Новые данные о патогенезе спорадических случаев болезни мелких церебральных сосудов

М. Ихара, И. Ямамото

Departments of Stroke and Cerebrovascular Diseases and Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita, Japan.


  1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689–701. doi: 10.1016/S1474-4422(10)70104-6.
  2. Bailey E.L., Smith C., Sudlow C.L., Wardlaw J.M. Pathology of lacunar ischemic stroke in humans–a systematic review. Brain Pathol. 2012;22:583–591. doi: 10.1111/j.1750-3639.2012.00575.x.
  3. Brandner S. Histopathology of cerebral microbleeds. In: Werring DJ, ed. Cerebral Microbleeds: Pathophysiology to Clinical Practice. 1st ed. Cambridge, UK: Cambridge University Press; 2011:49–64.
  4. Potter G.M., Chappell F.M., Morris Z., Wardlaw J.M. Cerebral perivascular spaces visible on magnetic resonance imaging: development ­of a qualitative rating scale and its observer reliability. Cerebrovasc Dis. 2015;39:224–231. doi: 10.1159/000375153.
  5. Yamamoto Y., Ihara M., Tham C., Low R.W., Slade J.Y., Moss T., et al. Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL. Stroke. 2009;40:2004–2011. doi: 10.1161/STROKEAHA.108.528299.
  6. Ihara M., Polvikoski T.M., Hall R., Slade J.Y., Perry R.H., Oakley A.E., ­et al. Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer’s disease, and dementia with Lewy bodies. Acta Neuropathol. 2010;119:579–589. doi: 10.1007/s00401-009-0635-8.
  7. Okamoto Y., Yamamoto T., Kalaria R.N., Senzaki H., Maki T., Hase Y., ­et al. Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol. 2012;123:381–394. doi: 10.1007/s00401-011-0925-9.
  8. Smith E.E., Schneider J.A., Wardlaw J.M., Greenberg S.M. Cerebral microinfarcts: the invisible lesions. Lancet Neurol. 2012;11:272–282. doi:10.1016/S1474-4422(11)70307-6.
  9. Bath P.M., Wardlaw J.M. Pharmacological treatment and prevention­ of cerebral small vessel disease: a review of potential interventions. ­Int J Stroke. 2015;10:469–478. doi: 10.1111/ijs.12466.
  10. Wardlaw J.M., Smith C., Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12:483–497. doi: 10.1016/S1474-4422(13)70060-7.
  11. Biffi A., Greenberg S.M. Cerebral amyloid angiopathy: a systematic review. J Clin Neurol. 2011;7:1–9. doi: 10.3988/jcn.2011.7.1.1.
  12. Kalaria R.N., Akinyemi R., Ihara M. Does vascular pathology contribute to Alzheimer changes? J Neurol Sci. 2012;322:141–147. ­doi: 10.1016/j.jns.2012.07.032.
  13. Wardlaw J.M., Allerhand M., Doubal F.N., Valdes Hernandez M., Morris Z., Gow A.J., et al. Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities. Neurology. 2014;82:1331–1338. doi:10.1212/WNL.0000000000000312.
  14. Haffner C., Malik R., Dichgans M. Genetic factors in cerebral small vessel disease and their impact on stroke and dementia
  15. Heye A.K., Thrippleton M.J., Chappell F.M., Valdes Hernandez M.D., Armitage P.A., Makin S.D., et al. Blood pressure and sodium: association with MRI markers in cerebral small vessel disease
  16. Fotuhi M., Hachinski V., Whitehouse P.J. Changing perspectives regarding late-life dementia. Nat Rev Neurol. 2009;5:649–658. ­doi: 10.1038/nrneurol.2009.175.
  17. Bamford J.M., Warlow C.P. Evolution and testing of the lacunar hypothesis. Stroke. 1988;19:1074–1082.
  18. Metz R.J., Bogousslavsky J. Lacunar stroke. In: Fisher M, Bogousslavsky J, eds. Current Review of Cerebrovascular Disease. 4th ed. Philadelphia, PA: Current Medicine Group; 2001:115–122.
