White matter degeneration in vascular and other ageing-related dementias

Journal of Neurochemistry

Volumn 144, Issue 5, 2018, Pages 617-633

  Hase, Yoshiki ^a   Horsburgh, Karen ^b   Ihara, Masafumi ^c   Kalaria, Raj N ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

^c NATIONAL CEREBRAL AND CARDIOVASCULAR CENTER   (Japan)

Author keywords

astrocytes; blood brain barrier; post stroke dementia; stroke; vascular dementia; white matter

Indexed keywords

AQUAPORIN 4;

AGING; ALZHEIMER DISEASE; ARTERIOLOSCLEROSIS; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN PERFUSION; CEREBROVASCULAR ACCIDENT; CEREBROVASCULAR DISEASE; COGNITIVE DEFECT; COMPUTER ASSISTED TOMOGRAPHY; DEGENERATIVE DISEASE; DIFFUSION TENSOR IMAGING; GLIA CELL; HUMAN; HYPOXIA; INFLAMMATION; LEUKOARAIOSIS; MICROGLIA; MULTIINFARCT DEMENTIA; NONHUMAN; OLIGODENDROGLIA; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PERICYTE; PRIORITY JOURNAL; REVIEW; WHITE MATTER DEGENERATION; WHITE MATTER LESION; ANIMAL; BRAIN; COMPLICATION; DEMENTIA; DIAGNOSTIC IMAGING; GLIA; MYELIN SHEATH; NERVE CELL; PATHOLOGY; WHITE MATTER;

AGING; ANIMALS; BLOOD-BRAIN BARRIER; BRAIN; DEMENTIA; DEMENTIA, VASCULAR; HUMANS; LEUKOARAIOSIS; MYELIN SHEATH; NEUROGLIA; NEURONS; WHITE MATTER;

EID: 85042220573     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.14271     Document Type: Review

References (174)

1. Abbott N. J., Ronnback L. and Hansson E. (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 7, 41–53.
2. Adalbert R. and Coleman M. P. (2013) Review: axon pathology in age-related neurodegenerative disorders. Neuropathol. Appl. Neurobiol. 39, 90–108.
3. Adib-Samii P., Rost N., Traylor M. et al. (2013) 17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status. Stroke 44, 1609–1615.
4. Adib-Samii P., Devan W., Traylor M. et al. (2015) Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke. Stroke 46, 348–353.
5. Akinyemi R. O. (2014) Profile, determinants and mechanisms of cerebral injury and cognitive impairment following stroke, in Institute of Neuroscience, PhD Thesis, pp. 280. Newcastle University, Newcastle upon Tyne.
6. Al-Mashhadi S., Simpson J. E., Heath P. R. et al. (2015) Oxidative glial cell damage associated with white matter lesions in the aging human brain. Brain Pathol. 25, 565–574.
7. Appelman A. P., Exalto L. G., van der Graaf Y., Biessels G. J., Mali W. P. and Geerlings M. I. (2009) White matter lesions and brain atrophy: more than shared risk factors? A systematic review. Cerebrovasc. Dis. 28, 227–242.
8. Atwood L. D., Wolf P. A., Heard-Costa N. L., Massaro J. M., Beiser A., D'Agostino R. B. and DeCarli C. (2004) Genetic variation in white matter hyperintensity volume in the Framingham Study. Stroke 35, 1609–1613.
9. Badaut J., Lasbennes F., Magistretti P. J. and Regli L. (2002) Aquaporins in brain: distribution, physiology, and pathophysiology. J. Cereb. Blood Flow Metab. 22, 367–378.
10. Baradaran H., Mtui E. E., Richardson J. E., Delgado D., Dunning A., Marshall R. S., Sanelli P. C. and Gupta A. (2016) White matter diffusion abnormalities in carotid artery disease: a systematic review and meta-analysis. J. Neuroimaging 26, 481–488.
11. Barker R., Wellington D., Esiri M. M. and Love S. (2013) Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins. J. Cereb. Blood Flow Metab. 33, 1050–1057.
12. Barker R., Ashby E. L., Wellington D., Barrow V. M., Palmer J. C., Kehoe P. G., Esiri M. M. and Love S. (2014) Pathophysiology of white matter perfusion in Alzheimer's disease and vascular dementia. Brain 137, 1524–1532.
13. Benfenati V. and Ferroni S. (2010) Water transport between CNS compartments: functional and molecular interactions between aquaporins and ion channels. Neuroscience 168, 926–940.
