Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

Circulation: Cardiovascular Genetics

Volumn 8, Issue 2, 2015, Pages 398-409

  Verhaaren, Benjamin F J ^a   Debette, Stéphanie ^b   Bis, Joshua C ^c   Smith, Jennifer A ^d   Ikram, M Kamran ^e   Adams, Hieab H ^f   Beecham, Ashley H ^g   Rajan, Kumar B ^h   Lopez, Lorna M ⁱ   Barral, Sandra ^j   Van Buchem, Mark A ^k   Van Der Grond, Jeroen ^l   Smith, Albert V ^m   Hegenscheid, Katrin ⁿ   Aggarwal, Neelum T ^o   De Andrade, Mariza ^l   Atkinson, Elizabeth J ^p   Beekman, Marian ^l   Beiser, Alexa S ^q   Blanton, Susan H ^r   Boerwinkle, Eric ^s   Brickman, Adam M ^t   Bryan, R Nick ^u   Chauhan, Ganesh ^v   Chen, Christopher P L H ^v   Chouraki, Vincent ^w   De Craen, Anton J M ^l   Crivello, Fabrice ^v   Deary, Ian J ^x,y   Deelen, Joris ^z   De Jager, Philip L ^aa   Dufouil, Carole ^ab   Elkind, Mitchell S V ^ac   Evans, Denis A ^ac   Freudenberger, Paul ^ac   Gottesman, Rebecca F ^ac   Gunason, Vilmundur ^ac   Habes, Mohamad ^ad   Heckbert, Susan R ^ae   Heiss, Gerardo ^af   Hilal, Saima ^ag   Hofer, Edith ^ah   Hofman, Albert ^ai   Ibrahim Verbaas, Carla A ^ai   Knopman, David S ^ai   Lewis, Cora E ^aj   Liao, Jiemin ^ak   Liewald, David C M ^a   Luciano, Michelle ^al   Van Der Lugt, Aad ^am   Martinez, Oliver O ^an   Mayeux, Richard ^ao   Mazoyer, Bernard ^ap   Nalls, Mike ^aq   Nauck, Matthias ^ah   Niessen, Wiro J ^ar   Oostra, Ben A ^as   Psaty, Bruce M ^at   Rice, Kenneth M ^au   Rotter, Jerome I ^av   Von Sarnowski, Bettina ^aw   Schmidt, Helena ^ax   Schreiner, Pamela J ^ay   Schuur, Maaike ^az   Sidney, Stephen S ^ba   Sigurdsson, Sigurdur ^bb   Slagboom, P Eline ^al   Stott, David J M ^bc   Van Swieten, John C ^bd   Teumer, Alexander ^be   Töglhofer, Anna Maria ^bf   Traylor, Matthew ^bg   Trompet, Stella ^bh   Turner, Stephen T ^bi   Tzourio, Christophe ^bj   Uh, Hae Won ^l   Uitterlinden, André G ^bk   Vernooij, Meike W ^bl   Wang, Jing J ^bm   Wong, Tien Y ^bn   Wardlaw, Joanna M ^l   Windham, B Gwen ^m   Wittfeld, Katharina ^bo   Wolf, Christiane ^bp   Wright, Clinton B ^bq   Yang, Qiong ^br   Zhao, Wei ^ad   Zijdenbos, Alex ^ah   Jukema, J Wouter ^ah   Sacco, Ralph L ^ah   Kardia, Sharon L R ^ah   Amouyel, Philippe ^ah   Mosley, Thomas H ^ai   Longstreth, W T ^ai   DeCarli, Charles C ^ai   Van Duijn, Cornelia M ^aj   Schmidt, Reinhold ^aj   Launer, Lenore J ^aj   Grabe, Hans J ^l   Seshadri, Sudha S ^l   Ikram, M Arfan ^l   Fornage, Myriam ^a   more..

