Potential serum biomarkers in the pathophysiological processes of stroke

Abstract

Stroke is a leading cause of death and serious long-term disability. Ischemic stroke is the major subtype of stroke. Currently, its diagnosis is mainly dependent upon clinical symptoms and neuroimaging techniques. Despite these clinical and imaging modalities, often strokes are not recognized after initial onset. As early intervention of medical or surgical therapy is often associated with improved outcomes, there is an urgent need to improve the speed and accuracy of stroke diagnosis. Stroke is a complex pathophysiological process involving; energy failure, imbalance of ion homeostasis, acidosis, intracellular calcium overload, neuronal excitotoxicity, free radical-mediated lipid oxidation, inflammatory cell infiltration, and glial cell activation. These events ultimately lead to neuronal apoptotic cell death or necrosis. In this review, we have summarized the serum biomarkers according to the pathophysiological processes of stroke, which have been intensively studied in clinical trials of stroke over the past five years, and also used Medline's ‘related article’ option to identify further articles. We focused on the potential biomarkers pertaining to vascular injury, metabolic changes, oxidative injury, and inflammation, and newly studied biomarkers, and discussed how these biomarkers could be used for the diagnosis or determining the prognosis of stroke.

Keywords::

• biomarkers
• cerebral ischemia
• clinical trial
• pathophysiology
• stroke

Financial & competing interests disclosure

This work was supported by the National Institutes of Health (NS07001) and the China Scholarship Council. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Cellular-fibronectin and matrix metalloproteinase-9 may be more indicative of hemorrhage transformation in acute ischemic stroke, especially in patients treated with tissue plasminogen activator.

• Precursor neuropeptides proenkephalin A is a new inflammatory marker, which could also serve as a marker of blood–brain barrier disruption in stroke.

• Markers of oxidative stress are not specific markers for stroke.

• The lipoprotein-associated phospholipase A2 blood test has been approved by the US FDA for assessing the risk of ischemic stroke and coronary artery disease. There is considerable agreement among clinical trials that lipoprotein-associated phospholipase A2 is a good predictor of primary and secondary strokes, stroke outcome and recanalization after tissue plasminogen activator treatment.

• A multiple biomarker strategy should increase the sensitivity and specificity for stroke diagnosis and prognosis.

• miRNAs may potentially be a good biomarker for stroke, because miRNAs could regulate processes that affect cerebral injury after stroke.

• Copeptin is an accurate blood marker for predicting stroke prognosis.

• Biomarkers, to date, lack sensitivity or specificity to be of clinical use in stroke.