Neuroinflammatory biomarkers: From stroke diagnosis and prognosis to therapy

Abstract

Stroke is the third leading cause of death in industrialized countries and one of the largest causes of permanent disability worldwide. Therapeutic options to fight stroke are still limited and the only approved drug is tissue-plasminogen activator (tPA) and/or mechanical thrombectomy. Post-stroke inflammation is well known to contribute to the expansion of the ischemic lesion, whereas its resolution stimulates tissue repair and neuroregeneration processes. As inflammation highly influences susceptibility of stroke patients to overcome the disease, there is an increasing need to develop new diagnostic, prognostic and therapeutic strategies for post-stroke inflammation. This review provides a brief overview of the contribution of the inflammatory mechanisms to the pathophysiology of stroke. It specially focuses on the role of inflammatory biomarkers to help predicting stroke patients' outcome since some of those biomarkers might turn out to be targets to be therapeutically altered overcoming the urgent need for the identification of potent drugs to modulate stroke-associated inflammation. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.

<p>The Role of Selected Pro-Inflammatory Cytokines in Pathogenesis of Ischemic Stroke</p>

“…The excitotoxicity and growth of ROS activates microglia and astrocytes that secrete cytokines, chemokine and matrix metalloproteinases (MMP). 16,25 These inflammatory mediators induce the expression of cell adhesion molecules on the endothelial surface (P-selectin, E-selectin, endothelial-leukocyte adhesion molecule (ELAM-1) and intercellular cell adhesion molecules-1 (ICAM-1)), which enable the neutrophils to infiltrate ischemic areas of the brain. 8,25 In addition, endothelial cells increase the expression of chemokines in order to bring the leukocytes to the site of damage.…”

“…8,25 In addition, endothelial cells increase the expression of chemokines in order to bring the leukocytes to the site of damage. 9 Infiltrating immune cells, regardless of their beneficial role, can also damage the ischemic brain by producing various destructive immune cytotoxic mediators (including NO, ROS and prostanoids 16,26 ), which prolong the inflammatory response, increasing the brain damage. They can also lead to secondary complications such as swelling and hemorrhagic transformation.…”

“…A particular object of controversy is the impact of inflammatory factors on prognosis in re-perfusion therapies of ischemic stroke (ICA) involving intravenous thrombolytic therapy using recombinant tissue plasminogen activator (rtPA) and endovascular therapy (mechanical thrombectomy). 15,16 Therefore, numerous studies of the diagnostic and prognostic value of proinflammatory factors of neuronal, glial and neuroendocrine origin, as well as inflammatory markers in ischemic stroke, are currently ongoing. Cytokines, as regulatory proteins produced by different types of cells, are an object of particular interest to researchers.…”

Takotsubo-Like Myocardial Dysfunction in Ischemic Stroke

“…This could reflect the presence of an acute inflammatory change in the myocardium with regard to brain natriuretic peptide/N-terminal-probrain natriuretic peptide release 21 or poststroke inflammation predicting prognosis or outcome. 21,22 In addition, patients with TMD had significantly lower triglycerides level. The total and low-density lipoprotein cholesterol levels seemed to be decreased.…”

The Link between Early Biomarker Analysis and the Neurological Outcome in Stroke Patients

“…They did not find that this addition significantly increased the discrimination ability of their model [11]. This further proves that, although there is evidence that biomarkers correlate to the outcome, actually implementing biomarkers into predictive models remains a challenge due to conflicting results [10,12,13].…”