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Genetic and Environmental Contributions to Variation in the Posterior Communicating Collaterals of the Circle of Willis

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Abstract

Variation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in the severity of tissue injury in obstructive disease. Evidence in animals and humans indicates that differences in the extent of PComs, i.e., their anatomic lumen diameter and whether they are present bilaterally, unilaterally, or absent, are a major factor. These differences arise during development since they are present at birth. However, the causal mechanisms are unknown. We used angiography after maximal dilation to examine involvement of genetic, environmental, and stochastic factors. The extent of PComs varied widely among seven genetically diverse strains of mice. Like pial collaterals in the microcirculation, aging and hypertension reduced PCom diameter, while in contrast, obesity, hyperlipidemia, metabolic syndrome, and diabetes mellitus had no effect. Naturally occurring intrauterine growth restriction had no effect on extent of PCom or pial collaterals in the adult. The number and diameter of PComs evidenced much larger apparent stochastic-dependent variation than pial collaterals. In addition, both PComs underwent flow-mediated outward remodeling after unilateral permanent MCA occlusion that varied with genetic background and was greater on the ipsilesional side. These findings indicate that variation in the number and diameter of PCom collateral arteries arises from stochastic factors and naturally occurring genetic variants that differ from those that cause variation in pial collateral arterioles. Environmental factors also contribute: aging and hypertension reduce PCom diameter. Our results suggest possible sources of variation of PComs in humans and provide information relevant when studying mouse models of occlusive cerebrovascular disease.

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Abbreviations

ACA:

Anterior cerebral artery

BA:

Basilar artery

CoW:

Circle of Willis

CSRFs:

Cardiovascular and stroke risk factors

E1:

Embryonic day 1(2,3…etc)

ICA:

Internal carotid artery

MCA:

Middle cerebral artery

pMCAO:

Permanent proximal M2-MCA occlusion P1 postnatal day 1(2,3…etc)

PCA:

Posterior cerebral artery

PCom:

Posterior communicating collateral artery

RTG:

Renin overexpressing transgenic mouse model of hypertension

SGA:

Small for gestational age

WT:

Wildtype strain

References

  1. Vrselja Z, Brkic H, Mrdenovic S, Radic R, Curic G. Function of circle of Willis. J Cereb Blood Flow Metab. 2014;34:578–84.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Liebeskind DS, Caplan LR. Intracranial arteries––anatomy and collaterals. Front Neurol Neurosci. 2016;40:1–20.

    PubMed  Google Scholar 

  3. Menshawi K, Mohr JP, Gutierrez J. A functional perspective on the embryology and anatomy of the cerebral blood supply. J Stroke. 2015;17:144–58.

    Article  PubMed  PubMed Central  Google Scholar 

  4. van Raamt AF, Mali WP, van Laar PJ, van der Graaf Y. The fetal variant of the circle of Willis and its influence on the cerebral collateral circulation. Cerebrovasc Dis. 2006;22:217–24.

    Article  PubMed  Google Scholar 

  5. van der Zwan A, Hillen B, Tulleken CA, Dujovny M. A quantitative investigation of the variability of the major cerebral arterial territories. Stroke. 1993;24:1951–9.

    Article  PubMed  Google Scholar 

  6. Alpers BJ, Berry RG, Paddison RM. Anatomical studies of the circle of Willis in normal brain. AMA Arch Neurol Psychiatry. 1959;81:409–18.

    Article  CAS  PubMed  Google Scholar 

  7. Zaninovich OA, Ramey WL, Walter CM, Dumont TM. Completion of the circle of Willis varies by gender, age, and indication for computed tomography angiography. World Neurosurg. 2017;106:953–63.

    Article  PubMed  Google Scholar 

  8. Macchi C, Catini C, Federico C, Gulisano M, Pacini P, Cecchi F, et al. Magnetic resonance angiographic evaluation of circulus arteriosus cerebri (circle of Willis): a morphologic study in 100 human healthy subjects. Ital J Anat Embryol. 1996;101:115–23.