  19. Kwok C.S., Shoamanesh A., Copley H.C., Myint P.K., Loke Y.K., Benavente O.R. Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke. 2015;46:1014–1023. doi: 10.1161/STROKEAHA.114.008422.
  20. Oyama N., Yagita Y., Sasaki T., Omura-Matsuoka E., Terasaki Y., Sugiyama Y., et al. An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive rats. J Neurosci Res. 2010;88:2889–2898. doi: 10.1002/jnr.22441.
  21. Fredriksson K., Nordborg C., Kalimo H., Olsson Y., Johansson B.B. Cerebral microangiopathy in stroke-prone spontaneously hypertensive rats. An immunohistochemical and ultrastructural study. ­Acta Neuropathol. 1988;75:241–252.
  22. Lin J.X., Tomimoto H., Akiguchi I., Wakita H., Shibasaki H., Horie R. White matter lesions and alteration of vascular cell composition in the brain of spontaneously hypertensive rats. Neuroreport. 2001;12:1835–1839.
  23. Bailey E.L., McBride M.W., Beattie W., McClure J.D., Graham D., Dominiczak A.F., et al. Differential gene expression in multiple neurological, inflammatory and connective tissue pathways ­in a spontaneous model of human small vessel stroke. Neuropathol Appl Neurobiol. 2014;40:855–872. doi: 10.1111/nan.12116.
  24. Bailey E.L., Wardlaw J.M., Graham D., Dominiczak A.F., Sudlow C.L., Smith C. Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: ­a blinded, controlled immunohistochemical study of 5- to 21-week-old rats. Neuropathol Appl Neurobiol. 2011;37:711–726. ­doi: 10.1111/j.1365-2990.2011.01170.x.
  25. Lopez L.M., Hill W.D., Harris S.E., Valdes Hernandez M., Munoz Maniega S., Bastin M.E., et al. Genes from a translational analysis support a multifactorial nature of white matter hyperintensities. Stroke. 2015;46:341–347. doi: 10.1161/STROKEAHA.114.007649.
  26. Bragulat E., de la Sierra A., Antonio M.T., Coca A. Endothelial dysfunction in salt-sensitive essential hypertension. Hypertension. 2001;37­(2 pt 2):444–448.
  27. Dickinson K.M., Clifton P.M., Keogh J.B. Endothelial function is impaired after a high-salt meal in healthy subjects. Am J Clin Nutr. 2011;93:500–505. doi: 10.3945/ajcn.110.006155.
  28. Ma X.J., Cheng J.W., Zhang J., Liu A.J., Liu W., Guo W., et al. E-selectin deficiency attenuates brain ischemia in mice. CNS Neurosci Ther. 2012;18:903–908. doi: 10.1111/cns.12000.
  29. Hainsworth A.H., Oommen A.T., Bridges L.R. Endothelial cells and human cerebral small vessel disease. Brain Pathol. 2015;25:44–50. doi:10.1111/bpa.12224.
  30. Traylor M., Farrall M., Holliday E.G., Sudlow C., Hopewell J.C., Cheng Y.C., et al; Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2); International Stroke Genetics Consortium. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis ­of genome-wide association studies. Lancet Neurol. 2012;11:951–962. doi: 10.1016/S1474-4422(12)70234-X.
  31. Manolio T.A., Collins F.S., Cox N.J., Goldstein D.B., Hindorff L.A., Hunter D.J., et al. Finding the missing heritability of complex diseases. Nature. 2009;461:747–753. doi: 10.1038/nature08494.
  32. Atwood L.D., Wolf P.A., Heard-Costa N.L., Massaro J.M., Beiser A., D’Agostino R.B., et al. Genetic variation in white matter hyperintensity volume in the Framingham Study. Stroke. 2004;35:1609–1613. doi:10.1161/01.STR.0000129643.77045.10.
  33. Adib-Samii P., Devan W., Traylor M., Lanfranconi S., Zhang C.R., Cloonan L., et al. Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke. Stroke. 2015;46:348–353. doi: 10.1161/STROKEAHA.114.006849.
