clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2025-103-10-11-697-703clinmed-1293Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESПатогенетические механизмы развития болезни мелких сосудов головного мозгаPathogenetic mechanisms of development of small vessel disease of the brainhttps://orcid.org/0000-0001-8391-1691ПаценкоМ. Б.PatsenkoM. B.

Паценко Михаил Борисович — д-р мед. наук, доцент, заведующий кафедрой терапии неотложных состояний филиала ВМедА им. С.М. Кирова Минобороны России в г. Москве, главный терапевт Минобороны России.

AuthorID 1122515

Mikhail B. Patsenko— Doctor of Medical Sciences, Associate Professor, Head of the department therapy of emergency conditions of the Branch of the Military Medical Academy named after S.M. Kirov in Moscow, Chief Therapist of the Ministry of Defense of the Russian Federation.

AuthorID 1122515

https://orcid.org/0000-0002-2727-4090ГлоткоВ. Л.GlotkoV. L.

Глотко Владимир Леонидович — канд. мед. наук, доцент кафедры терапии неотложных состояний филиала ВМедА им. С.М. Кирова Минобороны России в г. Москве.

AuthorID 638113

Vladimir L. Glotko— Candidate of Medical Sciences, Associate Professor of the department therapy of emergency conditions of the Branch of the Military Medical Academy named after S.M. Kirov in Moscow.

AuthorID 638113

vladimir.glatko@yandex.ruhttps://orcid.org/0000-0002-2330-8302ГайворонскийИ. Н.GaivoronskiiI. N.

Гайворонский Иван Николаевич — канд. мед. наук, доцент кафедры терапии неотложных состояний филиала ВМедА им. С.М. Кирова Минобороны России в г. Москве.

AuthorID 899062

Ivan N. Gaivoronskii— Candidate of Medical Sciences, Associate Professor of the department therapy of emergency conditions of the Branch of the Military Medical Academy named after S.M. Kirov in Moscow.

AuthorID 899062

Филиал ФГБВОУ ВО «Военно-медицинская академия имени С.М. Кирова» Минобороны России в г. МосквеРоссияBranch of Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russia in MoscowRussian Federation20251402202610310-11697703Copyright © Паценко М.Б., Глотко В.Л., Гайворонский И.Н., 20262026Паценко М.Б., Глотко В.Л., Гайворонский И.Н.Patsenko M.B., Glotko V.L., Gaivoronskii I.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/1293

Цереброваскулярная патология занимает лидирующие позиции среди причин смертности и длительного периода восстановления после нетрудоспособности населения в странах с разным уровнем дохода, что свидетельствует о необходимости поиска новых стратегических направлений по профилактике этих заболеваний. Сегодня среди наиболее распространенных форм цереброваскулярных заболеваний выделяют острый ишемический инсульт и сосудистые когнитивные нарушения, в частности, сосудистую деменцию. В патогенезе обоих этих состояний значительную роль играет повреждение мелких сосудов головного мозга. Статья посвящена анализу данных литературы по изучению цереброваскулярных заболеваний. В базе данных PubMed отобраны статьи по ключевым словам: болезни мелких сосудов, гиперинтенсивность белого вещества головного мозга, лакуны, расширенные периваскулярные пространства, атрофия мозга, сосудистые когнитивные нарушения. Заключение. Изучение патогенетических механизмов развития церебральной микроангиопатии, или болезни мелких сосудов позволит выработать направления в клинических и научных исследованиях на поиск генетически обоснованного лечения и стратегии профилактики, что крайне важно для пациентов пожилого возраста.

Cerebrovascular pathology occupies a leading position among the causes of mortality and long-term recovery from disability in countries with different income levels, which indicates the need to find new strategic directions for the prevention of these diseases. Today, among the most common forms of cerebrovascular diseases are acute ischemic stroke and vascular cognitive impairment, in particular vascular dementia. In the pathogenesis of both of these conditions, damage to small vessels of the brain plays a significant role. The article is devoted to the analysis of literature data on the study of cerebrovascular diseases was conducted. Articles were selected from the database PubMed by searching for keywords: small vessel diseases, white matter hyperintensivity of the brain, lacunae, dilated perivascular spaces, brain atrophy, vascular cognitive impairment. Conclusion. The study of pathogenetic mechanisms for the development of cerebral microangiopathy or small vessel disease will allow developing directions in clinical and scientific research to find genetically based treatment and prevention strategies, which is extremely important for elderly patients.

