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Annual Review of Physiology

Volume 84, 2022

Pericyte Control of Blood Flow Across Microvascular Zones in the Central Nervous System

Abstract

The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes current knowledge on the control of blood flow across microvascular zones by addressing issues with nomenclature and drawing on new developments from in vivo optical imaging and single-cell transcriptomics. Recent studies have highlighted important distinctions in mural cell morphology, gene expression, and contractile dynamics, which can explain observed differences in response to vasoactive mediators between arteriole, transitional, and capillary zones. Smooth muscle cells of arterioles and ensheathing pericytes of the arteriole-capillary transitional zone control large-scale, rapid changes in blood flow. In contrast, capillary pericytes downstream of the transitional zone act on slower and smaller scales and are involved in establishing resting capillary tone and flow heterogeneity. Many unresolved issues remain, including the vasoactive mediators that activate the different pericyte types in vivo, the role of pericyte-endothelial communication in conducting signals from capillaries to arterioles, and how neurological disease affects these mechanisms.

Keyword(s): capillary, cerebral blood flow, endothelium, neurovascular coupling, pericyte, vasoconstriction
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/content/journals/10.1146/annurev-physiol-061121-040127
2022-02-10
2024-04-26
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Literature Cited

  1. 1. 
    Kisler K, Nelson AR, Montagne A, Zlokovic BV 2017. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat. Rev. Neurosci. 18:419–34
     [Google Scholar]
  2. 2. 
    Dalkara T, Arsava EM. 2012. Can restoring incomplete microcirculatory reperfusion improve stroke outcome after thrombolysis?. J. Cereb. Blood Flow Metab. 32:2091–99
     [Google Scholar]
  3. 3. 
    Østergaard L, Engedal TS, Moreton F, Hansen MB, Wardlaw JM et al. 2016. Cerebral small vessel disease: capillary pathways to stroke and cognitive decline. J. Cereb. Blood Flow Metab. 36:302–25
     [Google Scholar]
  4. 4. 
    Duvernoy HM, Delon S, Vannson JL 1981. Cortical blood vessels of the human brain. Brain Res. Bull. 7:519–79
     [Google Scholar]
  5. 5. 
    Attwell D, Buchan AM, Charpak S, Lauritzen M, MacVicar BA, Newman EA. 2010. Glial and neuronal control of brain blood flow. Nature 468:232–43
     [Google Scholar]
  6. 6. 
    Hamilton NB, Attwell D, Hall CN 2010. Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Front. Neuroenerget. 2:5
     [Google Scholar]
  7. 7. 
    Armulik A, Genove G, Betsholtz C. 2011. Pericytes: developmental, physiological, and pathological perspectives, problems and promises. Dev. Cell 21:193–215
     [Google Scholar]
  8. 8. 
    Zheng Z, Chopp M, Chen J 2020. Multifaceted roles of pericytes in central nervous system homeostasis and disease. J. Cereb. Blood Flow Metab. 40:1381–401
     [Google Scholar]
  9. 9. 
    Lendahl U, Nilsson P, Betsholtz C. 2019. Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes. EMBO Rep 20:e48070
     [Google Scholar]
  10. 10. 
    Brown LS, Foster CG, Courtney JM, King NE, Howells DW, Sutherland BA. 2019. Pericytes and neurovascular function in the healthy and diseased brain. Front. Cell. Neurosci. 13:282
     [Google Scholar]
  11. 11. 
    Uemura MT, Maki T, Ihara M, Lee VMY, Trojanowski JQ 2020. Brain microvascular pericytes in vascular cognitive impairment and dementia. Front. Aging Neurosci. 12:80
     [Google Scholar]
  12. 12. 
    Török O, Schreiner B, Schaffenrath J, Tsai HC, Maheshwari U et al. 2021. Pericytes regulate vascular immune homeostasis in the CNS. PNAS 118:e2016587
     [Google Scholar]
  13. 13. 
