From Chronic Cerebral Hypoperfusion to Alzheimer-Like Brain Pathology and Neurodegeneration

Cellular and Molecular Neurobiology

Volumn 35, Issue 1, 2015, Pages 101-110

  Zhao, Yang ^a,b   Gong, Cheng Xin ^b  

^a THE FIRST HOSPITAL OF JILIN UNIVERSITY   (China)

^b NEW YORK STATE INSTITUTE FOR BASIC RESEARCH IN DEVELOPMENTAL DISABILITIES   (United States)

Author keywords

Alzheimer s disease; Cerebral vascular; Chronic cerebral hypoperfusion; Neurodegeneration

Indexed keywords

AMYLOID BETA PROTEIN; TAU PROTEIN;

ALZHEIMER DISEASE; BINSWANGER ENCEPHALOPATHY; BLOOD VISCOSITY; CEREBROVASCULAR DISEASE; CHRONIC CEREBRAL HYPOPERFUSION; COGNITIVE DEFECT; DISEASE COURSE; HUMAN; MULTIINFARCT DEMENTIA; NERVE DEGENERATION; NEUROPATHOLOGY; NONHUMAN; OXIDATIVE STRESS; POSTSYNAPTIC MEMBRANE; PRESYNAPTIC MEMBRANE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; WHITE MATTER LESION; ANIMAL; BRAIN; BRAIN CIRCULATION; DEGENERATIVE DISEASE; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; VASCULARIZATION;

ALZHEIMER DISEASE; ANIMALS; BRAIN; CEREBROVASCULAR CIRCULATION; HUMANS; NEURODEGENERATIVE DISEASES;

EID: 84922004295     PISSN: 02724340     EISSN: 15736830     Source Type: Journal    
DOI: 10.1007/s10571-014-0127-9     Document Type: Review

References (108)

