REFERENCES
1. Montagne A, Nation DA, Sagare AP, et al. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. Nature 2020;581:71-6.
2. Sweeney MD, Montagne A, Sagare AP, et al. Vascular dysfunction-the disregarded partner of Alzheimer's disease. Alzheimers Dement 2019;15:158-67.
3. Wevers NR, De Vries HE. Microfluidic models of the neurovascular unit: a translational view. Fluids Barriers CNS 2023;20:86.
4. Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood-brain barrier. Cell 2015;163:1064-78.
5. Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012;4:147ra111.
6. Nedergaard M, Goldman SA. Glymphatic failure as a final common pathway to dementia. Science 2020;370:50-6.
7. Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The glymphatic system: a beginner’s guide. Neurochem Res 2015;40:2583-99.
8. Backhouse EV, Boardman JP, Wardlaw JM. Cerebral small vessel disease: early-life antecedents and long-term implications for the brain, aging, stroke, and dementia. Hypertension 2024;81:54-74.
9. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013;12:483-97.
10. Abdul Hamid H, Hambali A, Okon U, et al. Is cerebral small vessel disease a central nervous system interstitial fluidopathy? IBRO Neurosci Rep 2024;16:98-105.
11. Duering M, Biessels GJ, Brodtmann A, et al. Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol 2023;22:602-18.
12. Frisoni GB, van der Flier W. STRIVEing to describe small vessel disease. Lancet Neurol 2023;22:548-9.
13. Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol 2019;18:684-96.
14. Osmaniye D, Ahmad I, Sağlık BN, et al. Design, synthesis and molecular docking and ADME studies of novel hydrazone derivatives for AChE inhibitory, BBB permeability and antioxidant effects. J Biomol Struct Dyn 2023;41:9022-38.
15. Lee MJ, Jang Y, Han J, et al. Endothelial-specific Crif1 deletion induces BBB maturation and disruption via the alteration of actin dynamics by impaired mitochondrial respiration. J Cereb Blood Flow Metab 2020;40:1546-61.
16. Zhang R, Huang P, Wang S, et al. Decreased cerebral blood flow and delayed arterial transit are independently associated with white matter hyperintensity. Front Aging Neurosci 2022;14:762745.
17. Chen J, Li CG, Yang LX, et al. MYPT1(SMKO) mice function as a novel spontaneous age- and hypertension-dependent animal model of CSVD. Transl Stroke Res 2024;15:606-19.
19. Taoka T, Naganawa S. Imaging for central nervous system (CNS) interstitial fluidopathy: disorders with impaired interstitial fluid dynamics. Jpn J Radiol 2021;39:1-14.
20. Menaceur C, Gosselet F, Fenart L, Saint-Pol J. The blood-brain barrier, an evolving concept based on technological advances and cell-cell communications. Cells 2021;11:133.
21. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010;37:13-25.
22. Badaut J, Ghersi-Egea JF, Thorne RG, Konsman JP. Blood-brain borders: a proposal to address limitations of historical blood-brain barrier terminology. Fluids Barriers CNS 2024;21:3.
23. Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 2017;96:17-42.
24. Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol 2002;38:323-37.
25. Takata F, Nakagawa S, Matsumoto J, Dohgu S. Blood-brain barrier dysfunction amplifies the development of neuroinflammation: understanding of cellular events in brain microvascular endothelial cells for prevention and treatment of BBB dysfunction. Front Cell Neurosci 2021;15:661838.
26. Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia 2013;61:1939-58.
28. Filosa JA, Iddings JA. Astrocyte regulation of cerebral vascular tone. Am J Physiol Heart Circ Physiol 2013;305:H609-19.
29. Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci 2007;10:1369-76.
30. Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 2009;32:638-47.
31. Winkler EA, Bell RD, Zlokovic BV. Central nervous system pericytes in health and disease. Nat Neurosci 2011;14:1398-405.
32. Armulik A, Genové G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 2011;21:193-215.
33. Dalkara T, Gursoy-Ozdemir Y, Yemisci M. Brain microvascular pericytes in health and disease. Acta Neuropathol 2011;122:1-9.
