ABSTRACT
In contrast to angiogenesis, vasculogenesis is defined as the formation of blood vessels de novo. Over the past two decades, a great deal of information has been learned about the basic mechanisms of blood vessel growth and development (1-3). One critical factor that is now understood as a central observation is that the delivery of oxygen to tissues is limited by passive diffusion to a distance of approximately 100 mm and that all cells must be relatively close to a capillary network (4). Even in post-natal development, tissue hypoxia is considered a driving force for the generation of a new vascular supply. However, in contrast to tissues like skeletal muscle, the brain is intolerant to episodic bouts of ischemia. During embryonic vascular development, the initial step in this process is vasculogenesis, or the differentiation of endothelial cells from their embryonic precursors, the angioblasts (5). Once endothelial cells have developed, they begin to assemble into a primitive vascular network, called the primary capillary plexus. This process requires the interplay and effects of a number of cytokine growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factors (bFGF), and their receptors in order to permit the differentiation of the endothelium and vascular cells that will comprise mature blood vessels (6). While vascularization of the endocardium of the heart and the dorsal aorta occurs by vasculogenesis, the brain is vascularized by angiogenesis, which is defined as the sprouting of new blood vessels from a pre-existing vascular network (7).
