Research progress on the correlation between blood-brain barrier and cerebral small vessel disease

doi:10.3969/j.issn.1672-6731.2023.11.004

Abstract

Abstract:

Cerebral small vessel disease (CSVD) is a leading cause of stoke and vascular dementia, and its pathogenesis remains unclear. Research on brain histopathology has identified that the blood-brain barrier plays a crucial role in the pathogenesis and progression of CSVD. This article reviews the research progress on the correlation between blood-brain barrier and CSVD from imaging biomarkers, blood biomarkers and pathophysiology, to provide ideas for better diagnosis and treatment of CSVD.

Key words: Cerebral small vessel disease, Blood-brain barrier, Review

摘要：

脑小血管病是脑卒中和血管性痴呆的常见病因，其潜在发病机制尚不清楚。病理学研究证实，血脑屏障损伤在脑小血管病发病机制中发挥重要作用。本文从影像学标志物、生物学标志物、病理生理学机制等方面对血脑屏障与脑小血管病相关研究最新进展进行综述，以为脑小血管病的诊断提供依据，并为其治疗提供潜在干预靶点。

关键词: 大脑小血管疾病, 血脑屏障, 综述

Qian-qian KONG, Hao HUANG, Xiang LUO. Research progress on the correlation between blood-brain barrier and cerebral small vessel disease[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2023, 23(11): 972-977.

孔倩倩, 黄浩, 骆翔. 血脑屏障与脑小血管病相关研究进展[J]. 中国现代神经疾病杂志, 2023, 23(11): 972-977.

