Skip to main content

Advertisement

SpringerLink
Log in

Cerebral Hypoperfusion and Other Shared Brain Pathologies in Ischemic Stroke and Alzheimer’s Disease

  • Original Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Newly emerged evidence reveals that ischemic stroke and Alzheimer’s disease (AD) share pathophysiological changes in brain tissue including hypoperfusion, oxidative stress, immune exhaustion, and inflammation. A mechanistic link between hypoperfusion and amyloid β accumulation can lead to cell damage as well as to motor and cognitive deficits. This review will discuss decreased cerebral perfusion and other related pathophysiological changes common to both ischemic stroke and AD, such as vascular damages, cerebral blood flow alteration, abnormal expression of amyloid β and tau proteins, as well as behavioral and cognitive deficits. Furthermore, this review highlights current treatment options and potential therapeutic targets that warrant further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hefter D, Draguhn A. APP as a protective factor in acute neuronal insults. Front Mol Neurosci. 2017;10:22. https://doi.org/10.3389/fnmol.2017.00022.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Kelly SC, He B, Perez SE, Ginsberg SD, Mufson EJ, Counts SE. Locus coeruleus cellular and molecular pathology during the progression of Alzheimer’s disease. Acta Neuropathol Commun. 2017;5(1):8. https://doi.org/10.1186/s40478-017-0411-2.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Reggiani AM, Simoni E, Caporaso R, Meunier J, Keller E, Maurice T, et al. In vivo characterization of ARN14140, a memantine/galantamine-based multi-target compound for Alzheimer’s disease. Sci Rep. 2016;6:33172. https://doi.org/10.1038/srep33172.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Qiu L, Ng G, Tan EK, Liao P, Kandiah N, Zeng L. Chronic cerebral hypoperfusion enhances tau hyperphosphorylation and reduces autophagy in Alzheimer’s disease mice. Sci Rep. 2016;6:23964. https://doi.org/10.1038/srep23964.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Tolppanen AM, Voutilainen A, Taipale H, Tanskanen A, Lavikainen P, Koponen M, et al. Regional changes in psychotropic use among Finnish persons with newly diagnosed Alzheimer’s disease in 2005-2011. PLoS One. 2017;12(3):e0173450. https://doi.org/10.1371/journal.pone.0173450.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Santos CY, Snyder PJ, Wu WC, Zhang M, Echeverria A, Alber J. Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: a review and synthesis. Alzheimers Dement (Amst). 2017;7:69–87. https://doi.org/10.1016/j.dadm.2017.01.005.

    Article  Google Scholar 

  7. Alzheimer’s A. Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459–509.

    Article  Google Scholar 

  8. Maillard P, Carmichael O, Fletcher E, Reed B, Mungas D, DeCarli C. Coevolution of white matter hyperintensities and cognition in the elderly. Neurology. 2012;79(5):442–8. https://doi.org/10.1212/WNL.0b013e3182617136.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Clark LR, Berman SE, Rivera-Rivera LA, Hoscheidt SM, Darst BF, Engelman CD, et al. Macrovascular and microvascular cerebral blood flow in adults at risk for Alzheimer’s disease. Alzheimers Dement (Amst). 2017;7:48–55. https://doi.org/10.1016/j.dadm.2017.01.002.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Imabayashi E, Yokoyama K, Tsukamoto T, Sone D, Sumida K, Kimura Y, et al. The cingulate island sign within early Alzheimer’s disease-specific hypoperfusion volumes of interest is useful for differentiating Alzheimer’s disease from dementia with Lewy bodies. EJNMMI Res. 2016;6(1):67. https://doi.org/10.1186/s13550-016-0224-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Chang T, Gajasinghe S, Arambepola C. Prevalence of stroke and its risk factors in urban Sri Lanka: population-based study. Stroke. 2015;46(10):2965–8. https://doi.org/10.1161/STROKEAHA.115.010203.

    Article  PubMed  Google Scholar 

  12. Lahoud N, Salameh P, Saleh N, Hosseini H. Prevalence of Lebanese stroke survivors: a comparative pilot study. J Epidemiol Glob Health. 2016;6(3):169–76. https://doi.org/10.1016/j.jegh.2015.10.001.

    Article  PubMed  Google Scholar 

  13. Wang W, Jiang B, Sun H, Ru X, Sun D, Wang L, et al. Prevalence, incidence, and mortality of stroke in China: results from a nationwide population-based survey of 480 687 adults. Circulation. 2017;135(8):759–71. https://doi.org/10.1161/CIRCULATIONAHA.116.025250.

