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Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury

Alterations in the expression of the vascular endothelial growth factors (VEGF) A and B occur during blood–brain barrier (BBB) breakdown and angiogenesis following brain injury. In this study, the temporal and spatial expression of VEGF-D and VEGF receptors-2 and -3 (VEGFR-2 and VEGFR-3, respectivel...

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Autores principales: Nag, Sukriti, Manias, Janet, Eubanks, James H., Stewart, Duncan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479775/
https://www.ncbi.nlm.nih.gov/pubmed/30935023
http://dx.doi.org/10.3390/ijms20071594
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author Nag, Sukriti
Manias, Janet
Eubanks, James H.
Stewart, Duncan J.
author_facet Nag, Sukriti
Manias, Janet
Eubanks, James H.
Stewart, Duncan J.
author_sort Nag, Sukriti
collection PubMed
description Alterations in the expression of the vascular endothelial growth factors (VEGF) A and B occur during blood–brain barrier (BBB) breakdown and angiogenesis following brain injury. In this study, the temporal and spatial expression of VEGF-D and VEGF receptors-2 and -3 (VEGFR-2 and VEGFR-3, respectively) was determined at the mRNA and protein level in the rat cortical cold-injury model over a period of 0.5 to 6 days post-injury. In order to relate endothelial VEGF-D protein expression with BBB breakdown, dual labeling immunofluorescence was performed using antibodies to VEGF-D and to fibronectin, a marker of BBB breakdown. In control rats, VEGF-D signal was only observed in scattered perivascular macrophages in the cerebral cortex. The upregulation of VEGF-D mRNA expression was observed in the injury site between days 0.5 to 4, coinciding with the period of BBB breakdown and angiogenesis. At the protein level, intracerebral vessels with BBB breakdown to fibronectin in the lesion on days 0.5 to 4 failed to show endothelial VEGF-D. Between days 0.5 to 6, an increased VEGF-D immunoreactivity was noted in the endothelium of pial vessels overlying the lesion site, in neutrophils, macrophages, and free endothelial cells within the lesion. The upregulation of VEGFR-2 and -3 mRNA and protein expression was observed early post-injury on day 0.5. Although there was concurrent expression of VEGF-A, VEGF-B, and VEGF-D post-injury, differences in their spatial expression during BBB breakdown and angiogenesis suggest that they have specific and separate roles in these processes.
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spelling pubmed-64797752019-04-29 Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury Nag, Sukriti Manias, Janet Eubanks, James H. Stewart, Duncan J. Int J Mol Sci Article Alterations in the expression of the vascular endothelial growth factors (VEGF) A and B occur during blood–brain barrier (BBB) breakdown and angiogenesis following brain injury. In this study, the temporal and spatial expression of VEGF-D and VEGF receptors-2 and -3 (VEGFR-2 and VEGFR-3, respectively) was determined at the mRNA and protein level in the rat cortical cold-injury model over a period of 0.5 to 6 days post-injury. In order to relate endothelial VEGF-D protein expression with BBB breakdown, dual labeling immunofluorescence was performed using antibodies to VEGF-D and to fibronectin, a marker of BBB breakdown. In control rats, VEGF-D signal was only observed in scattered perivascular macrophages in the cerebral cortex. The upregulation of VEGF-D mRNA expression was observed in the injury site between days 0.5 to 4, coinciding with the period of BBB breakdown and angiogenesis. At the protein level, intracerebral vessels with BBB breakdown to fibronectin in the lesion on days 0.5 to 4 failed to show endothelial VEGF-D. Between days 0.5 to 6, an increased VEGF-D immunoreactivity was noted in the endothelium of pial vessels overlying the lesion site, in neutrophils, macrophages, and free endothelial cells within the lesion. The upregulation of VEGFR-2 and -3 mRNA and protein expression was observed early post-injury on day 0.5. Although there was concurrent expression of VEGF-A, VEGF-B, and VEGF-D post-injury, differences in their spatial expression during BBB breakdown and angiogenesis suggest that they have specific and separate roles in these processes. MDPI 2019-03-30 /pmc/articles/PMC6479775/ /pubmed/30935023 http://dx.doi.org/10.3390/ijms20071594 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nag, Sukriti
Manias, Janet
Eubanks, James H.
Stewart, Duncan J.
Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury
title Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury
title_full Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury
title_fullStr Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury
title_full_unstemmed Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury
title_short Increased Expression of Vascular Endothelial Growth Factor-D Following Brain Injury
title_sort increased expression of vascular endothelial growth factor-d following brain injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479775/
https://www.ncbi.nlm.nih.gov/pubmed/30935023
http://dx.doi.org/10.3390/ijms20071594
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