Quantitative assessment of angiogenesis, perfused blood vessels and endothelial tip cells in the postnatal mouse brain

Nature Protocols

Volumn 10, Issue 1, 2015, Pages 53-74

  Wälchli, Thomas ^a,b   Mateos, José Mariá ^c   Weinman, Oliver ^b   Babic, Daniela ^a   Regli, Luca ^a   Hoerstrup, Simon P ^a   Gerhardt, Holger ^d,e,f   Schwab, Martin E ^b   Vogel, Johannes ^c  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b University of Zurich Brain Research Institute   (Switzerland)

^c UNIVERSITY OF ZURICH   (Switzerland)

^d UNIVERSITY OF LEUVEN   (Belgium)

^e DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^f IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EVANS BLUE; ISOLECTIN B4; LAMININ; LECTIN;

ANGIOGENESIS; ARTICLE; BRAIN BLOOD VESSEL; BRAIN PERFUSION; CELL DENSITY; CONFOCAL LASER MICROSCOPY; ENDOTHELIUM CELL; FILOPODIUM; IMMUNOFLUORESCENCE; NONHUMAN; PERINATAL PERIOD; PRIORITY JOURNAL; PROTEIN ANALYSIS; STEREOMETRY; ANIMAL; BRAIN; CONFOCAL MICROSCOPY; CYTOLOGY; METABOLISM; MOUSE; PHYSIOLOGY; PROCEDURES; SCINTIGRAPHY; VASCULARIZATION;

ANIMALS; BRAIN; ENDOTHELIAL CELLS; EVANS BLUE; LAMININ; LECTINS; MICE; MICROSCOPY, CONFOCAL; NEOVASCULARIZATION, PHYSIOLOGIC; PERFUSION IMAGING;

EID: 84925937125     PISSN: 17542189     EISSN: 17502799     Source Type: Journal    
DOI: 10.1038/nprot.2015.002     Document Type: Article

References (91)