34. Proebstl D, Voisin MB, Woodfin A, et al. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med 2012;209:1219-34.
35. Sagare AP, Bell RD, Zlokovic BV. Neurovascular dysfunction and faulty amyloid β-peptide clearance in Alzheimer disease. Cold Spring Harb Perspect Med 2012;2:a011452.
36. del Río-Hortega Bereciartu J. Pío del Río-Hortega: the revolution of glia. Anat Rec 2020;303:1232-41.
37. Brown LS, Foster CG, Courtney JM, King NE, Howells DW, Sutherland BA. Pericytes and neurovascular function in the healthy and diseased brain. Front Cell Neurosci 2019;13:282.
38. Rey JA, Farid UM, Najjoum CM, et al. Perivascular network segmentations derived from high-field MRI and their implications for perivascular and parenchymal mass transport in the rat brain. Sci Rep 2023;13:9205.
39. Tremblay MÈ, Lecours C, Samson L, Sánchez-Zafra V, Sierra A. From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia. Front Neuroanat 2015;9:45.
40. Sierra A, de Castro F, Del Río-Hortega J, Rafael Iglesias-Rozas J, Garrosa M, Kettenmann H. The “Big-Bang” for modern glial biology: translation and comments on Pío del Río-Hortega 1919 series of papers on microglia. Glia 2016;64:1801-40.
41. Dudiki T, Meller J, Mahajan G, et al. Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics. Nat Commun 2020;11:986.
42. Haruwaka K, Ikegami A, Tachibana Y, et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat Commun 2019;10:5816.
43. Lehmann ML, Weigel TK, Cooper HA, Elkahloun AG, Kigar SL, Herkenham M. Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility. Sci Rep 2018;8:11240.
44. Pinosanu LR, Capitanescu B, Glavan D, et al. Neuroglia cells transcriptomic in brain development, aging and neurodegenerative diseases. Aging Dis 2023;14:63-83.
45. Domogatskaya A, Rodin S, Tryggvason K. Functional diversity of laminins. Annu Rev Cell Dev Biol 2012;28:523-53.
46. Marchetti L, Engelhardt B. Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation. Vasc Biol 2020;2:H1-18.
47. Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010;468:562-6.
48. Yamazaki Y, Kanekiyo T. Blood-brain barrier dysfunction and the pathogenesis of Alzheimer's disease. Int J Mol Sci 2017;18:1965.
49. Menon DK, Schwab K, Wright DW, Maas AI. The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health. Position statement: definition of traumatic brain injury. Arch Phys Med Rehabil 2010;91:1637-40.
50. Li Y, Li M, Zhang X, et al. Higher blood-brain barrier permeability is associated with higher white matter hyperintensities burden. J Neurol 2017;264:1474-81.
52. Tabdili Y, Belmonte KCD, Brathaban N, et al. Blood-brain barrier dysfunction is associated with A/T/N biomarkers and cognition in the aging brain. Alzheimer's Dementia 2022;18:e066675.
53. Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. Blood-brain barrier: from physiology to disease and back. Physiol Rev 2019;99:21-78.
54. Custodia A, Aramburu-Núñez M, Rodríguez-Arrizabalaga M, et al. Biomarkers assessing endothelial dysfunction in Alzheimer's disease. Cells 2023;12:962.
55. Joo J, Jeong J, Park HJ. Blood biomarkers in patients with parkinson’s disease: a review in context of anesthetic care. Diagnostics 2023;13:693.
56. de Rus Jacquet A, Alpaugh M, Denis HL, et al. The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease. Nat Commun 2023;14:3651.
57. Cash A, Theus MH. Mechanisms of blood-brain barrier dysfunction in traumatic brain injury. Int J Mol Sci 2020;21:3344.
58. Huang J, Lan H, Xie C, et al. Pramipexole protects against traumatic brain injury-induced blood-brain barrier (BBB) dysfunction. Neurotox Res 2022;40:1020-8.
59. Zimmermann J, Nitsch L, Krauthausen M, Müller M. IL-17A facilitates entry of autoreactive T-cells and granulocytes into the CNS during EAE. Neuromol Med 2023;25:350-9.