    Article  PubMed  Google Scholar 

  14. Butler EN, Evenson KR. Prevalence of physical activity and sedentary behavior among stroke survivors in the United States. Top Stroke Rehabil. 2014;21(3):246–55. https://doi.org/10.1310/tsr2103-246.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Simpkins JW, Wen Y, Perez E, Yang S, Wang X. Role of nonfeminizing estrogens in brain protection from cerebral ischemia: an animal model of Alzheimer’s disease neuropathology. Ann N Y Acad Sci. 2005;1052:233–42. https://doi.org/10.1196/annals.1347.019.

    Article  PubMed  CAS  Google Scholar 

  16. Kalaria RN. The role of cerebral ischemia in Alzheimer’s disease. Neurobiol Aging. 2000;21(2):321–30.

    Article  PubMed  CAS  Google Scholar 

  17. Au JL, Weishaupt N, Nell HJ, Whitehead SN, Cechetto DF. Motor and hippocampal dependent spatial learning and reference memory assessment in a transgenic rat model of Alzheimer’s disease with stroke. J Vis Exp 2016(109). https://doi.org/10.3791/53089.

  18. Catanese L, Tarsia J, Fisher M. Acute ischemic stroke therapy overview. Circ Res. 2017;120(3):541–58. https://doi.org/10.1161/CIRCRESAHA.116.309278.

    Article  PubMed  CAS  Google Scholar 

  19. Khalil AA, Ostwaldt AC, Nierhaus T, Ganeshan R, Audebert HJ, Villringer K, et al. Relationship between changes in the temporal dynamics of the blood-oxygen-level-dependent signal and hypoperfusion in acute ischemic stroke. Stroke. 2017;48(4):925–31. https://doi.org/10.1161/STROKEAHA.116.015566.

    Article  PubMed  CAS  Google Scholar 

  20. Ma Y, Li L, Niu Z, Song J, Lin Y, Zhang H, et al. Effect of recombinant plasminogen activator timing on thrombolysis in a novel rat embolic stroke model. Pharmacol Res. 2016;107:291–9. https://doi.org/10.1016/j.phrs.2016.03.030.

    Article  PubMed  CAS  Google Scholar 

  21. Yueniwati Y, Darmiastini NK, Arisetijono E. Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients. Int J Gen Med. 2016;9:447–52. https://doi.org/10.2147/IJGM.S114577.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Kim BJ, Kim JS. Ischemic stroke subtype classification: an Asian viewpoint. J Stroke. 2014;16(1):8–17. https://doi.org/10.5853/jos.2014.16.1.8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Findler M, Molad J, Bornstein NM, Auriel E. Worse outcome in patients with acute stroke and atrial fibrillation following thrombolysis. Isr Med Assoc J. 2017;19(5):293–5.

    PubMed  Google Scholar 

  24. Salinet AS, Panerai RB, Robinson TG. The longitudinal evolution of cerebral blood flow regulation after acute ischaemic stroke. Cerebrovasc Dis Extra. 2014;4(2):186–97. https://doi.org/10.1159/000366017.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Harston GW, Okell TW, Sheerin F, Schulz U, Mathieson P, Reckless I, et al. Quantification of serial cerebral blood flow in acute stroke using arterial spin labeling. Stroke. 2017;48(1):123–30. https://doi.org/10.1161/STROKEAHA.116.014707.

    Article  PubMed  CAS  Google Scholar 

  26. Liu Z, Li Y. Cortical cerebral blood flow, oxygen extraction fraction, and metabolic rate in patients with middle cerebral artery stenosis or acute stroke. AJNR Am J Neuroradiol. 2016;37(4):607–14. https://doi.org/10.3174/ajnr.A4624.

    Article  PubMed  CAS  Google Scholar 

  27. Ostergaard L, Jespersen SN, Engedahl T, Gutierrez Jimenez E, Ashkanian M, Hansen MB, et al. Capillary dysfunction: its detection and causative role in dementias and stroke. Curr Neurol Neurosci Rep. 2015;15(6):37. https://doi.org/10.1007/s11910-015-0557-x.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508(7494):55–60. https://doi.org/10.1038/nature13165.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. ElAli A, Theriault P, Rivest S. The role of pericytes in neurovascular unit remodeling in brain disorders. Int J Mol Sci. 2014;15(4):6453–74. https://doi.org/10.3390/ijms15046453.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Liu W, Wong A, Au L, Yang J, Wang Z, Leung EY, et al. Influence of amyloid-beta on cognitive decline after stroke/transient ischemic attack: three-year longitudinal study. Stroke. 2015;46(11):3074–80. https://doi.org/10.1161/STROKEAHA.115.010449.

