Characterization of Angiogenesis and Microcirculation of High-Grade Glioma: An Intravital Multifluorescence Microscopic Approach in the Athymic Nude Mouse

The current study follows angiogenesis and microcirculatory changes associated with malignant glioma growth by means of an intravital fluorescence microscopic approach, which allows for the direct and continuous visualization of the glioma microvasculature and its quantitative analysis. Fluorescentl...

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Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 1998-05, Vol.18 (5), p.510-520
Main Authors: Vajkoczy, Peter, Schilling, Lothar, Ullrich, Axel, Schmiedek, Peter, Menger, Michael D.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Capillary Permeability
Disease Models, Animal
Glioma - blood supply
Glioma - pathology
Medical sciences
Mice
Mice, Nude
Microcirculation
Microscopy, Fluorescence
Neoplasms, Experimental - blood supply
Neoplasms, Experimental - pathology
Neovascularization, Pathologic
Neurology
Rats
Tumors of the nervous system. Phacomatoses
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Summary:The current study follows angiogenesis and microcirculatory changes associated with malignant glioma growth by means of an intravital fluorescence microscopic approach, which allows for the direct and continuous visualization of the glioma microvasculature and its quantitative analysis. Fluorescently labeled C6 rat glioma cells (5 × 105) were implanted into dorsal skinfold chamber preparations of athymic nude mice. Glioma growth, vascularization, microhemodynamics, vascular permeability, and leukocyte–endothelial cell interactions were simultaneously followed over a 22-day observation period using intravital epiillumination microscopy and a multifluorescent labeling technique. Analysis of the process of glioma vascularization revealed three stages with distinct microvascular characteristics: avascular stage (days 0 to 6), lag of glioma growth but initial glioma-induced angiogenesis within the host tissue in peritumoral areas; early vascular stage (days 6 to 14), glioma cell proliferation associated with a spatially homogeneous development of a glioma microvasculature; and late vascular stage (days 14 to 22), exponential tumor growth and expansion (> 400 mm3) with high vascular densities in the peritumoral region and reduced vascularization (microvascular perfusion) in the glioma center. Within the center, the functional vessel length per area correlated inversely with glioma size (P
ISSN:0271-678X
1559-7016
DOI:10.1097/00004647-199805000-00006