    CAS  PubMed  Google Scholar 

  9. Krabbe-Hartkamp MJ, van der Grond J, de Leeuw FE, de Groot JC, Algra A, Hillen B, et al. Circle of Willis: morphologic variation on three-dimensional time-of-flight MR angiograms. Radiology. 1998;207:103–11.

    Article  CAS  PubMed  Google Scholar 

  10. Li Q, Li J, Lv F, Li K, Luo T, Xie P. A multidetector CT angiography study of variations in the circle of Willis in a Chinese population. J Clin Neurosci. 2011;18:379–83.

    Article  PubMed  Google Scholar 

  11. Naveen SR, Bhat V, Karthik GA. Magnetic resonance angiographic evaluation of circle of Willis: a morphologic study in a tertiary hospital set up. Ann Indian Acad Neurol. 2015;18:391–7.

    PubMed  PubMed Central  Google Scholar 

  12. Chuang YM, Liu CY, Pan PJ, Lin CP. Posterior communicating artery hypoplasia as a risk factor for acute ischemic stroke in the absence of carotid artery occlusion. J Clin Neurosci. 2008;15:1376–81.

    Article  PubMed  Google Scholar 

  13. Qiu C, Zhang Y, Xue C, Jiang S, Zhang W. MRA study on variation of the circle of Willis in healthy Chinese male adults. Biomed Res Int. 2015;2015:976340

  14. Jin ZN, Dong WT, Cai XW, Zhang Z, Zhang LT, Gao F, et al. CTA characteristics of the circle of Willis and intracranial aneurysm in a Chinese crowd with family history of stroke. Biomed Res Int. 2016;2016:1743794.

    PubMed  PubMed Central  Google Scholar 

  15. De Silva KR, Silva R, Amaratunga D, Gunasekera WS, Jayesekera RW. Types of the cerebral arterial circle (circle of Willis) in a Sri Lankan population. BMC Neurol. 2011;11:5.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lazorthes G, Gouaze A, Santini JJ, Salamon G. The arterial circle of the brain (circulus arteriosus cerebri). Anatomia Clinica. 1979;1:241–57.

    Article  Google Scholar 

  17. el Khamlichi A, Azouzi M, Bellakhdar F, Ouhcein A, Lahlaidi A. Anatomic configuration of the circle of Willis in the adult studied by injection technics. Apropos of 100 brains. Neurochirurgie. 1985;31(4):287–93.

    PubMed  Google Scholar 

  18. Vasović L, Trandafilović M, Jovanović I, Ugrenović S, Vlajković S, Milić M, et al. Morphology of the cerebral arterial circle in the prenatal and postnatal period of Serbian population. Childs Nerv Syst. 2013;29:2249–61.

    Article  PubMed  Google Scholar 

  19. Eftekhar B, Dadmehr M, Ansari S, Ghodsi M, Nazparvar B, Ketabchi E. Are the distributions of variations of circle of Willis different in different populations?––results of an anatomical study and review of literature. BMC Neurol. 2006;6:22.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kapoor K, Singh B, Dewan LI. Variations in the configuration of the circle of Willis. Anat Sci Int. 2008;83:96–106.

    Article  PubMed  Google Scholar 

  21. Paget D. The circle of Willis: its embryology and anatomy. In: Dandy WE, editor. Intracranial artery aneurism. New York: Comstock; 1945. p. 74–85.

    Google Scholar 

  22. Takakuwa T, Koike T, Muranaka T, Uwabe C, Yamada S. Formation of the circle of Willis during human embryonic development. Congenit Anom (Kyoto). 2016;56:233–6.

    Article  Google Scholar 

  23. Degani S. Evaluation of fetal cerebrovascular circulation and brain development: the role of ultrasound and Doppler. Semin Perinatol. 2009;33(4):259–69.