болезнь мелких сосудов головного мозгацеребральная микроангиопатиялейкоареозгипертензивность белого веществарасширение периваскулярных пространствлакунылакунарные инфарктысосудистые когнитивные нарушенияcerebral small vessel diseasecerebral microangiopathyleukoaraiosiswhite matter hyperintensitydilated perivascular spaceslacunaelacunar infarctvascular cognitive impairmentReferencesLi Q.,Yang Y., Reis C. et al. Cerebral small vessel disease. Cell. Transplant. 2018;27(12):1711–1722. DOI: 10.1177/0963689718795148Li Q.,Yang Y., Reis C. et al. Cerebral small vessel disease. Cell. Transplant. 2018;27(12):1711–1722. DOI: 10.1177/0963689718795148Chojdak-Ukasiewicz J., Dziadkowiak E., Zimny A., Paradowski B. Cerebral small vessel disease: A review. Adv. Clin. Exp. Med. 2021;30(3):349–356. DOI: 10.17219/acem/131216.Chojdak-Ukasiewicz J., Dziadkowiak E., Zimny A., Paradowski B. Cerebral small vessel disease: A review. Adv. Clin. Exp. Med. 2021;30(3):349–356. DOI: 10.17219/acem/131216.Wardlaw J.M., Smith C., Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12(5):483–497. DOI: 10.1016/S1474-4422(13)70060-7Wardlaw J.M., Smith C., Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12(5):483–497. DOI: 10.1016/S1474-4422(13)70060-7Khan U., Porteous L., Hassan A., Markus H.S. Risk factor profile of cerebral small vessel disease and its subtypes. J. Neurol. Neurosurg. Psychiatry. 2007;78(7):702–706. DOI: 10.1136/jnnp.2006.103549Khan U., Porteous L., Hassan A., Markus H.S. Risk factor profile of cerebral small vessel disease and its subtypes. J. Neurol. Neurosurg. Psychiatry. 2007;78(7):702–706. DOI: 10.1136/jnnp.2006.103549Aribisala B.S., Morris Z., Eadie E. et al. Blood pressure, internal carotid artery flow parameters, and age-related white matter hyperintensities. Hypertension. 2014;63(5):1011–1018. DOI: 10.1161/HYPERTENSIONAHA.113.02735Aribisala B.S., Morris Z., Eadie E. et al. Blood pressure, internal carotid artery flow parameters, and age-related white matter hyperintensities. Hypertension. 2014;63(5):1011–1018. DOI: 10.1161/HYPERTENSIONAHA.113.02735Boulouis G., Charidimou A., Auriel E. et al. Intracranial atherosclerosis and cerebral small vessel disease in intracerebral hemorrhage patients. J. Neurol. Sci. 2016;369:324–329. DOI: 10.1016/j.jns.2016.08.049Boulouis G., Charidimou A., Auriel E. et al. Intracranial atherosclerosis and cerebral small vessel disease in intracerebral hemorrhage patients. J. Neurol. Sci. 2016;369:324–329. DOI: 10.1016/j.jns.2016.08.049Brisset M., Boutouyrie P., Pico F. et al. Large-vessel correlates of cerebral small-vessel disease. Neurology. 2013;80(7):662–669. DOI: 10.1212/WNL.0b013e318281ccc2Brisset M., Boutouyrie P., Pico F. et al. Large-vessel correlates of cerebral small-vessel disease. Neurology. 2013;80(7):662–669. DOI: 10.1212/WNL.0b013e318281ccc2Hannawi Y. Cerebral small vessel disease: a review of the pathophysiological mechanisms. Transl. Stroke Res. 2023. DOI: 10.1007/s12975-023-01195-9Hannawi Y. Cerebral small vessel disease: a review of the pathophysiological mechanisms. Transl. Stroke Res. 2023. DOI: 10.1007/s12975-023-01195-9Kitamura A., Saito S., Maki T. et al. Gradual cerebral hypoperfusion in spontaneously hypertensive rats induces slowly evolving white matter abnormalities and impairs working memory. J. Cereb. Blood Flow Metab. 2016;36(9):1592–1602. DOI: 10.1177/0271678X15606717Kitamura A., Saito S., Maki T. et al. Gradual cerebral hypoperfusion in spontaneously hypertensive rats induces slowly evolving white matter abnormalities and impairs working memory. J. Cereb. Blood Flow Metab. 