The Endothelin ETB Receptor Antagonist BQ788 Protects against Brain Edema after Fluid Percussion Injury by Decreasing Vascular Endothelial Growth Factor-A Expression in Mice.
Yakugaku Zasshi
; 137(10): 1241-1246, 2017.
Article
em Ja
| MEDLINE
| ID: mdl-28966265
ABSTRACT
Brain edema is a severe morbid complication of brain injury, characterized by excessive fluid accumulation and an elevation of intracranial pressure. However, effective anti-brain edema drugs are lacking. One of the causes of brain edema is disruption of blood-brain barrier (BBB) function, which results in extravasation of intravascular fluid. After brain damage, astrocytes are activated, and astrocyte-derived vascular endothelial growth factor-A (VEGF-A) is known to induce BBB dysfunction. Therefore maintaining BBB integrity by regulating astrocyte function is a potentially effective strategy for treating brain edema. In this review, we focus on the endothelin ETB receptor and its role in regulation of astrocyte functions. In mice, brain damage was induced by fluid percussion injury (FPI), and the resulting BBB disruption and brain edema were observed in the mouse cerebrum. BQ788, a selective ETB receptor antagonist, attenuated the FPI-induced BBB disruption and brain edema. Levels of brain VEGF-A increased after FPI, mainly in reactive astrocytes. BQ788 suppressed the FPI-induced increase in VEGF-A expression in reactive astrocytes. Moreover, intraventricular administration of VEGF neutralizing antibody also attenuated FPI-induced BBB disruption and brain edema. Claudin-5 is an endothelial tight junction protein essential for normal BBB structure and function. Levels of claudin-5 protein were reduced by FPI. Furthermore, VEGF neutralizing antibody blocked FPI-induced decrease in claudin-5. These results suggest that the ETB receptor antagonist BQ788 protects against brain edema by inhibiting VEGF-A-mediated decrease in claudin-5.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Piperidinas
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Edema Encefálico
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Astrócitos
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Fator A de Crescimento do Endotélio Vascular
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Receptor de Endotelina B
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Antagonistas do Receptor de Endotelina B
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
Ja
Ano de publicação:
2017
Tipo de documento:
Article