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

Sheng Chen, Zhigang Zhu, Damon Klebe, Hetao Bian, Paul R. Krafft, Jiping Tang, Jianmin Zhang, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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 postsurgery. 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. © 2014 Chen et al.
Original languageEnglish
Article numbere89042
JournalPLoS ONE
Volume9
Issue number2
DOIs
StatePublished - Feb 12 2014

ASJC Scopus Subject Areas

  • General

Keywords

  • Subarachnoid Hemorrhage/complications
  • Body Weight/drug effects
  • Animals
  • Neurologic Examination
  • Receptors, Purinergic P2X7/metabolism
  • Rats
  • Rosaniline Dyes/pharmacology
  • Lung/drug effects
  • Purinergic P2X Receptor Antagonists/pharmacology
  • Rats, Sprague-Dawley
  • Pulmonary Edema/complications

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