Cerebral Small Vessel Disease and Metabolism: Risk Factors, Therapeutic Targets, and Future Directions
QIU Yue1,2, XU Yang2, XUE Jing2,3,4, XU Jie2,3,4, WANG Yilong3,4
1 The Translational Research Institute for Neurological Disorders, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu 241001, China
2 Institutes of Brain Science, Wannan Medical College, Wuhu 241001, China
3 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
4 China National Clinical Research Center for Neurological Diseases, Beijing 100070, China
QIU Yue, XU Yang, XUE Jing, XU Jie, WANG Yilong. Cerebral Small Vessel Disease and Metabolism: Risk Factors, Therapeutic Targets, and Future Directions[J]. Chinese Journal of Stroke, 2024, 19(12): 1392-1399.
[1]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组. 中国脑小血管病诊治指南2020[J]. 中华神经科杂志,2022,55(8):807-818.
Chinese Society of Neurology,Chinese Stroke Society. Chinese guideline for diagnosis and treatment of cerebral small vessel disease 2020[J]. Chin J Neurol,2022,55(8):807-818.
[2] TSAO C W,ADAY A W,ALMARZOOQ Z I,et al. Heart disease and stroke statistics—2022 update:a report from the American Heart Association[J/OL]. Circulation,2022,145(8):e153-e639[2024-10-08]. https://doi.org/10.1161/CIR.0000000000001052.
[3] 许杰,王拥军. 代谢性脑血管病:概念、方法、挑战和未来方向[J]. 中国卒中杂志,2023,18(6):617-627.
XU J,WANG Y J. Cerebro-metabolic disease:concept,method,challenge and future directions[J]. Chin J Stroke,2023,18(6):617-627.
[4] 张枘南,王伊龙. 脑小血管病与卒中防治的“异”与“同”[J]. 中风与神经疾病杂志,2024,41(1):7-13.
ZHANG R N,WANG Y L. Differences and similarities in the prevention and treatment of cerebral small vessel disease and stroke[J]. Journal of Apoplexy and Nervous Diseases,2024,41(1):7-13.
[5] VAN DIJK E J,PRINS N D,VERMEER S E,et al. C-reactive protein and cerebral small-vessel disease:the Rotterdam scan study[J]. Circulation,2005,112(6):900-905.
[6] JIANG L L,CAI X L,YAO D X,et al. Association of inflammatory markers with cerebral small vessel disease in community-based population[J/OL]. J Neuroinflammation,2022,19(1):106[2024-10-08]. https://doi.org/10.1186/s12974-022-02468-0.
[7] ZHANG D D,CAO Y,MU J Y,et al. Inflammatory biomarkers and cerebral small vessel disease:a community-based cohort study[J]. Stroke Vasc Neurol,2022,7(4):302-309.
[8] NAM K W,KWON H M,JEONG H Y,et al. Monocyte to high-density lipoprotein cholesterol ratio is associated with cerebral small vessel diseases[J/OL]. BMC Neurol,2024,24(1):18[2024-10-08]. https://doi.org/10.1186/s12883-023-03524-9.
[9] TSAI H H,CHEN Y F,YEN R F,et al. Plasma soluble TREM2 is associated with white matter lesions independent of amyloid and tau[J]. Brain,2021,144(11):3371-3380.
[10] HU X,XIAO Z S,SHEN Y Q,et al. SERPINA3:a novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke[J/OL]. CNS Neurosci Ther,2024,30(3):e14472[2024-10-08]. https://doi.org/10.1111/cns.14472.
[11] MU L,JIANG L M,CHEN J,et al. Serum inflammatory factors and oxidative stress factors are associated with increased risk of frailty and cognitive frailty in patients with cerebral small vessel disease[J/OL]. Front Neurol,2021,12:786277[2024-10-08]. https://doi.org/10.3389/fneur.2021.786277.
[12] SHAN L L,WANG Y L,QIAO T C,et al. Association of serum interleukin-8 and serum amyloid A with anxiety symptoms in patients with cerebral small vessel disease[J/OL]. Front Neurol,2022,13:938655[2024-10-08]. https://doi.org/10.3389/fneur.2022.938655.
[13] HU M Y,LI T M,MA X M,et al. Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model[J/OL]. Nat Commun,2023,14(1):3945[2024-10-08]. https://doi.org/10.1038/s41467-023-39693-x.
[14] ZHANG M Y,LAN X Y,GAO Y,et al. Activation of NLRP3 inflammasome in a rat model of cerebral small vessel disease[J]. Exp Brain Res,2024,242(6):1387-1397.
[15] MANSO Y,HOLLAND P R,KITAMURA A,et al. Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease[J]. Glia,2018,66(1):34-46.
[16] LI L,HE G J,SHI M Y,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)[J/OL]. Eur J Pharmacol,2023,957:176036[2024-10-08]. https://doi.org/10.1016/j.ejphar.2023.176036.
[17] BROWN R B,TOZER D J,LOUBIÈRE L,et al. Minocycline to reduce inflammation and blood-brain barrier leakage in small vessel disease(MINERVA):a phase Ⅱ,randomized,double-blind,placebo-controlled experimental medicine trial[J]. Alzheimers Dement,2024,20(6):3852-3863.
[18] SHI Y C,ZHAO E,LI L,et al. Alteration and clinical potential in gut microbiota in patients with cerebral small vessel disease[J/OL]. Front Cell Infect Microbiol,2023,13:1231541[2024-10-08]. https://doi.org/10.3389/fcimb.2023.1231541.
[19] HUANG C J,ZHANG Y Y,LIU Y,et al. A bidirectional Mendelian randomization study of gut microbiota and cerebral small vessel disease[J]. J Nutr,2024,154(7):1994-2005.
