Obstructive sleep apnea aggravates neuroinflammation and pyroptosis in early brain injury following subarachnoid hemorrhage via ASC/HIF-1α pathway  

作　　者：Jun Xu Qian Li Chen-Yu Xu Shan Mao Jia-Jia Jin Wei Gu Ying Shi Chun-Fang Zou Liang Ye 

机构地区：[1]Department of Respiration,Nanjing First Hospital,Nanjing Medical University,Nanjing,Jiangsu Province,China [2]Department of Respiration,Nanjing Yuhua Hospital,Yuhua Branch of Nanjing First Hospital,Nanjing,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2022年第11期2537-2543,共7页中国神经再生研究（英文版）

基　　金：the Natural Science Foundation of Jiangsu Province(Youth Program),No.BK20190129;National Scientific Program of Jiangsu Colleges and Universities of China,No.19KJB320012(both to LY)。

摘　　要：Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea.We found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid hemorrhage.Then,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 hours.We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.We also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 cells.These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.

关 键 词：apoptosis associated speck like protein containing a CARD early brain injury hypoxia-inducible factor 1α nucleotide-binding domain and leucine-rich repeat protein 3 obstructive sleep apnea PYROPTOSIS NEUROINFLAMMATION subarachnoid hemorrhage 

分 类 号：R766[医药卫生—耳鼻咽喉科] R743.35[医药卫生—临床医学]