Smaller Absolute Quantities but Greater Relative Densities of Microvessels Are Associated with Cerebellar Degeneration in Lurcher Mice

Abstract

Degenerative affections of nerve tissues are often accompanied by changes of vascularization. In this regard, not much is known about hereditary cerebellar degeneration. In this study, we compared the vascularity of the individual cerebellar components and the mesencephalon of 3-month-old wild type mice (n = 5) and Lurcher mutant mice, which represent a model of hereditary olivocerebellar degeneration (n = 5). Paraformaldehyde-fixed brains were processed into 18-μm thick serial sections with random orientation. Microvessels were visualized using polyclonal rabbit anti-laminin antibodies. Then, the stacks comprised of three 5-μm thick optical sections were recorded using systematic uniform random sampling. Stereological assessment was conducted based on photo-documentation. We found that each of the cerebellar components has its own features of vascularity. The greatest number and length of vessels were found in the granular layer; the number of vessels was lower in the molecular layer, and the lowest number of vessels was observed in the cerebellar nuclei corresponding with their low volume. Nevertheless, the nuclei had the greatest density of blood vessels. The reduction of cerebellum volume in the Lurcher mice was accompanied by a reduction in vascularization in the individual cerebellar components, mainly in the cortex. Moreover, despite the lower density of microvessels in the Lurcher mice compared with the wild type mice, the relative density of microvessels in the cerebellar cortex and nuclei was greater in Lurcher mice. The complete primary morphometric data, in the form of continuous variables, is included as a supplement. Mapping of the cerebellar and midbrain microvessels has explanatory potential for studies using mouse models of neurodegeneration.

Using virtual microscopy for the development of sampling strategies in quantitative histology and design‐based stereology

“…Quantitative validation of potential abnormalities in total number of microvessels in the cerebellum layers of adult mice with degeneration of Purkinje cells (Kolinko et al, 2016).…”

Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer’s Disease

“…A microvessel (capillary) was defined as a loop created between two vessel branches nodes (branch point or saddle point) of the vascular network [45,46]. Total N cap , N endp , and L cap were quantified using 60 × oil objective (CFI, Plan Apo Lambda, NA 1.4) with 1-m guard zones at the top and bottom surfaces of each section.…”

“…Average microvascular length was calculated as the ratio of total microvascular length to total number of capillaries (Total L cap / Total N cap ). Finally, the potential diffusion distance of microvessels was determined in post-processing using the approach described in [46] with the gamma function calculated from average microvascular density. The coefficient of error (CE), a measure of sampling error, was estimated according to Gundersen et al, 1999 [51] with sampling across both hemispheres continued to a high level of sampling stringency [CE Total V = 0.03; CEs Total N cap and Total L cap = 0.13].…”

Basic quantitative morphological methods applied to the central nervous system

“…Both primary visual cortex volume and the neuron number in schizophrenics were found to be lower than in controls, but cell density did not differ (Dorph‐Petersen, Pierri, Wu, Sampson, & Lewis, 2007). While vascular density increases in the cerebellum of Lurcher mice, total vascular length actually decreases (Kolinko, Cendelin, Kralickova, & Tonar, 2016). Even large increases in cell number can go hand in hand with decreases in cell density in the canary song system following androgen treatments (Yamamura, Barker, Balthazart, & Ball, 2011).…”