    Article  PubMed  Google Scholar 

  24. Vasovic L, Milenkovic Z, Pavlovic S. Comparative morphological variations and abnormalities of circles of Willis: a minireview including two personal cases. Neurosurg Rev. 2002;25:247–51.

    Article  PubMed  Google Scholar 

  25. Yang K, Banerjee S, Proweller A. Regulation of pre-natal circle of Willis assembly by vascular smooth muscle Notch signaling. Dev Biol. 2013;381:107–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hiruma T, Nakajima Y, Nakamura H. Development of pharyngeal arch arteries in early mouse embryo. J Anat. 2002;201:15–29.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kaufman M. The atlas of mouse development. Cambridge: Academic Press; 2012.

  28. Van Overbeeke JJ, Hillen B, Tulleken CAA. Comparative study of the circle of Willis in fetal and adult life. The configuration of the posterior bifurcation of the posterior communicating artery. J Anat. 1991;176:45–54.

    PubMed  PubMed Central  Google Scholar 

  29. Malamateniou C, Adams ME, Srinivasan L, Allsop JM, Counsell SJ, Cowan FM, et al. The anatomic variations of the circle of Willis in preterm-at-term and term-born infants: an MR angiography study at 3T. Am J Neuroradiol. 2009;30:1955–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yamauchi H, Kudoh T, Sugimoto K, Takahashi M, Kishibe Y, Okazawa H. Pattern of collaterals, type of infarcts, and haemodynamic impairment in carotid artery occlusion. J Neurol Neurosurg Psychiatry. 2004;75:1697–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kayembe KN, Sasahara M, Hazama F. Cerebral aneurysms and variations in the circle of Willis. Stroke. 1984;15:846–50.

    Article  CAS  PubMed  Google Scholar 

  32. Hoksbergen AW, Legemate DA, Csiba L, Csáti G, Síró P, Fülesdi B. Absent collateral function of the circle of Willis as risk factor for ischemic stroke. Cerebrovasc Dis. 2003;16:191–8.

    Article  CAS  PubMed  Google Scholar 

  33. Hendrikse J, Hartkamp MJ, Hillen B, Mali WP, van der Grond J. Collateral ability of the circle of Willis in patients with unilateral internal carotid artery occlusion: border zone infarcts and clinical symptoms. Stroke. 2001;32:2768–73.

    Article  CAS  PubMed  Google Scholar 

  34. Lee SU, Hong JM, Kim SY, Bang OY, Demchuk AM, Lee JS. Differentiating carotid terminus occlusions into two distinct populations based on Willisian collateral status. J Stroke. 2016;18:179–86.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Alfano JM, Kolega J, Natarajan SK, Xiang J, Paluch RA, Levy EI, et al. Intracranial aneurysms occur more frequently at bifurcation sites that typically experience higher hemodynamic stresses. Neurosurgery. 2013;73:497–505.

    Article  PubMed  Google Scholar 

  36. Arteaga DF, Strother MK, Davis LT, Fusco MR, Faraco CC, Roach BA, et al. Planning-free cerebral blood flow territory mapping in patients with intracranial arterial stenosis. J Cereb Blood Flow Metab. 2017;37:1944–58.

    Article  PubMed  Google Scholar 

  37. Zhou H, Sun J, Ji X, Lin J, Tang S, Zeng J, et al. Correlation between the integrity of the circle of Willis and the severity of initial noncardiac cerebral infarction and clinical prognosis. Medicine (Baltimore). 2016;95:e2892.

    Article  Google Scholar 

  38. Kim KM, Kang H-S, Lee WJ, Cho YD, Kim JE, Han MH. Clinical significance of the circle of Willis in intracranial atherosclerotic stenosis. J Neurointerv Surg. 2016;8:251–5.

    Article  PubMed  Google Scholar 

  39. Kitagawa K, Matsumoto M, Yang G, Mabuchi T, Yagita Y, Hori M, et al. Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery. J Cereb Blood Flow Metab. 1998;18:570–9.