  34. Rouhl R.P., Damoiseaux J.G., Lodder J., Theunissen R.O., Knottnerus I.L., Staals J., et al. Vascular inflammation in cerebral small vessel disease. Neurobiol Aging. 2012;33:1800–1806. ­doi: 10.1016/j.neurobiolaging.2011.04.008.
  35. Aribisala B.S., Wiseman S., Morris Z., Valdes-Hernandez M.C., Royle N.A., Maniega S.M., et al. Circulating inflammatory markers are associated with magnetic resonance imaging-visible perivascular spaces but not directly with white matter hyperintensities. Stroke. 2014;45:605–607. doi: 10.1161/STROKEAHA.113.004059.
  36. Abbott N.J. Inflammatory mediators and modulation of blood–brain barrier permeability. Cell Mol Neurobiol. 2000;20:131–147.
  37. Leong X.F., Ng C.Y., Badiah B., Das S. Association between hypertension and periodontitis: possible mechanisms. SciWorldJ. 2014;2014:768237. doi: 10.1155/2014/768237.
  38. Emsley H.C., Tyrrell P.J. Inflammation and infection in clinical stroke. J Cereb Blood Flow Metab. 2002;22:1399–1419. doi:10.1097/00004647-200212000-00001.
  39. Emsley H.C., Hopkins S.J. Acute ischaemic stroke and infection: recent and emerging concepts. Lancet Neurol. 2008;7:341–353. ­doi: 10.1016/S1474-4422(08)70061-9.
  40. Friedland R.P. Mechanisms of molecular mimicry involving ­the microbiota in neurodegeneration. J Alzheimers Dis. 2015;45:349–362. doi:10.3233/JAD-142841.
  41. Mayer E.A., Tillisch K., Gupta A. Gut/brain axis and the microbiota. ­J Clin Invest. 2015;125:926–938. doi: 10.1172/JCI76304.
  42. Diaz Heijtz R., Wang S., Anuar F., Qian Y., Bjorkholm B., Samuelsson A., et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011;108:3047–3052. ­doi: 10.1073/pnas.1010529108.
  43. Karlsson F.H., Fak F., Nookaew I., Tremaroli V., Fagerberg B., Petranovic D., et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3:1245. doi: 10.1038/ncomms2266.
  44. Paster B.J., Boches S.K., Galvin J.L., Ericson R.E., Lau C.N., Levanos V.A., et al. Bacterial diversity in human subgingival plaque. J Bacteriol. 2001;183:3770–3783. doi: 10.1128/JB.183.12.3770-3783.2001.
  45. Kawato T., Tanaka H., Tabuchi M., Ooshima K., Nakai K., Yamashita Y., et al. Continual Gram-negative bacterial challenge accelerates stroke onset in stroke-prone spontaneously hypertensive rats. Clin Exp Hypertens. 2013;35:28–34. doi: 10.3109/10641963.2012.689042.
  46. Nakano K., Hokamura K., Taniguchi N., Wada K., Kudo C., Nomura R., et al. The collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke. Nat Commun. 2011;2:485. doi: 10.1038/ncomms1491.
  47. Lee Y.L., Hu H.Y., Huang N., Hwang D.K., Chou P., Chu D. Dental prophylaxis and periodontal treatment are protective factors to ischemic stroke. Stroke. 2013;44:1026–1030. doi: 10.1161/STROKEAHA.111.000076.
  48. Wu T., Trevisan M., Genco R.J., Dorn J.P., Falkner K.L., Sempos C.T. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch Intern Med. 2000;160:2749–2755.
  49. Fernandes C.P., Oliveira F.A., Silva P.G., Alves A.P., Mota M.R., Montenegro R.C., et al. Molecular analysis of oral bacteria in dental biofilm and atherosclerotic plaques of patients with vascular disease. Int J Cardiol. 2014;174:710–712. doi: 10.1016/j.ijcard.2014.04.201.
  50. Lockhart P.B., Brennan M.T., Sasser H.C., Fox P.C., Paster B.J., Bahrani-Mougeot F.K. Bacteremia associated with toothbrushing and dental extraction. Circulation. 2008;117:3118–3125. doi: 10.1161/CIRCULATIONAHA.107.758524.