1. Carmeliet, P., Jain, R.K. Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298-307 (2011).
2. Potente, M., Gerhardt, H., Carmeliet, P. Basic and therapeutic aspects of angiogenesis. Cell 146, 873-887 (2011).
3. Jain, R.K., Carmeliet, P. SnapShot: tumor angiogenesis. Cell 149, 1408-1408 (2012).
4. Burri, P.H., Hlushchuk, R., Djonov, V. Intussusceptive angiogenesis: its emergence, its characteristics, and its significance. Dev. Dyn. 231, 474-488 (2004).
5. Makanya, A.N., Hlushchuk, R., Djonov, V.G. Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling. Angiogenesis 12, 113-123 (2009).
6. Herbert, S.P., Stainier, D.Y. Molecular control of endothelial cell behaviour during blood vessel morphogenesis. Nat. Rev. Mol. Cell Biol. 12, 551-564 (2011).
7. Mancuso, M.R., Kuhnert, F., Kuo, C.J. Developmental angiogenesis of the central nervous system. Lymphat. Res. Biol. 6, 173-180 (2008).
8. Quaegebeur, A., Lange, C., Carmeliet, P. The neurovascular link in health and disease: molecular mechanisms and therapeutic implications. Neuron 71, 406-424 (2011).
9. Fantin, A., Vieira, J.M., Plein, A., Maden, C.H., Ruhrberg, C. The embryonic mouse hindbrain as a qualitative and quantitative model for studying the molecular and cellular mechanisms of angiogenesis. Nat. Protoc. 8, 418-429 (2013).
10. Daneman, R., Zhou, L., Kebede, A.A., Barres, B.A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468, 562-566 (2010).
11. Zeller, K., Vogel, J., Kuschinsky, W. Postnatal distribution of Glut1 glucose transporter and relative capillary density in blood-brain barrier structures and circumventricular organs during development. Brain Res. Dev. Brain Res. 91, 200-208 (1996).
12. Walchli, T. et al. Nogo-A is a negative regulator of CNS angiogenesis. Proc. Natl. Acad. Sci. USA 110, E1943-E1952 (2013).
13. Geudens, I., Gerhardt, H. Coordinating cell behaviour during blood vessel formation. Development 138, 4569-4583 (2011).
14. Eilken, H.M., Adams, R.H. Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr. Opin. Cell Biol. 22, 617-625 (2010).
15. Strilic, B. et al. The molecular basis of vascular lumen formation in the developing mouse aorta. Dev. Cell 17, 505-515 (2009).
16. Lammert, E., Axnick, J. Vascular lumen formation. Cold Spring Harb. Perspect. Med. 2, a006619 (2012).
17. Tung, J.J., Tattersall, I.W., Kitajewski, J. Tips, stalks, tubes: notch-mediated cell fate determination and mechanisms of tubulogenesis during angiogenesis. Cold Spring Harb. Perspect. Med. 2, a006601 (2012).
18. Wacker, A., Gerhardt, H. Endothelial development taking shape. Curr. Opin. Cell Biol. 23, 676-685 (2011).
19. Mazzone, M. et al. Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 136, 839-851 (2009).
20. Pries, A.R., Secomb, T.W., Gaehtgens, P. Structural adaptation and stability of microvascular networks: theory and simulations. Am. J. Physiol. 275, H349-H360 (1998).
21. Zhang, L., Cooper-Kuhn, C.M., Nannmark, U., Blomgren, K., Kuhn, H.G. Stimulatory effects of thyroid hormone on brain angiogenesis in vivo and in vitro. J. Cereb. Blood Flow Metab. 30, 323-335 (2010).
22. Frahm, K.A., Nash, C.P., Tobet, S.A. Endocan immunoreactivity in the mouse brain: method for identifying nonfunctional blood vessels. J. Immunol. Methods 398-399, 27-32 (2013).
23. Lobov, I.B. et al. Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc. Natl. Acad. Sci. USA 104, 3219-3224 (2007).
24. Blanco, R., Gerhardt, H. VEGF and Notch in tip and stalk cell selection. Cold Spring Harb. Perspect. Med. 3, a006569 (2013).
25. Phng, L.K., Gerhardt, H. Angiogenesis: a team effort coordinated by Notch. Dev. Cell 16, 196-208 (2009).
26. Thurston, G., Noguera-Troise, I., Yancopoulos, G.D. The delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat. Rev. Cancer 7, 327-331 (2007).
27. Yan, M. et al. Chronic DLL4 blockade induces vascular neoplasms. Nature 463, E6-E7 (2010).
28. Noguera-Troise, I. et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444, 1032-1037 (2006).
29. Ridgway, J. et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444, 1083-1087 (2006).
30. Noguera-Troise, I. et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Novartis Found. Symp. 283, 106-120 discussion 121-125, 238-241 (2007).
31. Gobel, U., Theilen, H., Kuschinsky, W. Congruence of total and perfused capillary network in rat brains. Circ. Res. 66, 271-281 (1990).