    Eberth CJ. 1871. Handbuch der Lehre von der Gewegen des Menschen und der Tiere Leipzig, Ger: Engelmann
  14. 14. 
    Rouget C. 1873. Memoire sur le developpement la structure et les proprietes physiologiques des capillaires sanguins et lymphatiques. Arch. Physiol. Norm. Path. 5:603–63
     [Google Scholar]
  15. 15. 
    Poole DC, Pittman RN, Musch TI, Østergaard L. 2020. August Krogh's theory of muscle microvascular control and oxygen delivery: a paradigm shift based on new data. J. Physiol. 598:4473–507
     [Google Scholar]
  16. 16. 
    Krogh A. 1920. A contribution to the physiology of the capillaries Nobel Lect. Dec. 11. https://www.nobelprize.org/prizes/medicine/1920/krogh/lecture/
  17. 17. 
    Sims DE. 1986. The pericyte—a review. Tissue Cell 18:153–74
     [Google Scholar]
  18. 18. 
    Zweifach BW, Kossmann CE. 1937. Micromanipulations of small blood vessels in the mouse. Am. J. Physiol. 120:23–35
     [Google Scholar]
  19. 19. 
    Kelley C, D'Amore P, Hechtman HB, Shepro D 1988. Vasoactive hormones and cAMP affect pericyte contraction and stress fibres in vitro. J. Muscle Res. Cell Motil. 9:184–94
     [Google Scholar]
  20. 20. 
    Kelley C, D'Amore P, Hechtman HB, Shepro D 1987. Microvascular pericyte contractility in vitro: comparison with other cells of the vascular wall. J. Cell Biol. 104:483–90
     [Google Scholar]
  21. 21. 
    Boado RJ, Pardridge WM. 1994. Differential expression of alpha-actin mRNA and immunoreactive protein in brain microvascular pericytes and smooth muscle cells. J. Neurosci. Res. 39:430–35
     [Google Scholar]
  22. 22. 
    Schönfelder U, Hofer A, Paul M, Funk RH 1998. In situ observation of living pericytes in rat retinal capillaries. Microvasc. Res. 56:22–29
     [Google Scholar]
  23. 23. 
    Puro DG. 2007. Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. Microcirculation 14:1–10
     [Google Scholar]
  24. 24. 
    Peppiatt CM, Howarth C, Mobbs P, Attwell D 2006. Bidirectional control of CNS capillary diameter by pericytes. Nature 443:642–43
     [Google Scholar]
  25. 25. 
    Berthiaume AA, Grant RI, McDowell KP, Underly RG, Hartmann DA et al. 2018. Dynamic remodeling of pericytes in vivo maintains capillary coverage in the adult mouse brain. Cell Rep 22:8–16
     [Google Scholar]
  26. 26. 
    Hartmann DA, Berthiaume AA, Grant RI, Harrill SA, Koski T et al. 2021. Brain capillary pericytes exert a substantial but slow influence on blood flow. Nat. Neurosci. 24:633–45
     [Google Scholar]
  27. 27. 
    Nelson AR, Sagare MA, Wang Y, Kisler K, Zhao Z, Zlokovic BV. 2020. Channelrhodopsin excitation contracts brain pericytes and reduces blood flow in the aging mouse brain in vivo. Front. Aging Neurosci. 12:108
     [Google Scholar]
  28. 28. 
    Fernández-Klett F, Offenhauser N, Dirnagl U, Priller J, Lindauer U 2010. Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain. PNAS 107:22290–95
     [Google Scholar]
  29. 29. 
    Shaw K, Bell L, Boyd K, Grijseels DM, Clarke D et al. 2021. Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences. Nat. Commun. 12:3190
     [Google Scholar]
  30. 30. 
    Sakadžić S, Mandeville ET, Gagnon L, Musacchia JJ, Yaseen MA et al. 2014. Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nat. Commun. 5:5734
     [Google Scholar]
  31. 31. 
