[1] Cannistraro RJ, Badi M, Eidelman BH, et al. CNS small vessel disease: a clinical review. Neurology, 2019; 92, 1146−56. doi:  10.1212/WNL.0000000000007654
[2] Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol, 2013; 12, 822−38. doi:  10.1016/S1474-4422(13)70124-8
[3] Low A, Mak E, Rowe JB, et al. Inflammation and cerebral small vessel disease: a systematic review. Ageing Res Rev, 2019; 53, 100916. doi:  10.1016/j.arr.2019.100916
[4] Low A, Mak E, Malpetti M, et al. In vivo neuroinflammation and cerebral small vessel disease in mild cognitive impairment and Alzheimer's disease. J Neurol Neurosurg Psychiatry, 2020; 92, 45−52.
[5] 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. doi:  10.1093/brain/awab003
[6] Hu X, Xiao ZS, Shen YQ, et al. SERPINA3: a novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke. CNS Neurosci Ther, 2024; 30, e14472. doi:  10.1111/cns.14472
[7] Gu YA, Gutierrez J, Meier IB, et al. Circulating inflammatory biomarkers are related to cerebrovascular disease in older adults. Neurol Neuroimmunol Neuroinflamm, 2019; 6, e521. doi:  10.1212/NXI.0000000000000521
[8] Zhang DD, Cao Y, Mu JY, et al. Inflammatory biomarkers and cerebral small vessel disease: a community-based cohort study. Stroke Vasc Neurol, 2022; 7, 302−9. doi:  10.1136/svn-2021-001102
[9] Wallin A, Kapaki E, Boban M, et al. Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - a consensus report. BMC Neurol, 2017; 17, 102. doi:  10.1186/s12883-017-0877-3
[10] Noz MP, Ter Telgte A, Wiegertjes K, et al. Trained immunity characteristics are associated with progressive cerebral small vessel disease. Stroke, 2018; 49, 2910−7. doi:  10.1161/STROKEAHA.118.023192
[11] Schmitz M, Hermann P, Oikonomou P, et al. Cytokine profiles and the role of cellular prion protein in patients with vascular dementia and vascular encephalopathy. Neurobiol Aging, 2015; 36, 2597−606. doi:  10.1016/j.neurobiolaging.2015.05.013
[12] Tarkowski E, Liljeroth AM, Minthon L, et al. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull, 2003; 61, 255−60. doi:  10.1016/S0361-9230(03)00088-1
[13] Li L, He GJ, Shi MY, et al. Edaravone dexborneol ameliorates cognitive impairment by regulating the NF-κB pathway through AHR and promoting microglial polarization towards the M2 phenotype in mice with bilateral carotid artery stenosis (BCAS). Eur J Pharmacol, 2023; 957, 176036. doi:  10.1016/j.ejphar.2023.176036
[14] Siracusa R, Impellizzeri D, Cordaro M, et al. Anti-inflammatory and neuroprotective effects of Co-UltraPEALut in a mouse model of vascular dementia. Front Neurol, 2017; 8, 233. doi:  10.3389/fneur.2017.00233
[15] Shu J, Zheng R, Chirinos J, et al. Inferring multi-organ genetic connections using imaging and clinical data through Mendelian randomization. Nat Biomed Eng, 2025.