32. Carmeliet, P. Angiogenesis in life, disease and medicine. Nature 438, 932-936 (2005).
33. Storkebaum, E., Quaegebeur, A., Vikkula, M., Carmeliet, P. Cerebrovascular disorders: molecular insights and therapeutic opportunities. Nat. Neurosci. 14, 1390-1397 (2011).
34. Pitulescu, M.E., Schmidt, I., Benedito, R., Adams, R.H. Inducible gene targeting in the neonatal vasculature and analysis of retinal angiogenesis in mice. Nat. Protoc. 5, 1518-1534 (2010).
35. Connor, K.M. et al. Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat. Protoc. 4, 1565-1573 (2009).
36. Rawson, R.A. The binding of T-1824 and structurally related diazo dyes by the plasma proteins. Am. J. Physiol. 138, 708-717 (1943).
37. Weintraub, H. et al. Storage of glycoprotein in NCTR-BALB/c mouse. Lectin histochemistry, and biochemical studies. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 62, 347-352 (1992).
38. DeGasperi, R. et al. Glycoprotein storage in Gaucher disease: lectin histochemistry and biochemical studies. Lab. Invest. 63, 385-392 (1990).
39. Laitinen, L. Griffonia simplicifolia lectins bind specifically to endothelial cells and some epithelial cells in mouse tissues. Histochem. J. 19, 225-234 (1987).
40. Laitinen, L., Virtanen, I., Saxen, L. Changes in the glycosylation pattern during embryonic development of mouse kidney as revealed with lectin conjugates. J. Histochem. Cytochem. 35, 55-65 (1987).
41. Alroy, J., Goyal, V., Warren, C.D. Lectin histochemistry of gangliosidosis. I. Neural tissue in four mammalian species. Acta Neuropathol. 76, 109-114 (1988).
42. Gerhardt, H. et al. Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system. Dev. Dyn. 231, 503-509 (2004).
43. Gerhardt, H. et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161, 1163-1177 (2003).
44. Sorokin, S.P., Hoyt, R.F. Jr. Macrophage development: I. Rationale for using Griffonia simplicifolia isolectin B4 as a marker for the line. Anat. Rec. 232, 520-526 (1992).
45. Sorokin, S.P., Hoyt, R.F. Jr., Blunt, D.G., McNelly, N.A. Macrophage development: II. Early ontogeny of macrophage populations in brain, liver, and lungs of rat embryos as revealed by a lectin marker. Anat. Rec. 232, 527-550 (1992).
46. Theilen, H., Schrock, H., Kuschinsky, W. Capillary perfusion during incomplete forebrain ischemia and reperfusion in rat brain. Am. J. Physiol. 265, H642-H648 (1993).
47. Gundersen, H.J. Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson. J. Microsc. 143, 3-45 (1986).
48. West, M.J. Basic Stereology for Biologists and Neuroscientists (Cold Spring Harbor Laboratory Press, 2012).
49. Gundersen, H.J., Jensen, E.B. The efficiency of systematic sampling in stereology and its prediction. J. Microsc. 147, 229-263 (1987).
50. Boyce, R.W., Dorph-Petersen, K.A., Lyck, L., Gundersen, H.J. Design-based stereology: introduction to basic concepts and practical approaches for estimation of cell number. Toxicol. Pathol. 38, 1011-1025 (2010).
51. Mouton, P.R., Gokhale, A.M., Ward, N.L., West, M.J. Stereological length estimation using spherical probes. J. Microsc. 206, 54-64 (2002).
52. Gundersen, H.J. et al. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96, 379-394 (1988).
53. Gundersen, H.J. et al. The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96, 857-881 (1988).
54. Schmitz, C., Hof, P.R. Design-based stereology in neuroscience. Neuroscience 130, 813-831 (2005).
55. Howard, C.V., Reed, M.G. Unbiased Stereology: Three-dimensional Measurements in Microscopy (QTP Publications, 2010).
56. Lokkegaard, A., Nyengaard, J.R., West, M.J. Stereological estimates of number and length of capillaries in subdivisions of the human hippocampal region. Hippocampus 11, 726-740 (2001).
57. Sawamiphak, S., Ritter, M., Acker-Palmer, A. Preparation of retinal explant cultures to study ex vivo tip endothelial cell responses. Nat. Protoc. 5, 1659-1665 (2010).
58. Gore, A.V., Monzo, K., Cha, Y.R., Pan, W., Weinstein, B.M. Vascular development in the zebrafish. Cold Spring Harb. Perspect. Med. 2, a006684 (2012).
59. Ellertsdottir, E. et al. Developmental role of zebrafish protease-activated receptor 1 (PAR1) in the cardiovascular system. PLoS ONE 7, e42131 (2012).
