Abstract
IntroductionNeurogenic 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.MethodsSAH 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.ResultsThe 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.ConclusionP2X7R inhibition prevented NPE after SAH by attenuating inflammation. Thus, BBG is a potential therapeutic application for NPE after SAH and warrants further research.
Highlights
Neurogenic pulmonary edema (NPE) is an acute and serious complication after subarachnoid hemorrhage (SAH) with high mortality
Observed SAH grading score were similar between the SAH+vehicle group and SAH+brilliant blue G (BBG) group (Fig. 2B)
Post-SAH administration of BBG significantly improved neurobehavioral deficits compared to vehicle animals at 24 hours after SAH (p,0.05 vs. SAH+vehicle group) (Fig. 2D)
Summary
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. Reducing pulmonary inflammation after experimental SAH was effective in preventing acute SAH-mediated lung injury [9], effective NPE management strategies have not been established. Brilliant Blue G (BBG) is a selective noncompetitive antagonist of the P2X7R, which has been described in SAH, ischemia, and traumatic brain injury with therapeutic effect [17,18,19]. We hypothesize that the P2X7R inhibition by BBG will attenuate lung inflammation, prevent lung-blood barrier disruption, and be a potential therapy for NPE after SAH
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