Open AccessKir6.1 Knockdown Aggravates Cerebral Ischemia/Reperfusion‐Induced Neural Injury in Mice
Author(s) -
Dong YinFeng,
Wang LinXiao,
Huang Xu,
Cao WenJing,
Lu Ming,
Ding JianHua,
Sun XiuLan,
Hu Gang
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12117
Subject(s) - gene knockdown , medicine , proinflammatory cytokine , ischemia , potassium channel , reperfusion injury , stroke (engine) , endoplasmic reticulum , unfolded protein response , endocrinology , cardiology , neuroscience , inflammation , microbiology and biotechnology , chemistry , biology , apoptosis , biochemistry , mechanical engineering , engineering
Summary Background and Purpose ATP ‐sensitive potassium (K‐ ATP ) channels couple energy metabolism with electric activity, which play important roles in brain diseases including stroke. However, the impacts of Kir6.1‐containing K‐ ATP channels that mainly expressed on glia in stroke remain unclear. Methods and Results In this study, we found that expression of Kir6.1 was significantly decreased in the ischemic brain area of C57 BL /6J mice after 1‐h middle cerebral artery occlusion ( MCAO ) and 24‐h reperfusion. Then, we subjected Kir6.1 heterozygote knockout (Kir6.1 +/− ) mice to cerebral ischemia/reperfusion (I/R) injury and found that Kir6.1 +/− mice exhibited exacerbated neurological disorder and enlarged infarct size, companied by glial over‐activation and blood–brain barrier ( BBB ) damages. Furthermore, we showed that Kir6.1 knockdown aggravated endoplasmic reticulum ( ER ) stress and thereby increased the levels of proinflammatory factors tumor necrosis factor‐α and interleukin‐1β ( TNF ‐α and IL ‐1β) in mouse brain. Conclusions Our findings reveal that Kir6.1 knockdown exacerbates cerebral I/R‐induced brain damages via increasing ER stress and inflammatory response, indicating that Kir6.1‐containing K‐ ATP channels may be a potential therapeutic target for stroke.