Quantification of 3D Brain Microangioarchitectures in an Animal Model of Krabbe Disease

Abstract

We performed a three-dimensional (3D) analysis of the microvascular network of the cerebral cortex of twitcher mice (an authentic model of Krabbe disease) using a restricted set of indexes that are able to describe the arrangement of the microvascular tree in CD31-stained sections. We obtained a near-linear graphical “fingerprint” of the microangioarchitecture of wild-type and twitcher animals that describes the amounts, spatial dispersion, and spatial relationships of adjacent classes of caliber-filtered microvessels. We observed significant alterations of the microangioarchitecture of the cerebral cortex of twitcher mice, whereas no alterations occur in renal microvessels, which is keeping with the observation that kidney is an organ that is not affected by the disease. This approach may represent an important starting point for the study of the microvascular changes that occur in the central nervous system (CNS) under different physiopathological conditions.

β-Galactosylceramidase Deficiency Causes Bone Marrow Vascular Defects in an Animal Model of Krabbe Disease

“…Previous observations from our laboratory had demonstrated that GALC deficiency induces significant endothelial alterations in the microvasculature of brain cortex and non-nervous tissues of twitcher mice, an authentic model of the disease [16][17][18][19]. In the present study, the vascular Previous observations had shown that psychosine exerts an anti-angiogenic activity on endothelial cells by hampering their cytoskeleton organization, proliferation, migration and response to growth factors [19].…”

“…At variance with what observed for the microvascular component of twitcher brain [16][17][18][19], these alterations occurred in the absence of a significant reduction of the BM vascular density. Thus, the alterations detected in GALC deficient diaphyseal microvasculature resemble, at least in part, those reported for the visceral organs of twitcher mice, including liver, kidney, and lungs, characterized by increased vascular permeability with no alterations of their vascular density [19].…”

“…Previous observations from our laboratory had demonstrated that GALC deficiency induces significant endothelial alterations in the microvasculature of brain cortex and non-nervous tissues of twitcher mice, an authentic model of the disease [16][17][18][19]. In the present study, the vascular component of the BM of homozygous twitcher mice was investigated for the first time.…”

“…The effect of GALC deficiency on CNS microvascularization and the angiogenic process has been previously investigated [16][17][18][19]. GALC deficiency, with consequent psychosine accumulation, induces ultrastructural and functional defects in the endothelium of the brain of twitcher mice.…”

3D imaging and morphometry of the heart capillary system in spontaneously hypertensive rats and normotensive controls

“…This technique enables high-resolution 3D reconstructions of the network; however, it confines the study to reduced volumes. Other approaches have exploited optical sectioning of fluorescent confocal microscopy to image brain and cardiac vascularization in rodents 9,10 , leading to 3D acquisitions of tissue sections with a micrometer resolution. Though, optical imaging is considerably limited by light scattering, a physical phenomenon that prevents light to penetrate deep into the tissue 11 .…”