    Article  PubMed  CAS  Google Scholar 

  31. Fisher M, Albers GW. Advanced imaging to extend the therapeutic time window of acute ischemic stroke. Ann Neurol. 2013;73(1):4–9. https://doi.org/10.1002/ana.23744.

    Article  PubMed  Google Scholar 

  32. Robbins NM, Swanson RA. Opposing effects of glucose on stroke and reperfusion injury: acidosis, oxidative stress, and energy metabolism. Stroke. 2014;45(6):1881–6. https://doi.org/10.1161/STROKEAHA.114.004889.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bardutzky J, Shen Q, Henninger N, Bouley J, Duong TQ, Fisher M. Differences in ischemic lesion evolution in different rat strains using diffusion and perfusion imaging. Stroke. 2005;36(9):2000–5. https://doi.org/10.1161/01.STR.0000177486.85508.4d.

  34. Magistretti PJ, Allaman I. A cellular perspective on brain energy metabolism and functional imaging. Neuron. 2015;86(4):883–901. https://doi.org/10.1016/j.neuron.2015.03.035.

    Article  PubMed  CAS  Google Scholar 

  35. von Kummer R, Dzialowski I. Imaging of cerebral ischemic edema and neuronal death. Neuroradiology. 2017;59(6):545–53. https://doi.org/10.1007/s00234-017-1847-6.

    Article  Google Scholar 

  36. Bakthavachalam P, Shanmugam PS. Mitochondrial dysfunction—silent killer in cerebral ischemia. J Neurol Sci. 2017;375:417–23. https://doi.org/10.1016/j.jns.2017.02.043.

    Article  PubMed  CAS  Google Scholar 

  37. Lee PH, Bang OY, Hwang EM, Lee JS, Joo US, Mook-Jung I, et al. Circulating beta amyloid protein is elevated in patients with acute ischemic stroke. J Neural Transm (Vienna). 2005;112(10):1371–9. https://doi.org/10.1007/s00702-004-0274-0.

    Article  CAS  Google Scholar 

  38. Takahashi RH, Nagao T, Gouras GK. Plaque formation and the intraneuronal accumulation of beta-amyloid in Alzheimer’s disease. Pathol Int. 2017;67(4):185–93. https://doi.org/10.1111/pin.12520.

    Article  PubMed  CAS  Google Scholar 

  39. Saito T, Matsuba Y, Mihira N, Takano J, Nilsson P, Itohara S, et al. Single App knock-in mouse models of Alzheimer’s disease. Nat Neurosci. 2014;17(5):661–3. https://doi.org/10.1038/nn.3697.

    Article  PubMed  CAS  Google Scholar 

  40. Sun S, Zhang H, Liu J, Popugaeva E, Xu NJ, Feske S, et al. Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron. 2014;82(1):79–93. https://doi.org/10.1016/j.neuron.2014.02.019.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Zhang H, Wu L, Pchitskaya E, Zakharova O, Saito T, Saido T, et al. Neuronal store-operated calcium entry and mushroom spine loss in amyloid precursor protein knock-in mouse model of Alzheimer’s disease. J Neurosci. 2015;35(39):13275–86. https://doi.org/10.1523/JNEUROSCI.1034-15.2015.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Price KA, Varghese M, Sowa A, Yuk F, Brautigam H, Ehrlich ME, et al. Altered synaptic structure in the hippocampus in a mouse model of Alzheimer’s disease with soluble amyloid-beta oligomers and no plaque pathology. Mol Neurodegener. 2014;9:41. https://doi.org/10.1186/1750-1326-9-41.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yang J, Wong A, Wang Z, Liu W, Au L, Xiong Y, et al. Risk factors for incident dementia after stroke and transient ischemic attack. Alzheimers Dement. 2015;11(1):16–23. https://doi.org/10.1016/j.jalz.2014.01.003.