60. Kamimura D, Murakami M. Neural stimulations regulate the infiltration of immune cells into the CNS. J Intern Med 2019;286:259-67.
61. Vezzani A. Brain autonomous mechanisms of seizure-induced BBB dysfunction: brain pathways to vessels dysfunction. Epilepsy Curr 2012;12:69-71.
62. Mohi-Ud-Din R, Mir RH, Mir PA, et al. Dysfunction of ABC transporters at the surface of BBB: potential implications in intractable epilepsy and applications of nanotechnology enabled drug delivery. Curr Drug Metab 2022;23:735-56.
63. Manukjan N, Ahmed Z, Fulton D, Blankesteijn WM, Foulquier S. A systematic review of WNT signaling in endothelial cell oligodendrocyte interactions: potential relevance to cerebral small vessel disease. Cells 2020;9:1545.
64. Walsh J, Tozer DJ, Sari H, et al. Microglial activation and blood-brain barrier permeability in cerebral small vessel disease. Brain 2021;144:1361-71.
65. Zhang J, You Q, Shu J, et al. GJA1 Gene polymorphisms and topographic distribution of cranial MRI lesions in cerebral small vessel disease. Front Neurol 2020;11:583974.
66. Erickson MA, Banks WA. Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease. J Cereb Blood Flow Metab 2013;33:1500-13.
67. Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006;7:41-53.
68. Nelson JW, Ganesh P, Ajami N, Bryan R, Durgan D. Gut dysbiosis in the development of cerebral small vessel disease. FASEB J 2018;32:582-4.
69. Shi Y, Wardlaw JM. Update on cerebral small vessel disease: a dynamic whole-brain disease. Stroke Vasc Neurol 2016;1:83-92.
70. Mustapha M, Nassir CMNCM, Aminuddin N, Safri AA, Ghazali MM. Cerebral small vessel disease (CSVD) - lessons from the animal models. Front Physiol 2019;10:1317.
71. Kaiser D, Weise G, Möller K, et al. Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease. Acta Neuropathol Commun 2014;2:169.
72. Bassi I, Grunspan M, Hen G, et al. Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity. BioRxiv 2023.
73. Hannawi Y. Cerebral small vessel disease: a review of the pathophysiological mechanisms. Transl Stroke Res 2023:1-20.
74. Montagne A, Barnes SR, Sweeney MD, et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 2015;85:296-302.
75. Freeman LR, Keller JN. Oxidative stress and cerebral endothelial cells: regulation of the blood-brain-barrier and antioxidant based interventions. Biochim Biophys Acta 2012;1822:822-9.
76. Liao FF, Lin G, Chen X, et al. Endothelial nitric oxide synthase-deficient mice: a model of spontaneous cerebral small-vessel disease. Am J Pathol 2021;191:1932-45.
77. Brown WR, Thore CR. Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol 2011;37:56-74.
78. Csiszar A, Ungvari Z, Edwards JG, et al. Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res 2002;90:1159-66.
79. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008;57:178-201.
80. Baumbach GL, Heistad DD. Cerebral circulation in chronic arterial hypertension. Hypertension 1988;12:89-95.
81. Guy R, Volkman R, Wilczynski E, et al. A novel rodent model of hypertensive cerebral small vessel disease with white matter hyperintensities and peripheral oxidative stress. Int J Mol Sci 2022;23:5915.
83. Iadecola C, Davisson RL. Hypertension and cerebrovascular dysfunction. Cell Metab 2008;7:476-84.
84. Faraco G, Iadecola C. Hypertension: a harbinger of stroke and dementia. Hypertension 2013;62:810-7.
85. Rosenberg GA, Wallin A, Wardlaw JM, et al. Consensus statement for diagnosis of subcortical small vessel disease. J Cereb Blood Flow Metab 2016;36:6-25.
86. Hainsworth AH, Allan SM, Boltze J, et al. Translational models for vascular cognitive impairment: a review including larger species. BMC Med 2017;15:16.