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References 44

1	Wardlaw JM , Smith C , Dichgans M . Small vessel disease: mechanisms and clinical implications. Lancet Neurol, 2019, 18: 684- 696. doi: 10.1016/S1474-4422(19)30079-1
2	Duering M , Biessels GJ , Brodtmann A , Chen C , Cordonnier C , de Leeuw FE , Debette S , Frayne R , Jouvent E , Rost NS , Ter Telgte A , Al-Shahi Salman R , Backes WH , Bae HJ , Brown R , Chabriat H , De Luca A , deCarli C , Dewenter A , Doubal FN , Ewers M , Field TS , Ganesh A , Greenberg S , Helmer KG , Hilal S , Jochems ACC , Jokinen H , Kuijf H , Lam BYK , Lebenberg J , MacIntosh BJ , Maillard P , Mok VCT , Pantoni L , Rudilosso S , Satizabal CL , Schirmer MD , Schmidt R , Smith C , Staals J , Thrippleton MJ , van Veluw SJ , Vemuri P , Wang Y , Werring D , Zedde M , Akinyemi RO , Del Brutto OH , Markus HS , Zhu YC , Smith EE , Dichgans M , Wardlaw JM . Neuroimaging standards for research into small vessel disease: advances since 2013. Lancet Neurol, 2023, 22: 602- 618. doi: 10.1016/S1474-4422(23)00131-X
3	Writing Group of the "Consensus of Experts on the Diagnosis and Treatment of Cerebrovascular Diseases in China", Professional Committee of Cerebrovascular Diseases of the Chinese Research Hospital Association . Expert consensus on diagnosis and treatment of cerebrovascular diseases in China, 2021. Zhongguo Zu Zhong Za Zhi, 2021, 16: 716- 726. doi: 10.3969/j.issn.1673-5765.2021.07.013
	中国研究型医院学会脑小血管病专业委员会《中国脑小血管病诊治专家共识》编写组. 中国脑小血管病诊治专家共识2021. 中国卒中杂志, 2021, 16: 716- 726. doi: 10.3969/j.issn.1673-5765.2021.07.013
4	Thrippleton MJ , Backes WH , Sourbron S , Ingrisch M , van Osch MJP , Dichgans M , Fazekas F , Ropele S , Frayne R , van Oostenbrugge RJ , Smith EE , Wardlaw JM . Quantifying blood-brain barrier leakage in small vessel disease: review and consensus recommendations. Alzheimers Dement, 2019, 15: 840- 858. doi: 10.1016/j.jalz.2019.01.013
5	Smith EE , Biessels GJ , De Guio F , de Leeuw FE , Duchesne S , Düring M , Frayne R , Ikram MA , Jouvent E , MacIntosh BJ , Thrippleton MJ , Vernooij MW , Adams H , Backes WH , Ballerini L , Black SE , Chen C , Corriveau R , DeCarli C , Greenberg SM , Gurol ME , Ingrisch M , Job D , Lam BYK , Launer LJ , Linn J , McCreary CR , Mok VCT , Pantoni L , Pike GB , Ramirez J , Reijmer YD , Romero JR , Ropele S , Rost NS , Sachdev PS , Scott CJM , Seshadri S , Sharma M , Sourbron S , Steketee RME , Swartz RH , van Oostenbrugge R , van Osch M , van Rooden S , Viswanathan A , Werring D , Dichgans M , Wardlaw JM . Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration. Alzheimers Dement (Amst), 2019, 11: 191- 204. doi: 10.1016/j.dadm.2019.01.002
6	Chai AB , Callaghan R , Gelissen IC . Regulation of P-glycoprotein in the brain. Int J Mol Sci, 2022, 23: 14667. doi: 10.3390/ijms232314667
7	Shao X , Ma SJ , Casey M , D'Orazio L , Ringman JM , Wang DJJ . Mapping water exchange across the blood-brain barrier using 3D diffusion-prepared arterial spin labeled perfusion MRI. Magn Reson Med, 2019, 81: 3065- 3079. doi: 10.1002/mrm.27632
8	Dobrynina LA , Shamtieva KV , Kremneva EI , Zabitova MR , Akhmetzyanov BM , Gnedovskaya EV , Krotenkova MV . Daily blood pressure profile and blood-brain barrier permeability in patients with cerebral small vessel disease. Sci Rep, 2022, 12: 7723. doi: 10.1038/s41598-022-11172-1
9	Li Y , Li M , Zhang X , Shi Q , Yang S , Fan H , Qin W , Yang L , Yuan J , Jiang T , Hu W . Higher blood-brain barrier permeability is associated with higher white matter hyperintensities burden. J Neurol, 2017, 264: 1474- 1481. doi: 10.1007/s00415-017-8550-8
10	Stringer MS , Heye AK , Armitage PA , Chappell F , Valdés Hernández MDC , Makin SDJ , Sakka E , Thrippleton MJ , Wardlaw JM . Tracer kinetic assessment of blood-brain barrier leakage and blood volume in cerebral small vessel disease: associations with disease burden and vascular risk factors. Neuroimage Clin, 2021, 32: 102883. doi: 10.1016/j.nicl.2021.102883
11	Wong SM , Jansen JFA , Zhang CE , Hoff EI , Staals J , van Oostenbrugge RJ , Backes WH . Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease. Neurology, 2019, 92: e1669- e1677. doi: 10.1212/WNL.0000000000007263
12	Freeze WM , Jacobs HIL , de Jong JJ , Verheggen ICM , Gronenschild EHBM , Palm WM , Hoff EI , Wardlaw JM , Jansen JFA , Verhey FR , Backes WH . White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed. Neurobiol Aging, 2020, 85: 113- 122. doi: 10.1016/j.neurobiolaging.2019.09.017