    Article  CAS  PubMed  Google Scholar 

  40. Majid A, He YY, Gidday JM, Kaplan SS, Gonzales ER, Park TS, et al. Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains. Stroke. 2000;31:2707–14.

    Article  CAS  PubMed  Google Scholar 

  41. Yang G, Kitagawa K, Matsushita K, Mabuchi T, Yagita Y, Yangihara T, et al. C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in murine transient forebrain ischemia. Brain Res. 1997;752:209–18.

    Article  CAS  PubMed  Google Scholar 

  42. Ward R, Collins RL, Tanguay G, Miceli DA. Quantitative study of cerebrovascular variation in inbred mice. J Anat. 1990;173:87–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Connolly ES Jr, Winfree CJ, Stern DM, Solomon RA, Pinsky DJ. Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia. Neurosurgery. 1996;38:523–31.

    PubMed  Google Scholar 

  44. Fujii M, Hara H, Meng W, Vonsattel JP, Huang Z, Moskowitz MA. Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice. Stroke. 1997;28:1805–10.

    Article  CAS  PubMed  Google Scholar 

  45. Barone FC, Knudsen DJ, Nelson AH, Feuerstein GZ, Willette RN. Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy. J Cereb Blood Flow Metab. 1993;13:683–92.

    Article  CAS  PubMed  Google Scholar 

  46. Wellons JC 3rd, Sheng H, Laskowitz DT, Mackensen GB, Pearlstein RD, Warner DS. A comparison of strain-related susceptibility in two murine recovery models of global cerebral ischemia. Brain Res. 2000;16(868):14–21.

    Article  Google Scholar 

  47. Maeda K, Hata R, Hossmann KA. Regional metabolic disturbances and cerebrovascular anatomy after permanent middle cerebral artery occlusion in C57black/6 and SV129 mice. Neurobiol Dis. 1999;6:101–8.

    Article  CAS  PubMed  Google Scholar 

  48. Hecht N, He J, Kremenetskaia I, Nieminen M, Vajkoczy P, Woitzik J. Cerebral hemodynamic reserve and vascular remodeling in C57/BL6 mice are influenced by age. Stroke. 2012;43:3052–62.

    Article  CAS  PubMed  Google Scholar 

  49. Carmichael ST. Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx. 2005;2:396–409.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Zhang H, Prabhakar P, Sealock RW, Faber JE. Wide genetic variation in the native pial collateral circulation is a major determinant of variation in severity of stroke. J Cereb Blood Flow Metab. 2010;30:923–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wang S, Zhang H, Wiltshire T, Sealock R, Faber JE. Genetic dissection of the Canq1 locus governing variation in extent of the collateral circulation. PLoS One. 2012;7:e31910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sealock R, Zhang, Lucitti J, Moore S, Faber J. Congenic fine-mapping identifies a major causal locus for variation in the native collateral circulation and ischemic injury in brain and lower extremity. Circ Res. 2014;114:660–71.

    Article  CAS  PubMed  Google Scholar 

  53. Lucitti JL, Sealock R, Buckley BK, Zhang H, Xiao L, Dudley AC, et al. Variants of Rab GTPase-effector binding protein-2 cause variation in the collateral circulation and severity of stroke. Stroke. 2016;47:3022–31.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Lucitti JL, Mackey J, Morrison JC, Haigh JJ, Adams RH, Faber JE. Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and A disintegrin and metalloprotease family members 10 and 17. Circ Res. 2012;111:1539–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Faber JE, Zhang H, Lassance-Soares RM, Prabhakar P, Najafi AH, Burnett MS, et al. Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues. Arterioscler Thromb Vasc Biol. 2011;31:1748–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Dai X, Faber JE. eNOS deficiency causes collateral vessel rarefaction and impairs activation of a cell cycle gene network during arteriogenesis. Circ Res. 2010;106:1870–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Moore SM, Zhang H, Maeda N, Doerschuk, Faber JE. Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury. Angiogenesis. 2015;18:265–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rzechorzek W, Zhang H, Buckley BK, Hua H, Pomp D, Faber JE. Exercise training prevents rarefaction of pial collaterals and increased severity of stroke with aging. J Cereb Blood Flow Metab. 2017;37:3544–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Menon BK, Smith EE, Coutts SB, Welsh DG, Faber JE, Damani Z, et al. Leptomeningeal collaterals are associated with modifiable metabolic risk factors. Ann Neurol. 2013;74:241–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Arsava EM, Vural A, Akpinar E, Gocmen R, Akcalar S, Oguz KK, et al. The detrimental effect of aging on leptomeningeal collaterals in ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23:421–6.