^a UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^b Departments of Radiology   (Netherlands)

^c Departments of Neurology   (Netherlands)

^d Medical Informatics   (Netherlands)

^e Internal Medicine   (Netherlands)

^f Clinical Chemistry   (Netherlands)

^g ERASMUS MEDICAL CENTER   (Netherlands)

^h INSERM   (France)

ⁱ DIF   (France)

^j BORDEAUX UNIVERSITY HOSPITAL   (France)

^k UNIVERSITÉ DE BORDEAUX   (France)

^l Department of Neurology ^*

^m Carolina Global Breastfeeding Institute   (United States)

ⁿ BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^o Cardiovascular Health Research Unit   (United States)

^p Health Services   (United States)

^q UNIVERSITY OF WASHINGTON   (United States)

^r UNIVERSITY OF MICHIGAN SCHOOL OF PUBLIC HEALTH   (United States)

^s SINGAPORE EYE RESEARCH INSTITUTE   (Singapore)

^t NATIONAL UNIVERSITY HEALTH SYSTEM   (Singapore)

^u NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^v UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^w Neuroscience Program   (United States)

^x RUSH UNIVERSITY MEDICAL CENTER   (United States)

^y UNIVERSITY OF EDINBURGH   (United Kingdom)

^z UNIVERSITY OF EDINBURGH   (United Kingdom)

^aa Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H Sergievsky Center   (United States)

^ab NewYork Presbyterian Hospital   (United States)

^ac LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^ad ICELANDIC HEART ASSOCIATION   (Iceland)

^ae Institute for Community Medicine   (Germany)

^af Lab Medicine and Clinical Chemistry   (Germany)

^ag Interfaculty Institute for Genetics and Functional Genomics   (Germany)

^ah UNIVERSITY MEDICINE GREIFSWALD   (Germany)

^ai MAYO CLINIC   (United States)

^aj FRAMINGHAM HEART STUDY   (United States)

^ak Human Genetics Center   (United States)

^al UNIVERSITY OF PENNSYLVANIA   (United States)

^am DELFT UNIVERSITY OF TECHNOLOGY   (Netherlands)

^an CENTER FOR HEALTH STUDIES   (United States)

^ao Division of Genomic Outcomes Department of Pediatrics Institute for Translational Genomics and Population Sciences   (United States)

^ap Los Angeles Biomedical Research Institute   (United States)

^aq HARBOR UCLA MEDICAL CENTER   (United States)

^ar UNIVERSITY OF MINNESOTA   (United States)

^as DIVISION OF RESEARCH   (United States)

^at UNIVERSITY OF GLASGOW   (United Kingdom)

^au ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^av ROYAL NETHERLANDS ACADEMY OF ARTS AND SCIENCES   (Netherlands)

^aw Division of Geriatrics Gerontology   (United States)

^ax UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

^ay GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^az INSTITUTE FOR RESEARCH IN IMMUNOLOGY AND CANCER   (Canada)

^ba UNIV LILLE   (France)

^bb UNIVERSITY OF TEXAS   (United States)

^bc UNIVERSITY OF PENNSYLVANIA   (United States)

^bd HARVARD MEDICAL SCHOOL   (United States)

^be BRIGHAM AND WOMEN S HOSPITAL   (United States)

^bf Department of Neurology College of Phys and Surg   (United States)

^bg Biospective Inc ^*  (United States)

^bh Institute of Molecular Biology and Biochemistry   (United States)

^bi Institute for Medical Informatics   (United States)

^bj MEDICAL UNIVERSITY OF GRAZ   (Austria)

^bk University School of Medicine   (United States)

^bl JOHNS HOPKINS UNIVERSITY   (United States)

^bm Department of Physiology   (United States)

^bn UNIVERSITY OF ICELAND   (Iceland)

^bo UNIVERSITY OF NORTH CAROLINA   (United States)

^bp University of Alabama at Birmingham   (United States)

^bq Imaging of Dementia and Aging (IDeA) Laboratory   (United States)

^br UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

cerebral small vessel diseases; cerebrovascular disorders; genome wide association study; hypertension; leukoencephalopathies; polymorphisms, single nucleotide

Indexed keywords

FBF1 PROTEIN; MEMBRANE PROTEIN; MRPL38 PROTEIN; PROGRAMMED CELL DEATH 11; PROTEIN; PROTEIN SH3; SH3 AND PX DOMAIN CONTAINING PROTEIN 2A; TRIM47 PROTEIN; UNCLASSIFIED DRUG;