13	Wardlaw JM , Doubal FN , Valdes-Hernandez M , Wang X , Chappell FM , Shuler K , Armitage PA , Carpenter TC , Dennis MS . Blood-brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease. Stroke, 2013, 44: 525- 527. doi: 10.1161/STROKEAHA.112.669994
14	Walsh J , Tozer DJ , Sari H , Hong YT , Drazyk A , Williams G , Shah NJ , O'Brien JT , Aigbirhio FI , Rosenberg G , Fryer TD , Markus HS . Microglial activation and blood-brain barrier permeability in cerebral small vessel disease. Brain, 2021, 144: 1361- 1371. doi: 10.1093/brain/awab003
15	Kerkhofs D , Wong SM , Zhang E , Uiterwijk R , Hoff EI , Jansen JFA , Staals J , Backes WH , van Oostenbrugge RJ . Blood-brain barrier leakage at baseline and cognitive decline in cerebral small vessel disease: a 2-year follow-up study. Geroscience, 2021, 43: 1643- 1652. doi: 10.1007/s11357-021-00399-x
16	Zhang CE , Wong SM , Uiterwijk R , Backes WH , Jansen JFA , Jeukens CRLPN , van Oostenbrugge RJ , Staals J . Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging. Brain Imaging Behav, 2019, 13: 389- 395. doi: 10.1007/s11682-018-9855-7
17	Kerkhofs D , Wong SM , Zhang E , Staals J , Jansen JFA , van Oostenbrugge RJ , Backes WH . Baseline blood-brain barrier leakage and longitudinal microstructural tissue damage in the periphery of white matter hyperintensities. Neurology, 2021, 96: e2192- e2200. doi: 10.1212/WNL.0000000000011783
18	Chen YC , Lu BZ , Shu YC , Sun YT . Spatiotemporal dynamics of cerebral vascular permeability in type 2 diabetes-related cerebral microangiopathy. Front Endocrinol (Lausanne), 2022, 12: 805637. doi: 10.3389/fendo.2021.805637
19	Li Y , Li M , Yang L , Qin W , Yang S , Yuan J , Jiang T , Hu W . The relationship between blood-brain barrier permeability and enlarged perivascular spaces: a cross-sectional study. Clin Interv Aging, 2019, 14: 871- 878. doi: 10.2147/CIA.S204269
20	Gattringer T , Valdes Hernandez M , Heye A , Armitage PA , Makin S , Chappell F , Pinter D , Doubal F , Enzinger C , Fazekas F , Wardlaw JM . Predictors of lesion cavitation after recent small subcortical stroke. Transl Stroke Res, 2020, 11: 402- 411. doi: 10.1007/s12975-019-00741-8
21	Bakhtiari A , Vestergaard MB , Benedek K , Fagerlund B , Mortensen EL , Osler M , Lauritzen M , Larsson HBW , Lindberg U . Changes in hippocampal volume during a preceding 10-year period do not correlate with cognitive performance and hippocampal blood-brain barrier permeability in cognitively normal late-middle-aged men. Geroscience, 2023, 45: 1161- 1175. doi: 10.1007/s11357-022-00712-2
22	Li Y , Li M , Zuo L , Shi Q , Qin W , Yang L , Jiang T , Hu W . Compromised blood-brain barrier integrity is associated with total magnetic resonance imaging burden of cerebral small vessel disease. Front Neurol, 2018, 9: 221. doi: 10.3389/fneur.2018.00221
23	Wang X , Chappell FM , Valdes Hernandez M , Lowe G , Rumley A , Shuler K , Doubal F , Wardlaw JM . Endothelial function, inflammation, thrombosis, and basal ganglia perivascular spaces in patients with stroke. J Stroke Cerebrovasc Dis, 2016, 25: 2925- 2931. doi: 10.1016/j.jstrokecerebrovasdis.2016.08.007
24	Sun J , Ou W , Han D , Paganini-Hill A , Fisher MJ , Sumbria RK . Comparative studies between the murine immortalized brain endothelial cell line (bEnd.3) and induced pluripotent stem cell-derived human brain endothelial cells for paracellular transport. PLoS One, 2022, 17: e0268860. doi: 10.1371/journal.pone.0268860
25	Chung CP , Peng LN , Chou KH , Liu LK , Lee WJ , Lin CP , Chen LK , Wang PN . High circulatory phosphate level is associated with cerebral small-vessel diseases. Transl Stroke Res, 2019, 10: 265- 272. doi: 10.1007/s12975-018-0639-6
26	Hassan A , Hunt BJ , O'Sullivan M , Parmar K , Bamford JM , Briley D , Brown MM , Thomas DJ , Markus HS . Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain, 2003, 126 (Pt 2): 424- 432. URL
27	Dobrynina LA , Shabalina AA , Zabitova MR , Kremneva EI , Gadzhieva ZS , Krotenkova MV , Gnedovskaya EV , Berdalin AB , Kalashnikova LA . Tissue plasminogen activator and MRI signs of cerebral small vessel disease. Brain Sci, 2019, 9: 266. doi: 10.3390/brainsci9100266
28	Rouhl RP , Damoiseaux JG , Lodder J , Theunissen RO , Knottnerus IL , Staals J , Henskens LH , Kroon AA , de Leeuw PW , Tervaert JW , van Oostenbrugge RJ . Vascular inflammation in cerebral small vessel disease. Neurobiol Aging, 2012, 33: 1800- 1806. doi: 10.1016/j.neurobiolaging.2011.04.008