87. Yan R, Liu H, Lv F, Deng Y, Li Y. Rac1/Wave2/Arp3 pathway mediates rat blood-brain barrier dysfunction under simulated microgravity based on proteomics strategy. Int J Mol Sci 2021;22:5165.
88. Tian F, Liu T, Xu G, et al. Surge of corticocardiac coupling in SHRSP rats exposed to forebrain cerebral ischemia. J Neurophysiol 2019;121:842-52.
89. Ma Y, Chen S, Li Y, et al. Effects of Dl-3-n-butylphthalide on cognitive functions and blood-brain barrier in chronic cerebral hypoperfusion rats. Naunyn Schmiedebergs Arch Pharmacol 2023;396:3207-20.
90. Yang L, Song J, Nan D, Wan Y, Guo H. Cognitive impairments and blood-brain barrier damage in a mouse model of chronic cerebral hypoperfusion. Neurochem Res 2022;47:3817-28.
91. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci 2011;12:723-38.
92. Farkas E, Luiten PGM, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 2007;54:162-80.
93. Kisler K, Nelson AR, Montagne A, Zlokovic BV. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 2017;18:419-34.
94. Jackman K, Iadecola C. Neurovascular regulation in the ischemic brain. Antioxid Redox Signal 2015;22:149-60.
95. Ergul A, Li W, Elgebaly MM, Bruno A, Fagan SC. Hyperglycemia, diabetes and stroke: focus on the cerebrovasculature. Vascul Pharmacol 2009;51:44-9.
96. Nelson AR, Sweeney MD, Sagare AP, Zlokovic BV. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. Biochim Biophys Acta 2016;1862:887-900.
97. Byun K, Yoo Y, Son M, et al. Advanced glycation end-products produced systemically and by macrophages: a common contributor to inflammation and degenerative diseases. Pharmacol Ther 2017;177:44-55.
98. Joutel A, Monet-Leprêtre M, Gosele C, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest 2010;120:433-45.
99. Ruchoux MM, Guerouaou D, Vandenhaute B, Pruvo JP, Vermersch P, Leys D. Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Acta Neuropathol 1995;89:500-12.
100. Monet-Leprêtre M, Haddad I, Baron-Menguy C, et al. Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD: a new pathomechanism in CADASIL. Brain 2013;136:1830-45.
101. Karlström H, Beatus P, Dannaeus K, Chapman G, Lendahl U, Lundkvist J. A CADASIL-mutated Notch 3 receptor exhibits impaired intracellular trafficking and maturation but normal ligand-induced signaling. Proc Natl Acad Sci USA 2002;99:17119-24.
102. Gupta A, Nair S, Schweitzer AD, et al. Neuroimaging of cerebrovascular disease in the aging brain. Aging Dis 2012;3:414.
103. Klakotskaia D, Agca C, Richardson RA, Stopa EG, Schachtman TR, Agca Y. Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer's disease. PLoS One 2018;13:e0195469.
104. Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, Pruzin J, Sperling R, van Veluw SJ. Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways. Nat Rev Neurol 2020;16:30-42.
105. Hampel H, Vassar R, De Strooper B, et al. The β-secretase BACE1 in Alzheimer’s disease. Biol Psychiatry 2021;89:745-56.
106. Yamamura H, Suzuki Y, Asai K, Imaizumi Y, Yamamura H. Oxidative stress facilitates cell death by inhibiting Orai1-mediated Ca2+ entry in brain capillary endothelial cells. Biochem Biophys Res Commun 2020;523:153-8.
107. Nation DA, Sweeney MD, Montagne A, et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med 2019;25:270-6.
108. DeStefano JG, Jamieson JJ, Linville RM, Searson PC. Benchmarking in vitro tissue-engineered blood-brain barrier models. Fluids Barriers CNS 2018;15:32.
109. Brown JA, Pensabene V, Markov DA, et al. Recreating blood-brain barrier physiology and structure on chip: a novel neurovascular microfluidic bioreactor. Biomicrofluidics 2015;9:054124.
110. Bai T, Yu S, Feng J. Advances in the role of endothelial cells in cerebral small vessel disease. Front Neurol 2022;13:861714.
