Cerebral small vessel disease (CSVD) is a common cause of small vessel damage in the brain caused by various etiologies, and is a common cause of stroke and cognitive impairment in the elderly. Although its pathogenesis is not yet clear, this article aims to provide a solid reference for clinical diagnosis and treatment by delving into the possible causes and pathogenesis of CSVD. We hope to provide more accurate diagnosis and treatment plans for CSVD patients through continuous research.

Bai Yu, Wang Tao. Progress in the Pathogenesis of Cerebral Small Vessel Disease. Academic Journal of Medicine & Health Sciences (2024), Vol. 5, Issue 10: 64-70. https://doi.org/10.25236/AJMHS.2024.051010.

[1] Wang HC, Li HF. Research progress on the correlation between adiponectin and cerebral small vessel disease[J].Chinese Modern Doctor, 2023,61 ( 22 ) : 122-125. 

[2] Wardlaw J M, Smith C, Dichgans M .Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging.[J].Lancet Neurology, 2013, 12(5):483-497. 

[3] Wang J, Wang B, Wang K .Review of neuroimaging research progress of cerebral small vessel disease[J].Folia neuropathologica, 2023, 61(1):12-12.

[4] Markus HS, de Leeuw FE. Cerebral small vessel disease: recent advances and future directions[J]. Int J Stroke, 2023, 18(1): 4-14.

[5] Mengfei C, Jacob M A, Norris D G,et al.Longitudinal Relation Between Structural Network Efficiency, Cognition, and Gait in Cerebral Small Vessel Disease[J].The Journals of Gerontology: Series A, 2021(3):3.

[6] Ibitoye RT, Castro P, Cooke J, et al. A link between frontal white matter integrity and dizziness in cerebral small vessel disease[J]. NeuroImage Clin, 2022; 35: 103098.

[7] Blumen HM, Jayakody O and Verghese J. Gait in cerebral small vessel disease, predementia, and dementia: a systematic review[J]. Int J Stroke, 2022; 18: 53–61. 

[8] Pasi M, Cordonnier C. Clinical relevance of cerebral small vessel diseases[J]. Stroke, 2020, 51(1): 47-53.

[9] Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges[J]. Lancet Neurol, 2010, 9(7): 689-701. 

[10] Cannistraro R J, Badi M, Eidelman B H, et al. CNS small vessel disease: a clinical review[J]. Neurology, 2019, 92(24): 1146-1156.

[11] Litak J, Mazurek M, Kulesza B,et al.Cerebral Small Vessel Disease[J].International Journal of Molecular Sciences, 2020, 21(24):9729.

[12] Fred R, Wright C B .Current pathophysiological concepts in cerebral small vessel disease[J]. Frontiers in Aging Neuroscience, 2014, 6:24-.

[13] Lawrence A J, Chung A W, Morris R G,et al. Structural network efficiency is associated with cognitive impairment in small-vessel disease.[J].Neurology, 2014, 83(4).

[14] Burtscher J, Mallet R T, Burtscher M, et al. Hypoxia and Brain Aging: Neurodegeneration or Neuroprotection?[J].Ageing Research Reviews, 2021, 68(4):101343.

[15] Duncombe J, Kitamura A, Hase Y, et al. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia[J].Clinical Science, 2017, 131(19): 2451-2468.

[16] Jalal F Y, Yang Y, Thompson J F,et al.Hypoxia-induced neuroinflammatory white-matter injury reduced by minocycline in SHR/SP.[J].J Cereb Blood Flow Metab, 2015, 35(7):1145.

[17] Langen U H, Ayloo S, Gu C .Development and Cell Biology of the Blood-Brain Barrier[J]. Annual Review of Cell and Developmental Biology, 2019, 35(1).

[18] Hainsworth A H , Markus H S , Schneider J A .Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia[J].Hypertension: An Official Journal of the American Heart Association, 2024(1):81.DOI:10.1161/HYPERTENSIONAHA.123.19943.

[19] Farrall A J, Wardlaw J M .Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis.[J].Journal of the Neurological Sciences, 2009, 30(3):337-352. 

[20] Knox E G, Aburto M R, Clarke G,et al.The blood-brain barrier in aging and neurodegeneration [J]. Molecular Psychiatry[2024-10-15]. 

