Blood-brain Barrier Disruption May Contribute to White Matter Lesions in the Setting of Internal Jugular Venous Stenosis

Author(s): Yali Wu, Ran Meng, Gary B. Rajah, Yuchuan Ding, Yaoming Xu, Xunming Ji*

Journal Name: Current Neurovascular Research

Volume 16 , Issue 4 , 2019

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Background and Purpose: Cloudy white matter lesions are associated imaging features of internal jugular venous stenosis (IJVS). However, the mechanism of the IJVS associated cloudy white matter lesions is still unclear. This study aims to evaluate blood-brain barrier integrity of the patients with IJVS.

Materials and Methods: A total of 45 eligible patients with IJVS confirmed by computed tomography venography (CTV) and 45 healthy controls were enrolled into this study. The levels of serum MMP-9 and the markers of tight junctions, including occludin and ZO-1 obtained from IJVS patients and control group were tested by enzyme-linked immune-sorbent assay and compared.

Results: Both the levels of serum MMP-9 (0.2ng/ml) and occludin (0.05ng/ml) in IJVS group were higher than in the control group (0.01ng/ml vs. 0 ng/ml, all p<0.001). While, the levels of serum ZO-1 showed no statistical significance between the two groups (0.55ng/ml vs 0.735ng/ml, P=0.34). The levels of serum MMP-9 between the subset with or without white matter lesions in IJVS group showed a significant difference (0.22 [0.06, 0.43] vs. 0.01 [0.01, 0.06], P =0.019).

Conclusion: BBB disruption may participate in the formation of IJVS-associated white matter lesions; the mechanism of BBB disruption may involve MMP-9 and occludin.

Keywords: Internal Jugular Venous Stenosis (IJVS), blood-brain barrier, occludin, ZO-1, matrix metalloproteinase-9, white matter lesions, neurological diseases.