29	Noz MP , Ter Telgte A , Wiegertjes K , Tuladhar AM , Kaffa C , Kersten S , Bekkering S , van der Heijden CDCC , Hoischen A , Joosten LAB , Netea MG , Duering M , de Leeuw FE , Riksen NP . Pro-inflammatory monocyte phenotype during acute progression of cerebral small vessel disease. Front Cardiovasc Med, 2021, 8: 639361. doi: 10.3389/fcvm.2021.639361
30	Zhao J , Li Q , Meng L , Wang F , Li Q , Yang F , Wang M , Yu M , Zhang J , Li S , Ji S . Relationship between MMP-9 serum levels and tHcy levels and total imaging load and cognitive dysfunction. J Stroke Cerebrovasc Dis, 2022, 31: 106759. doi: 10.1016/j.jstrokecerebrovasdis.2022.106759
31	Elahi FM , Casaletto KB , Altendahl M , Staffaroni AM , Fletcher E , Filshtein TJ , Glymour MM , Miller BL , Hinman JD , DeCarli C , Goetzl EJ , Kramer JH . "Liquid biopsy" of white matter hyperintensity in functionally normal elders. Front Aging Neurosci, 2018, 10: 343. doi: 10.3389/fnagi.2018.00343
32	Yadav BK , Yadav R , Kang HG , Kim KW , Lee CH , Shin BS . Association of genetic variation in a Wnt signaling pathway gene (β-catenin) with susceptibility to leukoaraiosis. Genet Test Mol Biomarkers, 2020, 24: 708- 716. doi: 10.1089/gtmb.2020.0111
33	Yadav BK , Shin BS . Single-nucleotide polymorphisms of the adherent junction component cadherin gene are associated with leukoaraiosis. Gene, 2018, 676: 65- 72. doi: 10.1016/j.gene.2018.07.007
34	Tachikawa M , Murakami K , Akaogi R , Akanuma SI , Terasaki T , Hosoya KI . Polarized hemichannel opening of pannexin 1/connexin 43 contributes to dysregulation of transport function in blood-brain barrier endothelial cells. Neurochem Int, 2020, 132: 104600. doi: 10.1016/j.neuint.2019.104600
35	Zhang J , You Q , Shu J , Gang Q , Jin H , Yu M , Sun W , Zhang W , Huang Y . GJA1 gene polymorphisms and topographic distribution of cranial MRI lesions in cerebral small vessel disease. Front Neurol, 2020, 11: 583974. doi: 10.3389/fneur.2020.583974
36	Candelario-Jalil E , Dijkhuizen RM , Magnus T . Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities. Stroke, 2022, 53: 1473- 1486. doi: 10.1161/STROKEAHA.122.036946
37	Zhang M , Zhu W , Yun W , Wang Q , Cheng M , Zhang Z , Liu X , Zhou X , Xu G . Correlation of matrix metalloproteinase-2 single nucleotide polymorphisms with the risk of small vessel disease (SVD). J Neurol Sci, 2015, 356: 61- 64. doi: 10.1016/j.jns.2015.04.056
38	Fernandez-Cadenas I , Mendioroz M , Domingues-Montanari S , Del Rio-Espinola A , Delgado P , Ruiz A , Hernandez-Guillamon M , Giralt D , Chacon P , Navarro-Sobrino M , Ribo M , Molina CA , Alvarez-Sabin J , Rosell A , Montaner J . Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients. Eur J Neurol, 2011, 18: 826- 835. doi: 10.1111/j.1468-1331.2010.03243.x
39	Knox EG , Aburto MR , Clarke G , Cryan JF , O'Driscoll CM . The blood-brain barrier in aging and neurodegeneration. Mol Psychiatry, 2022, 27: 2659- 2673. doi: 10.1038/s41380-022-01511-z
40	Li CC , Chen WX , Wang J , Xia M , Jia ZC , Guo C , Tang XQ , Li MX , Yin Y , Liu X , Feng H . Nicotinamide riboside rescues angiotensin Ⅱ-induced cerebral small vessel disease in mice. CNS Neurosci Ther, 2020, 26: 438- 447. doi: 10.1111/cns.13276
41	Toyama K , Spin JM , Deng AC , Huang TT , Wei K , Wagenhäuser MU , Yoshino T , Nguyen H , Mulorz J , Kundu S , Raaz U , Adam M , Schellinger IN , Jagger A , Tsao PS . MicroRNA-mediated therapy modulating blood-brain barrier disruption improves vascular cognitive impairment. Arterioscler Thromb Vasc Biol, 2018, 38: 1392- 1406. doi: 10.1161/ATVBAHA.118.310822
42	Sun Z , Gao C , Gao D , Sun R , Li W , Wang F , Wang Y , Cao H , Zhou G , Zhang J , Shang J . Reduction in pericyte coverage leads to blood-brain barrier dysfunction via endothelial transcytosis following chronic cerebral hypoperfusion. Fluids Barriers CNS, 2021, 18: 21. doi: 10.1186/s12987-021-00255-2
43	Huang J , Li J , Feng C , Huang X , Wong L , Liu X , Nie Z , Xi G . Blood-brain barrier damage as the starting point of leukoaraiosis caused by cerebral chronic hypoperfusion and its involved mechanisms: effect of agrin and aquaporin-4. Biomed Res Int, 2018, 2018: 2321797.
44	Miyamoto N , Pham LD , Maki T , Liang AC , Arai K . A radical scavenger edaravone inhibits matrix metalloproteinase-9 upregulation and blood-brain barrier breakdown in a mouse model of prolonged cerebral hypoperfusion. Neurosci Lett, 2014, 573: 40- 45. doi: 10.1016/j.neulet.2014.05.005

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