  51. Miyatani F., Kuriyama N., Watanabe I., Nomura R., Nakano K., Matsui D., et al. Relationship between Cnm-positive Streptococcus mutans and cerebral microbleeds in humans. Oral Dis. 2015;21:886–893. doi:10.1111/odi.12360.
  52. Pussinen P.J., Alfthan G., Jousilahti P., Paju S., Tuomilehto J. Systemic exposure to Porphyromonas gingivalis predicts incident stroke. Atherosclerosis. 2007;193:222–228. doi: 10.1016/j.atherosclerosis.2006.06.027.
  53. Lourbakos A., Yuan Y.P., Jenkins A.L., Travis J., Andrade-Gordon P., Santulli R., et al. Activation of protease-activated receptors by gingipains from Porphyromonas gingivalis leads to platelet aggregation: a new trait in microbial pathogenicity. Blood. 2001;97:3790–3797.
  54. Walter C., Zahlten J., Schmeck B., Schaudinn C., Hippenstiel S., Frisch E., et al. Porphyromonas gingivalis strain-dependent activation of human endothelial cells. Infect Immun. 2004;72:5910–5918. ­doi: 10.1128/IAI.72.10.5910-5918.2004.
  55. Henry-Feugeas M.C. Alzheimer’s disease in late-life dementia: a minor toxic consequence of devastating cerebrovascular dysfunction. Med Hypotheses. 2008;70:866–875. doi: 10.1016/j.mehy.2007.07.027.
  56. Laurent S., Briet M., Boutouyrie P. Large and small artery cross-talk and recent morbidity-mortality trials in hypertension. Hypertension. 2009;54:388–392. doi: 10.1161/HYPERTENSIONAHA.109.133116.
  57. Scuteri A., Nilsson P.M., Tzourio C., Redon J., Laurent S. Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications. J Hypertens. 2011;29:1469–1477. doi:10.1097/HJH.0b013e328347cc17.
  58. Aribisala B.S., Morris Z., Eadie E., Thomas A., Gow A., Valdés Hernández M.C., et al. Blood pressure, internal carotid artery flow parameters, and age-related white matter hyperintensities. Hypertension. 2014;63:1011–1018. doi: 10.1161/HYPERTENSIONAHA.113.02735.
  59. Xiong Y.Y., Mok V., Wong A., Leung T., Chen X.Y., Chu W.C., et al. Evaluation of age-related white matter changes using transcranial Doppler ultrasonography. J Neuroimaging. 2013;23:53–57. doi:10.1111/j.1552-6569.2011.00649.x.
  60. Bailey E.L., McCulloch J., Sudlow C., Wardlaw J.M. Potential animal models of lacunar stroke: a systematic review. Stroke. 2009;40:e451–e458. doi: 10.1161/STROKEAHA.108.528430.
  61. Bailey E.L., Smith C., Sudlow C.L., Wardlaw J.M. Is the spontaneously hypertensive stroke prone rat a pertinent model of sub cortical ischemic stroke? A systematic review. Int J Stroke. 2011;6:434–444. doi:10.1111/j.1747-4949.2011.00659.x.
  62. Ogata J., Fujishima M., Tamaki K., Nakatomi Y., Ishitsuka T., Omae T. Stroke-prone spontaneously hypertensive rats as an experimental model of malignant hypertension. I. A light- and electron-microscopic study of the brain. Acta Neuropathol. 1980;51:179–184.
  63. Kitamura A., Saito S., Maki A., Ayaki T., Oishi N., Kalaria R., ­et al. Gradual cerebral hypoperfusion in spontaneously hypertensive rats induces slowly evolving white matter abnormalities and impairs working memory
  64. Bink D.I., Ritz K., Aronica E., van der Weerd L., Daemen M.J. Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition. J Cereb Blood Flow Metab. 2013;33:1666–1684. doi:10.1038/jcbfm.2013.140.
  65. Coltman R., Spain A., Tsenkina Y., Fowler J.H., Smith J., Scullion G., ­et al. Selective white matter pathology induces a specific impairment in spatial working memory. Neurobiol Aging. 2011;32:2324.e7–2324.12. doi:10.1016/j.neurobiolaging.2010.09.005.
