CCL17 exerts neuroprotection through activation of CCR4/mTORC2 axis in microglia after subarachnoid haemorrhage in rats

作     者：Anke Zhang Yibo Liu Houshi Xu Zeyu Zhang Xiaoyu Wang Ling Yuan Cameron Lenahan Chuan Zhang Junkun Jiang Chaoyou Fang Yuanjian Fang Jianmin Zhang Sheng Chen 

作者机构：Department of NeurosurgeryZhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina Clinical Research Center for Neurological Diseases of Zhejiang ProvinceHangzhouZhejiangChina Department of NeurosurgeryShanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Biomedical SciencesBurrell College of Osteopathic MedicineLas CrucesNew MexicoUSA Department of BiologyTongji UniversityShanghaiChina 

出 版 物：《Stroke & Vascular Neurology》 (卒中与血管神经病学（英文）)

年 卷 期：2023年第8卷第1期

页      面：4-16页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：the National Natural Science Foundation of China(81870916 and 81971107) the Fundamental Research Funds for the Central Universities,China(2019QNA7038) 

主　　题：CCL17 CCR4 mTORC2 

摘      要：Background and purpose C-C motif chemokine ligand 17(CCL17)presents an important role in immune regulation,which is critical in the pathophysiology of brain injury after subarachnoid haemorrhage(SAH).There is rare evidence to illustrate the function of CCL17 towards *** this study,we try to reveal the therapeutic effects of CCL17 and its underlying mechanism in rat SAH *** SAH rat models were assigned to receive recombinant CCL17(rCCL17)or phosphate buffer saline(PBS).AZD2098 and JR-AB2-011 were applied to investigate the C-C motif chemokine receptor 4(CCR4)/mammalian target of rapamycin complex 2(mTORC2)axis in CCL17-mediated *** elucidate the underlying mechanism,the in vitro kinase assay was performed in primary ***-specific Rictor knockdown was administered via intracerebroventricular injection of adenovirus-associated *** water content,short-term neurobehavioural evaluation,western blot analysis,quantitative RT-PCR and histological staining were *** The expression of CCL17 was increased and secreted from neurons after oxyhaemoglobin *** rCCL17 significantly alleviated neuronal apoptosis,and alleviated short-term neurofunction after SAH in *** addition,rCCL17 increased M2-like polarisation of microglia in rats post-SAH and in primary microglia *** neuroprotection of rCCL17 was abolished via inhibition of either CCR4 or *** CCL17 activated the CCR4/mTORC2 axis in microglia,which can alleviate SAH-induced neurological deficits by promoting M2-like polarisation of microglia.