Examining Vascular Remodeling in the Hypoxic Central Nervous System

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.