TY - JOUR
T1 - Role of P2X purinoceptor 7 in neurogenic pulmonary edema after subarachnoid hemorrhage in rats
AU - Chen, Sheng
AU - Zhu, Zhigang
AU - Klebe, Damon
AU - Bian, Hetao
AU - Krafft, Paul R.
AU - Tang, Jiping
AU - Zhang, Jianmin
AU - Zhang, John H.
N1 - PLoS One. 2014 Feb 12;9(2):e89042. doi: 10.1371/journal.pone.0089042. eCollection 2014. Research Support, N.I.H., Extramural
PY - 2014/2/12
Y1 - 2014/2/12
N2 - 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.
AB - 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.
KW - Subarachnoid Hemorrhage/complications
KW - Body Weight/drug effects
KW - Animals
KW - Neurologic Examination
KW - Receptors, Purinergic P2X7/metabolism
KW - Rats
KW - Rosaniline Dyes/pharmacology
KW - Lung/drug effects
KW - Purinergic P2X Receptor Antagonists/pharmacology
KW - Rats, Sprague-Dawley
KW - Pulmonary Edema/complications
UR - http://www.scopus.com/inward/record.url?scp=84895726277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895726277&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/85e5208a-c264-36ab-91b7-45059db0e63a/
U2 - 10.1371/journal.pone.0089042
DO - 10.1371/journal.pone.0089042
M3 - Article
C2 - 24533168
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e89042
ER -