1. Adibhatla RM, Hatcher JF (2008) Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies. BMB Rep 41:560–567
2. Akinyemi RO, Mukaetova-Ladinska EB, Attems J, Ihara M, Kalaria RN (2013) Vascular risk factors and neurodegeneration in ageing related dementias: Alzheimer’s disease and vascular dementia. Curr Alzheimer Res 10:642–653
3. Austin BP, Nair VA, Meier TB, Xu G, Rowley HA, Carlsson CM, Johnson SC, Prabhakaran V (2011) Effects of hypoperfusion in Alzheimer’s disease. J Alzheimers Dis 26(Suppl 3):123–133
4. Bang J, Jeon WK, Lee IS, Han JS, Kim BY (2013) Biphasic functional regulation in hippocampus of rat with chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid artery. PLoS One 8:e70093
5. Battistin L, Cagnin A (2010) Vascular cognitive disorder. A biological and clinical overview. Neurochem Res 35:1933–1938
6. Bennett SA, Tenniswood M, Chen JH, Davidson CM, Keyes MT, Fortin T, Pappas BA (1998) Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment. NeuroReport 9:161–166
7. Bornemann KD, Staufenbiel M (2000) Transgenic mouse models of Alzheimer’s disease. Ann N Y Acad Sci 908:260–266
8. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259
9. Chan JY, Tsai CY, Wu CH, Li FC, Dai KY, Sun EY, Chan SH, Chang AY (2011) Sumoylation of hypoxia-inducible factor-1alpha ameliorates failure of brain stem cardiovascular regulation in experimental brain death. PLoS One 6:e17375
10. Chen Y, Tian Z, Liang Z, Sun S, Dai CL, Lee MH, LaFerla FM, Grundke-Iqbal I, Iqbal K, Liu F, Gong CX (2012) Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer’s disease. PLoS One 7:e51432
11. Chen Y, Liang Z, Blanchard J, Dai CL, Sun S, Lee MH, Grundke-Iqbal I, Iqbal K, Liu F, Gong CX (2013) A non-transgenic mouse model (icv-STZ mouse) of Alzheimer’s disease: similarities to and differences from the transgenic model (3xTg-AD mouse). Mol Neurobiol 47:711–725
12. Choi BR, Lee SR, Han JS, Woo SK, Kim KM, Choi DH, Kwon KJ, Han SH, Shin CY, Lee J, Chung CS, Kim HY (2011) Synergistic memory impairment through the interaction of chronic cerebral hypoperfusion and amlyloid toxicity in a rat model. Stroke 42:2595–2604
13. Crawford GL, Hart GW, Whiteheart SW (2008) Murine platelets are not regulated by O-linked beta-N-acetylglucosamine. Arch Biochem Biophys 474:220–224
14. de Diego-Otero Y, Romero-Zerbo Y, el Bekay R, Decara J, Sanchez L, Rodriguez-de Fonseca F, del Arco-Herrera I (2009) Alpha-tocopherol protects against oxidative stress in the fragile X knockout mouse: an experimental therapeutic approach for the Fmr1 deficiency. Neuropsychopharmacology 34:1011–1026
15. Dean OM, van den Buuse M, Berk M, Copolov DL, Mavros C, Bush AI (2011) N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: relevance to schizophrenia and bipolar disorder. Neurosci Lett 499:149–153
16. Du J, Ma M, Zhao Q, Fang L, Chang J, Wang Y, Fei R, Song X (2013) Mitochondrial bioenergetic deficits in the hippocampi of rats with chronic ischemia-induced vascular dementia. Neuroscience 231:345–352
17. Farkas E, Timmer NM, Domoki F, Mihaly A, Luiten PG, Bari F (2005) Post-ischemic administration of diazoxide attenuates long-term microglial activation in the rat brain after permanent carotid artery occlusion. Neurosci Lett 387:168–172
18. Farkas E, Luiten PG, Bari F (2007) Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 54:162–180
19. Fernando MS, Simpson JE, Matthews F, Brayne C, Lewis CE, Barber R, Kalaria RN, Forster G, Esteves F, Wharton SB, Shaw PJ, O’Brien JT, Ince PG (2006) White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 37:1391–1398
20. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F et al (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373:523–527
21. Gold G, Giannakopoulos P, Herrmann FR, Bouras C, Kovari E (2007) Identification of Alzheimer and vascular lesion thresholds for mixed dementia. Brain 130:2830–2836
22. Gong CX, Iqbal K (2008) Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr Med Chem 15:2321–2328