    Ji X, Ferreira T, Friedman B, Liu R, Liechty H et al. 2021. Brain microvasculature has a common topology with local differences in geometry that match metabolic load. Neuron 109:1168–87
     [Google Scholar]
  32. 32. 
    Hartmann DA, Underly RG, Grant RI, Watson AN, Lindner V, Shih AY. 2015. Pericyte structure and distribution in the cerebral cortex revealed by high-resolution imaging of transgenic mice. Neurophotonics 2:041402
     [Google Scholar]
  33. 33. 
    Grant RI, Hartmann DA, Underly RG, Berthiaume A-A, Bhat NR, Shih AY. 2017. Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex. J. Cereb. Blood Flow Metab. 39:411–25
     [Google Scholar]
  34. 34. 
    Shen Z, Lu Z, Chhatbar PY, O'Herron P, Kara P. 2012. An artery-specific fluorescent dye for studying neurovascular coupling. Nat. Methods 9:273–76
     [Google Scholar]
  35. 35. 
    Grubb S, Cai C, Hald BO, Khennouf L, Murmu RP et al. 2020. Precapillary sphincters maintain perfusion in the cerebral cortex. Nat. Commun. 11:395
     [Google Scholar]
  36. 36. 
    Ivanova E, Corona C, Eleftheriou CG, Bianchimano P, Sagdullaev BT. 2021. Retina-specific targeting of pericytes reveals structural diversity and enables control of capillary blood flow. J. Comp. Neurol. 529:1121–34
     [Google Scholar]
  37. 37. 
    Hill RA, Tong L, Yuan P, Murikinati S, Gupta S, Grutzendler J. 2015. Regional blood flow in the normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary pericytes. Neuron 87:95–110
     [Google Scholar]
  38. 38. 
    Wei HS, Kang H, Rasheed IY, Zhou S, Lou N et al. 2016. Erythrocytes are oxygen-sensing regulators of the cerebral microcirculation. Neuron 91:851–62
     [Google Scholar]
  39. 39. 
    Damisah EC, Hill RA, Tong L, Murray KN, Grutzendler J 2017. A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging. Nat. Neurosci. 20:1023–32
     [Google Scholar]
  40. 40. 
    Gonzales AL, Klug NR, Moshkforoush A, Lee JC, Lee FK et al. 2020. Contractile pericytes determine the direction of blood flow at capillary junctions. PNAS 117:27022–33
     [Google Scholar]
  41. 41. 
    Coelho-Santos V, Berthiaume AA, Ornelas S, Stuhlmann H, Shih AY. 2021. Imaging the construction of capillary networks in the neonatal mouse brain. PNAS 118:e2100866118
     [Google Scholar]
  42. 42. 
    Vanlandewijck M, He L, Mäe MA, Andrae J, Ando K et al. 2018. A molecular atlas of cell types and zonation in the brain vasculature. Nature 554:475–80
     [Google Scholar]
  43. 43. 
    McCaslin AF, Chen BR, Radosevich AJ, Cauli B, Hillman EM 2010. In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling. J. Cereb. Blood Flow Metab. 31:795–806
     [Google Scholar]
  44. 44. 
    Drew PJ, Shih AY, Kleinfeld D. 2011. Fluctuating and sensory-induced vasodynamics in rodent cortex extends arteriole capacity. PNAS 108:8473–78
     [Google Scholar]
  45. 45. 
    Summers PM, Hartmann DA, Hui ES, Nie X, Deardorff RL et al. 2017. Functional deficits induced by cortical microinfarcts. J. Cereb. Blood Flow Metab. 37:3599–614
     [Google Scholar]
  46. 46. 
    Steinman J, Koletar MM, Stefanovic B, Sled JG. 2017. Morphological analysis of the mouse cerebral vasculature: comparison of in vivo and ex vivo methods. PLOS ONE 12:e0186676
     [Google Scholar]
  47. 47. 