14. Benjamin P., Lawrence A. J., Lambert C., Patel B., Chung A. W., MacKinnon A. D., Morris R. G., Barrick T. R. and Markus H. S. (2014) Strategic lacunes and their relationship to cognitive impairment in cerebral small vessel disease. Neuroimage Clin. 4, 828–837.
15. Bolandzadeh N., Davis J. C., Tam R., Handy T. C. and Liu-Ambrose T. (2012) The association between cognitive function and white matter lesion location in older adults: a systematic review. BMC Neurol. 12, 126.
16. Boulanger J. J. and Messier C. (2014) From precursors to myelinating oligodendrocytes: contribution of intrinsic and extrinsic factors to white matter plasticity in the adult brain. Neuroscience 269, 343–366.
17. Bradl M. and Lassmann H. (2010) Oligodendrocytes: biology and pathology. Acta Neuropathol. 119, 37–53.
18. Brown W. R., Moody D. M., Thore C. R., Anstrom J. A. and Challa V. R. (2009) Microvascular changes in the white matter in dementia. J. Neurol. Sci. 283, 28–31.
19. Burton E. J., Kenny R. A., O'Brien J. et al. (2004) White matter hyperintensities are associated with impairment of memory, attention, and global cognitive performance in older stroke patients. Stroke 35, 1270–1275.
20. Cai Z., Lin S., Fan L. W., Pang Y. and Rhodes P. G. (2006) Minocycline alleviates hypoxic-ischemic injury to developing oligodendrocytes in the neonatal rat brain. Neuroscience 137, 425–435.
21. Carare R. O., Bernardes-Silva M., Newman T. A., Page A. M., Nicoll J. A., Perry V. H. and Weller R. O. (2008) Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol. Appl. Neurobiol. 34, 131–144.
22. Carmeliet P. and Jain R. K. (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298–307.
23. Charlton R. A., Barrick T. R., McIntyre D. J., Shen Y., O'Sullivan M., Howe F. A., Clark C. A., Morris R. G. and Markus H. S. (2006) White matter damage on diffusion tensor imaging correlates with age-related cognitive decline. Neurology 66, 217–222.
24. Chen A., Akinyemi R. O., Hase Y. et al. (2016) Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia. Brain 139, 242–258.
25. Choudhury G. R. and Ding S. (2016) Reactive astrocytes and therapeutic potential in focal ischemic stroke. Neurobiol. Dis. 85, 234–244.
26. Craggs L. J., Hagel C., Kuhlenbaeumer G. et al. (2013) Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases. Brain Pathol. 23, 547–557.
27. Craggs L. J., Yamamoto Y., Ihara M. et al. (2014) White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Neuropathol. Appl. Neurobiol. 40, 591–602.
28. Croall I. D., Lohner V., Moynihan B. et al. (2017) Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies. Clin. Sci. 131, 1361–1373.
29. Cuadrado A. and Nebreda A. R. (2010) Mechanisms and functions of p38 MAPK signalling. Biochem. J. 429, 403–417.
30. Debette S. and Markus H. S. (2010) The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 341, c3666.
31. Depienne C., Bugiani M., Dupuits C. et al. (2013) Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurol. 12, 659–668.
32. Deramecourt V., Slade J. Y., Oakley A. E., Perry R. H., Ince P. G., Maurage C. A. and Kalaria R. N. (2012) Staging and natural history of cerebrovascular pathology in dementia. Neurology 78, 1043–1050.
33. Ding R., Barsby J., Slade J. Y., Oakley A. E. and Kalaria R. (2017) The role of cerebral pericytes in the frontal white matter of ageing related dementias. Alzheimers Dement. 13, 1483–1484.
34. Dong Y. F., Kataoka K., Toyama K. et al. (2011) Attenuation of brain damage and cognitive impairment by direct renin inhibition in mice with chronic cerebral hypoperfusion. Hypertension 58, 635–642.
35. Duering M., Zieren N., Herve D. et al. (2011) Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL. Brain 134, 2366–2375.
36. Duering M., Righart R., Csanadi E., Jouvent E., Herve D., Chabriat H. and Dichgans M. (2012) Incident subcortical infarcts induce focal thinning in connected cortical regions. Neurology 79, 2025–2028.
37. Duering M., Csanadi E., Gesierich B. et al. (2013) Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease. Brain 136, 2717–2726.
38. Duering M., Gesierich B., Seiler S. et al. (2014) Strategic white matter tracts for processing speed deficits in age-related small vessel disease. Neurology 82, 1946–1950.