23. Gong CX, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K (2000) Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer’s disease. J Biol Chem 275:5535–5544
24. Gong CX, Grundke-Iqbal I, Iqbal K (2010) Targeting tau protein in Alzheimer’s disease. Drugs Aging 27:351–365
25. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83:4913–4917
26. Hai J, Wan JF, Lin Q, Wang F, Zhang L, Li H, Chen YY, Lu Y (2009) Cognitive dysfunction induced by chronic cerebral hypoperfusion in a rat model associated with arteriovenous malformations. Brain Res 1301:80–88
27. Halliwell B (2007) Oxidative stress and cancer: have we moved forward? Biochem J 401:1–11
28. Hattori K, Naguro I, Runchel C, Ichijo H (2009) The roles of ASK family proteins in stress responses and diseases. Cell Commun Signal 7:9
29. Hoshino A, Matoba S, Iwai-Kanai E, Nakamura H, Kimata M, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Ikeda K, Ueyama T, Okigaki M, Matsubara H (2012) p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. J Mol Cell Cardiol 52:175–184
30. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102
31. Iqbal K, Wang X, Blanchard J, Liu F, Gong CX, Grundke-Iqbal I (2010) Alzheimer’s disease neurofibrillary degeneration: pivotal and multifactorial. Biochem Soc Trans 38:962–966
32. Iqbal K, Gong CX, Liu F (2013) Hyperphosphorylation-induced tau oligomers. Front Neurol 4:112
33. Iwabuchi S, Kawahara K (2011) Inducible astrocytic glucose transporter-3 contributes to the enhanced storage of intracellular glycogen during reperfusion after ischemia. Neurochem Int 59:319–325
34. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80:1611–1617
35. Ji HJ, Hu JF, Wang YH, Chen XY, Zhou R, Chen NH (2010) Osthole improves chronic cerebral hypoperfusion induced cognitive deficits and neuronal damage in hippocampus. Eur J Pharmacol 636:96–101
36. Kelleher RJ, Soiza RL (2013) Evidence of endothelial dysfunction in the development of Alzheimer’s disease: is Alzheimer’s a vascular disorder? Am J Cardiovasc Dis 3:197–226
37. Kimata M, Matoba S, Iwai-Kanai E, Nakamura H, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Mita Y, Okigaki M, Ikeda K, Tatsumi T, Matsubara H (2010) p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress. Am J Physiol Heart Circ Physiol 299:H1908–H1916
38. Kitagawa K, Yagita Y, Sasaki T, Sugiura S, Omura-Matsuoka E, Mabuchi T, Matsushita K, Hori M (2005) Chronic mild reduction of cerebral perfusion pressure induces ischemic tolerance in focal cerebral ischemia. Stroke 36:2270–2274
39. Kitaguchi H, Tomimoto H, Ihara M, Shibata M, Uemura K, Kalaria RN, Kihara T, Asada-Utsugi M, Kinoshita A, Takahashi R (2009) Chronic cerebral hypoperfusion accelerates amyloid beta deposition in APPSwInd transgenic mice. Brain Res 1294:202–210
40. Koike MA, Green KN, Blurton-Jones M, Laferla FM (2010) Oligemic hypoperfusion differentially affects tau and amyloid-{beta}. Am J Pathol 177:300–310
41. Lee JS, Im DS, An YS, Hong JM, Gwag BJ, Joo IS (2011) Chronic cerebral hypoperfusion in a mouse model of Alzheimer’s disease: an additional contributing factor of cognitive impairment. Neurosci Lett 489:84–88
42. Li X, Lu F, Wang JZ, Gong CX (2006) Concurrent alterations of O-GlcNAcylation and phosphorylation of tau in mouse brains during fasting. Eur J Neurosci 23:2078–2086
43. Li L, Zhang X, Yang D, Luo G, Chen S, Le W (2009) Hypoxia increases Abeta generation by altering beta- and gamma-cleavage of APP. Neurobiol Aging 30:1091–1098
44. Liu F, Iqbal K, Grundke-Iqbal I, Hart GW, Gong CX (2004) O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer’s disease. Proc Natl Acad Sci USA 101:10804–10809
45. Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2005) Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur J Neurosci 22:1942–1950
46. Liu F, Shi J, Tanimukai H, Gu J, Grundke-Iqbal I, Iqbal K, Gong CX (2009) Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer’s disease. Brain 132:1820–1832
47. Liu H, Zhang J, Yang Y, Zhang L, Zeng X (2012) Decreased cerebral perfusion and oxidative stress result in acute and delayed cognitive impairment. Curr Neurovasc Res 9:152–158
