GABAB Receptor Activation Attenuates Neuronal Pyroptosis in Post-cardiac Arrest Brain Injury

被引:4
|
作者
Sun, Ye [1 ]
Li, Jinying [1 ]
Wu, Haikuo [1 ]
Zhao, Ziwei [2 ]
Cong, Ting [1 ]
Li, Liya [1 ]
Zhang, Xiaonan [2 ]
Yin, Shengming [2 ]
Xiao, Zhaoyang [1 ]
机构
[1] Dalian Med Univ, Dept Anesthesiol, Affiliated Hosp 2, Dalian 116027, Peoples R China
[2] Dalian Med Univ, Dept Physiol, Basic Med Coll, Dalian 116044, Peoples R China
基金
中国国家自然科学基金;
关键词
Key words; cardiac arrest; neuronal pyroptosis; caspase-11; SURVIVAL; STROKE;
D O I
10.1016/j.neuroscience.2023.06.001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
injury is a major cause of death and disability after cardiac arrest (CA). Previous studies have shown that activating GABAB receptors significantly improves neurological function after CA, but the mechanism of this neuronal protection of damaged neurons remains unclear. Thus, the present study aimed to investigate whether GABAB receptor activation protects against neuronal injury and to reveal the underlying protective mechanisms. In this study, rats underwent 10 min of asphyxia to induce CA, and SH-SY5Y cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to establish in vivo and in vitro models of hypoxic neuronal injury. Differential gene expression between CA rats and sham-operated rats was identified using RNA-seq. TUNEL and Nissl staining were used to evaluate cortical neuron damage, while Western blotting, qRT-PCR, and immunofluorescence assays were conducted to measure pyroptosis-related indicators. Furthermore, cellular models with high expression of caspase-11 were established to reveal the novel molecular mechanisms by which GABAB receptor activation exerts neuroprotective effects. Intriguingly, our results showed that caspase-11 and GSDMD were highly expressed in rats experiencing cardiac arrest. Specifically, GSDMD was expressed in neurons in the M1 area of the cerebral cortex. Moreover, activation of the GABAB receptor exerted a protective effect on neurons both in vivo and in vitro. Baclofen attenuated caspase-11 activation and neuronal pyroptosis after CA, and the anti-neuronal pyroptosis effect of baclofen was abolished by overexpression of caspase-11 in neuronal cells. In conclusion, GABAB receptor activation may play a neuroprotective role by alleviating neuronal pyroptosis through a mechanism involving caspase-11.& COPY; 2023 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:97 / 106
页数:10
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