    Nishimura N, Schaffer CB, Friedman B, Lyden PD, Kleinfeld D. 2007. Penetrating arterioles are a bottleneck in the perfusion of neocortex. PNAS 104:365–70
     [Google Scholar]
  48. 48. 
    Echagarruga CT, Gheres KW, Norwood JN, Drew PJ 2020. nNOS-expressing interneurons control basal and behaviorally evoked arterial dilation in somatosensory cortex of mice. eLife 9:e60533
     [Google Scholar]
  49. 49. 
    Rosenegger DG, Tran CH, Cusulin JIW, Gordon GR. 2015. Tonic local brain blood flow control by astrocytes independent of phasic neurovascular coupling. J. Neurosci. 35:13463–74
     [Google Scholar]
  50. 50. 
    Mateo C, Knutsen PM, Tsai PS, Shih AY, Kleinfeld D. 2017. Entrainment of arteriole vasomotor fluctuations by neural activity is a basis of blood-oxygenation-level-dependent “resting-state” connectivity. Neuron 96:936–48
     [Google Scholar]
  51. 51. 
    Haddock RE, Hill CE. 2005. Rhythmicity in arterial smooth muscle. J. Physiol. 566:645–56
     [Google Scholar]
  52. 52. 
    Gutiérrez-Jiménez E, Angleys H, Rasmussen PM, Mikkelsen IK, Mouridsen K, Østergaard L. 2018. The effects of hypercapnia on cortical capillary transit time heterogeneity (CTH) in anesthetized mice. J. Cereb. Blood Flow Metab. 38:290–303
     [Google Scholar]
  53. 53. 
    Unekawa M, Tomita Y, Masamoto K, Toriumi H, Osada T et al. 2017. Dynamic diameter response of intraparenchymal penetrating arteries during cortical spreading depression and elimination of vasoreactivity to hypercapnia in anesthetized mice. J. Cereb. Blood Flow Metab. 37:657–70
     [Google Scholar]
  54. 54. 
    Sekiguchi Y, Takuwa H, Kawaguchi H, Kikuchi T, Okada E et al. 2014. Pial arteries respond earlier than penetrating arterioles to neural activation in the somatosensory cortex in awake mice exposed to chronic hypoxia: An additional mechanism to proximal integration signaling?. J. Cereb. Blood Flow Metab. 34:1761–70
     [Google Scholar]
  55. 55. 
    Rungta RL, Chaigneau E, Osmanski BF, Charpak S. 2018. Vascular compartmentalization of functional hyperemia from the synapse to the pia. Neuron 99:362–75
     [Google Scholar]
  56. 56. 
    Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A et al. 2014. Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508:55–60
     [Google Scholar]
  57. 57. 
    Cai C, Fordsmann JC, Jensen SH, Gesslein B, Lønstrup M et al. 2018. Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses. PNAS 15:E5796–804
     [Google Scholar]
  58. 58. 
    Watson AN, Berthiaume AA, Faino AV, McDowell KP, Bhat NR et al. 2020. Mild pericyte deficiency is associated with aberrant brain microvascular flow in aged PDGFRβ+/− mice. J. Cereb. Blood Flow Metab. 40:2387–400
     [Google Scholar]
  59. 59. 
    Reeson P, Choi K, Brown CE 2018. VEGF signaling regulates the fate of obstructed capillaries in mouse cortex. eLife 7:e33670
     [Google Scholar]
  60. 60. 
    Hutchinson EB, Stefanovic B, Koretsky AP, Silva AC. 2006. Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia. Neuroimage 32:520–30
     [Google Scholar]
  61. 61. 
    Gutiérrez-Jiménez E, Cai C, Mikkelsen IK, Rasmussen PM, Angleys H et al. 2016. Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH). J. Cereb. Blood Flow Metab. 36:2072–86
     [Google Scholar]
  62. 62. 