    Article  PubMed  Google Scholar 

  61. Warnert EA, Rodrigues JC, Burchell AE, Neumann S, Ratcliffe LE, Manghat NE, et al. Is high blood pressure self-protection for the brain? Circ Res. 2016;119:e140–51.

    Article  CAS  PubMed  Google Scholar 

  62. Romanko-Hrushchak N. MDCTA diagnosis of cerebral vessel disease among patients with arterial hypertension. Pol J Radiol. 2013;78:28–34.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Shatri J, Bexheti D, Bexheti S, Kabashi S, Krasniqi S, Ahmetgjekaj I, et al. Influence of gender and age on average dimensions of arteries forming the circle of Willis study by magnetic resonance angiography on Kosovo’s population. Open Access Maced J Med Sci. 2017;5:714–9.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Sharma D, Shastri S, Sharma P. Intrauterine growth restriction: antenatal and postnatal aspects. Clin Med Insights Pediatr. 2016;10:67–83.

    PubMed  PubMed Central  Google Scholar 

  65. Koupilová I, Leon DA, McKeigue PM, Lithell HO. Is the effect of low birth weight on cardiovascular mortality mediated through high blood pressure? J Hypertens. 1999;17:19–25.

    Article  PubMed  Google Scholar 

  66. Koupil I, Leon DA, Lithell HO. Length of gestation is associated with mortality from cerebrovascular disease. J Epidemiol Community Health. 2005;59:473–4.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Lawlor DA, Ronalds G, Clark H, Smith GD, Leon DA. Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s: findings from the Aberdeen Children of the 1950s prospective cohort study. Circulation. 2005;112:1414–8.

    Article  PubMed  Google Scholar 

  68. Cambron BA, Ferrada P, Walcott R, Karthik S, Kaynar AM. Images in cardiovascular medicine. Demonstration of unilateral absence of the palmar arch without collateral circulation. Circulation. 2006;113:e6–7.

    Article  PubMed  Google Scholar 

  69. Faber JE, Moore SM, Lucitti JL, Aghajanian A, Zhang H. Sex differences in the cerebral collateral circulation. Transl Stroke Res. 2016;8:273–83.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Woods LL, Weeks DA. Naturally occurring intrauterine growth retardation and adult blood pressure in rats. Pediatr Res. 2004;56:763–7.

    Article  PubMed  Google Scholar 

  71. Keswani SG, Balaji S, Katz AB, King A, Omar K, Habli M, et al. Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction. Hum Gene Ther. 2015;26:172–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Khatri R, Rodriguez GJ, Suri MF, Vazquez G, Ezzeddine MA. Leptomeningeal collateral response and computed tomographic perfusion mismatch in acute middle cerebral artery occlusion. J Vasc Interv Neurol. 2011;4:1–4.

    PubMed  PubMed Central  Google Scholar 

  73. Phan TG, Hilton J, Beare R, Srikanth V, Sinnott M. Computer modeling of anterior circulation stroke: proof of concept in cerebrovascular occlusion. Front Neurol. 2014;5:176,1–11.

    Article  Google Scholar 

  74. Pham M, Bendszus M. Facing time in ischemic stroke: an alternative hypothesis for collateral failure. Clin Neuroradiol. 2016;26:141–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Luna RL, Kay VR, Rätsep MT, Khalaj K, Bidarimath M, Peterson N, et al. Placental growth factor deficiency is associated with impaired cerebral vascular development in mice. Mol Hum Reprod. 2016;22:130–42.

