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A B

C D

Figure 2. The structure and function of the human brain. (A) The composition of the brain. (B) The gray matter and white matter of the brain. (C) The
main lobes and functions of the cerebral cortex. (D) The multilayer structure of the cerebral cortex. Image created using Photoshop.

This process begins early in embryogenesis and continues the initial formation of blood vessels from endothelial
through postnatal development, ensuring the formation of progenitor cells, laying the foundation for the vascular
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a dense, intricate network of blood vessels that permeates network. This process predominantly occurs during
the brain. 38,39 Blood vessel formation in the brain is initiated embryonic development, when endothelial progenitor cells
prenatally through angiogenesis, which originates from an differentiate into ECs to form the initial vascular framework.
external vascular network. One of the earliest contributors This foundational network provides the structural basis for
to this process is the perineural vascular plexus, an subsequent angiogenesis and the sprouting of new vessels
external network that serves as the starting point for from existing ones. During angiogenesis, ECs migrate,
blood vessel invasion into the brain, guided by signaling proliferate, and differentiate to form new vascular branches,
molecule gradients (Figure 3A). 40,41 This invasion results ensuring that the developing neural tissue receives
in the establishment of a dense and intricate vascular adequate oxygen and nutrients. Tip cells lead the sprouting
network capable of meeting the high metabolic demands and migration of blood vessels, while stalk cells follow,
of the developing brain. As the vessels penetrate deeper proliferating to form the main structure and lumen of the
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into the brain, the perineural vascular plexus forms the new vessels. The regulated growth of capillaries through
subventricular vascular plexus, which further branches angiogenesis is vital for nourishing neural precursors and
out and establishes a hierarchical vascular network developing neurons, supporting their rapid proliferation
composed of arteries, veins, and capillaries (Figure 3B). and differentiation. Together, these processes ensure that
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The establishment of the brain’s vascular system is tightly the brain’s developing vasculature meets the metabolic
regulated by a combination of cells, growth factors, and demands of growing neural tissue, facilitating proper brain
signaling pathways that guide the formation, patterning, development and function.
and maturation of blood vessels within the brain. 43-45 Growth factors are critical regulators of brain
ECs play a crucial role in promoting brain vascularization vascularization, guiding both the formation and
by regulating both vasculogenesis and angiogenesis, stabilization of blood vessels. Vascular endothelial growth
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the two primary processes involved in the formation of factor (VEGF) is one of the primary signals regulating
the brain’s vascular network. Vasculogenesis refers to angiogenesis in the brain. Produced by neurons, neuroglial
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Volume 1 Issue 2 (2025) 4 doi: 10.36922/or.8162