39. Duncombe J., Lennen R. J., Jansen M. A., Marshall I., Wardlaw J. M. and Horsburgh K. (2016) Ageing causes prominent neurovascular dysfunction associated with loss of astrocytic contacts and gliosis. Neuropathol. Appl. Neurobiol. 43, 477–491.
40. Duncombe J., Kitamura A., Hase Y., Ihara M., Kalaria R. and Horsburgh K. (2017) Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia (VCID): closing the translational gap between rodent models and human VCID. Clin. Sci. 131, 2451–2468.
41. Emery B. (2010) Regulation of oligodendrocyte differentiation and myelination. Science 330, 779–782.
42. Fancy S. P., Chan J. R., Baranzini S. E., Franklin R. J. and Rowitch D. H. (2011) Myelin regeneration: a recapitulation of development? Annu. Rev. Neurosci. 34, 21–43.
43. Fazekas F., Kleinert R., Offenbacher H., Payer F., Schmidt R., Kleinert G., Radner H. and Lechner H. (1991) The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR Am. J. Neuroradiol. 12, 915–921.
44. Fernando M. S., O'Brien J. T., Perry R. H. et al. (2004) Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain. Neuropathol. Appl. Neurobiol. 30, 385–395.
45. Fernando M. S., Simpson J. E., Matthews F. et al. (2006) White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 37, 1391–1398.
46. Firbank M. J., He J., Blamire A. M., Singh B., Danson P., Kalaria R. N. and O'Brien J. T. (2011) Cerebral blood flow by arterial spin labeling in poststroke dementia. Neurology 76, 1478–1484.
47. Fornage M., Debette S., Bis J. C. et al. (2011) Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium. Ann. Neurol. 69, 928–939.
48. Foster V., Oakley A. E., Slade J. Y. et al. (2014) Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias. Brain 137, 2509–2521.
49. Frings L., Yew B., Flanagan E., Lam B. Y., Hull M., Huppertz H. J., Hodges J. R. and Hornberger M. (2014) Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease. PLoS ONE 9, e90814.
50. Funfschilling U., Supplie L. M., Mahad D. et al. (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485, 517–521.
51. Furuta A., Ishii N., Nishihara Y. and Horie A. (1991) Medullary arteries in aging and dementia. Stroke 22, 442–446.
52. Goodall E. F., Wang C., Simpson J. E., Baker D. J., Drew D. R., Heath P. R., Saffrey M. J., Romero I. A. and Wharton S. B. (2017) Age-associated changes in the blood-brain barrier: comparative studies in human and mouse. Neuropathol. Appl. Neurobiol. doi: 10.1111/nan.12408.
53. Gouw A. A., Seewann A., Vrenken H., van der Flier W. M., Rozemuller J. M., Barkhof F., Scheltens P. and Geurts J. J. (2008a) Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. Brain 131, 3286–3298.
54. Gouw A. A., van der Flier W. M., Fazekas F. et al. (2008b) Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study. Stroke 39, 1414–1420.
55. Gouw A. A., Seewann A., van der Flier W. M., Barkhof F., Rozemuller A. M., Scheltens P. and Geurts J. J. (2011) Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J. Neurol. Neurosurg. Psychiatry 82, 126–135.
56. Hachinski V. C., Potter P. and Merskey H. (1987) Leuko-araiosis. Arch. Neurol. 44, 21–23.
57. Hainsworth A. H., Minett T., Andoh J. et al. (2017) Neuropathology of white matter lesions, blood-brain barrier dysfunction, and dementia. Stroke 48, 2799–2804.
58. Hall C. N., Reynell C., Gesslein B. et al. (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508, 55–60.
59. Hase Y., Craggs L., Stevenson W., Hase M., Slade J. Y., Oakley A. E., Ihara M., Horsburgh K. and Kalaria R. N. (2016) Effects of environmental enrichment/physical exercise on white matter integrity and stroke injury in a mouse model of chronic cerebral hypoperfusion. Cerebrovasc. Dis. 41(Suppl 1), 199.
60. Hase Y., Craggs L., Hase M. et al. (2017) The effects of environmental enrichment on white matter pathology in a mouse model of chronic cerebral hypoperfusion. J. Cereb. Blood Flow Metab. doi: 10.1177/0271678X17694904.
61. Hattori Y., Enmi J., Iguchi S., Saito S., Yamamoto Y., Nagatsuka K., Iida H. and Ihara M. (2016a) Substantial reduction of parenchymal cerebral blood flow in mice with bilateral common carotid artery stenosis. Sci. Rep. 6, 32179.
