Publication: Microvascular adaptive changes in experimental endogenous brain gliomas
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Date
2009
Authors
Bulnes, Susana ; Bilbao, Juan ; Lafuente, José Vicente
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Glioma growth depends on microvascular
adaptation and angiogenesis. Our study focused on the
structural changes that occur in the microvasculature to
adapt to glioma growth.
Vascular morphology, morphometry and
permeability studies were performed in induced rat
gliomas. Tumours were identified by magnetic
resonance imaging and histopathology. Blood brain
barrier integrity was examined by EBA and GluT-1
immunostaining and correlated with vascular
permeability for gadolinium and intravital dyes.
VEGF165 immunoexpression was also analyzed.
Tumours were grouped in microtumours (6.69±0.99
mm3) displaying a homogeneous T2-w hyperintense
signal corresponding to low-grade gliomas, and
macrotumours (900.79±332.39 mm3) showing
gadolinium contrast enhancement, intravital dye
extravasation and histopathological features of highgrade
gliomas.
Results show that the microvascular network
becomes aberrant as we move from micro to
macrotumours. Vessel density decreases, whereas the
relative area occupied by the vascular network increases.
Microtumours display homogeneous angioarchitecture
composed of simple and mildly dilated vessels similar to
normal tissue. Macrotumours show different patterns,
following a gradient from the neoangiogenic border to
the hypoxic core. The tumour core contains scarce, huge,
dilated vessels with some profiles co-expressing GluT-1
and VEGF165, the peripheral tissue shows light dilated
vessels co-expressing EBA and GluT-1, and the border
area displays glomeruloid vessels strongly positive for
VEGF. Glucose uptake was maintained for some
vascular endothelial sections in areas where BBB function was lost.
In conclusion, during development of gliomas the
microvasculature becomes aberrant, undergoing a
sequence of adaptive changes which involve the
distribution and permeability of vessels. This explains
the disturbances of blood flow and the increased
permeability.
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