  66. Hattori Y., Okamoto Y., Maki T., Yamamoto Y., Oishi N., Yamahara K., et al. Silent information regulator 2 homolog 1 counters cerebral hypoperfusion injury by deacetylating endothelial nitric oxide synthase. Stroke. 2014;45:3403–3411. doi: 10.1161/STROKEAHA.114.006265.
  67. Holland P.R., Searcy J.L., Salvadores N., Scullion G., Chen G., Lawson G., et al. Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease. J Cereb Blood Flow Metab. 2015;35:1005–1014. doi: 10.1038/jcbfm.2015.12.
  68. Nakaji K., Ihara M., Takahashi C., Itohara S., Noda M., Takahashi R., ­et al. Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke. 2006;37:2816–2823. doi: 10.1161/01.STR.0000244808.17972.55.
  69. Shibata M., Ohtani R., Ihara M., Tomimoto H. White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke. 2004;35:2598–2603. doi: 10.1161/01.STR.0000143725.19053.60.
  70. Mead G.E., Lewis S.C., Wardlaw J.M., Dennis M.S., Warlow C.P. Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders? J Neurol. 2002;249:266–271.
  71. Potter G.M., Doubal F.N., Jackson C.A., Sudlow C.L., Dennis M.S., Wardlaw J.M. Lack of association of white matter lesions with ipsilateral carotid artery stenosis. Cerebrovasc Dis. 2012;33:378–384. doi:10.1159/000336762.
  72. Feng S., Cen J., Huang Y., Shen H., Yao L., Wang Y., et al. Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase ­the permeability of blood–brain barrier by disrupting tight junction proteins. PLoS One. 2011;6:e20599. doi: 10.1371/journal.pone.0020599.
  73. Corbin Z.A., Rost N.S., Lorenzano S., Kernan W.N., Parides M.K., Blumberg J.B., et al. White matter hyperintensity volume correlates with matrix metalloproteinase-2 in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23:1300–1306. doi: 10.1016/j.jstrokecerebrovasdis.2013.11.002.
  74. Ihara M., Tomimoto H. Lessons from a mouse model characterizing features of vascular cognitive impairment with white matter changes. ­J Aging Res. 2011;2011:978761. doi: 10.4061/2011/978761.
  75. Wardlaw 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;34:806–812. doi: 10.1161/01.STR.0000058480.77236.B3.
  76. Jellinger K.A. The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol. 2007;113:349–388. doi: 10.1007/s00401-006-0185-2.
  77. Udaka F., Sawada H., Kameyama M. White matter lesions and dementia: MRI-pathological correlation. Ann N Y Acad Sci. 2002;977:411–415.
  78. Hattori Y., Enmi J., Kitamura A., Yamamoto Y., Saito S., Takahashi Y., et al. A novel mouse model of subcortical infarcts with dementia. J Neurosci. 2015;35:3915–3928. doi: 10.1523/JNEUROSCI.3970-14.2015.
  79. Maniega S.M., Valdes Hernandez M.C., Clayden J.D., Royle N.A., Murray C., Morris Z., et al. White matter hyperintensities and normal-appearing white matter integrity in the aging brain. Neurobiol Aging. 2015;36:909–918. doi: 10.1016/j.neurobiolaging.2014.07.048.
  80. Wardlaw J.M., Valdes Hernandez M.C., Munoz-Maniega S. What are white matter hyperintensities made of? Relevance to vascular cognitive impairment. J Am Heart Assoc. 2015;4:001140. doi: 10.1161/JAHA.114.001140.
  81. Wardlaw J.M., Doubal F., Armitage P., Chappell F., Carpenter T., Muñoz Maniega S., et al. Lacunar stroke is associated with diffuse blood–brain barrier dysfunction. Ann Neurol. 2009;65:194–202. ­doi: 10.1002/ana.21549.
  82. Wardlaw J.M., Doubal F.N., Valdes-Hernandez M., Wang X., Chappell F.M., Shuler K., et al. Blood–brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease. Stroke. 2013;44:525–527. doi: 10.1161/STROKEAHA.112.669994.