2016;36(9):1592–1602. DOI: 10.1177/0271678X15606717Poels M.M., Zaccai K., Verwoert G.C. et al. Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study. Stroke. 2012;43(10):2637–2642. DOI: 10.1161/STROKEAHA.111.642264Poels M.M., Zaccai K., Verwoert G.C. et al. Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study. Stroke. 2012;43(10):2637–2642. DOI: 10.1161/STROKEAHA.111.642264Wardlaw J.M., Smith C., Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019;18(7):684–696. DOI: 10.1016/S1474-4422(19)30079-1Wardlaw J.M., Smith C., Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019;18(7):684–696. DOI: 10.1016/S1474-4422(19)30079-1Gomes J., Wachsman A.M. Types of stroke. In: Corrigan ML, Escuro A.A., Kirby D.F. editors. Handbook of Clinical Nutrition and Stroke. Totowa (NJ): Humana Press; 2013:15–32. DOI: 10.1007/978-1-62703-380-0_2Gomes J., Wachsman A.M. Types of stroke. In: Corrigan ML, Escuro A.A., Kirby D.F. editors. Handbook of Clinical Nutrition and Stroke. Totowa (NJ): Humana Press; 2013:15–32. DOI: 10.1007/978-1-62703-380-0_2Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9(7):689–701. DOI: 10.1016/S1474-4422(10)70104-6Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9(7):689–701. DOI: 10.1016/S1474-4422(10)70104-6Van Veluw S.J., Shih A.Y., Smith E.E. et al. Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol. 2017;16(9):730–740. DOI: 10.1016/S1474-4422(17)30196-5Van Veluw S.J., Shih A.Y., Smith E.E. et al. Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol. 2017;16(9):730–740. DOI: 10.1016/S1474-4422(17)30196-5Wardlaw J.M., Smith E.E., Biessels G.J. et al.; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–838. DOI: 10.1016/S1474-4422(13)70124-8Wardlaw J.M., Smith E.E., Biessels G.J. et al.; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–838. DOI: 10.1016/S1474-4422(13)70124-8Debette S., Schilling S., Duperron M.G., Larsson S.C., Markus H.S. Clinical significance of magnetic resonance imaging markers of vascular brain injury: a systematic review and meta-analysis. JAMA Neurol. 2019;76(1):81–94. DOI: 10.1001/jamaneurol.2018.3122Debette S., Schilling S., Duperron M.G., Larsson S.C., Markus H.S. Clinical significance of magnetic resonance imaging markers of vascular brain injury: a systematic review and meta-analysis. JAMA Neurol. 2019;76(1):81–94. DOI: 10.1001/jamaneurol.2018.3122Georgakis M.K., Duering M., Wardlaw J.M., Dichgans M. WMH and long-term outcomes in ischemic stroke: A systematic review and metaanalysis. Neurology. 2019;92(12):e1298–e1308. DOI: 10.1212/WNL.0000000000007142Georgakis M.K., Duering M., Wardlaw J.M., Dichgans M. WMH and long-term outcomes in ischemic stroke: A systematic review and metaanalysis. Neurology. 2019;92(12):e1298–e1308. DOI: 10.1212/WNL.0000000000007142Poggesi A., Pasi M., Pescini F., Pantoni L., Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review. J. Cereb. Blood Flow Metab. 2016;36(1):72–94. DOI: 10.1038/jcbfm.2015.116Poggesi A., Pasi M., Pescini F., Pantoni L., Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review. J. Cereb. Blood Flow Metab. 2016;36(1):72–94. DOI: 10.1038/jcbfm.2015.116Wardlaw J.M., Sandercock P.A., Dennis M.S., Starr J. Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia? Stroke. 2003;34(3):806–812. DOI: 10.1161/01.STR.0000058480.77236.B3Wardlaw J.M., Sandercock P.A., Dennis M.S., Starr J. Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia? Stroke. 2003;34(3):806–812. DOI: 10.1161/01.STR.0000058480.77236.B3Huisa B.N., Caprihan A., Thompson J., Prestopnik J., Qualls C.R., Rosenberg GA. Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease. Stroke. 