Hyperosmotic stimulus induces reversible angiogenesis within the hypothalamic magnocellular nuclei of the adult rat: a potential role for neuronal vascular endothelial growth factorReport as inadecuate




Hyperosmotic stimulus induces reversible angiogenesis within the hypothalamic magnocellular nuclei of the adult rat: a potential role for neuronal vascular endothelial growth factor - Download this document for free, or read online. Document in PDF available to download.

BMC Neuroscience

, 6:20

First Online: 24 March 2005Received: 18 January 2005Accepted: 24 March 2005

Abstract

BackgroundIn mammals, the CNS vasculature is established during the postnatal period via active angiogenesis, providing different brain regions with capillary networks of various densities that locally supply adapted metabolic support to neurons. Thereafter this vasculature remains essentially quiescent excepted for specific pathologies. In the adult rat hypothalamus, a particularly dense network of capillary vessels is associated with the supraoptic SON and paraventricular PVN nuclei containing the magnocellular neurons secreting vasopressin and oxytocin, two neurohormones involved in the control of the body fluid homoeostasis. In the seventies, it was reported that proliferation of astrocytes and endothelial cells occurs within these hypothalamic nuclei when strong metabolic activation of the vasopressinergic and oxytocinergic neurons was induced by prolonged hyperosmotic stimulation. The aim of the present study was to determine whether such proliferative response to osmotic stimulus is related to local angiogenesis and to elucidate the cellular and molecular mechanisms involved.

ResultsOur results provide evidence that cell proliferation occurring within the SON of osmotically stimulated adult rats corresponds to local angiogenesis. We show that 1 a large majority of the SON proliferative cells is associated with capillary vessels, 2 this proliferative response correlates with a progressive increase in density of the capillary network within the nucleus, and 3 SON capillary vessels exhibit an increased expression of nestin and vimentin, two markers of newly formed vessels. Contrasting with most adult CNS neurons, hypothalamic magnocellular neurons were found to express vascular endothelial growth factor VEGF, a potent angiogenic factor whose production was increased by osmotic stimulus. When VEGF was inhibited by dexamethasone treatment or by the local application of a blocking antibody, the angiogenic response was strongly inhibited within the hypothalamic magnocellular nuclei of hyperosmotically stimulated rats.

ConclusionThis study shows that the functional stimulation of hypothalamic magnocellular neurons of adult rats induces reversible angiogenesis via the local secretion of neuronal VEGF. Since many diseases are driven by unregulated angiogenesis, the hypothalamic magnocellular nuclei should provide an interesting model to study the cellular and molecular mechanisms involved in the regulation of angiogenesis processes within the adult CNS.

List of abbreviations usedANaccessory magnocellular nuclei

BrdUbromodeoxyuridine

CNScentral nervous system

EBAendothelial brain antigen

GFAPglial fibrillary protein

IgGimmunoglobulin type G

IsoB4isolectin B4

NeuNneuronal nuclear antigen

NG2NG2 chondroitin sulfate proteoglycan

OCoptic chiasma

OToxytocin

PVNparaventricular nucleus

SONsupraoptic nucleus

VPvasopressin

VEGFvascular endothelial growth factor

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-6-20 contains supplementary material, which is available to authorized users.

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Author: Gérard Alonso - Evelyne Galibert - Anne Duvoid-Guillou - Anne Vincent

Source: https://link.springer.com/







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