Dataset Information

Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke.

ABSTRACT:

Objective

In patients with acute ischemic stroke, we aimed to investigate the relation between preexisting small vessel disease (SVD) and the amount of blood-brain barrier (BBB) leakage in ischemic and nonischemic area before IV thrombolysis.

Methods

We retrospectively accessed anonymous patient-level data from the Stroke Imaging Repository and the Virtual International Stroke Trials Archive resources and included patients treated with IV thrombolysis with pretreatment MRI. We rated SVD features using validated qualitative magnetic resonance (MR) scales. Leakage of BBB was assessed with postprocessing of perfusion-weighted images. We evaluated associations between SVD features (individually and summed in a global SVD score) and BBB leakage using linear regression analysis, adjusting for major clinical confounders.

Results

A total of 212 patients, mean age (±SD) 69.5 years (±16.1), 102 (48%) male, had available MR before IV thrombolysis. Evidence of BBB leakage was present in 175 (80%) and 205 (94%) patients in the ischemic and nonischemic area, respectively. Lacunar infarcts (? = 0.17, p = 0.042) were associated with BBB leakage in the ischemic area, and brain atrophy was associated with BBB leakage in both ischemic (? = 0.20, p = 0.026) and nonischemic (? = 0.27, p = 0.001) areas. Increasing SVD grade was independently associated with BBB leakage in both ischemic (? = 0.26, p = 0.007) and nonischemic (? = 0.27, p = 0.003) area.

Conclusions

Global SVD burden is associated with increased BBB leakage in both acutely ischemic and nonischemic area. Our results support that SVD score has construct validity, and confirm a relation between SVD and BBB disruption also in patients with acute stroke.

SUBMITTER: Arba F

PROVIDER: S-EPMC5696647 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke.

Arba Francesco F Leigh Richard R Inzitari Domenico D Warach Steven J SJ Luby Marie M Lees Kennedy R KR

Neurology 20171025 21

<h4>Objective</h4>In patients with acute ischemic stroke, we aimed to investigate the relation between preexisting small vessel disease (SVD) and the amount of blood-brain barrier (BBB) leakage in ischemic and nonischemic area before IV thrombolysis.<h4>Methods</h4>We retrospectively accessed anonymous patient-level data from the Stroke Imaging Repository and the Virtual International Stroke Trials Archive resources and included patients treated with IV thrombolysis with pretreatment MRI. We rat ...[more]

PMID: 29070665

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Project description:ObjectivesWe aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients.MethodsThe DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed.ResultsWe included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively.ConclusionThe DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients.Clinical relevance statementThe DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications.Key points• The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.

Project description:Background and purposeRecent studies have shown that several proteins, including Axl, are related to hemorrhagic transformation (HT) following intravenous thrombolysis by affecting blood-brain barrier (BBB) function. However, the effects of these proteins on BBB function have been studied primarily in animal models. In this study, we aimed to identify serum protein markers that predict HT following intravenous thrombolysis in patients with acute ischemic stroke (AIS) and verify whether these serum proteins regulate BBB function and HT in animal stroke models.MethodsFirst, 118 AIS patients were enrolled in this study, including 52 HT patients and 66 non-HT patients. In Step 1, baseline serum levels of Axl, angiopoietin-like 4, C-reactive protein, ferritin, hypoxia-inducible factor-1 alpha, HTRA2, Lipocalin2, matrix metallopeptidase 9, platelet-derived growth factor-BB, and tumor necrosis factor alpha were measured using a quantitative cytokine chip. Next, sequence mutations and variations in genes encoding the differentially expressed proteins identified in Step 1 and subsequent function-related proteins were detected. Finally, we verified whether manipulation of differentially expressed proteins affected BBB function and HT in a hyperglycemia-induced rat stroke model.ResultsSerum Axl levels were significantly lower in the HT group than in the non-HT group; none of the other protein markers differed significantly between the two groups. Genetic testing revealed that sequence variations of GAS6 (the gene encoding the Axl ligand)-derived long non-coding RNA, GAS6-AS1, were significantly correlated with an increased risk of HT after intravenous thrombolysis. In animal studies, administration of recombinant GAS6 significantly reduced brain infarction and neurological deficits and attenuated BBB disruption and HT.ConclusionsLower serum Axl levels, which may result from sequence variations in GAS6-AS1, are correlated with an increased risk of HT after intravenous thrombolysis in stroke patients. Activation of the Axl signaling pathway by the GAS6 protein may serve as a therapeutic strategy to reduce HT in AIS patients.

Dataset Information

Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke.

Objective

Methods

Results

Conclusions

Publications

Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke.

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