Angiogenesis in the mature mouse cortex is governed in a region specific and Notch1 dependent manner

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 underlying mechanisms, is 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{micro}m of the cortical surface. There were no regional differences in vessel pruning or sex effects except for the length and depth of new capillaries. To understand mechanisms, we surveyed gene expression and found Notch related genes were enriched in ultra-stable retrosplenial versus visual 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 manipulations of Notch1 signaling could unlock the angiogenic potential of the mature vasculature.