62. Hattori Y., Enmi J., Iguchi S. et al. (2016b) Gradual carotid artery stenosis in mice closely replicates hypoperfusive vascular dementia in humans. J. Am. Heart Assoc. 5, e002757.
63. Highley J. R., Gebril O. H., Simpson J. E. et al. (2014) Axonal preservation in deep subcortical white matter lesions in the ageing brain. Aging Sci. 2, 118–119.
64. Hinman J. D., Lee M. D., Tung S., Vinters H. V. and Carmichael S. T. (2015) Molecular disorganization of axons adjacent to human lacunar infarcts. Brain 138, 736–745.
65. Hinson S. R., Pittock S. J., Lucchinetti C. F., Roemer S. F., Fryer J. P., Kryzer T. J. and Lennon V. A. (2007) Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 69, 2221–2231.
66. Holland P. R., Searcy J. L., Salvadores N. et al. (2015) Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease. J. Cereb. Blood Flow Metab. 35, 1005–1014. https://doi.org/10.1038/jcbfm.2015.12.
67. Hulse R. E., Winterfield J., Kunkler P. E. and Kraig R. P. (2001) Astrocytic clasmatodendrosis in hippocampal organ culture. Glia 33, 169–179.
68. Ihara M., Tomimoto H., Kinoshita M., Oh J., Noda M., Wakita H., Akiguchi I. and Shibasaki H. (2001) Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter. J. Cereb. Blood Flow Metab. 21, 828–834.
69. Ihara M., Polvikoski T. M., Hall R. et al. (2010) Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies. Acta Neuropathol. 119, 579–589.
70. Ince P. G., Minett T., Forster G., Brayne C. and Wharton S. B.; Medical Research Council Cognitive Function and Ageing Neuropathology Study (2017) Microinfarcts in an older population-representative brain donor cohort (MRC CFAS): prevalence, relation to dementia and mobility, and implications for the evaluation of cerebral Small Vessel disease. Neuropathol. Appl. Neurobiol. 43, 409–418.
71. Inzitari D., Pracucci G., Poggesi A. et al. (2009) Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort. BMJ 339, b2477.
72. Itoh Y., Toriumi H., Yamada S., Hoshino H. and Suzuki N. (2011) Astrocytes and pericytes cooperatively maintain a capillary-like structure composed of endothelial cells on gel matrix. Brain Res. 1406, 74–83.
73. Janaway B. M., Simpson J. E., Hoggard N. et al. (2014) Brain haemosiderin in older people: pathological evidence for an ischaemic origin of magnetic resonance imaging (MRI) microbleeds. Neuropathol. Appl. Neurobiol. 40, 258–269.
74. Jellinger K. A. (2007) The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol. 113, 349–388.
75. Jokinen H., Ryberg C., Kalska H. et al. (2007) Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study. J. Neurol. Neurosurg. Psychiatry 78, 491–496.
76. Jokinen H., Gouw A. A., Madureira S. et al. (2011) Incident lacunes influence cognitive decline: the LADIS study. Neurology 76, 1872–1878.
77. Kalaria R. N. (2016) Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer's disease. Acta Neuropathol. 131, 659–685.
78. Kalaria R. N. and Ihara M. (2013) Dementia: vascular and neurodegenerative pathways-will they meet?. Nat. Rev. Neurol. 9, 487–488.
79. Kalaria R. N., Perry R. H., O'Brien J. and Jaros E. (2012) Atheromatous disease in small intracerebral vessels, microinfarcts and dementia. Neuropathol. Appl. Neurobiol. 38, 505–508.
80. Kalaria R., Ferrer I. and Love S. (2015) Vascular disease, hypoxia and related conditions, in Greenfield's Neuropathology (Perry A., Love S., Ironside J. and Budka H., eds), Vol. 1, pp. 1–55. CRC Press, London.
81. Kandiah N., Goh O., Mak E., Marmin M. and Ng A. (2014) Carotid stenosis: a risk factor for cerebral white-matter disease. J. Stroke Cerebrovasc. Dis. 23, 136–139.
82. Kee Hyung P., Lee J. Y., Na D. L. et al. (2011) Different associations of periventricular and deep white matter lesions with cognition, neuropsychiatric symptoms, and daily activities in dementia. J. Geriatr. Psychiatry Neurol. 24, 84–90.
83. Kitamura A., Fujita Y., Oishi N. et al. (2012) Selective white matter abnormalities in a novel rat model of vascular dementia. Neurobiol. Aging 33(1012), e1025–e1035.
84. Kitamura A., Manso Y., Duncombe J. et al. (2017) Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion. Sci. Rep. 7, 4299.