111. Kutikhin AG, Shishkova DK, Velikanova EA, Sinitsky MY, Sinitskaya AV, Markova VE. Endothelial dysfunction in the context of blood-brain barrier modeling. J Evol Biochem Physiol 2022;58:781-806.
112. Allt G, Lawrenson JG. Pericytes: cell biology and pathology. Cells Tissues Organs 2001;169:1-11.
113. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005;57:173-85.
114. Béguin EP, van den Eshof BL, Hoogendijk AJ, et al. Integrated proteomic analysis of tumor necrosis factor α and interleukin 1β-induced endothelial inflammation. J Proteomics 2019;192:89-101.
115. Zhang L, Zhou L, Bao L, et al. SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration. Signal Transduct Target Ther 2021;6:337.
116. Fisher M, Feuerstein G, Howells DW, et al. STAIR Group. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009;40:2244-50.
117. Wang C, He Y, Yang M, Sun H, Zhang S, Wang C. Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22(phox) expression. Toxicol Appl Pharmacol 2013;273:59-67.
118. Tharakan B, Holder-Haynes JG, Hunter FA, Childs EW. Alpha lipoic acid attenuates microvascular endothelial cell hyperpermeability by inhibiting the intrinsic apoptotic signaling. Am J Surg 2008;195:174-8.
119. Wu F, Schuster DP, Tyml K, Wilson JX. Ascorbate inhibits NADPH oxidase subunit p47phox expression in microvascular endothelial cells. Free Radic Biol Med 2007;42:124-31.
120. Leclech C, Krishnamurthy A, Muller L, Barakat AI. Distinct contact guidance mechanisms in single endothelial cells and in monolayers. Adv Mater Inter 2023;10:2202421.
121. Cai Z, Qiao PF, Wan CQ, Cai M, Zhou NK, Li Q. Role of blood-brain barrier in Alzheimer's disease. J Alzheimers Dis 2018;63:1223-34.
122. Gastfriend BD, Palecek SP, Shusta EV. Modeling the blood-brain barrier: beyond the endothelial cells. Curr Opin Biomed Eng 2018;5:6-12.
123. Park JS, Choe K, Khan A, et al. Establishing Co-culture blood-brain barrier models for different neurodegeneration conditions to understand its effect on BBB integrity. Int J Mol Sci 2023;24:5283.
124. Sweeney MD, Ayyadurai S, Zlokovic BV. Pericytes of the neurovascular unit: key functions and signaling pathways. Nat Neurosci 2016;19:771-83.
126. Peng B, Hao S, Tong Z, et al. Blood-brain barrier (BBB)-on-a-chip: a promising breakthrough in brain disease research. Lab Chip 2022;22:3579-602.
127. Wang P, Jin L, Zhang M, et al. SARS-CoV-2 causes human BBB injury and neuroinflammation indirectly in a linked organ chip platform. BioRxiv 2010.
128. Kawakita S, Mandal K, Mou L, et al. Organ-on-a-chip models of the blood-brain barrier: recent advances and future prospects. Small 2022;18:e2201401.
129. Teixeira MI, Amaral MH, Costa PC, Lopes CM, Lamprou DA. Recent developments in microfluidic technologies for central nervous system targeted studies. Pharmaceutics 2020;12:542.
130. Yoon JK, Kim J, Shah Z, Awasthi A, Mahajan A, Kim Y. Advanced human BBB-on-a-chip: a new platform for Alzheimer's disease studies. Adv Healthc Mater 2021;10:e2002285.
131. Herland A, van der Meer AD, FitzGerald EA, Park TE, Sleeboom JJF, Ingber DE. Distinct contributions of astrocytes and pericytes to neuroinflammation identified in a 3D human blood-brain barrier on a chip. PLoS One 2016;11:e0150360.
132. Adriani G, Ma D, Pavesi A, Kamm RD, Goh ELK. A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier. Lab Chip 2017;17:448-59.
134. Wevers NR, Kasi DG, Gray T, et al. A perfused human blood-brain barrier on-a-chip for high-throughput assessment of barrier function and antibody transport. Fluids Barriers CNS 2018;15:23.