[16] Chen LL, Guillot A, Schneider CV. Attention to the misuse of Mendelian randomisation in medical research. eGastroenterology, 2025; 3, e100187. doi:  10.1136/egastro-2025-100187
[17] Chen LL, Rao Q, Gao MH, et al. Prospects of Mendelian randomization in hepatology: a comprehensive literature review with practice guidance. Clin Mol Hepatol, 2025; 31, 1115−38. doi:  10.3350/cmh.2025.0541
[18] Xu L, Borges MC, Hemani G, et al. The role of glycaemic and lipid risk factors in mediating the effect of BMI on coronary heart disease: a two-step, two-sample Mendelian randomisation study. Diabetologia, 2017; 60, 2210−20. doi:  10.1007/s00125-017-4396-y
[19] Ahola-Olli AV, Würtz P, Havulinna AS, et al. Genome-wide association study identifies 27 loci influencing concentrations of circulating cytokines and growth factors. Am J Hum Genet, 2017; 100, 40−50. doi:  10.1016/j.ajhg.2016.11.007
[20] Kalaoja M, Corbin LJ, Tan VY, et al. The role of inflammatory cytokines as intermediates in the pathway from increased adiposity to disease. Obesity, 2021; 29, 428−37. doi:  10.1002/oby.23060
[21] Davies G, Marioni RE, Liewald DC, et al. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151). Mol Psychiatry, 2016; 21, 758−67. doi:  10.1038/mp.2016.45
[22] Smith SM, Douaud G, Chen W, et al. An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank. Nat Neurosci, 2021; 24, 737−45. doi:  10.1038/s41593-021-00826-4
[23] Caro I, Western D, Namba S, et al. Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease. Nat Aging, 2025; 5, 2514−31. doi:  10.1038/s43587-025-01006-w
[24] Tchuisseu-Kwangoua LA, Omarov M, Shatunov A, et al. Genetic downregulation of interleukin-6 signaling and arteriolosclerotic cerebral small vessel disease: a drug target Mendelian randomization analysis. J Am Heart Assoc, 2025; 14, e041814. doi:  10.1161/JAHA.124.041814
[25] Knol MJ, Lu DW, Traylor M, et al. Association of common genetic variants with brain microbleeds: a genome-wide association study. Neurology, 2020; 95, e3331−43.
[26] Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017; 318, 1925−6.
[27] Nazarzadeh M, Pinho-Gomes AC, Smith Byrne K, et al. Systolic blood pressure and risk of valvular heart disease: a Mendelian randomization study. JAMA Cardiol, 2019; 4, 788−95. doi:  10.1001/jamacardio.2019.2202
[28] Pierce BL, Ahsan H, Vanderweele TJ. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. Int J Epidemiol, 2011; 40, 740−52. doi:  10.1093/ije/dyq151
[29] Kamat MA, Blackshaw JA, Young R, et al. PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinformatics, 2019; 35, 4851−3. doi:  10.1093/bioinformatics/btz469
[30] Liu QY, Li WD, Diao WL, et al. Gut microbiota as a causal mediator linking inflammatory cytokines and ageing phenotypes. Biogerontology, 2026; 27, 20. doi:  10.1007/s10522-025-10369-x
[31] Bowden J, Hemani G, Davey Smith G. Invited commentary: detecting individual and global horizontal pleiotropy in Mendelian randomization-a job for the humble heterogeneity statistic?. Am J Epidemiol, 2018; 187, 2681−5. doi:  10.1093/aje/kwy185
[32] Seyedsalehi A, Warrier V, Bethlehem RAI, et al. Educational attainment, structural brain reserve and Alzheimer's disease: a Mendelian randomization analysis. Brain, 2023; 146, 2059−74. doi:  10.1093/brain/awac392
[33] Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol, 2015; 44, 512−25. doi:  10.1093/ije/dyv080
[34] Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet, 2018; 50, 693−8. doi:  10.1038/s41588-018-0099-7
[35] Hemani G, Zheng J, Elsworth B, et al. The MR-base platform supports systematic causal inference across the human phenome. eLife, 2018; 7, e34408. doi:  10.7554/eLife.34408
[36] Chen K, Zhuang ZH, Shao CL, et al. Roles of cardiometabolic factors in mediating the causal effect of type 2 diabetes on cardiovascular diseases: a two-step, two-sample multivariable Mendelian randomization study. Front Cardiovasc Med, 2022; 9, 813208. doi:  10.3389/fcvm.2022.813208
[37] 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. doi:  10.1016/S1474-4422(23)00131-X
[38] Markus HS, van Der Flier WM, Smith EE, et al. Framework for clinical trials in cerebral small vessel disease (FINESSE): a review. JAMA Neurol, 2022; 79, 1187−98. doi:  10.1001/jamaneurol.2022.2262
[39] Sang D, Lin KT, Yang YN, et al. Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals. Cell, 2023; 186, 5500-16. e21.