    Article  CAS  PubMed  Google Scholar 

  76. Okudera T, Ohta T, Huang YP, Yokota A. Developmental and radiological anatomy of the superficial cerebral convexity vessels in the human fetus. J Neuroradiol. 1988;15:205–24.

    CAS  PubMed  Google Scholar 

  77. Gielecki J, Zurada A, Kozłowska H, Nowak D, Morphometric LM. Volumetric analysis of the middle cerebral artery in human fetuses. Acta Neurobiol Exp (Wars). 2009;69:129–37.

    Google Scholar 

  78. Chalothorn D, Clayton JA, Zhang H, Pomp D, Faber JE. Collateral density, remodeling and VEGF-A expression differ widely between mouse strains. Physiol Genomics. 2007;30:179–91.

    Article  CAS  PubMed  Google Scholar 

  79. Faber JE, Dai X, Lucitti J. Genetic and environmental mechanisms controlling formation and maintenance of the native collateral circulation. In: Deindl E, Schaper W, editors. Arteriogenesis––molecular regulation, pathophysiology and therapeutics I. Aachen: shaker Verlag; 2011, Ch 1. p. 1–22.

    Google Scholar 

  80. Hendrikse J, van Raamt AF, van der Graaf Y, Mali WP, van der Grond J. Distribution of cerebral blood flow in the circle of Willis. Radiology. 2005;235:184–9.

    Article  PubMed  Google Scholar 

  81. de Boorder MJ, van der Grond J, Van Dongen AJ, Klijn CJ, Jaap Kappelle L, van Rijk PP, et al. SPECT measurements of regional cerebral perfusion and carbon dioxide reactivity: correlation with cerebral collaterals in internal carotid artery occlusive disease. J Neurol. 2006;253:1285–91.

    Article  PubMed  Google Scholar 

  82. Engel O, Kolodziej S, Dirnagl U, Prinz V. Modeling stroke in mice––middle cerebral artery occlusion with the filament model. J Vis Exp. 2011;47. https://doi.org/10.3791/2423.

  83. Hurn P, Becker K, Swanson R, Choi D, Dirnagl U, Fisher M, et al. Neurovascular protection mechanisms. In: Final report of the stroke progress review Group 2012. https://www.ninds.nih.gov/About-NINDS/Strategic-Plans-Evaluations/Strategic-Plans/Final-Report-Stroke-Progress-Review-Group#neurovascular.

  84. Kapoor K, Kak VK, Singh B. Morphology and comparative anatomy of circulus arteriosus cerebri in mammals. Anat Histol Embryol. 2003;32:347–55.

    Article  CAS  PubMed  Google Scholar 

  85. Praud E, Labrune B, Lyon G, Mallet R. Familial case of progressive and bilateral hypoplasia of branches of the circle of Willis with anatomic examination. Arch Fr Pediatr. 1972;29:397–409.

    CAS  PubMed  Google Scholar 

  86. Hajdu MA, Baumbach GL. Mechanics of large and small cerebral arteries in chronic hypertension. Am J Phys. 1994;266:H1027–33.

    CAS  Google Scholar 

  87. Yamakawa H, Jezova M, Ando H, Saavedra JM. Normalization of endothelial and inducible nitric oxide synthase expression in brain microvessels of spontaneously hypertensive rats by angiotensin II AT1 receptor inhibition. J Cereb Blood Flow Metab. 2003;23:371–80.

    Article  CAS  PubMed  Google Scholar 

  88. Rizzoni D, De Ciuceis C, Porteri E, Paiardi S, Boari GE, Mortini P, et al. Altered structure of small cerebral arteries in patients with essential hypertension. J Hypertens. 2009;27:838–45.

