ABSTRACT
OBJECTIVE: To explore the related risk factors of hemorrhage in human brain cerebral arteriovenous malformations (AVM) and the relationship between endothelial progenitor cells (EPCs) content and stromal cell-derived factor-1 (SDF-1) in different ages. METHODS: A retrospective analysis was conducted on 130 patients with cerebral AVM who underwent surgical treatment from May 2012 to October 2018. Univariate and multivariate logistic analysis was used to investigate the related risk factors of cerebral AVM hemorrhage. Forty paraffin specimens of human brain AVM were harvested from 24 cases of cerebral hemorrhage patients and 16 cases of non-cerebral hemorrhage patients Paraffin samples of cerebral cortex from 8 patients with epilepsy during the same period were selected as control. Positive expression of CD34 and vascular endothelial growth factor receptor 2 (KDR2) in brain tissue samples of both groups were used to identify EPCs. Immunofluorescence double staining was used for KDR2 and CD34 positive localization to determine EPCs localization, and SDF-1 expression detection was performed. RESULTS: The size of brain AVM<3 cm, deep brain AVM and single venous drainage are independent risk factors for cerebral AVM hemorrhage. Immunohistochemical results showed that CD34 and KDR2 were expressed in cerebral AVM group, but not in the control group. Double immunofluorescence staining showed that EPCs mainly existed at the edge of vascular wall, while SDF-1 could co-stain with alpha-smooth muscle actin (α-SMA) positive cells and CD31 positive cells. SDF-1 expression in brain AVM tissue was higher than that in control group. There were significant differences in the number of EPCs among the patients of different ages ( P<0.05). There was no significant difference in EPCs between cerebral hemorrhage group and non-hemorrhage group ( P>0.05). CONCLUSION: Brain AVM (<3 cm), single venous drainage and deep brain AVM are independent risk factors for cerebral AVM hemorrhage. In human brain AVM, EPC appears high level but decrease with age, which may play a role in vascular remodeling in AVM.
Subject(s)
Brain , Cerebral Hemorrhage , Chemokine CXCL12 , Endothelial Progenitor Cells , Intracranial Arteriovenous Malformations , Antigens, CD34/genetics , Brain/physiopathology , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/genetics , Chemokine CXCL12/genetics , Chemokine CXCL12/metabolism , Gene Expression Profiling , Gene Expression Regulation , Humans , Intracranial Arteriovenous Malformations/complications , Intracranial Arteriovenous Malformations/genetics , Retrospective Studies , Risk Factors , Vascular Endothelial Growth Factor Receptor-2/geneticsABSTRACT
Previous studies had shown that CXC chemokine ligand-12 (CXCL12) plays a significant role in animal models of ischemic stroke, but its role in human stroke is unclear. The aim of this study was to test the relationship between elevated serum circulating CXCL12 levels and the 1-year stroke recurrence in Chinese patients with acute ischemic stroke (AIS). All consecutive patients with first-ever acute ischemic stroke from January 2011 to September 2013 were recruited to participate in the study. Serum levels of CXCL12 and National Institute of Health Stroke Scale (NIHSS) were measured at the time of admission. Logistic regression analysis was used to evaluate the stroke recurrence according to serum CXCL12 levels. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in predicting stroke recurrence. Clinical follow-up was performed at 1 year. In our study, 248 patients finished the 1-year follow-up. At 1-year follow-up, 31 patients had a recurrence ischemic stroke. The median CXCL12 levels were significantly higher in those who sustained a recurrence ischemic stroke compared with those who did not [24.2 ng/mL (IQR 15.4-33.7) vs 6.5 ng/mL (IQR 3.4-10.2); Z = 8.258, P < 0.0001]. In multivariate analysis, there was an increased risk of stroke recurrence associated with serum CXCL12 levels ≥12.15 ng/mL (OR 9.122, 95 % CI 6.103-15.104) after adjusting for above possible confounders. The time to recurrence stroke distribution between patients with baseline CXCL12 levels ≥12.15 ng/mL and those with baseline CXCL12 levels <12.15 ng/mL were significantly different (P < 0.0001, log-rank test). Elevated circulating CXCL12 levels at admission are strongly associated with the future recurrence of ischemic stroke in Chinese patients with AIS. Further studies are warranted to confirm this association and define the role for CXCL12 as a novel predictor biomarker for stroke recurrence.