    Article  PubMed  Google Scholar 

  44. Shi J, Yang SH, Stubley L, Day AL, Simpkins JW. Hypoperfusion induces overexpression of beta-amyloid precursor protein mRNA in a focal ischemic rodent model. Brain Res. 2000;853(1):1–4.

    Article  PubMed  CAS  Google Scholar 

  45. Ong LK, Zhao Z, Kluge M, Walker FR, Nilsson M. Chronic stress exposure following photothrombotic stroke is associated with increased levels of amyloid beta accumulation and altered oligomerisation at sites of thalamic secondary neurodegeneration in mice. J Cereb Blood Flow Metab. 2017;37(4):1338–48. https://doi.org/10.1177/0271678X16654920.

    Article  PubMed  CAS  Google Scholar 

  46. Lasek-Bal A, Jedrzejowska-Szypulka H, Rozycka J, Bal W, Kowalczyk A, Holecki M, et al. The presence of tau protein in blood as a potential prognostic factor in stroke patients. J Physiol Pharmacol. 2016;67(5):691–6.

    PubMed  CAS  Google Scholar 

  47. Bielewicz J, Kurzepa J, Czekajska-Chehab E, Stelmasiak Z, Bartosik-Psujek H. Does serum tau protein predict the outcome of patients with ischemic stroke. J Mol Neurosci. 2011;43(3):241–5. https://doi.org/10.1007/s12031-010-9403-4.

    Article  PubMed  CAS  Google Scholar 

  48. Stamer K, Vogel R, Thies E, Mandelkow E, Mandelkow EM. Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J Cell Biol. 2002;156(6):1051–63. https://doi.org/10.1083/jcb.200108057.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Li JF, Wang Z, Sun QJ, Du YF. Expression of tau protein in rats with cognitive dysfunction induced by cerebral hypoperfusion. Int J Clin Exp Med. 2015;8(10):19682–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  50. Zhao Y, Gu JH, Dai CL, Liu Q, Iqbal K, Liu F, et al. Chronic cerebral hypoperfusion causes decrease of O-GlcNAcylation, hyperphosphorylation of tau and behavioral deficits in mice. Front Aging Neurosci. 2014;6:10. https://doi.org/10.3389/fnagi.2014.00010.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Madineni A, Alhadidi Q, Shah ZA. Cofilin inhibition restores neuronal cell death in oxygen-glucose deprivation model of ischemia. Mol Neurobiol. 2016;53(2):867–78. https://doi.org/10.1007/s12035-014-9056-3.

    Article  PubMed  CAS  Google Scholar 

  52. Ploughman M, Shears J, Harris C, Hogan SH, Drodge O, Squires S, et al. Effectiveness of a novel community exercise transition program for people with moderate to severe neurological disabilities. NeuroRehabilitation. 2014;35(1):105–12. https://doi.org/10.3233/NRE-141090.

    Article  PubMed  Google Scholar 

  53. Sun JH, Tan L, Yu JT. Post-stroke cognitive impairment: epidemiology, mechanisms and management. Ann Transl Med. 2014;2(8):80. https://doi.org/10.3978/j.issn.2305-5839.2014.08.05.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Han MH, Lee EH, Koh SH. Current opinion on the role of neurogenesis in the therapeutic strategies for Alzheimer disease, Parkinson disease, and ischemic stroke; considering neuronal voiding function. Int Neurourol J. 2016;20(4):276–87. https://doi.org/10.5213/inj.1632776.388.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Love S, Miners JS. Cerebral hypoperfusion and the energy deficit in Alzheimer’s disease. Brain Pathol. 2016;26(5):607–17. https://doi.org/10.1111/bpa.12401.

    Article  PubMed  Google Scholar 

  56. Muller UC, Deller T, Korte M. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat Rev Neurosci. 2017;18(5):281–98. https://doi.org/10.1038/nrn.2017.29.

    Article  PubMed  CAS  Google Scholar 

  57. Kimbrough IF, Robel S, Roberson ED, Sontheimer H. Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer’s disease. Brain. 2015;138(Pt 12):3716–33. https://doi.org/10.1093/brain/awv327.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kandimalla R, Manczak M, Fry D, Suneetha Y, Sesaki H, Reddy PH. Reduced dynamin-related protein 1 protects against phosphorylated tau-induced mitochondrial dysfunction and synaptic damage in Alzheimer’s disease. Hum Mol Genet. 2016;25(22):4881–97. https://doi.org/10.1093/hmg/ddw312.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Marks SM, Lockhart SN, Baker SL, Jagust WJ. Tau and beta-amyloid are associated with medial temporal lobe structure, function and memory encoding in normal aging. J Neurosci. 2017; https://doi.org/10.1523/JNEUROSCI.3769-16.2017.