85. van der Knaap M. S. and Bugiani M. (2017) Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. Acta Neuropathol. 134, 351–382.
86. Kobayashi K., Hayashi M., Nakano H., Fukutani Y., Sasaki K., Shimazaki M. and Koshino Y. (2002) Apoptosis of astrocytes with enhanced lysosomal activity and oligodendrocytes in white matter lesions in Alzheimer's disease. Neuropathol. Appl. Neurobiol. 28, 238–251.
87. Kovari E., Gold G., Herrmann F. R., Canuto A., Hof P. R., Bouras C. and Giannakopoulos P. (2007) Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia. Neurology 68, 927–931.
88. Kraig R. P. and Chesler M. (1990) Astrocytic acidosis in hyperglycemic and complete ischemia. J. Cereb. Blood Flow Metab. 10, 104–114.
89. Lammie G. A., Brannan F., Slattery J. and Warlow C. (1997) Nonhypertensive cerebral small-vessel disease. An autopsy study. Stroke 28, 2222–2229.
90. Lampron A., Larochelle A., Laflamme N. et al. (2015) Inefficient clearance of myelin debris by microglia impairs remyelinating processes. J. Exp. Med. 212, 481–495.
91. de Leeuw F. E., de Groot J. C., Achten E. et al. (2001) Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J. Neurol. Neurosurg. Psychiatry 70, 9–14.
92. Longstreth W. T., Jr, Manolio T. A., Arnold A., Burke G. L., Bryan N., Jungreis C. A., Enright P. L., O'Leary D. and Fried L. (1996) Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. Stroke 27, 1274–1282.
93. Lundgaard I., Osorio M. J., Kress B. T., Sanggaard S. and Nedergaard M. (2014) White matter astrocytes in health and disease. Neuroscience 276, 161–173.
94. Ma J., Zhang J., Hou W. W. et al. (2015) Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion. Sci. Rep. 5, 12079.
95. Maclullich A. M., Wardlaw J. M., Ferguson K. J., Starr J. M., Seckl J. R. and Deary I. J. (2004) Enlarged perivascular spaces are associated with cognitive function in healthy elderly men. J. Neurol. Neurosurg. Psychiatry 75, 1519–1523.
96. Maki T., Ihara M., Fujita Y., Nambu T., Harada H., Ito H., Nakao K., Tomimoto H. and Takahashi R. (2011a) Angiogenic roles of adrenomedullin through vascular endothelial growth factor induction. NeuroReport 22, 442–447.
97. Maki T., Ihara M., Fujita Y. et al. (2011b) Angiogenic and vasoprotective effects of adrenomedullin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice. Stroke 42, 1122–1128.
98. Maki T., Maeda M., Uemura M. et al. (2015a) Potential interactions between pericytes and oligodendrocyte precursor cells in perivascular regions of cerebral white matter. Neurosci. Lett. 597, 164–169.
99. Maki T., Takahashi Y., Miyamoto N., Liang A. C., Ihara M., Lo E. H. and Arai K. (2015b) Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro. Stem Cell Res. 15, 68–74.
100. Makin S. D., Turpin S., Dennis M. S. and Wardlaw J. M. (2013) Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J. Neurol. Neurosurg. Psychiatry 84, 893–900.
101. Manso Y., Holland P. R., Kitamura A. et al. (2017) Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease. Glia 66, 34–46.
102. Marner L., Nyengaard J. R., Tang Y. and Pakkenberg B. (2003) Marked loss of myelinated nerve fibers in the human brain with age. J. Comp. Neurol. 462, 144–152.
103. Matthews F. E., Brayne C., Lowe J., McKeith I., Wharton S. B. and Ince P. (2009) Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med. 6, e1000180.
104. McAleese K. E., Firbank M., Hunter D. et al. (2013) Magnetic resonance imaging of fixed post mortem brains reliably reflects subcortical vascular pathology of frontal, parietal and occipital white matter. Neuropathol. Appl. Neurobiol. 39, 485–497.
105. Miners J. S., Schulz I. and Love S. (2017) Differing associations between Abeta accumulation, hypoperfusion, blood-brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer's disease. J. Cereb. Blood Flow Metab. doi: 10.1177/0271678X17690761.
106. Mitew S., Hay C. M., Peckham H., Xiao J., Koenning M. and Emery B. (2014) Mechanisms regulating the development of oligodendrocytes and central nervous system myelin. Neuroscience 276, 29–47.
107. Mitome-Mishima Y., Miyamoto N., Tanaka R., Shimosawa T., Oishi H., Arai H., Hattori N. and Urabe T. (2014) Adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion in mice. Biomed. Res. Int. 2014, 861632.
