机构：[1]Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland[2]Key Laboratory of Ministry of Education of China for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China[3]Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia[4]School of Chemistry and Bio21 Institute for Molecular Science and Biotechnology, The University of Melbourne, Parkville, Victoria, Australia[5]Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia[6]School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia[7]Present address: QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia[8]Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Locked Bag 2000, Herston, QLD 4029, Australia[9]Department of Neurology, State Key Laboratory of Biotherapy,West China Hospital, Sichuan University, Chengdu, Sichuan, China[10]Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China
Developing new therapies for stroke is urgently needed, as this disease is the leading cause of death and disability worldwide, and the existing treatment is only available for a small subset of patients. The interruption of blood flow to the brain during ischemic stroke launches multiple immune responses, characterized by infiltration of peripheral immune cells, the activation of brain microglial cells, and the accumulation of immune mediators. Copper is an essential trace element that is required for many critical processes in the brain. Copper homeostasis is disturbed in chronic neurodegenerative diseases and altered in stroke patients, and targeted copper delivery has been shown to be protective against chronic neurodegeneration. This study was undertaken to assess whether the copper bis(thiosemicarbazone) complex, CuII(atsm), is beneficial in acute brain injury, in preclinical mouse models of ischemic stroke. We demonstrate that the copper complex CuII(atsm) protects neurons from excitotoxicity and N2a cells from OGD in vitro, and is protective in permanent and transient ischemia models in mice as measured by functional outcome and lesion size. Copper delivery in the ischemic brains modulates the inflammatory response, specifically affecting the myeloid cells. It reduces CD45 and Iba1 immunoreactivity, and alters the morphology of Iba1 positive cells in the ischemic brain. CuII(atsm) also protects endogenous microglia against ischemic insult and reduces the proportion of invading monocytes. These results demonstrate that the copper complex CuII(atsm) is an inflammation-modulating compound with high therapeutic potential in stroke and is a strong candidate for the development of therapies for acute brain injury.
基金：
Academy of FinlandAcademy of Finland; Sigrid Juselius FoundationSigrid Juselius Foundation; Orion Finland; Australian Research CouncilAustralian Research Council; National Health & Medical Research Council of Australia (NHMRC)National Health and Medical Research Council of Australia; Cooperative Research Center for Mental Health; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81271403, 81471304, 81571236]
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区临床神经病学2 区神经科学2 区药学
最新[2023]版：
大类|2 区医学
小类|2 区临床神经病学2 区神经科学2 区药学
第一作者：
第一作者机构：[1]Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland[3]Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia[5]Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia[7]Present address: QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia[8]Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Locked Bag 2000, Herston, QLD 4029, Australia[9]Department of Neurology, State Key Laboratory of Biotherapy,West China Hospital, Sichuan University, Chengdu, Sichuan, China[10]Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China
推荐引用方式(GB/T 7714)：
Huuskonen Mikko T,Tuo Qing-Zhang,Loppi Sanna,et al.The Copper bis(thiosemicarbazone) Complex CuII(atsm) Is Protective Against Cerebral Ischemia Through Modulation of the Inflammatory Milieu.[J].NEUROTHERAPEUTICS.2017,14(2):519-532.doi:10.1007/s13311-016-0504-9.
APA：
Huuskonen Mikko T,Tuo Qing-Zhang,Loppi Sanna,Dhungana Hiramani,Korhonen Paula...&Kanninen Katja M.(2017).The Copper bis(thiosemicarbazone) Complex CuII(atsm) Is Protective Against Cerebral Ischemia Through Modulation of the Inflammatory Milieu..NEUROTHERAPEUTICS,14,(2)
MLA：
Huuskonen Mikko T,et al."The Copper bis(thiosemicarbazone) Complex CuII(atsm) Is Protective Against Cerebral Ischemia Through Modulation of the Inflammatory Milieu.".NEUROTHERAPEUTICS 14..2(2017):519-532
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