[21] Biron K E, Dickstein D L, Rayshad G,et al.Amyloid Triggers Extensive Cerebral Angiogenesis Causing Blood Brain Barrier Permeability and Hypervascularity in Alzheimer's Disease[J].Plos One, 2011, 6(8):e23789.

[22] Susana Muñoz Maniega, Chappell F M,Maria C Valdés Hernández,et al.Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease[J].J Cereb Blood Flow Metab, 2017, 37(2):644-656.

[23] Hainsworth A H, Fisher M J .A dysfunctional blood–brain barrier and cerebral small vessel disease [J].Neurology, 2017, 88(5):420.

[24] Wardlaw J M, Doubal F, Armitage P,et al.Lacunar Stroke Is Associated with Diffuse Blood-Brain Barrier Dysfunction[J].Annals of Neurology, 2009, 65(2):194-202.

[25] Hawkins, B. T .The blood-brain barrier/neurovascular unit in health and disease[J]. Pharmacological Reviews, 2005, 57(2):173-185.

[26] Mccaffrey G, Seelbach M J, Staatz W D,et al.Occludin oligomeric assembly at tight junctions of the blood-brain barrier is disrupted by peripheral inflammatory hyperalgesia.[J].Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry, 2008(6):106.

[27] Wardlaw J M, Smith C, Dichgans M .Small vessel disease: mechanisms and clinical implications [J]. The Lancet Neurology, 2019, 18(7). 

[28] Zhang M , Lan X ,Gao, YueZou, YuLi, ShenLiang, YajieJanowski, MiroslawWalczak, PiotrChu, Chengyan.Activation of NLRP3 inflammasome in a rat model of cerebral small vessel disease[J].Experimental Brain Research, 2024, 242(6):1387-1397.DOI:10.1007/s00221-024-06824-9.

[29] Neal M, Richardson J R .Epigenetic regulation of astrocyte function in Neuroinflammation and Neurodegeneration[J].Biochim Biophys Acta, 2017, 1864(2). 

[30] Nezu T, Hosomi N, Aoki S,et al.Endothelial dysfunction is associated with the severity of cerebral small vessel disease[J].Hypertension Research Official Journal of the Japanese Society of Hypertension, 2015, 38(4):291. 

[31] Rajani R M, Sophie Q, Ruigrok S R,et al.Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats[J].Science Translational Medicine, 2018, 10(448):eaam9507.

[32] Li T, Huang Y, Cai W,et al.Age-related cerebral small vessel disease and inflammaging[J].Cell Death & Disease[2024-10-15]. 

[33] Zheng JP, Xie L, Fang R, et al. Progress of biomarkers for cerebral small vessel disease[J]. Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology, 2021, 23(12): 4398-4405.

[34] Hao D, Li MW, Kong YN, et al. Serum Hcy and VEGF levels and significance in patients with cerebral small vessel disease[J]. Neural Injury and Functional Reconstruction, 2020, 15(7): 423-424.

[35] CHARIDIMOU A, PANTONI L,LOVE S. The concept of sporadic cerebral small vessel disease: a road map on key definitions and current concepts[J]. Int J Stroke,2016,11(1):6-18.

[36] Haffner C, Malik R, Dichgans M. Genetic factors in cerebral small vessel disease and their impact on stroke and dementia[J]. J Cereb Blood Flow Metab, 2016,36(1):158-171.

[37] Lanfranconi S, Markus H S .COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review.[J].Stroke, 2010, 41(8):513-518.

[38] Inoue Y , Shue F , Bu G ,et al.Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer's disease[J].Molecular Neurodegeneration, 2023, 18.DOI:10.1186/s13024-023-00640-5.

[39] Wardlaw J M, Chappell F M,Valdés Hernández, Maria del Carmen,et al.White matter hyperintensity reduction and outcomes after minor stroke[J].Neurology, 2017, 89(10):1003-1010.

[40] Zhang W, Zhou Y, Wang J, et al. Glymphatic clearance function in patients with cerebral small vessel disease[J]. Neuroimage, 2021, 238: 118257. 

[41] Owasil, O'Neill, Keable, et al. The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy[J].International Journal of Molecular Sciences, 2020, 21(4):1225.