In vivo demonstration of blood-brain barrier impairment in Moyamoya disease

Narducci, Alessandro; Kaku, Yasuyuki; Onken, Julia; Blecharz, Kinga; Vajkoczy, Peter

doi:10.1007/s00701-019-03811-w

Cited by 40 publications

(29 citation statements)

References 37 publications

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“…The present study showed that serum Ang-2 levels were significantly higher in patients with adult HMMD, and the ROC curve also identified that serum Ang-2 levels > 1230 ng/ml may be associated with the occurrence of adult HMMD with 88.39% sensitivity and 70.37% specificity. Although some previous studies also demonstrated that Ang-2 expression was significantly overexpressed in the M3 segment of MCA from patients with MMD [32,33], the upregulation of Ang-2 in MCA did not influence the concentration of Ang-2 in the circulation of MMD patients [32]. However, these results are not contradictory to our research, because the conclusion is based on the comparison with atherosclerotic cerebrovascular disease.…”

Section: Biomed Research Internationalcontrasting

confidence: 92%

Significance of Serum Angiopoietin-2 in Patients with Hemorrhage in Adult-Onset Moyamoya Disease

Huang

Pan

et al. 2020

BioMed Research International

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Background. Moyamoya disease (MMD) is a progressive occlusive cerebrovascular disease that is characterized by abnormal angiogenesis at the base of the brain. This pathological abnormal angiogenesis is susceptible to disturbances, including spontaneous hemorrhage and vasogenic edema. However, the underlying mechanisms of pathological angiogenesis and occurrence of hemorrhage are unclear. Angiopoietins play a fundamental role in the pathophysiology of central nervous system disorders in angiogenesis. This study was aimed at examining whether angiopoietins are associated with formation of abnormal collateral vessels and the occurrence of hemorrhage in adult-onset moyamoya disease (HMMD). Methods. A total of 27 consecutive adult patients with HMMD were enrolled from June 2011 to May 2017. Serum levels of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) were examined by enzyme-linked immunosorbent assay. Patients with HMMD were compared with those with spontaneous hemorrhage (controls) and nonhemorrhagic-onset MMD (NHMMD). Results. Serum Ang-2 levels were significantly higher in patients with adult HMMD than in those with spontaneous hemorrhage and NHMMD. The ROC curve identified that a baseline serum Ang-2 level>1230 ng/ml may be associated with adult HMMD with 88.39% sensitivity and 70.37% specificity (area under the curve (AUC), 0.89; 95% CI, 0.808-0.973; P<0.001). Moreover, serum Ang-2 levels were significantly elevated in stages II, III, and IV. In subgroup analysis of a high and low degree of moyamoya vessels, serum Ang-2 levels were significantly higher in the high moyamoya vessel group than in the low moyamoya vessel group. Serum Ang-2 levels were also significantly higher in the low moyamoya vessel group compared with the control group. Serum Ang-1 levels were not significantly different among the groups. Conclusion. Increased serum Ang-2 levels may contribute to pathological abnormal angiogenesis and/or to the instability of vascular structure and function, thus causing brain hemorrhage in adult HMMD.

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Section: Biomed Research Internationalcontrasting

confidence: 92%

Significance of Serum Angiopoietin-2 in Patients with Hemorrhage in Adult-Onset Moyamoya Disease

Huang

Pan

et al. 2020

BioMed Research International

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“…In support, children with MMD exhibited elevated levels of soluble endothelial adhesion molecules in CSF, indicating neuroinflammation followed by the disruption of the BBB [33]. A videoangiographic comparison of sodium fluorescein extravasation between patients with MMD, aterosclerotic cerebrovascular disease controls, and nonischemic controls revealed a compromised BBB in MMD [34]. The perturbation of the BBB may result in increased entry of inflammatory cytokines into the CNS from the peripheral enteric nervous system.…”

Section: Discussionmentioning

confidence: 95%

Association of Brain-Gut Peptides with Inflammatory Cytokines in Moyamoya Disease

Han

Jin

Zhang

et al. 2020

Mediators of Inflammation

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Systemic inflammation has been shown to play a pivotal role in the pathogenesis of moyamoya disease (MMD). Brain-gut peptides exhibit regulatory effects in the secretion of proinflammatory cytokines. To investigate the association between brain-gut peptides and inflammation in the occurrence of MMD, 41 patients with MMD, as well as 74 age- and sex-matched healthy individuals were enrolled. The levels of four brain-gut peptides (vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), somatostatin (SST), substance P (SP)) and three proinflammatory cytokines (interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-12) in the serum and cerebrospinal fluid (CSF) were measured using the enzyme-linked immunosorbent assay. The associations between brain-gut peptides and proinflammatory cytokines were estimated according to the multiple linear regression and correlation analyses. MMD patients exhibited significantly lower levels of VIP, CCK, and SST and higher levels of IL-1β, TNF-α, and IL-12 in the serum compared with healthy controls. Multiple logistic regression analysis showed that decreased VIP, CCK, and SST levels were independent predictors of the occurrence of MMD. Negative correlations were observed between the VIP and proinflammatory cytokines, including IL-1β, TNF-α, and IL-12 (serum vs. CSF). Significant negative correlations were also found between CCK and IL-1β, as well as IL-12 (serum vs. CSF). SST was negatively correlated with IL-1β and TNF-α in the serum and IL-1β only in the CSF. In addition, the levels of VIP, CCK, SST, and proinflammatory cytokines IL-1β and TNF-α in the serum were correlated with those measured in the CSF. Collectively, lower levels of VIP, CCK, and SST may be associated with the pathogenesis of MMD and act as clinically useful biomarkers along with the levels of proinflammatory cytokines.

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“…CLE imaging could be used to further investigate this phenomenon. Wide‐field fluorescein 31 and ICG 32 angiography have been used to investigate clinically relevant microcirculatory hemodynamics and blood‐brain barrier changes in patients with moyamoya disease 33 . In cerebrovascular bypass procedures, fluorescein angiography is a cost‐effective, fast, and safe intraoperative tool to assess patency of the anastomosis 34 .…”

Section: Discussionmentioning

confidence: 99%

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

et al. 2021

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Intraoperative visualization of blood flow characteristics is of keen interest during many neurosurgical procedures. Development of cerebral videoangiography with fluorescein sodium 1 and indocyanine green (ICG) 2,3 as contrast agents has provided extraordinarily useful intraoperative methods for neurosurgeons to rapidly assess blood flow in cerebral vessels. Although wide-field fluorescence imaging techniques with fluorescein and ICG are used extensively, their main drawbacks are the short temporal imaging resolution, which often requires several reinjections of the fluorophores, and the inability to resolve the flow of erythrocytes in the microvasculature of the microcirculatory network.

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In vivo demonstration of blood-brain barrier impairment in Moyamoya disease

Cited by 40 publications

References 37 publications

Significance of Serum Angiopoietin-2 in Patients with Hemorrhage in Adult-Onset Moyamoya Disease

Significance of Serum Angiopoietin-2 in Patients with Hemorrhage in Adult-Onset Moyamoya Disease

Association of Brain-Gut Peptides with Inflammatory Cytokines in Moyamoya Disease

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

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