Abstract
Background and PurposeYKL-40 is associated with various neurological disorders. However, circulatory YKL-40 levels early after onset of acute ischemic stroke (AIS) have not been systematically assessed. We aimed to identify the temporal changes and clinical usefulness of measuring serum YKL-40 immediately following AIS.MethodsSerum YKL-40 and C-reactive protein (CRP) levels were monitored over time in AIS patients (n = 105) and compared with those of stroke-free controls (n = 34). Infarct volume and stroke severity (National Institutes of Health Stroke Scale; NIHSS) were measured within 48 hours of symptom onset, and functional outcome (modified Rankin Scale; mRS) was measured 3 months after AIS.ResultsWithin 12 hours of symptom onset, levels of YKL-40 (251 vs. 41 ng/mL) and CRP (1.50 vs. 0.96 µg/mL) were elevated in AIS patients compared to controls. The power of YKL-40 for discriminating AIS patients from controls was superior to that of CRP (area under the curve 0.84 vs. 0.64) and YKL-40 (r = 0.26, P<0.001) but not CRP levels were correlated with mRS. On day 2 of admission (D2), YKL-40 levels correlated with infarct volume and NIHSS. High YKL-40 levels predicted poor functional outcome (odds ratio 5.73, P = 0.03). YKL-40 levels peaked on D2 and declined on D3, whereas CRP levels were highest on D3.ConclusionsOur results demonstrate serial changes in serum YKL-40 levels immediately following AIS and provide the first evidence that it is a valid indicator of AIS extent and an early predictor of functional outcome.
Highlights
YKL-40, known as human chitinase-like protein 1 (HCgp39), is a novel cerebrospinal fluid biomarker of various neuronal diseases, including Alzheimer’s disease, meningitis, and traumatic brain injury [1,2,3,4,5]
Interleukin (IL)-1b and tumor necrosis factor (TNF)-a are produced from macrophage in neuroinflammatory conditions [4,9,10], and both cytokines are capable of upregulating YKL-40 expression in reactive astrocytes or macrophages [5]
We aimed to identify the temporal dynamics of circulatory YKL-40 levels immediately following acute ischemic stroke (AIS), the relationship between YKL-40 levels and 3 key clinical parameters, and the practical clinical application of YKL-40 in AIS by comparing it with C-reactive protein (CRP)
Summary
YKL-40, known as human chitinase-like protein 1 (HCgp39), is a novel cerebrospinal fluid biomarker of various neuronal diseases, including Alzheimer’s disease, meningitis, and traumatic brain injury [1,2,3,4,5]. Elevated plasma YKL-40 levels are associated with increased risk of ischemic stroke in the general population [6]. Diverse inflammatory and tissue remodeling conditions, including atherosclerosis, are associated with elevated YKL-40 expression levels in infiltrating macrophages [4,5,6,7,8]. Interleukin (IL)-1b and tumor necrosis factor (TNF)-a are produced from macrophage in neuroinflammatory conditions [4,9,10], and both cytokines are capable of upregulating YKL-40 expression in reactive astrocytes or macrophages [5]. A recent study showed the abundant expression of YKL40 by astrocytes but not by macrophages in brain tissue from patients with acute bacterial meningitis and progressive multiple leukoencephalopathy [5]. Circulatory YKL-40 levels early after onset of acute ischemic stroke (AIS) have not been systematically assessed. We aimed to identify the temporal changes and clinical usefulness of measuring serum YKL-40 immediately following AIS
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