[20] CHEN Y Y,XU J,PAN Y S,et al. Association of trimethylamine N-oxide and its precursor with cerebral small vessel imaging markers[J/OL]. Front Neurol,2021,12:648702[2024-10-08]. https://doi.org/10.3389/fneur.2021.648702.
[21] LIU S,MEN X J,GUO Y,et al. Gut microbes exacerbate systemic inflammation and behavior disorders in neurologic disease CADASIL[J/OL]. Microbiome,2023,11(1):202[2024-10-08]. https://doi.org/10.1186/s40168-023-01638-3.
[22] HUANG J Y,LIU S X,LI P J,et al. Multi-omics analysis of gut-brain axis reveals novel microbial and neurotransmitter signatures in patients with arteriosclerotic cerebral small vessel disease[J/OL]. Pharmacol Res,2024,208:107385[2024-10-08]. https://doi.org/10.1016/j.phrs.2024.107385.
[23] CAI W,CHEN X D,MEN X J,et al. Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt[J/OL]. Sci Adv,2021,7(4):eabe4827[2024-10-08]. https://doi.org/10.1126/sciadv.abe4827.
[24] XU H P,XIAO H,TANG Q Q. Lipopolysaccharide-induced intestinal inflammation on AIM2-mediated pyroptosis in the brain of rats with cerebral small vessel disease[J/OL]. Exp Neurol,2024,375:114746[2024-10-08]. https://doi.org/10.1016/j.expneurol.2024.114746.
[25] WANG X Y,SUN G Q,FENG T,et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression[J]. Cell Res,2019,29(10):787-803.
[26] NAM K W,KWON H M,JEONG H Y,et al. Serum homocysteine level is related to cerebral small vessel disease in a healthy population[J/OL]. Neurology,2019,92(4):e317-e325[2024-10-08]. https://doi.org/10.1212/WNL.0000000000006816.
[27] CAO Y Z,SU N,ZHANG D D,et al. Correlation between total homocysteine and cerebral small vessel disease:a Mendelian randomization study[J]. Eur J Neurol,2021,28(6):1931-1938.
[28] KLOPPENBORG R P,GEERLINGS M I,VISSEREN F L,et al. Homocysteine and progression of generalized small-vessel disease:the SMART-MR study[J]. Neurology,2014,82(9):777-783.
[29] LIU C H,GAO Y,SONG B,et al. Elevated serum homocysteine associated with distal type of single small subcortical infarction[J]. Curr Neurovasc Res,2020,17(5):629-635.
[30] TENG Z J,FENG J,LIU R H,et al. Cerebral small vessel disease mediates the association between homocysteine and cognitive function[J/OL]. Front Aging Neurosci,2022,14:868777[2024-10-08]. https://doi.org/10.3389/fnagi.2022.868777.
[31] CAVALIERI M,SCHMIDT R,CHEN C,et al. B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke:the vitamins to prevent stroke(VITATOPS)MRI-substudy[J]. Stroke,2012,43(12):3266-3270.
[32] LIU R,HAO M,HUI J,et al. Effect of hyperbaric oxygen combined with folic acid on clinical efficacy and cognitive function in patients with cerebral small vessel disease[J]. Am J Transl Res,2023,15(3):1897-1904.
[33] CROSTA F,OCCHIUZZI U,PASSALACQUA G,et al. Association between the serum uric acid levels and lacunar infarcts in the elderly[J]. J Mol Neurosci,2018,65(3):385-390.
[34] YANG S N,ZHANG X Y,YUAN J L,et al. Serum uric acid is independently associated with enlarged perivascular spaces[J/OL]. Sci Rep,2017,7(1):16435[2024-10-08]. https://doi.org/10.1038/s41598-017-16715-5.
[35] JEONG S M,YOO T G,NAM Y S,et al. Sex-dependent effects of uric acid on cerebral microbleed:a cross-sectional study in the general population[J]. Eur J Neurol,2017,24(10):1300-1306.
[36] SCHRETLEN D J,INSCORE A B,VANNORSDALL T D,et al. Serum uric acid and brain ischemia in normal elderly adults[J]. Neurology,2007,69(14):1418-1423.
[37] VANNORSDALL T D,JINNAH H A,GORDON B,et al. Cerebral ischemia mediates the effect of serum uric acid on cognitive function[J]. Stroke,2008,39(12):3418-3420.
[38] LV H,SUN J,ZHANG T,et al. Associations of serum uric acid variability with neuroimaging metrics and cognitive decline:a population-based cohort study[J/OL]. BMC Med,2024,22(1):256[2024-10-08]. https://doi.org/10.1186/s12916-024-03479-9.
[39] YU L,YI M,GUO J Y,et al. Lower serum uric acid and impairment of right cerebral hemisphere structural brain networks are related to depressive symptoms in cerebral small vessel disease:a cross-sectional study[J/OL]. Heliyon,2024,10(6):e27947[2024-10-08]. https://doi.org/10.1016/j.heliyon.2024. e27947.
[40] YANG L,LV P,AI W P,et al. Lipidomic analysis of plasma in patients with lacunar infarction using normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry[J]. Anal Bioanal Chem,2017,409(12):3211-3222.
[41] HARSHFIELD E L,SANDS C J,TULADHAR A M,et al. Metabolomic profiling in small vessel disease identifies multiple associations with disease severity[J]. Brain,2022,145(7):2461-2471.
[42]HARSHFIELD E L,MARKUS H S. Association of baseline metabolomic profiles with incident stroke and dementia and with imaging markers of cerebral small vessel disease[J/OL]. Neurology,2023,101(5):e489-e501[2024-10-08]. https://doi.org/10.1212/WNL.0000000000207458.