Postnatal development of cerebrovascular structure and the neurogliovascular unit

Abstract

The unceasing metabolic demands of brain function are supported by an intricate three-dimensional network of arterioles, capillaries, and venules, designed to effectively distribute blood to all neurons and to provide shelter from harmful molecules in the blood. The development and maturation of this microvasculature involves a complex interplay between endothelial cells with nearly all other brain cell types (pericytes, astrocytes, microglia, and neurons), orchestrated throughout embryogenesis and the first few weeks after birth in mice. Both the expansion and regression of vascular networks occur during the postnatal period of cerebrovascular remodeling. Pial vascular networks on the brain surface are dense at birth and are then selectively pruned during the postnatal period, with the most dramatic changes occurring in the pial venular network. This is contrasted to an expansion of subsurface capillary networks through the induction of angiogenesis. Concurrent with changes in vascular structure, the integration and cross talk of neurovascular cells lead to establishment of blood-brain barrier integrity and neurovascular coupling to ensure precise control of macromolecular passage and metabolic supply. While we still possess a limited understanding of the rules that control cerebrovascular development, we can begin to assemble a view of how this complex process evolves, as well as identify gaps in knowledge for the next steps of research.

Structural and Functional Features of Developing Brain Capillaries, and Their Alteration in Schizophrenia

“…The NVU is a relatively recent concept ( Iadecola, 2017 ) that refers to the cellular components [e.g., endothelial cells (ECs), pericyte and astrocyte] that contribute to the functional relationship between brain cells and cerebral vasculature ( Coelho-Santos and Shih, 2020 ) with each cell type having their specific molecular signature ( Vanlandewijck et al, 2018 ). This relationship notably allows for neurovascular coupling (NVC) between neuronal activity and blood flow and the establishment of a properly selective blood-brain barrier (BBB) required to protect the brain against homeostatic disturbance from the periphery ( Bell et al, 2019 ; Sweeney et al, 2019 ).…”

Hierarchical imaging and computational analysis of three-dimensional vascular network architecture in the entire postnatal and adult mouse brain

“…The human brain crucially depends on its vasculature for proper functioning, as it – despite accounting for only 2% of the body mass – consumes 20% of the cardiac output and 20% of the oxygen and glucose of the entire body, corresponding to a 10-fold higher rate of energy metabolism compared to an equivalent tissue volume in the rest of the body 17,18 . The brain vasculature is constituted of a complex 3D vascular network of 644 kilometers (400 miles) 19,20 , anatomically organized in a way that each individual neuron is not more than 15μm away from the closest microcapillary, thereby assuring proper oxygen delivery 21 .…”

“…The INVP is expanded and refined via subsequent vessel sprouting, branching and anastomosis 6,31,36,37 while these vascular sprouts migrate from the PNVP radially inwards towards the ventricles 3,27,36 . These important angiogenic processes of blood vessel formation and remodeling start during embryonic CNS development 31,36 and continue at the postnatal stage of brain development 17,27,30,38–40 . The expansion and remodeling of the intricate 3D CNS vascular network 38,39 is required in order to adapt to local metabolic needs and neural activity 27,38,39,41 .…”

Structural and Functional Remodeling of the Brain Vasculature Following Stroke

“…For example, signaling factors associated with axonal guidance (Netrins, Semaphorins, and Ephrins) as well as angiogenic factors (VEGFs) are common signals orchestrating the regulation of both vessels and neuronal development ( Gu et al, 2005 ; Oh and Gu, 2013 ). Detailed reviews about neuro-vascular development can be consulted ( Tam and Watts, 2010 ; Eichmann and Thomas, 2013 ; Andreone et al, 2015 ; He et al, 2018 ; Paredes et al, 2018 ; Coelho-Santos and Shih, 2020 ).…”