  60. Chu J, Lauretti E, Pratico D. Caspase-3-dependent cleavage of Akt modulates tau phosphorylation via GSK3beta kinase: implications for Alzheimer’s disease. Mol Psychiatry. 2017; https://doi.org/10.1038/mp.2016.214.

  61. Konietzny A, Bar J, Mikhaylova M. Dendritic actin cytoskeleton: structure, functions, and regulations. Front Cell Neurosci. 2017;11:147. https://doi.org/10.3389/fncel.2017.00147.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Islam BU, Tabrez S. Management of Alzheimer’s disease—an insight of the enzymatic and other novel potential targets. Int J Biol Macromol. 2017;97:700–9. https://doi.org/10.1016/j.ijbiomac.2017.01.076.

    Article  PubMed  CAS  Google Scholar 

  63. Goedert M, Spillantini MG. Propagation of tau aggregates. Mol Brain. 2017;10(1):18. https://doi.org/10.1186/s13041-017-0298-7.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Castillo-Carranza DL, Nilson AN, Van Skike CE, Jahrling JB, Patel K, Garach P, et al. Cerebral microvascular accumulation of tau oligomers in Alzheimer’s disease and related tauopathies. Aging Dis. 2017;8(3):257–66. 10.14336/AD.2017.0112.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kolarova M, Sengupta U, Bartos A, Ricny J, Kayed R. Tau oligomers in sera of patients with Alzheimer’s disease and aged controls. J Alzheimers Dis. 2017;58(2):471–8. https://doi.org/10.3233/JAD-170048.

    Article  PubMed  CAS  Google Scholar 

  66. Nicolakakis N, Hamel E. Neurovascular function in Alzheimer’s disease patients and experimental models. J Cereb Blood Flow Metab. 2011;31(6):1354–70. https://doi.org/10.1038/jcbfm.2011.43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease. J Neurosci Res. 2017;95(4):943–72. https://doi.org/10.1002/jnr.23777.

    Article  PubMed  CAS  Google Scholar 

  68. Vijayan M, Reddy PH. Stroke, vascular dementia, and Alzheimer’s disease: molecular links. J Alzheimers Dis. 2016;54(2):427–43. https://doi.org/10.3233/JAD-160527.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Kalaria RN. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease. Acta Neuropathol. 2016;131(5):659–85. https://doi.org/10.1007/s00401-016-1571-z.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Zhou J, Yu JT, Wang HF, Meng XF, Tan CC, Wang J, et al. Association between stroke and Alzheimer’s disease: systematic review and meta-analysis. J Alzheimers Dis. 2015;43(2):479–89. https://doi.org/10.3233/JAD-140666.

    Article  PubMed  Google Scholar 

  71. Tosto G, Bird TD, Bennett DA, Boeve BF, Brickman AM, Cruchaga C, et al. The role of cardiovascular risk factors and stroke in familial Alzheimer disease. JAMA Neurol. 2016;73(10):1231–7. https://doi.org/10.1001/jamaneurol.2016.2539.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Chi NF, Chien LN, Ku HL, Hu CJ, Chiou HY. Alzheimer disease and risk of stroke: a population-based cohort study. Neurology. 2013;80(8):705–11. https://doi.org/10.1212/WNL.0b013e31828250af.

    Article  PubMed  Google Scholar 

  73. Liu H, Zhang J. Cerebral hypoperfusion and cognitive impairment: the pathogenic role of vascular oxidative stress. Int J Neurosci. 2012;122(9):494–9. https://doi.org/10.3109/00207454.2012.686543.

    Article  PubMed  CAS  Google Scholar 

  74. Lucke-Wold BP, Turner RC, Logsdon AF, Simpkins JW, Alkon DL, Smith KE, et al. Common mechanisms of Alzheimer’s disease and ischemic stroke: the role of protein kinase C in the progression of age-related neurodegeneration. J Alzheimers Dis. 2015;43(3):711–24. https://doi.org/10.3233/JAD-141422.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Janssen B, Vugts DJ, Funke U, Molenaar GT, Kruijer PS, van Berckel BN, et al. Imaging of neuroinflammation in Alzheimer’s disease, multiple sclerosis and stroke: recent developments in positron emission tomography. Biochim Biophys Acta. 2016;1862(3):425–41. https://doi.org/10.1016/j.bbadis.2015.11.011.