Zhou D, Ding JY, Ya JY, et al. Understanding jugular venous outflow disturbance. CNS Neurosci Ther 2018; 24(6): 473-82.
[] [PMID: 29687619]
Lin J, Lan L, Wang D, Qiu B, Fan Y. Cerebral venous collagen remodeling in a modified white matter lesions animal model. Neuroscience 2017; 367: 72-84.
[] [PMID: 29111361]
Chung CP, Beggs C, Wang PN, et al. Jugular venous reflux and white matter abnormalities in Alzheimer’s disease: A pilot study. J Alzheimers Dis 2014; 39(3): 601-9.
[] [PMID: 24217278]
Ding J, Zhou D, Geng T, et al. To predict visual deterioration according to the degree of intracranial hypertension in patients with cerebral venous sinus thrombosis. Eur Neurol 2018; 80(1-2): 28-33.
[] [PMID: 30134236]
Nakase H, Nagata K, Otsuka H, Sakaki T, Kempski O. Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat. J Neurosurg 1998; 89(1): 118-24.
[] [PMID: 9647182]
Zhou D, Meng R, Zhang X, et al. Intracranial hypertension induced by internal jugular vein stenosis can be resolved by stenting. Eur J Neurol 2018; 25(2): 365-e13.
[] [PMID: 29114973]
Müller LO, Toro EF, Haacke EM, Utriainen D. Impact of CCSVI on cerebral haemodynamics: A mathematical study using MRI angiographic and flow data. Phlebology 2016; 31(5): 305-24.
[] [PMID: 26036249]
Zivadinov R, Chung CP. Potential involvement of the extracranial venous system in central nervous system disorders and aging. BMC Med 2013; 11: 260.
[] [PMID: 24344742]
Lin J, Wang D, Lan L, Fan Y. multiple factors involved in the pathogenesis of white matter lesions. BioMed Res Int 2017; 20179372050
[] [PMID: 28316994]
Fan Y, Yang X, Tao Y, Lan L, Zheng L, Sun J. Tight junction disruption of blood-brain barrier in white matter lesions in chronic hypertensive rats. Neuroreport 2015; 26(17): 1039-43.
[] [PMID: 26426859]
Diaz R, Miguel PM, Deniz BF, et al. Environmental enrichment attenuates the blood brain barrier dysfunction induced by the neonatal hypoxia-ischemia. Int J Dev Neurosci 2016; 53: 35-45.
[] [PMID: 27326908]
Tajes M, Ramos-Fernández E, Weng-Jiang X, et al. The blood-brain barrier: Structure, function and therapeutic approaches to cross it. Mol Membr Biol 2014; 31(5): 152-67.
[] [PMID: 25046533]
Shi S, Qi Z, Ma Q, et al. Normobaric hyperoxia reduces blood occludin fragments in rats and patients with acute ischemic stroke. Stroke 2017; 48(10): 2848-54.
[] [PMID: 28931617]
Egashira Y, Zhao H, Hua Y, Keep RF, Xi G. White matter injury after subarachnoid hemorrhage: Role of blood-brain barrier disruption and matrix metalloproteinase-9. Stroke 2015; 46(10): 2909-15.
[] [PMID: 26374478]
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 1987; 149(2): 351-6.
[] [PMID: 3496763]
Zaharchuk G, Fischbein NJ, Rosenberg J, Herfkens RJ, Dake MD. Comparison of MR and contrast venography of the cervical venous system in multiple sclerosis. AJNR Am J Neuroradiol 2011; 32(8): 1482-9.
[] [PMID: 21757521]
van Agtmaal MJM, Houben AJHM, Pouwer F, Stehouwer CDA, Schram MT. Association of microvascular dysfunction with late-life depression: A systematic review and meta-analysis. JAMA Psychiatry 2017; 74(7): 729-39.
[] [PMID: 28564681]
Kuchel GA, Moscufo N, Guttmann CR, et al. Localization of brain white matter hyperintensities and urinary incontinence in community-dwelling older adults. J Gerontol A Biol Sci Med Sci 2009; 64(8): 902-9.
[] [PMID: 19386575]
Au R, Massaro JM, Wolf PA, et al. Association of white matter hyperintensity volume with decreased cognitive functioning: The framingham heart study. Arch Neurol 2006; 63(2): 246-50.
[] [PMID: 16476813]
Abdullahi W, Tripathi D, Ronaldson PT. Blood-brain barrier dysfunction in ischemic stroke: Targeting tight junctions and transporters for vascular protection. Am J Physiol Cell Physiol 2018; 315(3): C343-56.
[] [PMID: 29949404]
Zhou D, Ding J, Asmaro K, et al. Clinical characteristics and neuroimaging findings in internal jugular venous outflow disturbance. Thromb Haemost 2019; 119(2): 308-18.
[] [PMID: 30605919]
Bai C, Xu Y, Zhou D, et al. The comparative analysis of non-thrombotic internal jugular vein stenosis and cerebral venous sinus stenosis. J Thromb Thrombolysis 2019; 48(1): 61-7.
[] [PMID: 30689154]
Chung CP, Hsu HY, Chao AC, Cheng CY, Lin SJ, Hu HH. Jugular venous reflux affects ocular venous system in transient monocular blindness. Cerebrovasc Dis 2010; 29(2): 122-9.
[] [PMID: 19955735]
Schaller B, Graf R. Cerebral venous infarction: The pathophysiological concept. Cerebrovasc Dis 2004; 18(3): 179-88.
[] [PMID: 15273432]
Jiao X, He P, Li Y, et al. The role of circulating tight junction proteins in evaluating blood brain barrier disruption following intracranial hemorrhage. Dis Markers 2015; 2015860120
[] [PMID: 26586924]
Li W, Pan R, Qi Z, Liu KJ. Current progress in searching for clinically useful biomarkers of blood-brain barrier damage following cerebral ischemia. Brain Circ 2018; 4(4): 145-52.
[] [PMID: 30693340]
Qi Z, Liang J, Pan R, et al. Zinc contributes to acute cerebral ischemia-induced blood-brain barrier disruption. Neurobiol Dis 2016; 95: 12-21.
[] [PMID: 27388935]
Li N, Liu YF, Ma L, et al. Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage. Stroke 2013; 44(3): 658-63.
[] [PMID: 23391772]
Higgins JN, Garnett MR, Pickard JD, Axon PR. An evaluation of styloidectomy as an adjunct or alternative to jugular stenting in idiopathic intracranial hypertension and disturbances of cranial venous outflow. J Neurol Surg B Skull Base 2017; 78(2): 158-63.
[PMID: 28321380]
Gianesini S, Menegatti E, Mascoli F, Salvi F, Bastianello S, Zamboni P. The omohyoid muscle entrapment of the internal jugular vein. A still unclear pathogenetic mechanism. Phlebology 2014; 29(9): 632-5.
[] [PMID: 23761870]
Ding JY, Zhou D, Pan LQ, et al. Cervical spondylotic internal jugular venous compression syndrome. CNS Neurosci Ther 2019. [Epub ahead of Print]
[] [PMID: 31119898]
Kim Y, Kim YK, Kim NK, Kim SH, Kim OJ, Oh SH. Circulating matrix metalloproteinase-9 level is associated with cerebral white matter hyperintensities in non-stroke individuals. Eur Neurol 2014; 72(3-4): 234-40.
[] [PMID: 25248031]
Yang Y, Kimura-Ohba S, Thompson JF, et al. Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury. Neurobiol Dis 2018; 114: 95-110.
[] [PMID: 29486300]
Atkinson W, Forghani R, Wojtkiewicz GR, et al. Ligation of the jugular veins does not result in brain inflammation or demyelination in mice. PLoS One 2012; 7(3)e33671
[] [PMID: 22457780]
Annunziata P, Cioni C, Masi G, Tassi M, Marotta G, Severi S. Fingolimod reduces circulating tight-junction protein levels and in vitro peripheral blood mononuclear cells migration in multiple sclerosis patients. Sci Rep 2018; 8(1): 15371.
[] [PMID: 30337577]
Zamboni P, Tesio L, Galimberti S, et al. Efficacy and safety of extracranial vein angioplasty in multiple sclerosis: A randomized clinical trial. JAMA Neurol 2018; 75(1): 35-43.
[] [PMID: 29150995]

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Article Details

Year: 2019
Published on: 23 December, 2019
Page: [328 - 334]
Pages: 7
DOI: 10.2174/1567202616666191001110421
Price: $65

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