  83. Wardlaw J.M., Farrall A., Armitage P.A., Carpenter T., Chappell F., Doubal F., et al. Changes in background blood–brain barrier integrity between lacunar and cortical ischemic stroke subtypes. Stroke. 2008;39:1327–1332. doi: 10.1161/STROKEAHA.107.500124.
  84. Farrall A.J., Wardlaw J.M. Blood–brain barrier: ageing and microvascular disease–systematic review and meta-analysis. Neurobiol Aging. 2009;30:337–352. doi: 10.1016/j.neurobiolaging. 2007.07.015.
  85. Montagne A., Barnes S.R., Sweeney M.D., Halliday M.R., Sagare A.P., Zhao Z., et al. Blood–brain barrier breakdown in the aging human hippocampus. Neuron. 2015;85:296–302. doi: 10.1016/j.neuron.2014.12.032.
  86. Armulik A., Abramsson A., Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97:512–523. doi: 10.1161/01.RES.0000182903.16652.d7.
  87. Craggs L.J., Fenwick R., Oakley A.E., Ihara M., Kalaria R.N. Immunolocalization of platelet-derived growth factor receptor-β (PDGFR-β) and pericytes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Neuropathol Appl Neurobiol. 2015;41:557–570. doi: 10.1111/nan.12188.
  88. Craggs L.J., Yamamoto Y., Ihara M., Fenwick R., Burke M., Oakley A.E., et al. White matter pathology and disconnection in the frontal lobe ­in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Neuropathol Appl Neurobiol. 2014;40:591–602. doi: 10.1111/nan.12073.
  89. Bell R.D., Winkler E.A., Sagare A.P., Singh I., LaRue B., Deane R., et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68:409–427. doi:10.1016/j.neuron.2010.09.043.
  90. Miyamoto N., Maki T., Shindo A., Liang A.C., Maeda M., Egawa N., ­et al. Astrocytes promote oligodendrogenesis after white matter damage via brain-derived neurotrophic factor. J Neurosci. 2015;35:14002–14008. doi: 10.1523/JNEUROSCI.1592-15.2015.
  91. Bonkowski D., Katyshev V., Balabanov R.D., Borisov A., Dore-Duffy P. The CNS microvascular pericyte: pericyte-astrocyte crosstalk ­in the regulation of tissue survival. Fluids Barriers CNS. 2011;8:8. doi:10.1186/2045-8118-8-8.
  92. Abbott N.J., Ronnback L., Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7:41–53. doi:10.1038/nrn1824.
  93. Seo J.H., Maki T., Maeda M., Miyamoto N., Liang A.C., Hayakawa K., ­et al. Oligodendrocyte precursor cells support blood–brain barrier integrity via TGF-β signaling. PLoS One. 2014;9:e103174. doi: 10.1371/journal.pone.0103174.
  94. Maki T., Maeda M., Uemura M., Lo E.K., Terasaki Y., Liang A.C., et al. Potential interactions between pericytes and oligodendrocyte precursor cells in perivascular regions of cerebral white matter. Neurosci Lett. 2015;597:164–169. doi: 10.1016/j.neulet.2015.04.047.
  95. Hu J., Van den Steen P.E., Sang Q.X., Opdenakker G. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov. 2007;6:480–498. doi: 10.1038/nrd2308.
  96. Chaar L.J., Alves T.P., Batista Junior A.M., Michelini L.C. Early traininginduced reduction of angiotensinogen in autonomic areas-the main effect of exercise on brain renin–angiotensin system in hypertensive rats. PloS One. 2015;10:e0137395. doi: 10.1371/journal.pone.0137395.
  97. Gow A.J., Bastin M.E., Munoz Maniega S., Valdes Hernandez M.C., Morris Z., Murray C., et al. Neuroprotective lifestyles and the aging brain: activity, atrophy, and white matter integrity. Neurology. 2012;79:1802–1808. doi: 10.1212/WNL.0b013e3182703fd2.
  98. Briet M., Schiffrin E.L. Treatment of arterial remodeling in essential hypertension. Curr Hypertens Rep. 2013;15:3–9. doi: 10.1007/s11906-012-0325-0.

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