Altered hemodynamics and vascular reactivity in a mouse model with severe pericyte deficiency
Jillian L. Stobart, Eva Erlebach, Chaim Glück, Sheng‐Fu Huang, Matthew Barrett, Max Li, Sergei A. Vinogradov, Jan Klohs, Yvette Zarb, Annika Keller, Bruno Weber
Abstract
Pericytes are the mural cells of the microvascular network that are in close contact with underlying endothelial cells. Endothelial-secreted PDGFB leads to recruitment of pericytes to the vessel wall, but this is disrupted in Pdgfb ret/ret mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels. In this study, we investigated vascular abnormalities and hemodynamics in Pdgfb ret/ret mice throughout the cerebrovascular network and in different cortical layers by in vivo two-photon microscopy. We confirmed that Pdgfb ret/ret mice are severely deficient in pericytes throughout the vascular network, with enlarged brain blood vessels and a reduced number of vessel branches. Red blood cell velocity, linear density, and tube hematocrit were reduced in Pdgfb ret/ret mice, which may impair oxygen delivery to the tissue. We also measured intravascular PO 2 and found that concentrations were higher in cortical Layer 2/3 in Pdgfb ret/ret mice, indicative of reduced blood oxygen extraction. Finally, we found that Pdgfb ret/ret mice had a reduced capacity for vasodilation in response to an acetazolamide challenge during functional MRI imaging. Taken together, these results suggest that severe pericyte deficiency can lead to vascular abnormalities and altered cerebral blood flow, reminiscent of pathologies such as arteriovenous malformations.