Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.

INTRODUCTION: Neurogenic pulmonary edema (NPE) is an acute and serious complication after subarachnoid hemorrhage (SAH) with high mortality. The present study aimed to test the therapeutic potential of brilliant blue G (BBG), a selective P2X purinoceptor 7 (P2X7R) antagonist, on NPE in a rat SAH mod...

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Main Authors: Sheng Chen, Zhigang Zhu, Damon Klebe, Hetao Bian, Paul R Krafft, Jiping Tang, Jianmin Zhang, John H Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3923073?pdf=render
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author Sheng Chen
Zhigang Zhu
Damon Klebe
Hetao Bian
Paul R Krafft
Jiping Tang
Jianmin Zhang
John H Zhang
author_facet Sheng Chen
Zhigang Zhu
Damon Klebe
Hetao Bian
Paul R Krafft
Jiping Tang
Jianmin Zhang
John H Zhang
author_sort Sheng Chen
collection DOAJ
description INTRODUCTION: Neurogenic pulmonary edema (NPE) is an acute and serious complication after subarachnoid hemorrhage (SAH) with high mortality. The present study aimed to test the therapeutic potential of brilliant blue G (BBG), a selective P2X purinoceptor 7 (P2X7R) antagonist, on NPE in a rat SAH model. METHODS: SAH was induced by endovascular perforation. 86 Sprague-Dawley rats were randomly divided into sham, vehicle-, or BBG-treatment groups. Mortality, body weight, SAH grading, neurological deficits, NPE clinical symptoms, and pulmonary index were measured at 24 hours following SAH. Western blot, gelatin zymography, lung histopathology, and immunofluorescence staining were performed in the left lung lobe to explore the underlying mechanisms at 24 hours post-surgery. RESULTS: The incidence of clinical symptoms was correlated with pulmonary index. P2X7R and the marker of alveolar type I epithelial cells (the mucin-type glycoprotein T1-α) immunoreactivities were generally co-localized. BBG administration decreased mature interleukin-1β, myeloperoxidase, and matrix metallopeptidase-9 activation, but increased tight junction proteins, such as ZO-1 and occludin, which ameliorated pulmonary edema via anti-inflammation and improved neurological deficits. CONCLUSION: P2X7R inhibition prevented NPE after SAH by attenuating inflammation. Thus, BBG is a potential therapeutic application for NPE after SAH and warrants further research.
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spelling doaj.art-dc5fb9120c124239a9d422ae83ad10a02022-12-21T19:56:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8904210.1371/journal.pone.0089042Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.Sheng ChenZhigang ZhuDamon KlebeHetao BianPaul R KrafftJiping TangJianmin ZhangJohn H ZhangINTRODUCTION: Neurogenic pulmonary edema (NPE) is an acute and serious complication after subarachnoid hemorrhage (SAH) with high mortality. The present study aimed to test the therapeutic potential of brilliant blue G (BBG), a selective P2X purinoceptor 7 (P2X7R) antagonist, on NPE in a rat SAH model. METHODS: SAH was induced by endovascular perforation. 86 Sprague-Dawley rats were randomly divided into sham, vehicle-, or BBG-treatment groups. Mortality, body weight, SAH grading, neurological deficits, NPE clinical symptoms, and pulmonary index were measured at 24 hours following SAH. Western blot, gelatin zymography, lung histopathology, and immunofluorescence staining were performed in the left lung lobe to explore the underlying mechanisms at 24 hours post-surgery. RESULTS: The incidence of clinical symptoms was correlated with pulmonary index. P2X7R and the marker of alveolar type I epithelial cells (the mucin-type glycoprotein T1-α) immunoreactivities were generally co-localized. BBG administration decreased mature interleukin-1β, myeloperoxidase, and matrix metallopeptidase-9 activation, but increased tight junction proteins, such as ZO-1 and occludin, which ameliorated pulmonary edema via anti-inflammation and improved neurological deficits. CONCLUSION: P2X7R inhibition prevented NPE after SAH by attenuating inflammation. Thus, BBG is a potential therapeutic application for NPE after SAH and warrants further research.http://europepmc.org/articles/PMC3923073?pdf=render
spellingShingle Sheng Chen
Zhigang Zhu
Damon Klebe
Hetao Bian
Paul R Krafft
Jiping Tang
Jianmin Zhang
John H Zhang
Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.
PLoS ONE
title Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.
title_full Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.
title_fullStr Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.
title_full_unstemmed Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.
title_short Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.
title_sort role of p2x purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats
url http://europepmc.org/articles/PMC3923073?pdf=render
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