Brain angioarchitecture and intussusceptive microvascular growth in a murine model of Krabbe disease

Arianna Giacomini, Maximilian Ackermann, Mirella Belleri, Daniela Coltrini, Beatrice Nico, Domenico Ribatti, Moritz A. Konerding, Marco Presta, Marco Righi

Research output: Contribution to journalArticlepeer-review

Abstract

Defects of the angiogenic process occur in the brain of twitcher mouse, an authentic model of human Krabbe disease caused by genetic deficiency of lysosomal β-galactosylceramidase (GALC), leading to lethal neurological dysfunctions and accumulation of neurotoxic psychosine in the central nervous system. Here, quantitative computational analysis was used to explore the alterations of brain angioarchitecture in twitcher mice. To this aim, customized ImageJ routines were used to assess calibers, amounts, lengths and spatial dispersion of CD31+ vessels in 3D volumes from the postnatal frontal cortex of twitcher animals. The results showed a decrease in CD31 immunoreactivity in twitcher brain with a marked reduction in total vessel lengths coupled with increased vessel fragmentation. No significant changes were instead observed for the spatial dispersion of brain vessels throughout volumes or in vascular calibers. Notably, no CD31+ vessel changes were detected in twitcher kidneys in which psychosine accumulates at very low levels, thus confirming the specificity of the effect. Microvascular corrosion casting followed by scanning electron microscopy morphometry confirmed the presence of significant alterations of the functional angioarchitecture of the brain cortex of twitcher mice with reduction in microvascular density, vascular branch remodeling and intussusceptive angiogenesis. Intussusceptive microvascular growth, confirmed by histological analysis, was paralleled by alterations of the expression of intussusception-related genes in twitcher brain. Our data support the hypothesis that a marked decrease in vascular development concurs to the onset of neuropathological lesions in twitcher brain and suggest that neuroinflammation-driven intussusceptive responses may represent an attempt to compensate impaired sprouting angiogenesis.

Original languageEnglish
Pages (from-to)499-510
Number of pages12
JournalAngiogenesis
Volume18
Issue number4
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • Angioarchitecture
  • Brain
  • Computational analysis
  • Corrosion casting
  • Intussusceptive angiogenesis
  • Neurodegenerative Krabbe disease

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Clinical Biochemistry

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