135. Wei W, Cardes F, Hierlemann A, Modena MM. 3D in vitro blood-brain-barrier model for investigating barrier insults. Adv Sci 2023;10:e2205752.
136. Chen X, Liu C, Muok L, Zeng C, Li Y. Dynamic 3D on-chip BBB model design, development, and applications in neurological diseases. Cells 2021;10:3183.
137. Potjewyd G, Kellett KAB, Hooper NM. 3D hydrogel models of the neurovascular unit to investigate blood-brain barrier dysfunction. Neuronal Signal 2021;5:NS20210027.
138. Bouhrira N, DeOre BJ, Sazer DW, Chiaradia Z, Miller JS, Galie PA. Disturbed flow disrupts the blood-brain barrier in a 3D bifurcation model. Biofabrication 2020;12:025020.
139. Gallo G, Volpe M, Savoia C. Endothelial dysfunction in hypertension: current concepts and clinical implications. Front Med 2021;8:798958.
140. Paradis T, Bègue H, Basmaciyan L, Dalle F, Bon F. Tight junctions as a key for pathogens invasion in intestinal epithelial cells. Int J Mol Sci 2021;22:2506.
141. Downie LE, Choi J, Lim JKH, Chinnery HR. Longitudinal changes to tight junction expression and endothelial cell integrity in a mouse model of sterile corneal inflammation. Invest Ophthalmol Vis Sci 2016;57:3477-84.
142. Velagapudi S, Wang D, Poti F, et al. Sphingosine-1-phosphate receptor 3 regulates the transendothelial transport of high-density lipoproteins and low-density lipoproteins in opposite ways. Cardiovasc Res 2024;120:476-89.
143. Voirin AC, Perek N, Roche F. Inflammatory stress induced by a combination of cytokines (IL-6, IL-17, TNF-α) leads to a loss of integrity on bEnd.3 endothelial cells in vitro BBB model. Brain Res 2020;1730:146647.
144. Nair AL, Groenendijk L, Overdevest R, et al. Human BBB-on-a-chip reveals barrier disruption, endothelial inflammation, and T cell migration under neuroinflammatory conditions. Front Mol Neurosci 2023;16:1250123.
145. Li Y, Zhu ZY, Huang TT, et al. The peripheral immune response after stroke-A double edge sword for blood-brain barrier integrity. CNS Neurosci Ther 2018;24:1115-28.
146. Morton L, Arndt P, Garza AP, et al. Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states. Acta Neuropathol Commun 2023;11:204.
147. Gao C, Jiang J, Tan Y, Chen S. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduct Target Ther 2023;8:359.
148. Song K, Li Y, Zhang H, et al. Oxidative Stress-Mediated Blood-Brain Barrier (BBB) Disruption in Neurological Diseases. Oxid Med Cell Longev 2020;2020:1-27.
149. Al-Kuraishy HM, Al-Gareeb AI, Al-Niemi MS, et al. The prospective effect of allopurinol on the oxidative stress index and endothelial dysfunction in Covid-19. Inflammation 2022;45:1651-67.
150. Sun J, Xu X, Su H, Yan L, Zhang Y, Zhang L. The role of Nrf2 in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated MMP9. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2023;41:2-7.
151. Liu WC, Zhu YR, Zhao ZH, Jiang P, Yin FQ. Effects of dietary supplementation of algae-derived polysaccharides on morphology, tight junctions, antioxidant capacity and immune response of duodenum in broilers under heat stress. Animals 2021;11:2279.
152. Shaito A, Aramouni K, Assaf R, et al. Oxidative stress-induced endothelial dysfunction in cardiovascular diseases. Front Biosci 2022;27:105.
153. Amruta N, Bix G. ATN-161 ameliorates ischemia/reperfusion-induced oxidative stress, fibro-inflammation, mitochondrial damage, and apoptosis-mediated tight junction disruption in bEnd.3 cells. Inflammation 2021;44:2377-94.
154. Chen S, Li L, Peng C, et al. Targeting oxidative stress and inflammatory response for blood-brain barrier protection in intracerebral hemorrhage. Antioxid Redox Signal 2022;37:115-34.
