%A Wu,Ling-Yun %A Ye,Zhen-Nan %A Zhou,Chen-Hui %A Wang,Chun-Xi %A Xie,Guang-Bin %A Zhang,Xiang-Sheng %A Gao,Yong-Yue %A Zhang,Zi-Huan %A Zhou,Meng-Liang %A Zhuang,Zong %A Liu,Jing-Peng %A Hang,Chun-Hua %A Shi,Ji-Xin %D 2017 %J Frontiers in Molecular Neuroscience %C %F %G English %K Subarachnoid Hemorrhage,Pannexin-1,TLR,NFkB,early brain injury %Q %R 10.3389/fnmol.2017.00175 %W %L %M %P %7 %8 2017-June-06 %9 Original Research %+ Chun-Hua Hang,Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University,Nanjing, China,hang_neurosurgery@163.com %+ Chun-Hua Hang,Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University,Nanjing, China,hang_neurosurgery@163.com %+ Ji-Xin Shi,Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University,Nanjing, China,hang_neurosurgery@163.com %# %! Roles of Pannexin-1 channels in inflammatory response following subarachnoid hemorrhage %* %< %T Roles of Pannexin-1 Channels in Inflammatory Response through the TLRs/NF-Kappa B Signaling Pathway Following Experimental Subarachnoid Hemorrhage in Rats %U https://www.frontiersin.org/articles/10.3389/fnmol.2017.00175 %V 10 %0 JOURNAL ARTICLE %@ 1662-5099 %X Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet.Methods: Adult male Sprague-Dawley rats were divided into six groups: sham group (n = 20), SAH group (n = 20), SAH + LV-Scramble-ShRNA group (n = 20), SAH + LV-ShRNA-Panx1 group (n = 20), SAH + LV-NC group (n = 20), and SAH + LV-Panx1-EGFP group (n = 20). The rat SAH model was induced by injection of 0.3 ml fresh arterial, non-heparinized blood into the prechiasmatic cistern in 20 s. In SAH + LV-ShRNA-Panx1 group and SAH + LV-Panx1-EGFP group, lentivirus was administered via intracerebroventricular injection (i.c.v.) at 72 h before the induction of SAH. The Quantitative real-time polymerase chain reaction, electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting were performed to explore the potential interactive mechanism between Pannexin-1 channels and TLR2/TLR4/NF-κB-mediated signaling pathway. Cognitive and memory changes were investigated by the Morris water maze test.Results: Administration with LV-ShRNA-Panx1 markedly decreased the expression levels of TLR2/4/NF-κB pathway-related agents in the brain cortex and significantly ameliorated neurological cognitive and memory deficits in this SAH model. On the contrary, administration of LV-Panx1-EGFP elevated the expressions of TLR2/4/NF-κB pathway-related agents, which correlated with augmented neuronal apoptosis.Conclusion: Pannexin-1 channels may contribute to inflammatory response and neurobehavioral dysfunction through the TLR2/TLR4/NF-κB-mediated pathway signaling after SAH, suggesting a potential role of Pannexin-1 channels could be a potential therapeutic target for the treatment of SAH.