48. Lyons K, Pahwa R (2013) Statement of Retraction: “Mohamad Goldust, Mahnaz Talebi, Jafar Majidi, Mohammad Amin Rezazadeh Saatlou, and Elham Rezaee. Evaluation of antiphospholipid antibodies in youths suffering from cerebral ischemia.”. Int J Neurosci 123:597
49. Meyer JS, Rauch G, Rauch RA, Haque A (2000) Risk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia. Neurobiol Aging 21:161–169
50. Mizobuchi H (1989) Changes in muscarinic cholinergic receptor and choline acetyltransferase in experimental ischemic brain. Nihon Geka Hokan 58:93–106
51. Mukaetova-Ladinska EB, Garcia-Siera F, Hurt J, Gertz HJ, Xuereb JH, Hills R, Brayne C, Huppert FA, Paykel ES, McGee M, Jakes R, Honer WG, Harrington CR, Wischik CM (2000) Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer’s disease. Am J Pathol 157:623–636
52. Nakaji K, Ihara M, Takahashi C, Itohara S, Noda M, Takahashi R, 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
53. Ni JW, Matsumoto K, Li HB, Murakami Y, Watanabe H (1995) Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat. Brain Res 673:290–296
54. Ni B, Stephenson D, Wu X, Smalstig EB, Clemens J, Paul SM (1997) Selective loss of neuronal Na + -dependent phosphate cotransporter mRNA in CA1 pyramidal neuron following global ischemia. Brain Res Mol Brain Res 48:132–139
55. Nishio K, Ihara M, Yamasaki N, Kalaria RN, Maki T, Fujita Y, Ito H, Oishi N, Fukuyama H, Miyakawa T, Takahashi R, Tomimoto H (2010) A mouse model characterizing features of vascular dementia with hippocampal atrophy. Stroke 41:1278–1284
56. Okamoto Y, Yamamoto T, Kalaria RN, Senzaki H, Maki T, Hase Y, Kitamura A, Washida K, Yamada M, Ito H, Tomimoto H, Takahashi R, Ihara M (2012) Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol 123:381–394
57. Orsucci D, Mancuso M, Ienco EC, Simoncini C, Siciliano G, Bonuccelli U (2013) Vascular factors and mitochondrial dysfunction: a central role in the pathogenesis of Alzheimer’s disease. Curr Neurovasc Res 10:76–80
58. Pappas BA, de la Torre JC, Davidson CM, Keyes MT, Fortin T (1996) Chronic reduction of cerebral blood flow in the adult rat: late-emerging CA1 cell loss and memory dysfunction. Brain Res 708:50–58
59. Petito CK, Olarte JP, Roberts B, Nowak TS Jr, Pulsinelli WA (1998) Selective glial vulnerability following transient global ischemia in rat brain. J Neuropathol Exp Neurol 57:231–238
60. Pimentel-Coelho PM, Michaud JP, Rivest S (2013) Effects of mild chronic cerebral hypoperfusion and early amyloid pathology on spatial learning and the cellular innate immune response in mice. Neurobiol Aging 34:679–693
61. Pluta R, Kocki J, Maciejewski R, Ulamek-Koziol M, Jablonski M, Bogucka-Kocka A, Czuczwar SJ (2012) Ischemia signalling to Alzheimer-related genes. Folia Neuropathol 50:322–329
62. Pluta R, Furmaga-Jablonska W, Maciejewski R, Ulamek-Koziol M, Jablonski M (2013a) Brain ischemia activates beta- and gamma-secretase cleavage of amyloid precursor protein: significance in sporadic Alzheimer’s disease. Mol Neurobiol 47:425–434
63. Pluta R, Jablonski M, Ulamek-Koziol M, Kocki J, Brzozowska J, Januszewski S, Furmaga-Jablonska W, Bogucka-Kocka A, Maciejewski R, Czuczwar SJ (2013b) Sporadic Alzheimer’s disease begins as episodes of brain ischemia and ischemically dysregulated Alzheimer’s disease genes. Mol Neurobiol 48:500–515
64. Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S (1993) Apolipoprotein E polymorphism and Alzheimer’s disease. Lancet 342:697–699
65. Pristera A, Saraulli D, Farioli-Vecchioli S, Strimpakos G, Costanzi M, di Certo MG, Cannas S, Ciotti MT, Tirone F, Mattei E, Cestari V, Canu N (2013) Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory. Neurobiol Aging 34:2551–2563
66. Roh JH, Lee JH (2014) Recent updates on subcortical ischemic vascular dementia. J Stroke 16:18–26
67. Roman GC (2002) Vascular dementia revisited: diagnosis, pathogenesis, treatment, and prevention. Med Clin North Am 86:477–499
68. Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, Breteler MM (2005) Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 57:789–794
69. Sarti C, Pantoni L, Bartolini L, Inzitari D (2002) Cognitive impairment and chronic cerebral hypoperfusion: what can be learned from experimental models. J Neurol Sci 203–204:263–266
70. Scheff SW, Price DA, Schmitt FA, Scheff MA, Mufson EJ (2011) Synaptic loss in the inferior temporal gyrus in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 24:547–557
71. Scherr M, Trinka E, Mc Coy M, Krenn Y, Staffen W, Kirschner M, Bergmann HJ, Mutzenbach JS (2012) Cerebral hypoperfusion during carotid artery stenosis can lead to cognitive deficits that may be independent of white matter lesion load. Curr Neurovasc Res 9:193–199
72. Sekhon LH, Spence I, Morgan MK, Weber NC (1997) Chronic cerebral hypoperfusion inhibits calcium-induced long-term potentiation in rats. Stroke 28:1043–1047
73. Shibata M, Ohtani R, Ihara M, Tomimoto H (2004) White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35:2598–2603
74. Shibata M, Yamasaki N, Miyakawa T, Kalaria RN, Fujita Y, Ohtani R, Ihara M, Takahashi R, Tomimoto H (2007) Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. Stroke 38:2826–2832
75. Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R, Dhanasekaran M, Suppiramaniam V (2012) Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents. Neurobiol Aging 33:430-e5
76. Shu Y, Zhang H, Kang T, Zhang JJ, Yang Y, Liu H, Zhang L (2013) PI3 K/Akt signal pathway involved in the cognitive impairment caused by chronic cerebral hypoperfusion in rats. PLoS One 8:e81901
77. Singh N, Dhalla AK, Seneviratne C, Singal PK (1995) Oxidative stress and heart failure. Mol Cell Biochem 147:77–81
78. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90:1977–1981
79. Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, Ledermann B, Burki K, Frey P, Paganetti PA, Waridel C, Calhoun ME, Jucker M, Probst A, Staufenbiel M, Sommer B (1997) Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci USA 94:13287–13292
80. Sugai K (1989) The effects of ischemia and postischemic reperfusion on the brain cholinergic system of the rat. Masui 38:350–356
81. Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, Staufenbiel M, Huang LE, Song W (2006) Hypoxia facilitates Alzheimer’s disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci USA 103:18727–18732
82. Tanaka K, Ogawa N, Asanuma M, Kondo Y, Nomura M (1996) Relationship between cholinergic dysfunction and discrimination learning disabilities in Wistar rats following chronic cerebral hypoperfusion. Brain Res 729:55–65
83. Tang KF, Cai L, Zhou JN (2009) Observation of the density and size of cells in hippocampus and vascular lesion in thalamus of GFAP-apoE transgenic mice. Neurosci Bull 25:167–178
84. Thiebaut de Schotten M, Tomaiuolo F, Aiello M, Merola S, Silvetti M, Lecce F, Bartolomeo P, Doricchi F (2014) Damage to white matter pathways in subacute and chronic spatial neglect: a group study and 2 single-case studies with complete virtual “in vivo” tractography dissection. Cereb Cortex 24:691–706
85. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M (1996) beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature 380:168–171
86. Toyama K, Koibuchi N, Uekawa K, Hasegawa Y, Kataoka K, Katayama T, Sueta D, Ma MJ, Nakagawa T, Yasuda O, Tomimoto H, Ichijo H, Ogawa H, Kim-Mitsuyama S (2014) Apoptosis signal-regulating kinase 1 is a novel target molecule for cognitive impairment induced by chronic cerebral hypoperfusion. Arterioscler Thromb Vasc Biol 34:616–625
87. Urabe T (2012) Molecular mechanism and new protective strategy for ischemic white matter damages. Rinsho Shinkeigaku 52:908–910
88. Valerio Romanini C, Dias Fiuza Ferreira E, Correia Bacarin C, Verussa MH, de Weffort Oliveira RM, Milani H (2013) Neurohistological and behavioral changes following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats. Behav Brain Res 252:214–221
89. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84
