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Glial vascular endothelial growth factor overexpression in rat brainstem under tolerable hypoxia: Evidence for a central chemosensitivity
Author(s) -
Perrin J.S.,
Araneda S.,
Catteau J.,
Autran S.,
DenavitSaubié M.,
Pequignot J.M.
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21837
Subject(s) - hypoxia (environmental) , brainstem , colocalization , vascular endothelial growth factor , biology , immunolabeling , glial fibrillary acidic protein , angiogenesis , astrocyte , vascular endothelial growth factor a , hypoxia inducible factors , endocrinology , microbiology and biotechnology , medicine , chemistry , immunohistochemistry , central nervous system , immunology , neuroscience , cancer research , vegf receptors , gene , biochemistry , organic chemistry , oxygen
The ventilatory response to hypoxia is mediated by peripheral inputs arising from the arterial chemoreceptors. In their absence, hypoxic adaptation can be achieved, possibly as a result of central cellular reorganization. To study this reorganization, we used chemodenervated rats to investigate the expression and localization of vascular endothelial growth factor (VEGF) in the brainstem. VEGF is a target gene of hypoxia‐inducible factor (HIF) that is responsible for the morphofunctional remodeling induced by hypoxia. Intact and chemodenervated rats were subjected to normoxia or hypoxia for 6 hr (10% O 2 in N 2 ). VEGF protein was quantified in micropunches of brainstem tissue. Only chemodenervated animals showed an increased VEGF expression in response to hypoxia, whereas, in normoxia, VEGF expression was not modified by chemodenervation. The same hypoxic condition was repeated for 8 days before immunocytochemical staining with anti‐VEGF; antiglial fibrillary acidic protein (GFAP), a marker of astrocytes; and anti‐rat endothelial cell antigen‐1 (anti‐RECA‐1) that recognizes endothelial cells. Confocal analysis showed a cellular colocalization of GFAP and VEGF, indicating that VEGF was overexpressed predominantly in astrocytes. Increased RECA‐1 immunolabeling indicated an enhanced angiogenesis in chemodenervated rats subjected to hypoxia. These results indicate that glial cells and the vascular network contribute to the brainstem remodeling. The peripheral chemodenervation reveals a central O 2 chemosensitivity involving a cascade of gene expression triggered by hypoxia, which in intact animals may act synergically with peripheral chemosensory inputs. © 2008 Wiley‐Liss, Inc.