Multi-time point metabolomics reveals key metabolic features from the ultra-early stage of intracerebral hemorrhage in mice

作者全名："Xiao, Zhongsong; Li, Peizheng; Shen, Yiqing; Manaenko, Anatol; Yang, Wensong; Wang, Peng; Li, Xinhui; Liu, Fangyu; Xie, Peng; Li, Qi"

作者地址："[Xiao, Zhongsong; Li, Peizheng; Shen, Yiqing; Manaenko, Anatol; Yang, Wensong; Wang, Peng; Li, Xinhui; Liu, Fangyu; Xie, Peng; Li, Qi] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing 400016, Peoples R China; [Xiao, Zhongsong; Li, Peizheng; Shen, Yiqing; Manaenko, Anatol; Yang, Wensong; Wang, Peng; Li, Xinhui; Liu, Fangyu; Xie, Peng; Li, Qi] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China"

通信作者："Xie, P; Li, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing 400016, Peoples R China."

来源：EXPERIMENTAL NEUROLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001072568200001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：368

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：ICH; Metabolomic; Purine metabolism; Cysteine; Glutathione; ABC transporter; Synaptic function

摘要："Despite decades of intensive research, there are still very limited options for the effective treatment of intracerebral hemorrhage (ICH). Recently, mounting evidence has indicated that the ultra-early stage (<3 h), serving as the primary phase of ICH, plays a pivotal role and may even surpass other stages in terms of its significance. Therefore, uncovering the metabolic alterations induced by ICH in the ultra-early stage is of crucial importance. To investigate this, the collagenase ICH mouse model was employed in this study. ICH or sham-operated mice were euthanized at the ultra-early stage of 3 h and the acute stage of 24 h and 72 h after the operation. Then, the metabolic changes in the perihematomal tissues were detected by liquid chromatography coupled with tandem mass spectrometry. In total, alterations in the levels of 465 metabolites were detected. A total of 136 metabolites were significantly changed at 3 h. At 24 h and 72 h, the amounts were 132 and 126, respectively. Additionally, the key corresponding metabolic pathways for these time points were analyzed through KEGG. To gather additional information, quantitative real-time transcription polymerase chain reaction, enzyme-linked immunosorbent assay and Western blots were performed to validate the metabolic changes. Overall, ICH significantly alters important physiological functions such as cysteine metabolism, purine metabolism, synaptic alterations, the synaptic vesicle cycle, and the ATP-binding cassette transporter system. These might be the key pathologic mechanisms of the ultra-early stage induced by ICH."

基金机构："National Key Research and Development Program of China [2018YFC1312200, 2018YFC1312203]; National Natural Science Foundation of China [82071337, 81820108015]; Chongqing High-end Young Investigator Project [2019GDRC005]; Science and Technology Innovation Project of ""Chengdu-Chongqing Economic Circle"" [KJCXZD2020019]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320002]; Chongqing Innovation Support Program for Returned Overseas Chinese Scholars [cx2020002]; Chongqing Science Fund for Distinguished Young Scholars [cstc2021jcyj-jqX0029]"

基金资助正文："This study was supported by the National Key Research and Development Program of China (grant Nos. 2018YFC1312200, and 2018YFC1312203) , the National Natural Science Foundation of China (grant Nos. 82071337 and 81820108015) , the Chongqing High-end Young Investigator Project (grant No. 2019GDRC005) , the Science and Technology Innovation Project of ""Chengdu-Chongqing Economic Circle"" (grant No. KJCXZD2020019) , The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (grant No. 2019PT320002) , the Chongqing Innovation Support Program for Returned Overseas Chinese Scholars (grant No. cx2020002) , and the Chongqing Science Fund for Distinguished Young Scholars (grant No. cstc2021jcyj-jqX0029) ."