    Article  CAS  PubMed  Google Scholar 

  89. Nishijima Y, Akamatsu Y, Yang SY, Lee CC, Baran U, Song S, et al. Impaired collateral flow compensation during chronic cerebral hypoperfusion in the type 2 diabetic mice. Stroke. 2016;47:3014–21.

    Article  PubMed  PubMed Central  Google Scholar 

  90. DeFelice C, Tassi R, De Capua B, Jaubert F, Gentile M, Quartulli L, et al. A new phenotypical variant of intrauterine growth restriction? Pediatrics. 2007;119:e983–90.

    Article  PubMed  Google Scholar 

  91. Uflacker R. Atlas of vascular anatomy: an angiogenic approach. 2nd ed. Philadelphia: Lippicott, Williams and Wilkins; 2007.

    Google Scholar 

  92. Busch HJ, Buschmann IR, Mies G, Bode C, Hossmann KA. Arteriogenesis in hypoperfused rat brain. J Cereb Blood Flow Metab. 2003;23:621–8.

    Article  PubMed  Google Scholar 

  93. Gutierrez J, Goldman J, Honig LS, Elkind MS, Morgello S, Marshall RS. Determinants of cerebrovascular remodeling: do large brain arteries accommodate stenosis? Atherosclerosis. 2014;235:371–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Neff KW, Horn P, Dinter D, Vajkoczy P, Schmiedek P, Duber C. Extracranial–intracranial arterial bypass surgery improves total brain blood supply in selected symptomatic patients with unilateral internal carotid artery occlusion and insufficient collateralization. Neuroradiology. 2004;46:730–7.

    Article  CAS  PubMed  Google Scholar 

  95. Zhu G, Yuan Q, Yang J, Yeo J. Experimental study of hemodynamics in the circle of Willis. Biomed Eng Online. 2015;14(Suppl 1):S10.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Hoksbergen AW, Majoie CB, Hulsmans FJ, Legemate DA. Assessment of the collateral function of the circle of Willis: three-dimensional time-of-flight MR angiography compared with transcranial color-coded duplex sonography. AJNR Am J Neuroradiol. 2003;24:456–62.

    PubMed  PubMed Central  Google Scholar 

  97. Korshunov VA, Berk BC. Strain-dependent vascular remodeling: the “Glagov phenomenon” is genetically determined. Circulation. 2004;110:220–6.

    Article  PubMed  Google Scholar 

  98. van Seeters T, Biessels GJ, Kappelle LJ, van der Graaf Y, Velthuis BK. Dutch acute stroke study (DUST) investigators. Determinants of leptomeningeal collateral flow in stroke patients with a middle cerebral artery occlusion. Neuroradiology. 2016;58:969–77.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The sources of funding are the National Institutes of Health and National Institute of Neurological Diseases and Stroke grant NS083633.

Funding

This study was funded by the National Institutes of Health and National Institute of Neurological Diseases and Stroke grant NS083633.

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Authors and Affiliations

  1. Department of Cell Biology and Physiology, McAllister Heart Institute, University of North Carolina, 6309 MBRB, Chapel Hill, NC, 27599-7545, USA

    James E. Faber, Hua Zhang, Wojciech Rzechorzek, Kathy Z. Dai, Benjamin T. Summers, Cooper Blazek & Samuel J. Hedges

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  1. James E. Faber
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  2. Hua Zhang
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  7. Samuel J. Hedges
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Contributions

JF designed the study and figures and wrote the manuscript. HZ performed angiography, pMCAO, pial collateral morphometry, statistical analysis, animal husbandry, and finalized the figures. WR, KD, BS, CB, and SH performed the morphometry of PComs and primary cerebral arteries and statistical analysis.

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Correspondence to James E. Faber.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Faber, J.E., Zhang, H., Rzechorzek, W. et al. Genetic and Environmental Contributions to Variation in the Posterior Communicating Collaterals of the Circle of Willis. Transl. Stroke Res. 10, 189–203 (2019). https://doi.org/10.1007/s12975-018-0626-y

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  • DOI: https://doi.org/10.1007/s12975-018-0626-y

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