2015;46(9):2413–2418. DOI: 10.1161/STROKEAHA.115.009589Huisa B.N., Caprihan A., Thompson J., Prestopnik J., Qualls C.R., Rosenberg GA. Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease. Stroke. 2015;46(9):2413–2418. DOI: 10.1161/STROKEAHA.115.009589Tao W., Cheng Y., Guo W. et al. Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts. BMC Neurol. 2022;23;22(1):311. DOI: 10.1186/s12883-022-02824-wTao W., Cheng Y., Guo W. et al. Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts. BMC Neurol. 2022;23;22(1):311. DOI: 10.1186/s12883-022-02824-wWardlaw J.M., Doubal F., Armitage P. et al. Lacunar stroke is associated with diffuse blood-brain barrier dysfunction. Ann. Neurol. 2009;65(2):194–202. DOI: 10.1002/ana.21549Wardlaw J.M., Doubal F., Armitage P. et al. Lacunar stroke is associated with diffuse blood-brain barrier dysfunction. Ann. Neurol. 2009;65(2):194–202. DOI: 10.1002/ana.21549Wardlaw J.M., Makin S.J., Vald s Hernndez M.C. et al. Bloodbrain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study. Alzheimers Dement. 2017;13(6):634–643. DOI: 10.1016/j.jalz.2016.09.006Wardlaw J.M., Makin S.J., Vald s Hernndez M.C. et al. Bloodbrain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study. Alzheimers Dement. 2017;13(6):634–643. DOI: 10.1016/j.jalz.2016.09.006Zhang C.E., Wong S.M., Van de Haar H.J., et al. Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease. Neurology. 2017;88(5):426–432. DOI: 10.1212/WNL.0000000000003556Zhang C.E., Wong S.M., Van de Haar H.J., et al. Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease. Neurology. 2017;88(5):426–432. DOI: 10.1212/WNL.0000000000003556Farrall A.J., Wardlaw J.M. Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis. Neurobiol. Aging. 2009;30(3):337–352. DOI: 10.1016/j.neurobiolaging.2007.07.015Farrall A.J., Wardlaw J.M. Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis. Neurobiol. Aging. 2009;30(3):337–352. DOI: 10.1016/j.neurobiolaging.2007.07.015Ihara M., Yamamoto Y. Emerging evidence for pathogenesis of sporadic cerebral small vessel disease. Stroke. 2016;47(2):554–560. DOI: 10.1161/STROKEAHA.115.009627Ihara M., Yamamoto Y. Emerging evidence for pathogenesis of sporadic cerebral small vessel disease. Stroke. 2016;47(2):554–560. DOI: 10.1161/STROKEAHA.115.009627Rajani R.M., Williams A. Endothelial cell-oligodendrocyte interactions in small vessel disease and aging. Clin. Sci. (Lond.). 2017;131(5):369–379. DOI: 10.1042/CS20160618Rajani R.M., Williams A. Endothelial cell-oligodendrocyte interactions in small vessel disease and aging. Clin. Sci. (Lond.). 2017;131(5):369–379. DOI: 10.1042/CS20160618Deplanque D., Lavallee P.C., Labreuche J. et al.; Lacunar-BICHAT Investigators. Cerebral and extracerebral vasoreactivity in symptomatic lacunar stroke patients: a case-control study. Int. J. Stroke. 2013;8(6):413–421. DOI: 10.1111/j.1747-4949.2011.00755.xDeplanque D., Lavallee P.C., Labreuche J. et al.; Lacunar-BICHAT Investigators. Cerebral and extracerebral vasoreactivity in symptomatic lacunar stroke patients: a case-control study. Int. J. Stroke. 2013;8(6):413–421. DOI: 10.1111/j.1747-4949.2011.00755.xYoung V.G., Halliday G.M., Kril J.J. Neuropathologic correlates of white matter hyperintensities. Neurology. 2008;71(11):804–811. DOI: 10.1212/01.wnl.0000319691.50117.54Young V.G., Halliday G.M., Kril J.J. Neuropathologic correlates of white matter hyperintensities. Neurology. 2008;71(11):804–811. DOI: 10.1212/01.wnl.0000319691.50117.54Markus H.S., Hunt B., Palmer K., Enzinger C., Schmidt H., Schmidt R. Markers of endothelial and hemostatic activation and progression of cerebral white matter hyperintensities: longitudinal results of the Austrian Stroke Prevention Study. Stroke. 