Relevance of Distinct Monocyte Subsets to Clinical Course of Ischemic Stroke Patients

Abstract

Background and PurposeThe most common strategy for treating patients with acute ischemic stroke is thrombolytic therapy, though only a few patients receive benefits because of the narrow time window. Inflammation occurring in the central nervous system (CNS) in association with ischemia is caused by immune cells including monocytes and involved in lesion expansion. If the specific roles of monocyte subsets in stroke can be revealed, they may become an effective target for new treatment strategies.MethodsWe performed immunological examinations of 36 consecutive ischemic stroke patients within 2 days of onset and compared the results with 24 age-matched patients with degenerative disorders. The stroke patients were repeatedly tested for the proportions of monocyte subsets in blood, and serum levels of pro- and anti-inflammatory cytokines immediately after admission, on days 3-7 and 12-16 after stroke onset, and on the day of discharge. In addition, immunological measurements were analyzed for relationships to stroke subtypes and complications, including progressive infarction (PI) and stroke-associated infection (SAI).ResultsMonocyte count was significantly increased from 0–16 days after stroke as compared to the controls (p<0.05). CD14highCD16- classical and CD14highCD16+ intermediate monocytes were significantly increased from 0-7 and 3-16 days after stroke, respectively (p<0.05), whereas CD14 dimCD16high non-classical monocytes were decreased from 0–7 days (p<0.05). Cardioembolic infarction was associated with a persistent increase in intermediate monocytes. Furthermore, intermediate monocytes were significantly increased in patients with PI (p<0.05), while non-classical monocytes were decreased in those with SAI (p<0.05). IL-17A levels were positively correlated with monocyte count (r=0.485, p=0.012) as well as the percentage of non-classical monocytes (r=0.423, p=0.028), and negatively with that of classical monocytes (r=-0.51, p=0.007) during days 12-16.ConclusionsOur findings suggest that CD14highCD16+ intermediate monocytes have a role in CNS tissue damage during acute and subacute phases in ischemic stroke especially in relation to cardioembolism.

Monocyte count at onset predicts poststroke outcomes during a 90-day follow-up

“…Indeed, Kaito et al showed that different monocyte subsets can have different role in AIS pathophysiology [47]. First, the small size (30 smokers and 59 nonsmokers enrolled) of a single-centre study may not represent the complexity of all AIS patients and, for this reason, the results cannot be extended to a general population.…”

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

“…About different subtypes, classical monocyte subset (CD14 ++ CD16 − ) significantly increased, while the non-classical monocyte subset (CD14 + CD16 ++ ) significantly decreased [29]. Progression and severity of brain ischemia directly correlate with CD14 ++ CD16 − increase and CD14 + CD16 ++ reduction [29]. As already known in another model [30], the splenic monocyte reserves were critical in the pathophysiology of brain infarction [31,32].…”

“…Early after brain injury, an increased number of total monocytes in the blood circulation has been described in humans [29]. About different subtypes, classical monocyte subset (CD14 ++ CD16 − ) significantly increased, while the non-classical monocyte subset (CD14 + CD16 ++ ) significantly decreased [29]. Progression and severity of brain ischemia directly correlate with CD14 ++ CD16 − increase and CD14 + CD16 ++ reduction [29].…”

Ischemic Stroke Activates Hematopoietic Bone Marrow Stem Cells

“…Importantly, brain ischemia also triggers a systemic immune response. While blood lymphocyte numbers decline, levels of circulating neutrophils and monocytes increase in stroke patients 1, 2 . These myeloid cells are recruited to the brain 3 where they may contribute to the brain’s recovery but also to reperfusion injury.…”