    Kisler K, Nelson AR, Rege SV, Ramanathan A, Wang Y et al. 2017. Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nat. Neurosci. 20:406–16
     [Google Scholar]
  63. 63. 
    Glück C, Ferrari KD, Binini N, Keller A, Saab AS et al. 2021. Distinct signatures of calcium activity in brain mural cells. eLife 10:e70591
     [Google Scholar]
  64. 64. 
    Epp R, Schmid F, Weber B, Jenny P 2020. Predicting vessel diameter changes to up-regulate biphasic blood flow during activation in realistic microvascular networks. Front. Physiol. 11:566303
     [Google Scholar]
  65. 65. 
    Alarcon-Martinez L, Yilmaz-Ozcan S, Yemisci M, Schallek J, Kılıç K et al. 2018. Capillary pericytes express α-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection. eLife 7:e34861
     [Google Scholar]
  66. 66. 
    Alarcon-Martinez L, Yilmaz-Ozcan S, Yemisci M, Schallek J, Kılıç K et al. 2019. Retinal ischemia induces α-SMA-mediated capillary pericyte contraction coincident with perivascular glycogen depletion. Acta Neuropathol. Commun. 7:134
     [Google Scholar]
  67. 67. 
    Longden TA, Dabertrand F, Koide M, Gonzales AL, Tykocki NR et al. 2017. Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow. Nat. Neurosci. 20:717–26
     [Google Scholar]
  68. 68. 
    Thakore P, Alvarado MG, Ali S, Mughal A, Pires PW et al. 2021. Brain endothelial cell TRPA1 channels initiate neurovascular coupling. eLife 10:e63040
     [Google Scholar]
  69. 69. 
    Kovacs-Oller T, Ivanova E, Bianchimano P, Sagdullaev BT. 2020. The pericyte connectome: spatial precision of neurovascular coupling is driven by selective connectivity maps of pericytes and endothelial cells and is disrupted in diabetes. Cell Discov 6:39
     [Google Scholar]
  70. 70. 
    Zhang T, Wu DM, Xu GZ, Puro DG. 2011. The electrotonic architecture of the retinal microvasculature: modulation by angiotensin II. J. Physiol. 589:2383–99
     [Google Scholar]
  71. 71. 
    Alarcon-Martinez L, Villafranca-Baughman D, Quintero H, Kacerovsky JB, Dotigny F et al. 2020. Interpericyte tunnelling nanotubes regulate neurovascular coupling. Nature 585:91–95
     [Google Scholar]
  72. 72. 
    Ornelas S, Berthiaume AA, Bonney SK, Coelho-Santos V, Underly RG et al. 2021. Three-dimensional ultrastructure of the brain pericyte-endothelial interface. J. Cereb. Blood Flow Metab 41:2185–200
     [Google Scholar]
  73. 73. 
    Ivanova E, Kovacs-Oller T, Sagdullaev BT. 2019. Domain-specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina. J. Comp. Neurol. 527:2675–93
     [Google Scholar]
  74. 74. 
    Arango-Lievano M, Boussadia B, De Terdonck LDT, Gault C, Fontanaud P et al. 2018. Topographic reorganization of cerebrovascular mural cells under seizure conditions. Cell Rep 23:1045–59
     [Google Scholar]
  75. 75. 
    Nikolakopoulou AM, Montagne A, Kisler K, Dai Z, Wang Y et al. 2019. Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss. Nat. Neurosci. 22:1089–98
     [Google Scholar]
  76. 76. 
    Kuschinsky W, Paulson OB. 1992. Capillary circulation in the brain. Cerebrovasc. Brain Metab. Rev. 4:261–86
     [Google Scholar]
  77. 77. 
    Li Y, Wei W, Wang RK 2018. Capillary flow homogenization during functional activation revealed by optical coherence tomography angiography based capillary velocimetry. Sci. Rep. 8:4107
     [Google Scholar]
  78. 78. 