AFRICAN; AGE; ALZHEIMER DISEASE; ARTICLE; ASIAN; BRAIN HEMORRHAGE; COPY NUMBER VARIATION; ETHNICITY; EUROPEAN; FAMILY STUDY; GENE CONTROL; GENE EXPRESSION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC ASSOCIATION; GENETIC CONSERVATION; GENETIC IDENTIFICATION; GENETIC VARIABILITY; GENOTYPE; GLIOMA; HEREDITY; HISPANIC; HUMAN; HYPERTENSION; MAJOR CLINICAL STUDY; NERVOUS SYSTEM INFLAMMATION; NEUROIMAGING; NEUROPATHOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SCANNER; PHENOTYPE; POPULATION RESEARCH; PRIORITY JOURNAL; SEX; SINGLE NUCLEOTIDE POLYMORPHISM; WHITE MATTER HYPERINTENSITY; WHITE MATTER LESION; AGED; ANCESTRY GROUP; BIOLOGICAL MODEL; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; ETHNOLOGY; FEMALE; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HUMAN CHROMOSOME; MALE; META ANALYSIS (TOPIC); MIDDLE AGED; MULTICENTER STUDY; PATHOLOGY; VERY ELDERLY; WHITE MATTER;

AGED; AGED, 80 AND OVER; CHROMOSOMES, HUMAN; CONTINENTAL POPULATION GROUPS; FEMALE; GENETIC LOCI; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MALE; META-ANALYSIS AS TOPIC; MIDDLE AGED; MODELS, GENETIC; STROKE; WHITE MATTER;

EID: 84942844748     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.114.000858     Document Type: Article

References (53)

1. Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010;341:c3666.
2. Launer LJ. Epidemiology of white matter lesions. Top Magn Reson Imaging. 2004;15:365-367.
3. Pantoni L. Pathophysiology of age-related cerebral white matter changes. Cerebrovasc Dis. 2002;13(Suppl 2):7-10. doi: 49143.
4. Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rozemuller AM, Scheltens P, et al. Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry. 2011;82:126-135. doi: 10.1136/jnnp.2009.204685.
5. Fornage M, Chiang YA, O'Meara ES, Psaty BM, Reiner AP, Siscovick DS, et al. Biomarkers of Inflammation and MRI-Defined Small Vessel Disease of the Brain: The Cardiovascular Health Study. Stroke. 2008;39:1952-1959. doi: 10.1161/STROKEAHA.107.508135.
6. Wright CB, Moon Y, Paik MC, Brown TR, Rabbani L, Yoshita M, et al. Inflammatory biomarkers of vascular risk as correlates of leukoariosis. Stroke. 2009;40:3466-3471. doi: 10.1161/STROKEAHA.109.559567.
7. Carmelli D, DeCarli C, Swan GE, Jack LM, Reed T, Wolf PA, et al. Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke. 1998;29:1177-1181.
8. Atwood LD, Wolf PA, Heard-Costa NL, Massaro JM, Beiser A, D'Agostino RB, et al. Genetic variation in white matter hyperintensity volume in the Framingham Study. Stroke. 2004;35:1609-1613.
9. Turner ST, Jack CR, Fornage M, Mosley TH, Boerwinkle E, de Andrade M. Heritability of leukoaraiosis in hypertensive sibships. Hypertension. 2004;43:483-487. doi: 10.1161/01.HYP.0000112303.26158.92.
10. Freudenberger P, Schmidt R, Schmidt H. Genetics of age-related white matter lesions from linkage to genome wide association studies. J Neurol Sci. 2012;322:82-86. doi: 10.1016/j.jns.2012.06.016.
11. Fornage M, Debette S, Bis JC, Schmidt H, Ikram MA, Dufouil C, et al. Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium. Ann Neurol. 2011;69:928-939. doi: 10.1002/ana.22403.
12. Verhaaren BF, de Boer R, Vernooij MW, Rivadeneira F, Uitterlinden AG, Hofman A, et al. Replication study of chr17-25 with cerebral white matter lesion volume. Stroke. 2011;42:3297-3299. doi: 10.1161/STROKEAHA.111.623090.
13. Adib-Samii P, Rost N, Traylor M, Devan W, Biffi A, Lanfranconi S, et al; Australian Stroke Genetics Collaborative; Wellcome Trust Case-Control Consortium-2 (WTCCC2); METASTROKE; International Stroke Genetics Consortium. 17-25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status. Stroke. 2013;44:1609-1615. doi: 10.1161/STROKEAHA.113.679936.
14. Tabara Y, Igase M, Okada Y, Nagai T, Uetani E, Kido T, et al. Association of Chr17-25 with cerebral white matter hyperintensities and cognitive impairment: the J-SHIPP study. Eur J Neurol. 2013;20:860-862. doi: 10.1111/j.1468-1331.2012.03879.x.
15. Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190-2191. doi: 10.1093/bioinformatics/btq340.
16. Pereira TV, Patsopoulos NA, Salanti G, Ioannidis JP. Discovery properties of genome-wide association signals from cumulatively combined data sets. Am J Epidemiol. 2009;170:1197-1206. doi: 10.1093/aje/kwp262.
17. Senn S. Trying to be precise about vagueness. Stat Med. 2007;26:1417-1430. doi: 10.1002/sim.2639.
18. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248-249. doi: 10.1038/nmeth0410-248.
19. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4:1073-1081. doi: 10.1038/nprot.2009.86.
20. Boyle AP, Hong EL, Hariharan M, Cheng Y, Schaub MA, Kasowski M, et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 2012;22:1790-1797. doi: 10.1101/gr.137323.112.
21. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011;478:103-109.
22. Bertram L MM, Mullin K, Blacker D, Tanzi R. The AlzGene Database. Alzheimer Research Forum. http://www.alzgene.org. Accessed October 1, 2013.
23. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, et al. Genomewide association studies of stroke. N Engl J Med. 2009;360:1718-1728. doi: 10.1056/NEJMoa0900094.
24. Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng YC, 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.
25. Holliday EG, Maguire JM, Evans TJ, Koblar SA, Jannes J, Sturm JW, et al; Australian Stroke Genetics Collaborative; International Stroke Genetics Consortium; Wellcome Trust Case Control Consortium 2. Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nat Genet. 2012;44:1147-1151. doi: 10.1038/ng.2397.
26. Dastani Z, Hivert MF, Timpson N, Perry JR, Yuan X, Scott RA, et al; DIAGRAM+ Consortium; MAGIC Consortium; GLGC Investigators; MuTHER Consortium; DIAGRAM Consortium; GIANT Consortium; Global B Pgen Consortium; Procardis Consortium; MAGIC investigators; GLGC Consortium. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8:e1002607. doi: 10.1371/journal. pgen.1002607.
27. Lacana E, D'Adamio L. Regulation of Fas ligand expression and cell death by apoptosis-linked gene 4. Nat Med. 1999;5:542-547. doi: 10.1038/8420.
28. Sweet T, Khalili K, Sawaya BE, Amini S. Identification of a novel protein from glial cells based on its ability to interact with NF-kappaB subunits. J Cell Biochem. 2003;90:884-891. doi: 10.1002/jcb.10701.
