Angiogenesis in the mature mouse cortex is governed in a regional- and Notch1-dependent manner

Abstract

Cerebral angiogenesis is well appreciated in development and after injury, but the extent to which it occurs across cortical regions in normal adult mice and the underlying mechanisms are incompletely understood. Using in vivo imaging, we show that angiogenesis in anterior-medial cortical regions (retrosplenial and sensorimotor cortex) was exceptionally rare. By contrast, angiogenesis was significantly elevated in posterior-lateral regions such as visual cortex, primarily within 200 μm of the cortical surface. There was no effect of sex on angiogenesis rates, nor were there regional differences in vessel pruning (for either sex). To understand the mechanisms, we surveyed gene expression and found that Notch-related genes were enriched in ultra-stable retrosplenial cortex. Using endothelial-specific knockdown of Notch1, cerebral angiogenesis was significantly increased along with genes implicated in angiogenesis (Apln, Angpt2, Cdkn1a). Our study shows that angiogenesis is regionally dependent and that manipulations of Notch1 could unlock the angiogenic potential of the mature vasculature.

Keywords: CP: Molecular biology; CP: Neuroscience; Notch; VEGF; angiogenesis; blood flow; capillary; microcirculation; plasticity; rarefaction.