Abstract
The goal of this chapter is to highlight techniques used to determine the role of molecular mechanisms involved in remodeling of cerebral blood vessels. Enhanced vascularization in the central nervous system (CNS) is seen in many diseases including stroke, cancer, and multiple sclerosis (MS). However, despite the prevalence of this phenomenon in these different pathological conditions, the exact nature of how it occurs still remains unclear. To better understand the process of cerebrovascular remodeling, we use the chronic hypoxia model, in which a vigorous and robust angiogenic remodeling response takes place. In this model, mice are placed in a hypoxic chamber (8 % O2 for up to 14 days), which results in strong vascular remodeling and increased vessel density within the CNS. Using an immunofluorescent (IF)-based approach, different aspects of this vascular remodeling response can be examined. By employing this method, we have shown that chronic mild hypoxia triggers both angiogenic (capillary sprouting) and arteriogenic (widening of arterial vessels) responses. Furthermore, we have used this system to define both the expression pattern and potential role of candidate adhesion molecules in this vascular remodeling process. Thus, the techniques described in this chapter can be used to define the importance of different molecular mechanisms in vascular remodeling in the CNS.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Forget MA, Desrosiers RR, Beliveau R (1999) Physiological roles of matrix metalloproteinase: implications for tumor growth and metastasis. Can J Physiol Pharmacol 77(7):465–480
Kirk S, Frank AJ, Karlik S (2004) Angiogenesis in multiple sclerosis: is it good, bad or an epiphenomenon? J Neurol Sci 217(2):125–130
Polverini PJ (1995) The pathophysiology of angiogenesis. Crit Rev Oral Biol Med 6(3):230–247
Winkler JD, Jackson JR (2000) Chronic inflammation and angiogenesis. In: Rubanyi GM (ed) Angiogenesis in health and disease: basic mechanisms and clinical applications. Marcel Dekker, New York, pp 407–416
Li L, Welser JV, Dore-Duffy P, del Zoppo GJ, LaManna JC, Milner R (2010) In the hypoxic central nervous system, endothelial cell proliferation is followed by astrocytes activation, proliferation, and increased expression of the α6β4 integrin and dystroglycan. Glia 58(10):1157–1167
Boroujerdi A, Welser-Alves JV, Tigges U, Milner R (2012) Chronic cerebral hypoxia promotes arteriogenic remodeling events that can be identified by reducing endoglin (CD105) expression and a switch in β1 integrins. J Cereb Blood Flow Metab 32:1820–1830
Milner R, Campbell IL (2002) Developmental regulation of β1 integrins during angiogenesis in the central nervous system. Mol Cell Neurosci 20:616–626
Milner R, Hung S, Erokwu B, Dore-Duffy P, LaManna JC, del Zoppo GJ (2008) Increased expression of fibronectin and the alpha5 beta 1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia. Mol Cell Neurosci 38(1):43–52
Li L, Welser-Alves JV, van der Flier A, Boroujerdi A, Hynes RO, Milner R (2012) An angiogenic role for the α5β1 integrin in promoting endothelial cell proliferation during cerebral hypoxia. Exp Neurol 237(1):46–54
Brooks PC, Klemke RL, Schon S, Lewis JM, Schwartz MA, Cheresh DA (1997) Insulin-like growth factor receptors cooperates with integrin alpha v beta 5 to promote tumor cell dissemination in vivo. J Clin Invest 99:1390–1398
Lorger M, Krueger JS, O’Neal M, Staflin K, Felding-Habermann B (2009) Activation of tumor cell integrin αvβ3 controls angiogenesis and metastatic growth in the brain. Proc Natl Acad Sci U S A 106(26):10666–10671
Acknowledgments
This work was supported by the American Heart Association (Western State Affiliate) Postdoctoral Fellowship (A.B.) and by the National Multiple Sclerosis Society, Harry Weaver Neuroscience Scholar Award (R.M.), and Postdoctoral Fellowship (J.V.W.).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this protocol
Cite this protocol
Boroujerdi, A., Welser-Alves, J.V., Milner, R. (2014). Examining Vascular Remodeling in the Hypoxic Central Nervous System. In: Milner, R. (eds) Cerebral Angiogenesis. Methods in Molecular Biology, vol 1135. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0320-7_15
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0320-7_15
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-0319-1
Online ISBN: 978-1-4939-0320-7
eBook Packages: Springer Protocols