    Li B, Lee J, Boas DA, Lesage F. 2016. Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice. J. Cereb. Blood Flow Metab. 36:1351–56
     [Google Scholar]
  79. 79. 
    Stefanovic B, Hutchinson E, Yakovleva V, Schram V, Russell JT et al. 2007. Functional reactivity of cerebral capillaries. J. Cereb. Blood Flow Metab. 28:961–72
     [Google Scholar]
  80. 80. 
    Lee J, Wu W, Boas DA. 2016. Early capillary flux homogenization in response to neural activation. J. Cereb. Blood Flow Metab. 36:375–80
     [Google Scholar]
  81. 81. 
    Jespersen SN, Østergaard L. 2012. The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism. J. Cereb. Blood Flow Metab. 32:264–77
     [Google Scholar]
  82. 82. 
    Li B, Esipova TV, Sencan I, Kılıç K, Fu B et al. 2019. More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction. eLife 8:e42299
     [Google Scholar]
  83. 83. 
    Hariharan A, Weir N, Robertson C, He L, Betsholtz C, Longden TA. 2020. The ion channel and GPCR toolkit of brain capillary pericytes. Front. Cell. Neurosci. 14:601324
     [Google Scholar]
  84. 84. 
    Kawamura H, Oku H, Li Q, Sakagami K, Puro DG. 2002. Endothelin-induced changes in the physiology of retinal pericytes. Investig. Opthalmol. Vis. Sci. 43:882–88
     [Google Scholar]
  85. 85. 
    Newman EA. 2001. Propagation of intercellular calcium waves in retinal astrocytes and Müller cells. J. Neurosci. 21:2215–23
     [Google Scholar]
  86. 86. 
    Mishra A, Reynolds JP, Chen Y, Gourine AV, Rusakov DA, Attwell D. 2016. Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles. Nat. Neurosci. 19:1619–27
     [Google Scholar]
  87. 87. 
    Bekar LK, Wei HS, Nedergaard M 2012. The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand. J. Cereb. Blood Flow Metab. 32:2135–45
     [Google Scholar]
  88. 88. 
    Cohen Z, Molinatti G, Hamel E 1997. Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J. Cereb. Blood Flow Metab. 17:894–904
     [Google Scholar]
  89. 89. 
    Zambach SA, Cai C, Helms HCC, Hald BO, Dong Y et al. 2021. Precapillary sphincters and pericytes at first-order capillaries as key regulators for brain capillary perfusion. PNAS 118:e2023749118
     [Google Scholar]
  90. 90. 
    Zhang W, Davis CM, Zeppenfeld DM, Golgotiu K, Wang MX et al. 2021. Role of endothelium-pericyte signaling in capillary blood flow response to neuronal activity. J. Cereb. Blood Flow Metab 41:1873–85
     [Google Scholar]
  91. 91. 
    Li Q, Puro DG 2001. Adenosine activates ATP-sensitive K+ currents in pericytes of rat retinal microvessels: role of A1 and A2a receptors. Brain Res 907:93–99
     [Google Scholar]
  92. 92. 
    Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T. 2009. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat. Med. 15:1031–37
     [Google Scholar]
  93. 93. 
    Khennouf L, Gesslein B, Brazhe A, Octeau JC, Kutuzov N et al. 2018. Active role of capillary pericytes during stimulation-induced activity and spreading depolarization. Brain 141:2032–46
     [Google Scholar]
  94. 94. 
    Erdener ŞE, Tang J, Kılıç K, Postnov D, Giblin JT et al. 2020. Dynamic capillary stalls in reperfused ischemic penumbra contribute to injury: a hyperacute role for neutrophils in persistent traffic jams. J. Cereb. Blood Flow Metab. 41:236–52
     [Google Scholar]
  95. 95. 
    El Amki M, Glück C, Binder N, Middleham W, Wyss MT et al. 2020. Neutrophils obstructing brain capillaries are a major cause of no-reflow in ischemic stroke. Cell Rep 33:108260
     [Google Scholar]
  96. 96. 
