemical diagnostic of stroke by means of the identification of a biomarkers panel that distinguish between a stroke and other stroke-mimicking conditions. This might contribute to refer only to real stroke patients to the stroke centres, saving huge resources to the system.
These two examples, identification of biomarkers to predict tPA related bleedings and a stroke diagnostic test are examples of translational research in which the Neurovascular Research Lab is filing patents to be licensed to Biotech companies able to develop diagnostic kits in which our biomarkers might be placed and used in the clinical practice. That might close the circle of applied research.
Reviews of our group in which you may find detailed info about those biomarkers:
Foerch C, Montaner J, Furie KL, Ning MM, Lo EH.
Searching for oracles? Blood biomarkers in acute stroke
Blood biomarkers to guide stroke thrombolysis.
Front Biosci (Elite Ed). 2009 Jun 1;1:200-208.
García-Berrocoso T, Fernández-Cadenas I, Delgado P, Rosell A, Montaner J.
Blood Biomarkers to Identify Stroke Etiologies.
Therapy 2010 (in press).
We are involved in several projects with public or private funding supporting our research on stroke biomarkers. One of such exciting projects is FIS PI 08/361 “Identificación y uso de biomarcadores pronósticos en el ictus isquémico”, aiming to identify biomarkers that predict main causes of stroke worsening (Infarct growth, cardiac complications, hemorrhagic transformation, infections, recurrence or new vascular events) to guide Stroke Unit allocation and stay of our patients.
Discovery and validation of good candidate biomarkers, requires multidisciplinary approaches and replication in well designed multicentric and international studies. For that purpose we are actively collaborating with well known stroke research leading groups:
- Eng Lo, Xiaoing Wang, Ming Ming Ning (Boston, USA).
- Jean Charles Sanchez, Natacha Turck (Geneva, Switzerland).
- Denis Vivien, Carine Ali, Eduardo Anglés-Cano (Caen, France).
Research Tools and Techniques
We are using a combination of discovery techniques and biological human and animal samples to identify new stroke-related biomarkers:
One example is the “protein arrays”. In our laboratory, we have been using these new technologies and we actually use the SearchLight Assays (Aushon Biosystems) that allows us to study more than 170 human proteins and also many candidates from different animal species. We offer access to our technology to other groups. For more information, please refer to http://www.lin-bcn.com/
Also those biomarkers may be specifically tested not only as circulating markers in plasma or serum but in the components of interest of the Neurovascular Unit, that we may dissect by using the LCM Leica LMD6000 microscope, for Laser Capture microdissection. An example in which combine both thecniques may be found at:
Cuadrado E, Rosell A, Penalba A, Slevin M, Alvarez-Sabin J, Ortega-Aznar A, Montaner J. Vascular MMP-9/TIMP-2 and neuronal MMP-10 up-regulation in human brain after stroke: a combined Laser Microdissection and Protein Array Study. Journal of Proteome Research 2009;8(6):3191-3197.
All these results have been possible since the development of a “blood library” including more than 2000 stroke samples and a “brain library” that allowed us to describe for the first time the “human stroke proteome” with the outstanding collaboration of so many patients, relatives and clinicians of the Stroke Unit.