    Article  PubMed  CAS  Google Scholar 

  76. Xiong XY, Liu L, Yang QW. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. Prog Neurobiol. 2016;142:23–44. https://doi.org/10.1016/j.pneurobio.2016.05.001.

    Article  PubMed  CAS  Google Scholar 

  77. Minter MR, Taylor JM, Crack PJ. The contribution of neuroinflammation to amyloid toxicity in Alzheimer’s disease. J Neurochem. 2016;136(3):457–74. https://doi.org/10.1111/jnc.13411.

    Article  PubMed  CAS  Google Scholar 

  78. Minogue AM. Role of infiltrating monocytes/macrophages in acute and chronic neuroinflammation: effects on cognition, learning and affective behaviour. Prog Neuropsychopharmacol Biol Psychiatry. 2017;79(Pt A):15–8. https://doi.org/10.1016/j.pnpbp.2017.02.008.

    Article  PubMed  CAS  Google Scholar 

  79. Mracsko E, Veltkamp R. Neuroinflammation after intracerebral hemorrhage. Front Cell Neurosci. 2014;8:388. https://doi.org/10.3389/fncel.2014.00388.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Bagyinszky E, Giau VV, Shim K, Suk K, An SSA, Kim S. Role of inflammatory molecules in the Alzheimer’s disease progression and diagnosis. J Neurol Sci. 2017;376:242–54. https://doi.org/10.1016/j.jns.2017.03.031.

    Article  PubMed  CAS  Google Scholar 

  81. Ramberg V, Tracy LM, Samuelsson M, Nilsson LN, Iverfeldt K. The CCAAT/enhancer binding protein (C/EBP) delta is differently regulated by fibrillar and oligomeric forms of the Alzheimer amyloid-beta peptide. J Neuroinflammation. 2011;8:34. https://doi.org/10.1186/1742-2094-8-34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. McNaull BB, Todd S, McGuinness B, Passmore AP. Inflammation and anti-inflammatory strategies for Alzheimer’s disease—a mini-review. Gerontology. 2010;56(1):3–14. https://doi.org/10.1159/000237873.

    Article  PubMed  CAS  Google Scholar 

  83. Wulker N, Zwipp H, Tscherne H. Experimental study of the classification of intra-articular calcaneus fractures. Unfallchirurg. 1991;94(4):198–203.

    PubMed  CAS  Google Scholar 

  84. Rawji KS, Mishra MK, Michaels NJ, Rivest S, Stys PK, Yong VW. Immunosenescence of microglia and macrophages: impact on the ageing central nervous system. Brain. 2016;139(Pt 3):653–61. https://doi.org/10.1093/brain/awv395.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Li W, Tong HI, Gorantla S, Poluektova LY, Gendelman HE, Lu Y. Neuropharmacologic approaches to restore the brain’s microenvironment. J NeuroImmune Pharmacol. 2016;11(3):484–94. https://doi.org/10.1007/s11481-016-9686-5.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Norden DM, Muccigrosso MM, Godbout JP. Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease. Neuropharmacology. 2015;96(Pt A):29–41. https://doi.org/10.1016/j.neuropharm.2014.10.028.

    Article  PubMed  CAS  Google Scholar 

  87. Alonso E, Vieira AC, Rodriguez I, Alvarino R, Gegunde S, Fuwa H, et al. Tetracyclic truncated analogue of the marine toxin gambierol modifies NMDA, tau, and amyloid beta expression in mice brains: implications in AD pathology. ACS Chem Neurosci. 2017; https://doi.org/10.1021/acschemneuro.7b00012.

  88. Kim HA, Miller AA, Drummond GR, Thrift AG, Arumugam TV, Phan TG, et al. Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress. Naunyn Schmiedeberg’s Arch Pharmacol. 2012;385(10):953–9. https://doi.org/10.1007/s00210-012-0790-7.

