Digital Reconstruction of the Neuro-Glia-Vascular Architecture

Abstract

Astrocytes connect the vasculature to neurons mediating the supply of nutrients and biochemicals. They are involved in a growing number of physiological and pathophysiological processes that result from biophysical, physiological, and molecular interactions in this neuro-glia-vascular ensemble (NGV). The lack of a detailed cytoarchitecture severely restricts the understanding of how they support brain function. To address this problem, we used data from multiple sources to create a data-driven digital reconstruction of the NGV at micrometer anatomical resolution. We reconstructed 0.2 mm3 of the rat somatosensory cortex with 16 000 morphologically detailed neurons, 2500 protoplasmic astrocytes, and its microvasculature. The consistency of the reconstruction with a wide array of experimental measurements allows novel predictions of the NGV organization, allowing the anatomical reconstruction of overlapping astrocytic microdomains and the quantification of endfeet connecting each astrocyte to the vasculature, as well as the extent to which they cover the latter. Structural analysis showed that astrocytes optimize their positions to provide uniform vascular coverage for trophic support and signaling. However, this optimal organization rapidly declines as their density increases. The NGV digital reconstruction is a resource that will enable a better understanding of the anatomical principles and geometric constraints, which govern how astrocytes support brain function.

Ultraliser: a framework for creating multiscale, high-fidelity and geometrically realistic 3D models for in silico neuroscience

“…Resulting astrocytic meshes were therefore applicable for skeletonization, with which we have successfully developed a novel pipeline to synthesize a digital reconstruction of the NGV ensemble at micrometer anatomical resolution 15 . Moreover, all the resulting meshes were tetrahedralized using T et G en 38 and Gmsh 40 to create corresponding volume, or simulation-ready, meshes for STEPS 31 simulations with which we have successfully completed the objectives of the collaboration.…”

“…In terms of representation, processes of astroglial cells are similar to neuronal arborizations, except that they have relatively compact extents and star-shaped structure, and are excessively oversampled in certain cases 15 . Moreover, astrocytic morphologies contain triangular surface patches that represent their endfeet geometries ( Supplementary Fig.…”

Astrocyte development in the cerebral cortex: Complexity of their origin, genesis, and maturation

“…Cajal already observed a complex arborization using Golgi’s method ( Ramón y Cajal, 1909 ; García-Marín et al, 2007 ). Recent works relying on endogenous sparse labeling techniques ( Hösli et al, 2022 ) and digital reconstructions ( Zisis et al, 2021 ) have revealed the complex three-dimensional structural details of astroglia processes at the vascular but also at the synaptic interfaces ( Torres-Ceja and Olsen, 2022 ). Astrocyte arborization has been underestimated for a long time due to the lack of immunomarkers labeling not only main processes, as shown with GFAP, S100β, or Aldh1l1 staining, but also fine branches.…”

The Specific Role of Reactive Astrocytes in Stroke

“…Accumulating evidence supports that astrocyte undergoes significant changes after the stroke in morphology, gene expression, and cell proliferation, and these cells are known as RAs ( Zisis et al, 2021 ). Currently, it is known that the RAs’ effects may include scarring, neurotrophic factor secretion, BBB damaging and repairing, and inhibition of synaptic formation.…”