60. Carmeliet, P., De Smet, F., Loges, S., Mazzone, M. Branching morphogenesis and antiangiogenesis candidates: tip cells lead the way. Nat. Rev. Clin. Oncol. 6, 315-326 (2009).
61. Hellstrom, M. et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445, 776-780 (2007).
62. Tammela, T. et al. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature 454, 656-660 (2008).
63. Strasser, G.A., Kaminker, J.S., Tessier-Lavigne, M. Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching. Blood 115, 5102-5110 (2010).
64. del Toro, R. et al. Identification and functional analysis of endothelial tip cell-enriched genes. Blood 116, 4025-4033 (2010).
65. Siemerink, M.J. et al. CD34 marks angiogenic tip cells in human vascular endothelial cell cultures. Angiogenesis 15, 151-163 (2012).
66. Jakobsson, L. et al. Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat. Cell Biol. 12, 943-953 (2010).
67. Vogel, J., Gehrig, M., Kuschinsky, W., Marti, H.H. Massive inborn angiogenesis in the brain scarcely raises cerebral blood flow. J. Cereb. Blood Flow Metab. 24, 849-859 (2004).
68. Heinzer, S. et al. Novel three-dimensional analysis tool for vascular trees indicates complete micro-networks, not single capillaries, as the angiogenic endpoint in mice overexpressing human VEGF(165) in the brain. Neuroimage 39, 1549-1558 (2008).
69. Kienast, Y. et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat. Med. 16, 116-122 (2010).
70. Whiteus, C., Freitas, C., Grutzendler, J. Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period. Nature 505, 407-411 (2014).
71. Harb, R., Whiteus, C., Freitas, C., Grutzendler, J. In vivo imaging of cerebral microvascular plasticity from birth to death. J. Cereb. Blood Flow Metab. 33, 146-156 (2013).
72. Chappell, J.C., Wiley, D.M., Bautch, V.L. Regulation of blood vessel sprouting. Semin. Cell Dev. Biol. 22, 1005-1011 (2011).
73. Chappell, J.C., Wiley, D.M., Bautch, V.L. How blood vessel networks are made and measured. Cells Tissues Organs 195, 94-107 (2012).
74. West, M.J., Slomianka, L., Gundersen, H.J. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat. Rec. 231, 482-497 (1991).
75. West, M.J. Introduction to stereology. Cold Spring Harb. Protoc. 2012 doi:10.1101/pdb.top070623 (2012).
76. West, M.J. The precision of estimates in stereological analyses. Cold Spring Harb. Protoc. 2012, 937-949 (2012).
77. West, M.J. Estimating object number in biological structures. Cold Spring Harb. Protoc. 2012, 1049-1066 (2012).
78. West, M.J. Estimating volume in biological structures. Cold Spring Harb. Protoc. 2012, 1129-1139 (2012).
79. West, M.J. Systematic versus random sampling in stereological studies. Cold Spring Harb. Protoc. 2012 doi:10.1101/pdb.top071837 (2012).
80. Reed, M.G., Howard, C.V., GS, D.E.Y. One-stop stereology: the estimation of 3D parameters using isotropic rulers. J. Microsc. 239, 54-65 (2010).
81. Howard, C.V., Reed, M.G. Unbiased Stereology (BIOS Scientific Publishers, 1998).
82. Sawamiphak, S. et al. Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 465, 487-491 (2010).
83. Gampel, A. et al. VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial storage compartment. Blood 108, 2624-2631 (2006).
84. Jopling, H.M., Howell, G.J., Gamper, N., Ponnambalam, S. The VEGFR2 receptor tyrosine kinase undergoes constitutive endosome-to-plasma membrane recycling. Biochem. Biophys. Res. Commun. 410, 170-176 (2011).
85. Nakayama, M. et al. Spatial regulation of VEGF receptor endocytosis in angiogenesis. Nat. Cell Biol. 15, 249-260 (2013).
86. Gaengel, K., Betsholtz, C. Endocytosis regulates VEGF signalling during angiogenesis. Nat. Cell Biol. 15, 233-235 (2013).
87. Wang, Y. et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 465, 483-486 (2010).
88. Kent, T.A. et al. Cerebral blood volume in a rat model of ischemia by MR imaging at 4.7 T. AJNR Am. J. Neuroradiol. 10, 335-338 (1989).
89. Lin, W., Paczynski, R.P., Kuppusamy, K., Hsu, C.Y., Haacke, E.M. Quantitative measurements of regional cerebral blood volume using MRI in rats: effects of arterial carbon dioxide tension and mannitol. Magn. Reson. Med. 38, 420-428 (1997).
90. Ruhrberg, C., Bautch, V.L. Neurovascular development and links to disease. Cell. Mol. Life Sci. 70, 1675-1684 (2013).
91. Eichmann, A., Thomas, J.L. Molecular parallels between neural and vascular development. Cold Spring Harb. Perspect. Med. 3, a006551 (2013).