108. Miyamoto N., Maki T., Pham L. D. et al. (2013a) Oxidative stress interferes with white matter renewal after prolonged cerebral hypoperfusion in mice. Stroke 44, 3516–3521.
109. Miyamoto N., Pham L. D., Hayakawa K. et al. (2013b) Age-related decline in oligodendrogenesis retards white matter repair in mice. Stroke 44, 2573–2578.
110. Miyamoto N., Pham L. D., Maki T., Liang A. C. and Arai K. (2014) A radical scavenger edaravone inhibits matrix metalloproteinase-9 upregulation and blood-brain barrier breakdown in a mouse model of prolonged cerebral hypoperfusion. Neurosci. Lett. 573, 40–45.
111. Miyamoto N., Maki T., Shindo A. et al. (2015) Astrocytes promote oligodendrogenesis after white matter damage via brain-derived neurotrophic factor. J. Neurosci. 35, 14002–14008.
112. Mori S., Sadoshima S., Ibayashi S., Lino K. and Fujishima M. (1994) Relation of cerebral blood flow to motor and cognitive functions in chronic stroke patients. Stroke 25, 309–317.
113. Mueller S. M. (1982) The blood-brain barrier in young spontaneously hypertensive rats. Acta Neurol. Scand. 65, 623–628.
114. Nagelhus E. A. and Ottersen O. P. (2013) Physiological roles of aquaporin-4 in brain. Physiol. Rev. 93, 1543–1562.
115. Nahirnyj A., Livne-Bar I., Guo X. and Sivak J. M. (2013) ROS detoxification and proinflammatory cytokines are linked by p38 MAPK signaling in a model of mature astrocyte activation. PLoS ONE 8, e83049.
116. Nakaji K., Ihara M., Takahashi C., Itohara S., Noda M., Takahashi R. and Tomimoto H. (2006) Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke 37, 2816–2823.
117. Nave K. A. and Werner H. B. (2014) Myelination of the nervous system: mechanisms and functions. Annu. Rev. Cell Dev. Biol. 30, 503–533.
118. Nedergaard M., Ransom B. and Goldman S. A. (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 26, 523–530.
119. Nishio K., Ihara M., Yamasaki N. et al. (2010) A mouse model characterizing features of vascular dementia with hippocampal atrophy. Stroke 41, 1278–1284.
120. Nitkunan A., McIntyre D. J., Barrick T. R., O'Sullivan M., Shen Y., Clark C. A., Howe F. A. and Markus H. S. (2006) Correlations between MRS and DTI in cerebral small vessel disease. NMR Biomed. 19, 610–616.
121. Ovbiagele B. and Saver J. L. (2006) Cerebral white matter hyperintensities on MRI: current concepts and therapeutic implications. Cerebrovasc. Dis. 22, 83–90.
122. Pantoni L. (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 9, 689–701.
123. Poggesi A., Pantoni L., Inzitari D. et al. (2011) 2001-2011: a decade of the LADIS (Leukoaraiosis And DISability) study: what have we learned about white matter changes and small-vessel disease? Cerebrovasc. Dis. 32, 577–588.
124. Pollock H., Hutchings M., Weller R. O. and Zhang E. T. (1997) Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes. J. Anat. 191(Pt 3), 337–346.
125. Popescu B. F., Parisi J. E., Cabrera-Gomez J. A., Newell K., Mandler R. N., Pittock S. J., Lennon V. A., Weinshenker B. G. and Lucchinetti C. F. (2010) Absence of cortical demyelination in neuromyelitis optica. Neurology 75, 2103–2109.
126. Prins N. D. and Scheltens P. (2015) White matter hyperintensities, cognitive impairment and dementia: an update. Nat. Rev. Neurol. 11, 157–165.
127. Qin A. P., Liu C. F., Qin Y. Y., Hong L. Z., Xu M., Yang L., Liu J., Qin Z. H. and Zhang H. L. (2010) Autophagy was activated in injured astrocytes and mildly decreased cell survival following glucose and oxygen deprivation and focal cerebral ischemia. Autophagy 6, 738–753.
128. Rajani R. M. and Williams A. (2017) Endothelial cell-oligodendrocyte interactions in small vessel disease and aging. Clin. Sci. 131, 369–379.
129. Reimer M. M., McQueen J., Searcy L. et al. (2011) Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion. J. Neurosci. 31, 18185–18194.
130. Richardson W. D., Pringle N., Mosley M. J., Westermark B. and Dubois-Dalcq M. (1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 53, 309–319.
