title: Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  P2X7R inhibition prevented NPE after SAH by attenuating inflammation. Thus, BBG is a potential therapeutic application for NPE after SAH and warrants further research.
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China ; Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Damon
authors.initials: D
authors.lastname: Klebe
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Hetao
authors.initials: H
authors.lastname: Bian
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Krafft
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009460:Neurologic Examination; D011654:Pulmonary Edema / Q000150:complications* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D012394:Rosaniline Dyes / Q000494:pharmacology / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000150:complications*
chemical_list: D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes; C004692:coomassie Brilliant Blue