[40] Kalin NH, Shelton SE, Engeland CG, et al. Stress decreases, while central nucleus amygdala lesions increase, IL-8 and MIP-1α gene expression during tissue healing in non-human primates. Brain, Behav, Immun, 2006; 20, 564−8. doi:  10.1016/j.bbi.2006.01.003
[41] Altendahl M, Maillard P, Harvey D, et al. An IL-18-centered inflammatory network as a biomarker for cerebral white matter injury. PLoS One, 2020; 15, e0227835. doi:  10.1371/journal.pone.0227835
[42] Xuan W, Xie WQ, Li FS, et al. Dualistic roles and mechanistic insights of macrophage migration inhibitory factor in brain injury and neurodegenerative diseases. J Cereb Blood Flow Metab, 2023; 43, 341−56. doi:  10.1177/0271678X221138412
[43] Martirosian RA, Wiedner CD, Sanchez J, et al. Association of incident stroke risk with an IL-18-centered inflammatory network biomarker composite. Stroke, 2024; 55, 1601−8. doi:  10.1161/STROKEAHA.123.044719
[44] Shi YC, Deng JY, Mao HX, et al. Macrophage migration inhibitory factor as a potential plasma biomarker of cognitive impairment in cerebral small vessel disease. ACS Omega, 2024; 9, 15339−49. doi:  10.1021/acsomega.3c10126
[45] Zhao JH, Wang XT, Yu M, et al. The relevance of serum macrophage migration inhibitory factor level and executive function in patients with white matter hyperintensity in cerebral small vessel disease. Brain Sci, 2023; 13, 616. doi:  10.3390/brainsci13040616
[46] Pagoni P, Korologou-Linden RS, Howe LD, et al. Causal effects of circulating cytokine concentrations on risk of Alzheimer's disease and cognitive function. Brain, Behav, Immun, 2022; 104, 54−64. doi:  10.1016/j.bbi.2022.05.006
[47] Toth ZE, Leker RR, Shahar T, et al. The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia. Blood, 2008; 111, 5544−52. doi:  10.1182/blood-2007-10-119073
[48] Kawada H, Takizawa S, Takanashi T, et al. Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation, 2006; 113, 701−10. doi:  10.1161/CIRCULATIONAHA.105.563668
[49] Shang JK, Li W, Zhang HW, et al. C-kit controls blood-brain barrier permeability by regulating caveolae-mediated transcytosis after chronic cerebral hypoperfusion. Biomed Pharmacother, 2024; 170, 115778. doi:  10.1016/j.biopha.2023.115778
[50] Zhang SC, Fedoroff S. Cellular localization of stem cell factor and c-kit receptor in the mouse nervous system. J Neurosci Res, 1997; 47, 1−15. doi:  10.1002/(sici)1097-4547(19970101)47:1<1::aid-jnr1>3.0.co;2-n
[51] Qiu XC, Ping SN, Kyle M, et al. Stem cell factor and granulocyte colony-stimulating factor promote remyelination in the chronic phase of severe traumatic brain injury. Cells, 2023; 12, 705. doi:  10.3390/cells12050705
[52] Zhao LR, Singhal S, Duan WM, et al. Brain repair by hematopoietic growth factors in a rat model of stroke. Stroke, 2007; 38, 2584−91. doi:  10.1161/STROKEAHA.106.476457
[53] Ping SN, Qiu XC, Gonzalez-Toledo ME, et al. Stem cell factor in combination with granulocyte colony-stimulating factor protects the brain from capillary thrombosis-induced ischemic neuron loss in a mouse model of CADASIL. Front Cell Dev Biol, 2021; 8, 627733. doi:  10.3389/fcell.2020.627733
[54] Ping SN, Qiu XC, Kyle M, et al. Stem cell factor and granulocyte colony-stimulating factor promote brain repair and improve cognitive function through VEGF-A in a mouse model of CADASIL. Neurobiol Dis, 2019; 132, 104561. doi:  10.1016/j.nbd.2019.104561