131. Rosenberg G. A. (2017) Extracellular matrix inflammation in vascular cognitive impairment and dementia. Clin. Sci. 131, 425–437.
132. Ryberg C., Rostrup E., Paulson O. B. et al. (2011) Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort. J. Neurol. Sci. 307, 100–105.
133. Sachdev P. S., Thalamuthu A., Mather K. A., Ames D., Wright M. J., Wen W. and Team O. C. R. (2016) White matter hyperintensities are under strong genetic influence. Stroke 47, 1422–1428.
134. Saggu R., Schumacher T., Gerich F., Rakers C., Tai K., Delekate A. and Petzold G. C. (2016) Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia. Acta Neuropathol. Commun. 4, 76.
135. Sahlas D. J., Bilbao J. M., Swartz R. H. and Black S. E. (2002) Clasmatodendrosis correlating with periventricular hyperintensity in mixed dementia. Ann. Neurol. 52, 378–381.
136. Salat D. H., Tuch D. S., Greve D. N. et al. (2005) Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol. Aging 26, 1215–1227.
137. Sandoval K. E. and Witt K. A. (2008) Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiol. Dis. 32, 200–219.
138. Schmidt R., Fazekas F., Kapeller P., Schmidt H. and Hartung H. P. (1999) MRI white matter hyperintensities: three-year follow-up of the Austrian Stroke Prevention Study. Neurology 53, 132–139.
139. Schmidt R., Ropele S., Enzinger C., Petrovic K., Smith S., Schmidt H., Matthews P. M. and Fazekas F. (2005) White matter lesion progression, brain atrophy, and cognitive decline: the Austrian stroke prevention study. Ann. Neurol. 58, 610–616.
140. Seo J. H., Miyamoto N., Hayakawa K., Pham L. D., Maki T., Ayata C., Kim K. W., Lo E. H. and Arai K. (2013) Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury. J. Clin. Investig. 123, 782–786.
141. Shen H., Hu X., Liu C., Wang S., Zhang W., Gao H., Stetler R. A., Gao Y. and Chen J. (2010) Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms. Neurobiol. Dis. 37, 711–722.
142. Shi Y., Thrippleton M. J., Makin S. D., Marshall I., Geerlings M. I., de Craen A. J., van Buchem M. A. and Wardlaw J. M. (2016) Cerebral blood flow in small vessel disease: a systematic review and meta-analysis. J. Cereb. Blood Flow Metab. 36, 1653–1667.
143. Shibata M., Ohtani R., Ihara M. and Tomimoto H. (2004) White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35, 2598–2603.
144. Simpson J. E., Fernando M. S., Clark L. et al. (2007a) White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol. Appl. Neurobiol. 33, 410–419.
145. Simpson J. E., Ince P. G., Higham C. E. et al. (2007b) Microglial activation in white matter lesions and nonlesional white matter of ageing brains. Neuropathol. Appl. Neurobiol. 33, 670–683.
146. Simpson J. E., Hosny O., Wharton S. B. et al. (2009) Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways. Stroke 40, 369–375.
147. Simpson J. E., Wharton S. B., Cooper J. et al. (2010) Alterations of the blood-brain barrier in cerebral white matter lesions in the ageing brain. Neurosci. Lett. 486, 246–251.
148. Sjobeck M., Haglund M. and Englund E. (2005) Decreasing myelin density reflected increasing white matter pathology in Alzheimer's disease–a neuropathological study. Int. J. Geriatr. Psychiatry 20, 919–926.
149. Skripuletz T., Hackstette D., Bauer K. et al. (2013) Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain 136, 147–167.
150. Skrobot O. A., Attems J., Esiri M. et al. (2016) Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment. Brain 139, 2957–2969.
151. Tang J. P., Xu Z. Q., Douglas F. L., Rakhit A. and Melethil S. (1993) Increased blood-brain barrier permeability of amino acids in chronic hypertension. Life Sci. 53, PL417–PL420.
152. Taniguchi M., Yamashita T., Kumura E. et al. (2000) Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat. Brain Res. Mol. Brain Res. 78, 131–137.
153. Toledo J. B., Arnold S. E., Raible K., Brettschneider J., Xie S. X., Grossman M., Monsell S. E., Kukull W. A. and Trojanowski J. Q. (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. Brain 136, 2697–2706.
154. Tomimoto H., Akiguchi I., Suenaga T., Nishimura M., Wakita H., Nakamura S. and Kimura J. (1996) Alterations of the blood-brain barrier and glial cells in white-matter lesions in cerebrovascular and Alzheimer's disease patients. Stroke 27, 2069–2074.
