Calcification is a clinical marker of atherosclerosis. This review focuses on recent findings on the association between calcification and plaque vulnerability. Calcified plaques have traditionally been regarded as stable atheromas, those causing stenosis may be more stable than non-calcified plaques. With the advances in intravascular imaging technology, the detection of the calcification and its surrounding plaque components have evolved. Microcalcifications and spotty calcifications represent an active stage of vascular calcification correlated with inflammation, whereas the degree of plaque calcification is strongly inversely related to macrophage infiltration. Asymptomatic patients have a higher content of plaque calcification than that in symptomatic patients. The effect of calcification might be biphasic. Plaque rupture has been shown to correlate positively with the number of spotty calcifications, and inversely with the number of large calcifications. There may be certain stages of calcium deposition that may be more atherogenic. Moreover, superficial calcifications are independently associated with plaque rupture and intraplaque hemorrhage, which may be due to the concentrated and asymmetrical distribution of biological stress in plaques. Conclusively, calcification of differential amounts, sizes, shapes, and positions may play differential roles in plaque homeostasis. The surrounding environments around the calcification within plaques also have impacts on plaque homeostasis. The interactive effects of these important factors of calcifications and plaques still await further study.
Background
Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia.
Methods
We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(−)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice.
Results
After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed.
Conclusions
The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.
ObjectiveTo determine the influence of renal impairment (RI) on clinical outcomes at 3 months and the risk of recurrent stroke in patients presenting with emergent large vessel occlusion (ELVO) treated with emergent endovascular treatment (EVT).MethodsConsecutive patients with anterior circulation stroke due to ELVO treated with EVT in 21 endovascular centers were included. Multivariate regressions were used to evaluate the association of RI with mortality, functional independence (modified Rankin Scale [mRS] score 0–2), and functional improvement (shift in mRS score) at 3 months. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses.ResultsA total of 628 patients with ELVO (mean age 64.7 ± 12.5 years, median NIH Stroke Scale score 17 points, 99 [15.8%] with RI) who underwent EVT were enrolled. After adjustment for other relevant variables, multivariate regression analysis indicated that RI was independently associated with functional independence (adjusted odds ratio 0.53, 95% confidence interval [CI] 0.29–0.96, p = 0.035) at 3 months but not with mortality or functional improvement. Multivariate competing-risk regression analysis showed that patients with RI who received EVT had a significantly higher risk of recurrent stroke (adjusted hazard ratio 2.56, 95% CI 1.27–5.18, p = 0.009) compared to those with normal renal function.ConclusionOur results suggest that RI is an independent predictor of functional independence at 3 months and long-term risk of recurrent stroke in patients with ELVO treated with EVT.
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