Vascular Neuroembryology: The Genesis of the Intracranial Arterial System and the Circle of Willis

Cerebrovascular disorders, encompassing conditions such as stroke, aneurysms, and arteriovenous malformations, are often associated with developmental malformations of the intracranial arterial system, including the circle of Willis. The circle of Willis plays a crucial role in establishing a collateral vascular network essential for ensuring adequate cerebral blood supply. However, the intricate process of human intracranial vascular development, known as vascular neuroembryology, remains complex and incompletely understood. The diverse array of anatomical vascular variations observed in clinical practice is a direct outcome of this developmental process. We present a chronological overview of human neurovascular embryology using stage-resolved three-dimensional reconstructions of the developing intracranial arterial system. Histological sections of 26 human embryos ranging from Carnegie stages (CS) 11 to 23 were digitally reconstructed and manually segmented in Amira software (versions 5.3–5.6; Thermo Fisher Scientific, Waltham, MA, USA) to generate detailed 3D models of the cranial vasculature and adjacent anatomical structures, including the neural tube, cranial nerves, eye, and ear. Sequential 3D reconstruction revealed progressive remodeling of the primitive cranial vasculature and key developmental transitions underlying formation of the circle of Willis. By integrating these developmental observations with existing embryological literature, we refine current models of neurovascular development, with particular emphasis on the ophthalmic and trigeminal arterial systems. These findings provide an updated developmental framework for interpreting normal and variant intracranial vascular anatomy encountered in clinical practice.