(Read Only) Jickling_relayout_US_Neuro 16/02/2010 10:10 Page 52
Brain Trauma Stroke
Biomarkers of Ischemic Stroke
Glen Jickling, MD,
1
Huichun Xu, MD, PhD
1
and Frank Sharp, MD
2
1. Fellow; 2. Professor, Department of Neurology and MIND Institute, University of California at Davis
Abstract
The diagnosis and management of patients with ischemic stroke is primarily based on clinical assessment in conjunction with imaging tests.
Development of molecular biomarkers as additional tools to support a clinical diagnosis, identify patients at risk of disease, and help guide patient
treatment and prognosis would be of great value. Currently, no such biomarkers are used in the management of patients with ischemic stroke;
however, several promising proteomic and genomic markers have been identified, as presented in this review.
Keywords
Biomarker, ischemic stroke, cerebrovascular disease
Disclosure: The authors have no conflicts of interest to declare.
Received: February 10, 2009 Accepted: August 5, 2009
Correspondence: Glen Jickling, MD, MIND Institute and Department of Neurology, University of California at Davis, 2805 50th Street, Room 2434, Sacramento, CA 95817.
E:
gcjickling@ucdavis.edu
Ischemic stroke remains the leading cause of adult disability in developed response to ischemic brain tissue have been identified. Finally, a number
countries.
1
Although clinical assessment is the key feature of patient of biomarkers have been associated with ischemic stroke, although their
management, additional tools such as biomarkers can be used to support links with its pathophysiology remain unknown.
a clinical diagnosis, identify patients at risk of disease, and help guide
patient treatment and prognosis. In cerebrovascular disease, computed Classification of Biomarkers
tomography (CT) and magnetic resonance imaging (MRI) are frequently Proteomics
used to confirm clinically suspected disease. However, there are several Proteomics is the study of the entire complement of proteins, including the
limitations to neuroimaging in acute ischemic stroke, with the CT brain modifications made to proteins. Common techniques to identify protein
scan often having subtle findings and MRI not always readily accessible. biomarkers include western blot, immunohistochemical staining, enzyme-
The limitations of CT and MRI make the development of other supportive linked immunosorbent assay, and mass spectrometry (matrix-assisted
biomarkers valuable in the care of patients with acute stroke. Peripheral laser desorption/ionisation analysis). Using these techniques, a number of
blood biomarkers are very useful in clinical practice because they are proteins have been identified as biomarkers of ischemic stroke (see Table
readily available and low-cost, as shown by the use of troponin for 1). Protein biomarkers of ischemic brain injury include S100 calcium-
myocardial infarction. Currently, no blood test for ischemic stroke is used binding protein B (S100B), neuron-specific enolase (NSE), myelin basic
in clinical practice, although substantial efforts are ongoing to develop protein, and glial fibrillary acidic protein (GFAP).
2–4
Brain tissue injury
such a test. This article presents a summary of this work, focusing biomarkers are limited by several factors in their use as biomarkers for
primarily on the use of proteomics and genomics to develop a blood- ischemic stroke. They are not specific to it, as many disease processes can
based biomarker of ischemic stroke. damage brain tissue and cause their release into the systemic circulation.
Levels of such biomarkers also depend on the extent of blood–brain
Biomarkers and Pathophysiology barrier breakdown, which is variable between ischemic strokes. Several
The identification of biomarkers for ischemic stroke stems from a growing proteins involved in inflammation have been identified as biomarkers of
understanding of stroke pathophysiology. Initial studies identified ischemic stroke. These include C-reactive protein,
5
interleukin-6 (IL-6),
biomarkers specific to brain tissue, representing molecules that are tumor necrosis factor-alpha (TNF-α), vascular cell adhesion molecule 1
released into the systemic circulation following ischemic injury to the (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1), and matrix
brain. Biomarkers relating to the coagulation cascade have been metalloproteinases (MMPs).
6,7
Molecules involved in acute thrombosis
associated with ischemic stroke, representing acute thrombus in cerebral have also been associated with ischemic stroke, including fibrinogen,
8
circulation. Inflammation also plays an important role in ischemic stroke. A D-dimer,
9,10
and von Willebrand factor (vWF).
11,12
Finally, a number of
number of biomarkers relating to atherosclerosis and the inflammatory proteins have been associated with ischemic stroke that as yet do not
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© TOUCH BRIEFINGS 2009
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