Abstract: The brain is a high-energy demanding organ, consuming around 20% of the metabolic energy generated. To fulfill this demand, cerebral blood flow (CBF) supplies oxygen and glucose continuously through the intricate network of cerebral blood vessels. Although for many years brain activity and blood flow were conceived as independent processes, MRI-based functional brain imaging demonstrated that there is a coupling between them, leading to the concept of the neurovascular unit (NVU) to reflect their interplay (Raichle and Mintun, 2006). The cerebrovascular system is far from being homogeneous throughout its structure; rather, each specific region of the brain presents multiple architectures. The NVU structure is divided into three main regions: cerebral arteries, including the middle cerebral artery. Middle cerebral artery gives rise to a second region, the pial arteries from the surface of the brain within the subarachnoid space. The endothelial cells (ECs) of pial arteries are covered by smooth muscle cells (SMCs) and are separated by a collagenous elastic lamina. From pial arteries, a subset of arterioles penetrates deep into the brain (penetrating arterioles) through the perivascular space, which limits glial cells. The perivascular space allocates several cell types; perivascular macrophages, mato, pial and mast cells. In this region, most external penetrating arterioles preserve a thin layer of SMCs and innervation. As arterioles get deeper into the brain, they become thinner, glial membrane and vascular basement membrane fuse occluding the perivascular space, innervation and SMCs disappear, which is ultimately substituted by pericytes in the microvascular capillaries, going to a less contractile vascularization. The collagen-rich matrix of pial arteries and brain capillaries are more abundant in proteoglycans and regulatory factors.