155. Grochowski C, Litak J, Kamieniak P, Maciejewski R. Oxidative stress in cerebral small vessel disease. Role of reactive species. Free Radic Res 2018;52:1-13.
156. Wang S, Lv W, Zhang H, et al. Aging exacerbates impairments of cerebral blood flow autoregulation and cognition in diabetic rats. Geroscience 2020;42:1387-410.
157. Ali M, Falkenhain K, Njiru BN, et al. VEGF signalling causes stalls in brain capillaries and reduces cerebral blood flow in Alzheimer’s mice. Brain 2022;145:1449-63.
158. Wu MM, Chan ST, Mazumder D, et al. Improved accuracy of cerebral blood flow quantification in the presence of systemic physiology cross-talk using multi-layer Monte Carlo modeling. Neurophotonics 2021;8:015001.
159. Ling YH, Chi NF, Pan LLH, et al. Association between impaired dynamic cerebral autoregulation and BBB disruption in reversible cerebral vasoconstriction syndrome. J Headache Pain 2023;24:170.
160. Ying Y, Li Y, Yao T, et al. Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases. Alzheimers Dement 2024;20:4527-39.
161. Jiménez-Sánchez L, Hamilton OKL, Clancy U, et al. Sex differences in cerebral small vessel disease: a systematic review and meta-analysis. Front Neurol 2021;12:756887.
162. Chen BA, Lee WJ, Meng LC, et al. Sex-specific implications of inflammation in covert cerebral small vessel disease. BMC Neurol 2024;24:220.
163. Collignon A, Dion-Albert L, Ménard C, Coelho-Santos V. Sex, hormones and cerebrovascular function: from development to disorder. Fluids Barriers CNS 2024;21:2.
164. Banks WA. Brain meets body: the blood-brain barrier as an endocrine interface. Endocrinology 2012;153:4111-9.
165. Maggioli E, McArthur S, Mauro C, et al. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking. Brain Behav Immun 2016;51:212-22.
166. Weber CM, Clyne AM. Sex differences in the blood-brain barrier and neurodegenerative diseases. APL Bioeng 2021;5:011509.
167. van Zijl P, Knutsson L. In vivo magnetic resonance imaging and spectroscopy. Technological advances and opportunities for applications continue to abound. J Magn Reson 2019;306:55-65.
168. Jahng GH, Li KL, Ostergaard L, Calamante F. Perfusion magnetic resonance imaging: a comprehensive update on principles and techniques. Korean J Radiol 2014;15:554-77.
169. Acharya D, Mukherjea A, Cao J, et al. Non-invasive spectroscopy for measuring cerebral tissue oxygenation and metabolism as a function of cerebral perfusion pressure. Metabolites 2022;12:667.
170. Amendola C, Cavallaro G, Amelio G, et al. Cerebral hemodynamics monitoring during extracorporeal membrane oxygenation in piglets; 2023. Available from: https://opg.optica.org/abstract.cfm?uri=ECBO-2023-126280F [Last accessed on 26 Jul 2023].
171. Deseoe J, Schwarz A, Pipping T, et al. Cerebral blood flow velocity progressively decreases with increasing levels of verticalization in healthy adults. A cross-sectional study with an observational design. Front Neurol 2023;14:1149673.
172. Nisha NN, Podder KK, Chowdhury MEH, et al. A deep learning framework for the detection of abnormality in cerebral blood flow velocity using transcranial doppler ultrasound. Diagnostics 2023;13:2000.
173. Jickling GC, Ander BP, Zhan X, Noblett D, Stamova B, Liu D. microRNA expression in peripheral blood cells following acute ischemic stroke and their predicted gene targets. PLoS One 2014;9:e99283.
174. Alim I, Caulfield JT, Chen Y, et al. Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell 2019;177:1262-79.e25.
175. Zhang B, Korolj A, Lai BFL, Radisic M. Advances in organ-on-a-chip engineering. Nat Rev Mater 2018;3:257-78.
176. Vanlandewijck M, He L, Mäe MA, et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 2018;554:475-80.
177. Ståhl PL, Salmén F, Vickovic S, et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 2016;353:78-82.