2005;36(7):1410–1414. DOI: 10.1161/01.STR.0000169924.60783.d4Markus H.S., Hunt B., Palmer K., Enzinger C., Schmidt H., Schmidt R. Markers of endothelial and hemostatic activation and progression of cerebral white matter hyperintensities: longitudinal results of the Austrian Stroke Prevention Study. Stroke. 2005;36(7):1410–1414. DOI: 10.1161/01.STR.0000169924.60783.d4Fornage M., Chiang Y.A., O’Meara E.S. et al. Biomarkers of Inflammation and MRI-Defined Small Vessel Disease of the Brain: The Cardiovascular Health Study. Stroke. 2008;39(7):1952–1959. DOI: 10.1161/STROKEAHA.107.508135Fornage M., Chiang Y.A., O’Meara E.S. et al. Biomarkers of Inflammation and MRI-Defined Small Vessel Disease of the Brain: The Cardiovascular Health Study. Stroke. 2008;39(7):1952–1959. DOI: 10.1161/STROKEAHA.107.508135Satizabal C.L., Zhu Y.C., Mazoyer B., Dufouil C., Tzourio C. Circulating IL-6 and CRP are associated with MRI findings in the elderly: the 3C-Dijon Study. Neurology. 2012;78(10):720–727. DOI: 10.1212/WNL.0b013e318248e50fSatizabal C.L., Zhu Y.C., Mazoyer B., Dufouil C., Tzourio C. Circulating IL-6 and CRP are associated with MRI findings in the elderly: the 3C-Dijon Study. Neurology. 2012;78(10):720–727. DOI: 10.1212/WNL.0b013e318248e50fVan Dijk E.J., Prins N.D., Vermeer S.E. et al. C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation. 2005;112(6):900–905. DOI: 10.1161/CIRCULATIONAHA.104.506337Van Dijk E.J., Prins N.D., Vermeer S.E. et al. C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation. 2005;112(6):900–905. DOI: 10.1161/CIRCULATIONAHA.104.506337Notsu Y., Nabika T., Bokura H. et al. Evaluation of asymmetric dimethylarginine and homocysteine in microangiopathy-related cerebral damage. Am. J. Hypertens. 2009;22(3):257–262. DOI: 10.1038/ajh.2008.346Notsu Y., Nabika T., Bokura H. et al. Evaluation of asymmetric dimethylarginine and homocysteine in microangiopathy-related cerebral damage. Am. J. Hypertens. 2009;22(3):257–262. DOI: 10.1038/ajh.2008.346Pikula A., Bger R.H, Beiser A.S., et al. Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study. Stroke. 2009;40(9):2959–2964. DOI: 10.1161/STROKEAHA.109.557116Pikula A., Bger R.H, Beiser A.S., et al. Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study. Stroke. 2009;40(9):2959–2964. DOI: 10.1161/STROKEAHA.109.557116Kim Y., Kim Y.K., Kim N.K., Kim S.H., Kim O.J., Oh S.H. Circulating matrix metalloproteinase-9 level is associated with cerebral white matter hyperintensities in non-stroke individuals. Eur. Neurol. 2014;72(3–4):234–240. DOI: 10.1159/000362876Kim Y., Kim Y.K., Kim N.K., Kim S.H., Kim O.J., Oh S.H. Circulating matrix metalloproteinase-9 level is associated with cerebral white matter hyperintensities in non-stroke individuals. Eur. Neurol. 2014;72(3–4):234–240. DOI: 10.1159/000362876Rouhl R.P., Damoiseaux J.G., Lodder J. et al. Vascular inflammation in cerebral small vessel disease. Neurobiol. Aging. 2012;33(8):1800–1806. DOI: 10.1016/j.neurobiolaging.2011.04.008Rouhl R.P., Damoiseaux J.G., Lodder J. et al. Vascular inflammation in cerebral small vessel disease. Neurobiol. Aging. 2012;33(8):1800–1806. DOI: 10.1016/j.neurobiolaging.2011.04.008Rudilosso S., Mena L., Esteller D. et al. Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts. J. Stroke Cerebrovasc. Dis. 2021;30(7):105824. DOI: 10.1016/j.jstrokecerebrovasdis.2021.105824Rudilosso S., Mena L., Esteller D. et al. Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts. J. Stroke Cerebrovasc. Dis. 2021;30(7):105824. DOI: 10.1016/j.jstrokecerebrovasdis.2021.105824Pescini F., Cesari F., Giusti B. et al. Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2010;41(2):218–223. DOI: 10.1161/STROKEAHA.109.563726Pescini F., Cesari F., Giusti B. et al. Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2010;41(2):218–223. DOI: 10.1161/STROKEAHA.109.563726Kloppenborg R.P., Nederkoorn P.J., Van der Graaf Y., Geerlings M.I. Homocysteine and cerebral small vessel disease in patients with symptomatic atherosclerotic disease. The SMART-MR study. Atherosclerosis. 2011;216(2):461-466. DOI: 10.1016/j.atherosclerosis.2011.02.027Kloppenborg R.P., Nederkoorn P.J., Van der Graaf Y., Geerlings M.I. Homocysteine and cerebral small vessel disease in patients with symptomatic atherosclerotic disease. The SMART-MR study. Atherosclerosis. 2011;216(2):461-466. DOI: 10.1016/j.atherosclerosis.2011.02.027Sachdev P., Parslow R., Salonikas C. et al. Homocysteine and the brain in midadult life: evidence for an increased risk of leukoaraiosis in men. Arch. Neurol. 2004;61(9):1369–1376. DOI: 10.1001/arch-neur.61.9.1369Sachdev P., Parslow R., Salonikas C. et al. Homocysteine and the brain in midadult life: evidence for an increased risk of leukoaraiosis in men. Arch. Neurol. 2004;61(9):1369–1376. DOI: 10.1001/arch-neur.61.9.1369Vermeer S.E., Van Dijk E.J., Koudstaal P.J. et al. Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann. Neurol. 2002;51(3):285–289. DOI: 10.1002/ana.10111Vermeer S.E., Van Dijk E.J., Koudstaal P.J. et al. Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann. Neurol. 2002;51(3):285–289. DOI: 10.1002/ana.10111Arsava E.M., Yilmaz E., Topcuoglu M.A. Incidental DWI Lesions in Patients with Recent Small Subcortical Infarctions. J. Stroke Cerebrovasc. Dis. 2022;31(4):106304. DOI: 10.1016/j.jstrokecerebrovas-dis.2022.106304Arsava E.M., Yilmaz E., Topcuoglu M.A. Incidental DWI Lesions in Patients with Recent Small Subcortical Infarctions. J. Stroke Cerebrovasc. Dis. 2022;31(4):106304. DOI: 10.1016/j.jstrokecerebrovas-dis.2022.106304Bridges L.R., Andoh J., Lawrence A.J. et al. Blood-brain barrier dysfunction and cerebral small vessel disease (arteriolosclerosis) in brains of older people. J. Neuropathol. Exp. Neurol. 2014;73(11):1026–1033. DOI: 10.1097/NEN.0000000000000124Bridges L.R., Andoh J., Lawrence A.J. et al. Blood-brain barrier dysfunction and cerebral small vessel disease (arteriolosclerosis) in brains of older people. J. Neuropathol. Exp. Neurol. 2014;73(11):1026–1033. DOI: 10.1097/NEN.0000000000000124Knottnerus I.L., Winckers K., Ten Cate H. et al. Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients. Neurology. 2012;78(7):493–498. DOI: 10.1212/WNL.0b013e318246d6b7Knottnerus I.L., Winckers K., Ten Cate H. et al. Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients. Neurology. 2012;78(7):493–498. DOI: 10.1212/WNL.0b013e318246d6b7Simpson J.E., Fernando M.S., Clark L. et al.; MRC Cognitive Function and Ageing Neuropathology Study Group. White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol. Appl. Neurobiol. 2007;33(4):410–419. DOI: 10.1111/j.1365-2990.2007.00828.xSimpson J.E., Fernando M.S., Clark L. et al.; MRC Cognitive Function and Ageing Neuropathology Study Group. White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol. Appl. Neurobiol. 2007;33(4):410–419. DOI: 10.1111/j.1365-2990.2007.00828.xSkoog I., Wallin A., Fredman P. et al. A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology. 1998;50(4):966–971. DOI: 10.1212/wnl.50.4.966Skoog I., Wallin A., Fredman P. et al. A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology. 