90. van Groen T, Puurunen K, Maki HM, Sivenius J, Jolkkonen J (2005) Transformation of diffuse beta-amyloid precursor protein and beta-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats. Stroke 36:1551–1556
91. Volpe BT, Waczek B, Davis HP (1988) Modified T-maze training demonstrates dissociated memory loss in rats with ischemic hippocampal injury. Behav Brain Res 27:259–268
92. Volpe BT, Davis HP, Towle A, Dunlap WP (1992) Loss of hippocampal CA1 pyramidal neurons correlates with memory impairment in rats with ischemic or neurotoxin lesions. Behav Neurosci 106:457–464
93. Wakita H, Tomimoto H, Akiguchi I, Kimura J (1994) Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunohistochemical study. Acta Neuropathol 87:484–492
94. Wakita H, Tomimoto H, Akiguchi I, Kimura J (1995) Protective effect of cyclosporin A on white matter changes in the rat brain after chronic cerebral hypoperfusion. Stroke 26:1415–1422
95. Wang X, Xing A, Xu C, Cai Q, Liu H, Li L (2010) Cerebrovascular hypoperfusion induces spatial memory impairment, synaptic changes, and amyloid-beta oligomerization in rats. J Alzheimers Dis 21:813–822
96. Wang F, Wang Y, Geng X, Asmaro K, Peng C, Sullivan JM, Ding JY, Ji X, Ding Y (2012a) Neuroprotective effect of acute ethanol administration in a rat with transient cerebral ischemia. Stroke 43:205–210
97. Wang Z, Tsai LK, Munasinghe J, Leng Y, Fessler EB, Chibane F, Leeds P, Chuang DM (2012b) Chronic valproate treatment enhances postischemic angiogenesis and promotes functional recovery in a rat model of ischemic stroke. Stroke 43:2430–2436
98. Watanabe M, Masaoka N, Nakajima Y, Nagaishi M, Yamamoto T (2009) Changes of expression of glucose transporters in the fetal lamb brain after MCI-186 administration to the maternal circulation with 10-min persistent umbilical cord occlusion. J Matern Fetal Neonatal Med 22:829–836
99. Xi Y, Wang M, Zhang W, Bai M, Du Y, Zhang Z, Li Z, Miao J (2014) Neuronal damage, central cholinergic dysfunction and oxidative damage correlate with cognitive deficits in rats with chronic cerebral hypoperfusion. Neurobiol Learn Mem 109:7–19
100. Yamada M, Ihara M, Okamoto Y, Maki T, Washida K, Kitamura A, Hase Y, Ito H, Takao K, Miyakawa T, Kalaria RN, Tomimoto H, Takahashi R (2011) The influence of chronic cerebral hypoperfusion on cognitive function and amyloid beta metabolism in APP overexpressing mice. PLoS One 6:e16567
101. Yan J, Zhou B, Taheri S, Shi H (2011) Differential effects of HIF-1 inhibition by YC-1 on the overall outcome and blood-brain barrier damage in a rat model of ischemic stroke. PLoS One 6:e27798
102. Yao ZH, Zhang JJ, Xie XF (2012) Enriched environment prevents cognitive impairment and tau hyperphosphorylation after chronic cerebral hypoperfusion. Curr Neurovasc Res 9:176–184
103. Yoshizaki K, Adachi K, Kataoka S, Watanabe A, Tabira T, Takahashi K, Wakita H (2008) Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice. Exp Neurol 210:585–591
104. Yuan LB, Dong HL, Zhang HP, Zhao RN, Gong G, Chen XM, Zhang LN, Xiong L (2011) Neuroprotective effect of orexin-A is mediated by an increase of hypoxia-inducible factor-1 activity in rat. Anesthesiology 114:340–354
105. Zhang X, Zhou K, Wang R, Cui J, Lipton SA, Liao FF, Xu H, Zhang YW (2007) Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 282:10873–10880
106. Zhao Y, Gu JH, Dai CL, Liu Q, Iqbal K, Liu F, Gong CX (2014) Chronic cerebral hypoperfusion causes decrease of O-GlcNAcylation, hyperphosphorylation of tau and behavioral deficits in mice. Front Aging Neurosci 6:10
107. Zhiyou C, Yong Y, Shanquan S, Jun Z, Liangguo H, Ling Y, Jieying L (2009) Upregulation of BACE1 and beta-amyloid protein mediated by chronic cerebral hypoperfusion contributes to cognitive impairment and pathogenesis of Alzheimer’s disease. Neurochem Res 34:1226–1235
108. Zhu J, Wang Y, Li J, Deng J, Zhou H (2014) Intracranial artery stenosis and progression from mild cognitive impairment to Alzheimer disease. Neurology 82:842–849