Inflammatory molecules might become both biomarkers and therapeutic targets for stroke management

Abstract

Stroke is the fifth leading cause of death and the most frequent cause of disability worldwide. Currently, stroke diagnosis is based on neuroimaging; therefore, the lack of a rapid tool to diagnose stroke is still a major concern. In addition, therapeutic approaches to combat ischemic stroke are still scarce, since the only approved therapies are directed toward restoring blood flow to the affected brain area. However, due to the reduced time window during which these therapies are effective, few patients benefit from them; therefore, alternative treatments are urgently needed to reduce stroke brain damage in order to improve patients’ outcome. The inflammatory response triggered after the ischemic event plays an important role in the progression of stroke; consequently, the study of inflammatory molecules in the acute phase of stroke has attracted increasing interest in recent decades. Here, we provide an overview of the inflammatory processes occurring during ischemic stroke, as well as the potential for these inflammatory molecules to become stroke biomarkers and the possibility that these candidates will become interesting neuroprotective therapeutic targets to be blocked or stimulated in order to modulate inflammation after stroke.

The effect of post‐stroke hyperglycaemia on the levels of brain damage and repair‐related circulating biomarkers: the Glycaemia in Acute Stroke Study II

“…requiring recruitment of a higher number of EPCs, but these might be dysfunctional. Finally, there is ample evidence in the literature that inflammatory mechanisms are associated with poor outcomes in stroke patients, and IL-6 is one of the most widely studied cytokines as a biomarker in stroke-related inflammation [14]. Similarly, in the present report, IL-6 was related to poor outcomes independently of the presence of PSH.…”

<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.…”

“…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. 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.…”

“…In addition, the disproportionate concentration of pro-inflammatory mediators activates the autonomic nervous system, which leads to the inhibition of pro-inflammatory pathways and stimulation of antiinflammatory mechanisms by the release of interleukins and growth factors. 25,27 Furthermore, necrotic neurons release "hazard signals" that activate the immune system and secrete molecular patterns (DAMP). 19,27 DAMP induces the Toll-like receptors (TLRs) on microglia, which in turn stimulates the NF-κB to synthesize most of the pro-inflammatory cytokines.…”

“…28 M1 microglia produce pro-inflammatory cytokines (IL-1β, interleukin 6 (IL-6), IL-18 and tumor necrosis factor (TNF-α)) and chemokines, while M2 microglia produce anti-inflammatory cytokines (interleukin 10 (IL-10), interleukin 4 (IL-4) and transforming growth factor-beta (TGFβ)), 25 which are released a few days after acute brain damage leading to inhibition of inflammation. 9,25 MMP, secreted by microglia, astrocytes and neurons, mediates in the destruction of the base plate, increasing BBB permeability and facilitating the entrance of additional peripheral immune cells into the brain area affected by stroke. This is because acute ischemia of the brain not only causes a local inflammatory reaction, but also triggers a systemic immune response.…”