155. Tomimoto H., Akiguchi I., Wakita H., Suenaga T., Nakamura S. and Kimura J. (1997) Regressive changes of astroglia in white matter lesions in cerebrovascular disease and Alzheimer's disease patients. Acta Neuropathol. 94, 146–152.
156. Tomimoto H., Ihara M., Wakita H., Ohtani R., Lin J. X., Akiguchi I., Kinoshita M. and Shibasaki H. (2003) Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat. Acta Neuropathol. 106, 527–534.
157. Tomimoto H., Lin J. X., Matsuo A., Ihara M., Ohtani R., Shibata M., Miki Y. and Shibasaki H. (2004) Different mechanisms of corpus callosum atrophy in Alzheimer's disease and vascular dementia. J. Neurol. 251, 398–406.
158. Trigiani L. J. and Hamel E. (2017) An endothelial link between the benefits of physical exercise in dementia. J. Cereb. Blood Flow Metab. 37, 2649–2664.
159. Turner S. T., Jack C. R., Fornage M., Mosley T. H., Boerwinkle E. and de Andrade M. (2004) Heritability of leukoaraiosis in hypertensive sibships. Hypertension 43, 483–487.
160. Uemura M. T., Ihara M., Maki T. et al. (2017) Pericyte-derived bone morphogenetic protein 4 underlies white matter damage after chronic hypoperfusion. Brain Pathol. doi: 10.1111/bpa.12523.
161. Wake H., Moorhouse A. J., Jinno S., Kohsaka S. and Nabekura J. (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29, 3974–3980.
162. Wang J., Yang Z., Liu C., Zhao Y. and Chen Y. (2013) Activated microglia provide a neuroprotective role by balancing glial cell-line derived neurotrophic factor and tumor necrosis factor-alpha secretion after subacute cerebral ischemia. Int. J. Mol. Med. 31, 172–178.
163. Wardlaw J. M., Doubal F. N., Valdes-Hernandez M., Wang X., Chappell F. M., Shuler K., Armitage P. A., Carpenter T. C. and Dennis M. S. (2013a) Blood-brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease. Stroke 44, 525–527.
164. Wardlaw J. M., Smith E. E., Biessels G. J. et al. (2013b) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 12, 822–838.
165. Washida K., Ihara M., Nishio K. et al. (2010) Nonhypotensive dose of telmisartan attenuates cognitive impairment partially due to peroxisome proliferator-activated receptor-gamma activation in mice with chronic cerebral hypoperfusion. Stroke 41, 1798–1806.
166. Weiss N., Miller F., Cazaubon S. and Couraud P. O. (2009) The blood-brain barrier in brain homeostasis and neurological diseases. Biochem. Biophys. Acta. 1788, 842–857.
167. Weller R. O., Subash M., Preston S. D., Mazanti I. and Carare R. O. (2008) Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol. 18, 253–266.
168. Wolf G., Lotan A., Lifschytz T. et al. (2017) Differentially severe cognitive effects of compromised cerebral blood flow in aged mice: association with myelin degradation and microglia activation. Front. Aging Neurosci. 9, 191.
169. Yamashita T., Kamiya T., Deguchi K. et al. (2009) Dissociation and protection of the neurovascular unit after thrombolysis and reperfusion in ischemic rat brain. J. Cereb. Blood Flow Metab. 29, 715–725.
170. Yamauchi H., Fukuyama H. and Shio H. (2000) Corpus callosum atrophy in patients with leukoaraiosis may indicate global cognitive impairment. Stroke 31, 1515–1520.
171. Yang Z., Zhang N., Shen H., Lin C., Lin L. and Yuan B. (2014) Microglial activation with reduction in autophagy limits white matter lesions and improves cognitive defects during cerebral hypoperfusion. Curr. Neurovasc. Res. 11, 223–229.
172. Yao Y., Chen Z. L., Norris E. H. and Strickland S. (2014) Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat. Commun. 5, 3413.
173. Zambenedetti P., Schmitt H. P. and Zatta P. (2002) Metallothionein I-II immunocytochemical reactivity in Binswanger's encephalopathy. J. Alzheimers Dis. 4, 459–466.
174. Zhai Y., Yamashita T., Nakano Y., Sun Z., Morihara R., Fukui Y., Ohta Y., Hishikawa N. and Abe K. (2016) Disruption of white matter integrity by chronic cerebral hypoperfusion in Alzheimer's disease mouse model. J. Alzheimers Dis. 52, 1311–1319.