1998;50(4):966–971. DOI: 10.1212/wnl.50.4.966Pantoni L., Inzitari D., Pracucci G. et al. Cerebrospinal fluid proteins in patients with leucoaraiosis: possible abnormalities in blood-brain barrier function. J. Neurol. Sci. 1993;115(2):125–131. DOI: 10.1016/0022-510x(93)90214-jPantoni L., Inzitari D., Pracucci G. et al. Cerebrospinal fluid proteins in patients with leucoaraiosis: possible abnormalities in blood-brain barrier function. J. Neurol. Sci. 1993;115(2):125–131. DOI: 10.1016/0022-510x(93)90214-jVogels S.C., Emmelot-Vonk M.H., Verhaar H.J., Koek H.L. The association of chronic kidney disease with brain lesions on MRI or CT: a systematic review. Maturitas. 2012;71(4):331–336. DOI: 10.1016/j.maturitas.2012.01.008Vogels S.C., Emmelot-Vonk M.H., Verhaar H.J., Koek H.L. The association of chronic kidney disease with brain lesions on MRI or CT: a systematic review. Maturitas. 2012;71(4):331–336. DOI: 10.1016/j.maturitas.2012.01.008Stehouwer C.D., Smulders Y.M. Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms. J. Am. Soc. Nephrol. 2006;17(8):2106–2111. DOI: 10.1681/ASN.2005121288Stehouwer C.D., Smulders Y.M. Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms. J. Am. Soc. Nephrol. 2006;17(8):2106–2111. DOI: 10.1681/ASN.2005121288Uiterwijk R., Van Oostenbrugge R.J., Huijts M., De Leeuw P.W., Kroon A.A., Staals J. Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension. Front Aging Neurosci. 2016;8:301. DOI: 10.3389/fnagi/2016/00301Uiterwijk R., Van Oostenbrugge R.J., Huijts M., De Leeuw P.W., Kroon A.A., Staals J. Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension. Front Aging Neurosci. 2016;8:301. DOI: 10.3389/fnagi/2016/00301Gattringer T., Pinter D., Enzinger C. et al. Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology. 2017;89(20):2108–2114. DOI: 10.1212/WNL.0000000000004645Gattringer T., Pinter D., Enzinger C. et al. Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology. 2017;89(20):2108–2114. DOI: 10.1212/WNL.0000000000004645Armulik A., Abramsson A., Betsholtz C. Endothelial/pericyte interactions. Circ. Res. 2005;97(6):512–523. DOI: 10.1161/01.RES.0000182903.16652.d7Armulik A., Abramsson A., Betsholtz C. Endothelial/pericyte interactions. Circ. Res. 2005;97(6):512–523. DOI: 10.1161/01.RES.0000182903.16652.d7Rajashekhar G., Willuweit A., Patterson C.E. et al. Continuous endothelial cell activation increases angiogenesis: evidence for the direct role of endothelium linking angiogenesis and inflammation. J. Vasc. Res. 2006;43(2):193–204. DOI: 10.1159/000090949Rajashekhar G., Willuweit A., Patterson C.E. et al. Continuous endothelial cell activation increases angiogenesis: evidence for the direct role of endothelium linking angiogenesis and inflammation. J. Vasc. Res. 2006;43(2):193–204. DOI: 10.1159/000090949Vermeer S.E., Longstreth W.T. Jr, Koudstaal P.J. Silent brain infarcts: a systematic review. Lancet Neurol. 2007;6(7):611–619. DOI: 10.1016/S1474-4422(07)70170-9Vermeer S.E., Longstreth W.T. Jr, Koudstaal P.J. Silent brain infarcts: a systematic review. Lancet Neurol. 2007;6(7):611–619. DOI: 10.1016/S1474-4422(07)70170-9Norrving B. Evolving Concept of Small Vessel Disease through Advanced Brain Imaging. J. Stroke. 2015;17(2):94–100. DOI: 10.5853/jos.2015.17.2.94Norrving B. Evolving Concept of Small Vessel Disease through Advanced Brain Imaging. J. Stroke. 2015;17(2):94–100. DOI: 10.5853/jos.2015.17.2.94Staals J., Makin S.D., Doubal F.N., Dennis M.S., Wardlaw J.M. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;83(14):1228–1234. DOI: 10.1212/WNL.0000000000000837Staals J., Makin S.D., Doubal F.N., Dennis M.S., Wardlaw J.M. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;83(14):1228–1234. DOI: 10.1212/WNL.0000000000000837Lyoubi-Idrissi A.L., Jouvent E., Poupon C., Chabriat H. Diffusion magnetic resonance imaging in cerebral small vessel disease. Rev. Neurol. (Paris). 2017;173(4):201–210. DOI: 10.1016/j.neurol.2017.03.005Lyoubi-Idrissi A.L., Jouvent E., Poupon C., Chabriat H. Diffusion magnetic resonance imaging in cerebral small vessel disease. Rev. Neurol. (Paris). 2017;173(4):201–210. DOI: 10.1016/j.neurol.2017.03.005Blair G.W., Thrippleton M.J., Shi Y. et al. Intracranial hemodynamic relationships in patients with cerebral small vessel disease. Neurology. 2020;94(21):e2258–e2269. DOI: 10.1212/WNL.0000000000009483Blair G.W., Thrippleton M.J., Shi Y. et al. Intracranial hemodynamic relationships in patients with cerebral small vessel disease. Neurology. 2020;94(21):e2258–e2269. DOI: 10.1212/WNL.0000000000009483De Guio F., Mangin J.F., Duering M., Ropele S., Chabriat H., Jouvent E. White matter edema at the early stage of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2015;46(1):258–261. DOI: 10.1161/STROKEAHA.114.007018De Guio F., Mangin J.F., Duering M., Ropele S., Chabriat H., Jouvent E. White matter edema at the early stage of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2015;46(1):258–261. DOI: 10.1161/STROKEAHA.114.007018Rost N.S., Cougo P., Lorenzano S. et al. Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke. J. Cereb. Blood Flow Metab. 2018;38(1):75–86. DOI: 10.1177/0271678X17706449Rost N.S., Cougo P., Lorenzano S. et al. Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke. J. Cereb. Blood Flow Metab. 2018;38(1):75–86. DOI: 10.1177/0271678X17706449Sam K., Crawley A.P., Conklin J. et al. Development of White Matter Hyperintensity Is Preceded by Reduced Cerebrovascular Reactivity. Ann. Neurol. 2016;80(2):277–285. DOI: 10.1002/ana.24712Sam K., Crawley A.P., Conklin J. et al. Development of White Matter Hyperintensity Is Preceded by Reduced Cerebrovascular Reactivity. Ann. Neurol. 2016;80(2):277–285. DOI: 10.1002/ana.24712Shi Y., Thrippleton M.J., Blair G.W. et al. Small vessel disease is associated with altered cerebrovascular pulsatility but not resting cerebral blood flow. J. Cereb. Blood Flow Metab. 2020;40(1):85–99. DOI: 10.1177/0271678X18803956Shi Y., Thrippleton M.J., Blair G.W. et al. Small vessel disease is associated with altered cerebrovascular pulsatility but not resting cerebral blood flow. J. Cereb. Blood Flow Metab. 2020;40(1):85–99. DOI: 10.1177/0271678X18803956Esther MC van Leijsen, Ingeborg WM van Uden, Ghafoorian M. et al. Nonlinear temporal dynamics of cerebral small vessel disease: The RUN DMC study. Neurology. 2017;89(15):1569–1577. DOI: 10.1212/WNL.0000000000004490Esther MC van Leijsen, Ingeborg WM van Uden, Ghafoorian M. et al. Nonlinear temporal dynamics of cerebral small vessel disease: The RUN DMC study. Neurology. 2017;89(15):1569–1577. DOI: 10.1212/WNL.0000000000004490Kario K., Matsuo T., Kobayashi H., Hoshide S., Shimada K. Hyperinsulinemia and hemostatic abnormalities are associated with silent lacunar cerebral infarcts in elderly hypertensive subjects. J. Am. Coll. Cardiol. 2001;37(3):871–877. DOI: 10.1016/s0735-1097(00)01172-4Kario K., Matsuo T., Kobayashi H., Hoshide S., Shimada K. Hyperinsulinemia and hemostatic abnormalities are associated with silent lacunar cerebral infarcts in elderly hypertensive subjects. J. Am. Coll. Cardiol. 2001;37(3):871–877. DOI: 10.1016/s0735-1097(00)01172-4

The authors declare that there are no conflicts of interest present.