[55] Zhang K, Tian L, Liu L, et al. CXCL1 contributes to β-amyloid-induced transendothelial migration of monocytes in Alzheimer's disease. PLoS One, 2013; 8, e72744. doi:  10.1371/journal.pone.0072744
[56] Shang Y, Tian L, Chen TJ, et al. CXCL1 promotes the proliferation of neural stem cells by stimulating the generation of reactive oxygen species in APP/PS1 mice. Biochem Biophys Res Commun, 2019; 515, 201−6. doi:  10.1016/j.bbrc.2019.05.130
[57] Korbecki J, Barczak K, Gutowska I, et al. CXCL1: gene, promoter, regulation of expression, mRNA stability, regulation of activity in the intercellular space. Int J Mol Sci, 2022; 23, 792. doi:  10.3390/ijms23020792
[58] Barajas A, Riquelme-Alacid G, Vera-Montecinos A, et al. Cognition, cytokines, blood-brain barrier, and beyond in COVID-19: a narrative review. Int J Mol Sci, 2026; 27, 546. doi:  10.3390/ijms27010546
[59] Torres-Acosta N, O'Keefe JH, O'Keefe EL, et al. Therapeutic potential of TNF-α inhibition for Alzheimer's disease prevention. J Alzheimers Dis, 2020; 78, 619−26. doi:  10.3233/JAD-200711
[60] Belenguer G, Duart-Abadia P, Jordán-Pla A, et al. Adult neural stem cells are alerted by systemic inflammation through TNF-α receptor signaling. Cell Stem Cell, 2021; 28, 285-99. e9.
[61] Ortí-Casañ N, Zuhorn IS, Naudé PJW, et al. A TNF receptor 2 agonist ameliorates neuropathology and improves cognition in an Alzheimer's disease mouse model. Proc Natl Acad Sci USA, 2022; 119, e2201137119. doi:  10.1073/pnas.2201137119
[62] Zhang Y, Xu H, Zhang F, et al. Deficiencies of microglia and TNFα in the mPFC-mediated cognitive inflexibility induced by social stress during adolescence. Brain, Behav, Immun, 2019; 79, 256−66. doi:  10.1016/j.bbi.2019.02.010
[63] Ortí-Casañ N, Boerema AS, Köpke K, et al. The TNFR1 antagonist Atrosimab reduces neuronal loss, glial activation and memory deficits in an acute mouse model of neurodegeneration. Sci Rep, 2023; 13, 10622. doi:  10.1038/s41598-023-36846-2
[64] Lyu D, Pappas I, Menon DK, et al. A precuneal causal loop mediates external and internal information integration in the human brain. J Neurosci, 2021; 41, 9944−56. doi:  10.1523/JNEUROSCI.0647-21.2021
[65] Burgess S, Cronjé HT. Incorporating biological and clinical insights into variant choice for Mendelian randomisation: examples and principles. eGastroenterology, 2024; 2, e100042. doi:  10.1136/egastro-2023-100042
[66] Pang XL, Yang HZ, Li MY, et al. To explore the causal association between the serum lipid profile and inflammatory bowel disease using bidirectional Mendelian randomisation analysis. eGastroenterology, 2024; 2, e100034. doi:  10.1136/egastro-2023-100034
[67] Wang Z, Li S, Liu DD, et al. Coronary atherosclerosis and subclinical cerebral small vessel disease: a robust association beyond intracranial atherosclerosis and cardiac systolic function. J Am Heart Assoc, 2025; 14, e042081. doi:  10.1161/JAHA.125.042081
[68] Sun ZH, Harshfield EL, de Leeuw FE, et al. Proteins involved in endothelial function and inflammation are implicated in cerebral small vessel disease. Stroke, 2025; 56, 692−704. doi:  10.1161/STROKEAHA.124.049079