    Article  CAS  Google Scholar 

  89. Sun YY, Li Y, Wali B, Li Y, Lee J, Heinmiller A, et al. Prophylactic edaravone prevents transient hypoxic-ischemic brain injury: implications for perioperative neuroprotection. Stroke. 2015;46(7):1947–55. https://doi.org/10.1161/STROKEAHA.115.009162.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Li H, Wang J, Wang P, Rao Y, Chen L. Resveratrol reverses the synaptic plasticity deficits in a chronic cerebral hypoperfusion rat model. J Stroke Cerebrovasc Dis. 2016;25(1):122–8. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.09.004.

    Article  PubMed  CAS  Google Scholar 

  91. Dam K, Fuchtemeier M, Farr TD, Boehm-Sturm P, Foddis M, Dirnagl U, et al. Increased homocysteine levels impair reference memory and reduce cortical levels of acetylcholine in a mouse model of vascular cognitive impairment. Behav Brain Res. 2017;321:201–8. https://doi.org/10.1016/j.bbr.2016.12.041.

    Article  PubMed  CAS  Google Scholar 

  92. Zou W, Song Y, Li Y, Du Y, Zhang X, Fu J. The role of autophagy in the correlation between neuron damage and cognitive impairment in rat chronic cerebral hypoperfusion. Mol Neurobiol. 2017; https://doi.org/10.1007/s12035-016-0351-z.

  93. Wang D, Lin Q, Su S, Liu K, Wu Y, Hai J. URB597 improves cognitive impairment induced by chronic cerebral hypoperfusion by inhibiting mTOR-dependent autophagy. Neuroscience. 2017;344:293–304. https://doi.org/10.1016/j.neuroscience.2016.12.034.

    Article  PubMed  CAS  Google Scholar 

  94. Ong CT, Wong YS, Wu CS, Su YH. Outcome of stroke patients receiving different doses of recombinant tissue plasminogen activator. Drug Des Devel Ther. 2017;11:1559–66. https://doi.org/10.2147/DDDT.S133759.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Li X, Ling L, Li C, Ma Q. Efficacy and safety of desmoteplase in acute ischemic stroke patients: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(18):e6667. https://doi.org/10.1097/MD.0000000000006667.

    Article  CAS  Google Scholar 

  96. Abushouk AI, Elmaraezy A, Aglan A, Salama R, Fouda S, Fouda R, et al. Bapineuzumab for mild to moderate Alzheimer’s disease: a meta-analysis of randomized controlled trials. BMC Neurol. 2017;17(1):66. https://doi.org/10.1186/s12883-017-0850-1.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Farina N, Llewellyn D, Isaac MG, Tabet N. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2017;1:CD002854. https://doi.org/10.1002/14651858.CD002854.pub4.

    Article  PubMed  Google Scholar 

  98. Chau S, Herrmann N, Ruthirakuhan MT, Chen JJ, Lanctot KL. Latrepirdine for Alzheimer’s disease. Cochrane Database Syst Rev. 2015;4:CD009524. https://doi.org/10.1002/14651858.CD009524.pub2.

    Article  Google Scholar 

Download references

Funding

This study was funded by the Chinese National Natural Science Foundation (No. 81402930, S.D.), the NIH grants (R01 NS38118, R01 NS48216), and the VA grant I01BX002891 (D.S.).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Bengbu Medical College, Bengbu, Anhui, China

    Shuying Dong

  2. Department of Neurology, University of Pittsburgh, S-598 South Biomedical Science Tower, 3500 Terrace St., Pittsburgh, PA, 15213, USA

    Shuying Dong, Shelly Maniar & Dandan Sun

  3. Lake Erie College of Osteopathic Medicine at Seton Hill, Greensburg, Pennsylvania, 15601, USA

    Shelly Maniar

  4. Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA

    Mioara D. Manole

  5. Veterans Affairs Pittsburgh Health Care System, Geriatric Research, Educational and Clinical Center, Pittsburgh, PA, USA

    Dandan Sun

Authors
  1. Shuying Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shelly Maniar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mioara D. Manole
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dandan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dandan Sun.

Ethics declarations

Conflict of Interest

Shuying Dong, Shelly Maniar, Mioara D. Manole, and Dandan Sun declare that they have no conflicts of interest to disclose.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dong, S., Maniar, S., Manole, M.D. et al. Cerebral Hypoperfusion and Other Shared Brain Pathologies in Ischemic Stroke and Alzheimer’s Disease. Transl. Stroke Res. 9, 238–250 (2018). https://doi.org/10.1007/s12975-017-0570-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-017-0570-2

Keywords

Search

Navigation