Increased blood-brain barrier permeability in contralateral hemisphere predicts worse outcome in acute ischemic stroke after reperfusion therapy

Liu, Chang; Yan, Shiyu; Zhang, Ruiting; Chen, Zhicai; Shi, Feina; Zhou, Ying; Zhang, Meixia; Lou, Min

doi:10.1136/neurintsurg-2017-013663

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…In support of this hypothesis, prior work in patients with AIS has shown that the K 2 coefficient of the DWI lesion is inversely associated with rates of reperfusion post alteplase,33 and positively associated with the DWI volume and severity of intracranial haemorrhage postendovascular thrombectomy 34. Based on what has been shown previously on the relationship of increasing BBB permeability and poor functional outcomes after AIS,7 8 35 our findings are promising and hypothesis generating for a role of microvascular integrity in the sex-disparity of stroke outcomes.…”

Section: Discussionsupporting

confidence: 83%

Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Etherton

Cougo

et al. 2019

Stroke Vasc Neurol

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Background and purposeFunctional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differences in microvascular integrity in individuals with acute ischaemic stroke.MethodsA retrospective analysis of subjects with acute ischaemic stroke and brain MRI with diffusion-weighted (DWI) and dynamic-susceptibility contrast-enhanced (DSC) perfusion-weighted imaging obtained within 9 hours of last known well was performed. In the hemisphere contralateral to the acute infarct, normal-appearing white matter (NAWM) microvascular integrity was measured using the K2 coefficient and apparent diffusion coefficient (ADC) values. Regression analyses for predictors of K2 coefficient, DWI volume and good outcome (90-day modified Rankin scale (mRS) score <2) were performed.Results105 men and 79 women met inclusion criteria for analysis. Despite no difference in age, women had increased NAWM K2 coefficient (1027.4 vs 692.7×10–6/s; p=0.006). In women, atrial fibrillation (β=583.6; p=0.04) and increasing NAWM ADC (β=4.4; p=0.02) were associated with increased NAWM K2 coefficient. In multivariable regression analysis, the K2 coefficient was an independent predictor of DWI volume in women (β=0.007; p=0.01) but not men.ConclusionsIn women with acute ischaemic stroke, increased NAWM K2 coefficient is associated with increased infarct volume and chronic white matter structural integrity. Prospective studies investigating sex-specific differences in white matter microvascular integrity are needed.

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Section: Discussionsupporting

confidence: 83%

Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Etherton

Cougo

et al. 2019

Stroke Vasc Neurol

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“…BBB disruption begins at the onset of ischemic stroke and increases with sustained hypoperfusion. Maintenance of the BBB immediately after stroke onset might be expected to stop the downstream progression of ischemic brain injury and improve clinical outcomes[ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…Minutes after ischemic stroke, dramatic cerebral pathological changes occur at the genomic, molecular, and cellular levels. One of the major pathological changes is the disruption of the blood–brain barrier (BBB)[ 2 ]. Under pathological conditions, such as ischemic stroke, the BBB can be disrupted, followed by extravasation of blood components into the brain, thereby compromising the normal neuronal function.…”

Section: Introductionmentioning

confidence: 99%

Relationship between treatment types and blood–brain barrier disruption in patients with acute ischemic stroke: Two case reports

Seo¹,

Kim²,

Chang³

et al. 2022

WJCC

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BACKGROUND Blood-brain barrier (BBB) disruption plays an important role in the development of neurological dysfunction in ischemic stroke. However, diagnostic modalities that can clearly diagnose the degree of BBB disruption in ischemic stroke are limited. Here, we describe two cases in which the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting BBB disruption was evaluated after treatment of acute ischemic stroke using two different methods. CASE SUMMARY The two patients of similar age and relatively similar cerebral infarction locations were treated conservatively or with thrombectomy, although their sex was different. As a result of analysis by performing DCE-MRI, it was confirmed that BBB disruption was significantly less severe in the patient who underwent thrombectomy ( P = 3.3 × 10 -7 ), whereas the average K trans of the contralateral hemisphere in both patients was similar (2.4 × 10 -5 min -1 and 2.0 × 10 -5 min -1 ). If reperfusion is achieved through thrombectomy, it may indicate that the penumbra can be saved and BBB recovery can be promoted. CONCLUSION Our cases suggest that BBB disruption could be important if BBB permeability is used to guide clinical treatment.

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“…It is also strongly implicated in a variety of disease states. The leakage of microcirculatory flow caused by increasing endothelial permeability contributes to the progression of life-threatening illnesses such as sepsis [54,55], stroke [56], acute respiratory distress syndrome [57] and others, subsequently inducing organ failure [52,58]. In addition, the disruption of bloodbrain barrier tight junction is associated with cognition impairment via central nervous system injury [59,60].…”

Section: Discussionmentioning

confidence: 99%

S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway

et al. 2021

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Background Vascular endothelial barrier function is maintained by cell-to-cell junctional proteins and contributes to vascular homeostasis. Various risk factors such as inflammation disrupt barrier function through down-regulation of these proteins and promote vascular diseases such as atherosclerosis. Previous studies have demonstrated that aged garlic extract (AGE) and its sulfur-containing constituents exert the protective effects against several vascular diseases such as atherosclerosis. In this study, we examined whether AGE and its sulfur-containing constituents improve the endothelial barrier dysfunction elicited by a pro-inflammatory cytokine, Tumor-necrosis factor-α (TNF-α), and explored their mode of action on TNF-α signaling pathway. Methods Human umbilical vein endothelial cells (HUVECs) were treated with test substances in the presence of TNF-α for various time periods. The endothelial permeability was measured by using a transwell permeability assay. The localization of cell-to-cell junctional proteins and actin cytoskeletons were visualized by immunostaining. RhoA and Rac activities were assessed by using GTP-binding protein pulldown assay. Gene and protein expression levels of signaling molecules were analyzed by real-time PCR and western blotting, respectively. Results We found that AGE and its major sulfur-containing constituent, S-1-propenylcysteine (S1PC), reduced hyperpermeability elicited by TNF-α in HUVECs. In addition, S1PC inhibited TNF-α-induced production of myosin light chain (MLC) kinase and inactivation of MLC phosphatase through the suppression of the Rac and RhoA signaling pathways, respectively, which resulted in the dephosphorylation of MLC2, a key factor of actin remodeling. Moreover, S1PC inhibited the phosphorylation and activation of guanine nucleotide exchange factor-H1 (GEF-H1), a common upstream key molecule and activator of Rac and RhoA. These effects of S1PC were accompanied by its ability to prevent the disruption of junctional proteins on the cell–cell contact regions and the increase of actin stress fibers induced by TNF-α. Conclusions The present study suggested that AGE and its major constituent, S1PC, improve endothelial barrier disruption through the protection of junctional proteins on plasma membrane.

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Increased blood-brain barrier permeability in contralateral hemisphere predicts worse outcome in acute ischemic stroke after reperfusion therapy

Abstract: BBBP in both the hypoperfusion region and its contralateral mirror region are associated with stroke severity, but only increased BBBP in the contralateral mirror hypoperfusion region relates to worse outcome after reperfusion therapy.

Cited by 12 publications

References 30 publications

Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Relationship between treatment types and blood–brain barrier disruption in patients with acute ischemic stroke: Two case reports

S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway

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