    Ratelade J, Klug NR, Lombardi D, Angelim MKSC, Dabertrand F et al. 2020. Reducing hypermuscularization of the transitional segment between arterioles and capillaries protects against spontaneous intracerebral hemorrhage. Circulation 141:2078–98
     [Google Scholar]
  97. 97. 
    Ding R, Hase Y, Ameen-Ali KE, Ndung'u M, Stevenson W et al. 2020. Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease. Brain Pathol 30:1087–1101
     [Google Scholar]
  98. 98. 
    Halliday MR, Rege SV, Ma Q, Zhao Z, Miller CA et al. 2016. Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease. J. Cereb. Blood Flow Metab. 36:216–27
     [Google Scholar]
  99. 99. 
    Miners JS, Schulz I, Love S. 2017. Differing associations between Aβ 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. 38:103–15
     [Google Scholar]
  100. 100. 
    Montagne A, Nation DA, Sagare AP, Barisano G, Sweeney MD et al. 2020. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. Nature 581:71–76
     [Google Scholar]
  101. 101. 
    Dziewulska D, Lewandowska E. 2012. Pericytes as a new target for pathological processes in CADASIL. Neuropathology 32:515–21
     [Google Scholar]
  102. 102. 
    Montagne A, Nikolakopoulou AM, Huuskonen MT, Sagare AP, Lawson EJ et al. 2021. APOE4 accelerates advanced-stage vascular and neurodegenerative disorder in old Alzheimer's mice via cyclophilin A independently of amyloid-β. Nature Aging 1:506–20
     [Google Scholar]
  103. 103. 
    Bell RD, Winkler EA, Singh I, Sagare AP, Deane R et al. 2012. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485:512–16
     [Google Scholar]
  104. 104. 
    Nortley R, Korte N, Izquierdo P, Hirunpattarasilp C, Mishra A et al. 2019. Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes. Science 365:eaav9518
     [Google Scholar]
  105. 105. 
    Eskildsen SF, Gyldensted L, Nagenthiraja K, Nielsen RB, Hansen MB et al. 2017. Increased cortical capillary transit time heterogeneity in Alzheimer's disease: a DSC-MRI perfusion study. Neurobiol. Aging 50:107–18
     [Google Scholar]
  106. 106. 
    Leal-Campanario R, Alarcon-Martinez L, Rieiro H, Martinez-Conde S, Alarcon-Martinez T et al. 2017. Abnormal capillary vasodynamics contribute to ictal neurodegeneration in epilepsy. Sci. Rep. 7:43276
     [Google Scholar]
  107. 107. 
    Attwell D, Mishra A, Hall CN, O'Farrell FM, Dalkara T. 2015. What is a pericyte?. J. Cereb. Blood Flow Metab. 36:451–55
     [Google Scholar]
  108. 108. 
    Lu Y, Zhang C, Lu X, Moeini M, Thorin E, Lesage F. 2019. Impact of atherosclerotic disease on cerebral microvasculature and tissue oxygenation in awake LDLR−/−hApoB+/+ transgenic mice. Neurophotonics 6:045003
     [Google Scholar]
  109. 109. 
    Tajima Y, Takuwa H, Kokuryo D, Kawaguchi H, Seki C et al. 2014. Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy. J. Cereb. Blood Flow Metab. 34:1363–72
     [Google Scholar]
  110. 110. 
    Derdeyn CP. 2018. Hemodynamics and oxygen extraction in chronic large artery steno-occlusive disease: clinical applications for predicting stroke risk. J. Cereb. Blood Flow Metab. 38:1584–97
     [Google Scholar]
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Pericyte Control of Blood Flow Across Microvascular Zones in the Central Nervous System
Annual Review of Physiology 84, 331 (2022); https://doi.org/10.1146/annurev-physiol-061121-040127
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