29. Teider N, Scott DK, Neiss A, Weeraratne SD, Amani VM, Wang Y, et al. Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma. Neuro Oncol. 2010;12:1244-1256. doi: 10.1093/neuonc/noq091.
30. Nakamura H, Yoshida M, Tsuiki H, Ito K, Ueno M, Nakao M, et al. Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region. Oncogene. 1998;16:1009-1019. doi: 10.1038/sj.onc.1201618.
31. Stylli SS, I ST, Kaye AH, Lock P. Prognostic significance of Tks5 expression in gliomas. J Clin Neurosci. 2012;19:436-442. doi: 10.1016/j. jocn.2011.11.013.
32. Malinin NL, Wright S, Seubert P, Schenk D, Griswold-Prenner I. Amyloid-beta neurotoxicity is mediated by FISH adapter protein and ADAM12 metalloprotease activity. Proc Natl Acad Sci USA. 2005;102:3058-3063. doi: 10.1073/pnas.0408237102.
33. Harold D, Jehu L, Turic D, Hollingworth P, Moore P, Summerhayes P, et al. Interaction between the ADAM12 and SH3MD1 genes may confer susceptibility to late-onset Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:448-452. doi: 10.1002/ajmg.b.30456.
34. Boada M, Antúnez C, López-Arrieta J, Galán JJ, Morón FJ, Hernández I, et al. CALHM1 P86L polymorphism is associated with late-onset Alzheimer's disease in a recessive model. J Alzheimers Dis. 2010;20:247-251. doi: 10.3233/JAD-2010-1357.
35. Calero O, Bullido MJ, Clarimón J, Hortiguëla R, Frank-Garciá A, Martínez-Martín P, et al. Genetic variability of the gene cluster CALHM 1-3 in sporadic Creutzfeldt-Jakob disease. Prion. 2012;6:407-412. doi: 10.4161/pri.20785.
36. Guillemin GJ. Quinolinic acid, the inescapable neurotoxin. FEBS J. 2012;279:1356-1365. doi: 10.1111/j.1742-4658.2012.08485.x.
37. Schwarcz R, Okuno E, White RJ, Bird ED, Whetsell WO Jr. 3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims. Proc Natl Acad Sci USA. 1988;85:4079-4081.
38. Stone TW, Forrest CM, Darlington LG. Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection. FEBS J. 2012;279:1386-1397. doi: 10.1111/j.1742-4658.2012.08487.x.
39. Tan L, Yu JT, Tan L. The kynurenine pathway in neurodegenerative diseases: mechanistic and therapeutic considerations. J Neurol Sci. 2012;323:1-8. doi: 10.1016/j.jns.2012.08.005.
40. Obuse C, Iwasaki O, Kiyomitsu T, Goshima G, Toyoda Y, Yanagida M. A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nat Cell Biol. 2004;6:1135-1141. doi: 10.1038/ncb1187.
41. Wang Y, Devereux W, Woster PM, Stewart TM, Hacker A, Casero RA Jr. Cloning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure. Cancer Res. 2001;61:5370-5373.
42. Aleman A, Cebrian V, Alvarez M, Lopez V, Orenes E, Lopez-Serra L, et al. Identification of PMF1 methylation in association with bladder cancer progression. Clin Cancer Res. 2008;14:8236-8243. doi: 10.1158/1078-0432.CCR-08-0778.
43. Woo D, Falcone GJ, Devan WJ, Brown WM, Biffi A, Howard TD, et al; International Stroke Genetics Consortium. Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage. Am J Hum Genet. 2014;94:511-521. doi: 10.1016/j. ajhg.2014.02.012.
44. Folsom AR, Yatsuya H, Mosley TH Jr, Psaty BM, Longstreth WT Jr. Risk of intraparenchymal hemorrhage with magnetic resonance imaging-defined leukoaraiosis and brain infarcts. Ann Neurol. 2012;71:552-559. doi: 10.1002/ana.22690.
45. Hu B, Thirtamara-Rajamani KK, Sim H, Viapiano MS. Fibulin-3 is uniquely upregulated in malignant gliomas and promotes tumor cell motility and invasion. Mol Cancer Res. 2009;7:1756-1770. doi: 10.1158/1541-7786.MCR-09-0207.
46. Hu B, Nandhu MS, Sim H, Agudelo-Garcia PA, Saldivar JC, Dolan CE, et al. Fibulin-3 promotes glioma growth and resistance through a novel paracrine regulation of Notch signaling. Cancer Res. 2012;72:3873-3885. doi: 10.1158/0008-5472.CAN-12-1060.
47. Just A, Canaple S, Joly H, Piussan C, Rosa A. Neurologic complications in a case of Werner syndrome. Rev Neurol (Paris). 1996;152:634-636.
48. De Stefano N, Dotti MT, Battisti C, Sicurelli F, Stromillo ML, Mortilla M, et al. MR evidence of structural and metabolic changes in brains of patients with Werner's syndrome. J Neurol. 2003;250:1169-1173. doi: 10.1007/s00415-003-0167-4.
49. Taylor LP. Diagnosis, treatment, and prognosis of glioma: five new things. Neurology. 2010;75(18 suppl 1):S28-S32. doi: 10.1212/WNL.0b013e3181fb3661.
50. Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer. 2004;101:2293-2299. doi: 10.1002/cncr.20621.
51. Falahati S, Breu M, Waickman AT, Phillips AW, Arauz EJ, Snyder S, et al. Ischemia-induced neuroinflammation is associated with disrupted development of oligodendrocyte progenitors in a model of periventricular leukomalacia. Dev Neurosci. 2013;35:182-196. doi: 10.1159/000346682.
52. Wakita H, Tomimoto H, Akiguchi I, Kimura J. Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunohistochemical study. Acta Neuropathol. 1994;87:484-492.
53. Masumura M, Hata R, Nagai Y, Sawada T. Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats. Neurosci Res. 2001;39:401-412.