Elevated plasma biomarkers of inflammation in acute ischemic stroke patients with underlying dementia

Abstract

Background The blood-brain barrier has been a hindrance to developing blood-based diagnostic tests for dementias, as it limits the appearance of brain biomarkers in the blood. Our aim was to see if the natural opening of the blood-brain barrier induced by ischemic stroke would increase serum levels of inflammatory biomarkers known to be elevated in the brains of patients with Alzheimer’s disease and other neurodegenerative dementias. Methods Forty-three patients with acute ischemic stroke presenting to Stony Brook University Hospital were prospectively enrolled in the study. Eight of these patients were clinically diagnosed as having an underlying neurodegenerative dementia. Blood was drawn acutely within 72 h of stroke symptom onset, and serum levels of the classic inflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured, along with levels of S100B protein (S100B) and complement C3 (CC3). Results Serum levels of IL-6 and CRP in patients with acute ischemic stroke and underlying dementia (AIS + D) were significantly higher ( p = 0.002 and 0.003, respectively) than in patients with acute ischemic stroke alone (AIS). Serum levels of S100B and CC3 did not differ significantly between the groups. Conclusions This study supports the possibility that opening of the blood-brain barrier may enhance the blood appearance of brain tissue markers of inflammation associated with neurodegenerative dementia. Further study is warranted to test this possibility, given the recent emergence of methods to open the blood-brain barrier for diagnostic or therapeutic purposes.

Promoter polymorphism of TNF‑α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population

“…IL-6 and TNF-α are potent pro-inflammatory cytokines that serve vital roles in the immune response during inflammation ( 19 ). IL-6 levels have been suggested as a potential biomarker that is associated with stroke outcomes ( 20 ), short-term acute ischemic stroke death ( 21 ) and post-stroke dementia ( 22 ). It has also been shown that the overexpression of TNF-α transcripts is an independent risk factor for the incidence of IS ( 13 ).…”

Study of Morphofunctional Parameters of Blood Cells in Ischemic Stroke Using a Genome-wide Research

“…The obtained results demonstrated the relationship of osteoprotegrin levels with age, low body mass index, functional class of chronic heart failure, left ventricular ejection fraction, heart rate, glomerular filtration rate, levels of very low density lipoproteins, triglycerides, NT-proBNP, Creactive protein [17]. The authors also showed that the level of osteoprotegrin is a risk factor for the progression of heart failure and an increase in the frequency of hospitalizations [18].…”

The exo‐microRNA (miRNA) signaling pathways in pathogenesis and treatment of stroke diseases: Emphasize on mesenchymal stem cells (MSCs)

“…41 Nonetheless, tight junctions, such as occludin and zonula occludens 1, are even stable up to 24 h after middle cerebral artery occlusion (MCAO), and tight junction proteins and vascular endothelial cells begin to deteriorate after roughly 24-48 h once a second opening of the BBB takes place. 41 During the first of the two BBB openings, matrix metalloproteinases (MMPs) have the potential to irreversibly damage the tight junction proteins, whereas COX-2 has an impact on the BBB. 42 When Cyclooxygenase-2 (COX-2) and MMP inhibitors were used, the COX-2 inhibitor showed advantages in the second opening while the MMP inhibitor demonstrated effects during the early phase, suggesting that using both inhibitors would be more preventive as opposed to BBB disruption.…”

“…Immune cells have a variety of entry points through which they can reach the brain's stroke lesion. The BBB is opened soon after a stroke begins, as evidenced by the rise in endothelial caveolae and transcytosis within a short period 41 . Nonetheless, tight junctions, such as occludin and zonula occludens 1, are even stable up to 24 h after middle cerebral artery occlusion (MCAO), and tight junction proteins and vascular endothelial cells begin to deteriorate after roughly 24–48 h once a second opening of the BBB takes place 41 .…”

“…The BBB is opened soon after a stroke begins, as evidenced by the rise in endothelial caveolae and transcytosis within a short period 41 . Nonetheless, tight junctions, such as occludin and zonula occludens 1, are even stable up to 24 h after middle cerebral artery occlusion (MCAO), and tight junction proteins and vascular endothelial cells begin to deteriorate after roughly 24–48 h once a second opening of the BBB takes place 41 . During the first of the two BBB openings, matrix metalloproteinases (MMPs) have the potential to irreversibly damage the tight junction proteins, whereas COX‐2 has an impact on the BBB 42 .…”