title: A neuroproteomic and systems biology analysis of rat brain post intracerebral hemorrhagic stroke.
abstract: Intracerebral hemorrhage (ICH) is a devastating form of stroke leading to a high rate of death and disability worldwide. Although it has been hypothesized that much of the IHC insult occurs in the subacute period mediated via a series of complex pathophysiological cascades, the molecular mechanisms involved in ICH have not been systematically characterized. Among the best approaches to understand the underlying mechanisms of injury and recovery, protein dynamics assessment via proteomics/systems biology platforms represent one of the cardinal techniques optimized for mechanisms investigation and biomarker identification. A proteomics approach may provide a biomarker focused framework from which to identify candidate biomarkers of pathophysiological processes involved in brain injury after stroke. In this work, a neuroproteomic approach (LC-MS/MS) was applied to investigate altered expression of proteins that are induced in brain tissue 3 h after injury in a rat model of ICH. Data from sham and focal ischemic models were also obtained and used for comparison. Based on the differentially expressed protein profile, systems biology analysis was conducted to identify associated cellular processes and related interaction maps. After LC-MS/MS analysis of the 3 h brain lysates, 86 proteins were differentially expressed between hemorrhagic and sham tissues. Furthermore, 38 proteins were differentially expressed between ischemic and sham tissues. On the level of global pathway analysis, hemorrhagic stroke proteins were shown to be involved in autophagy, ischemia, necrosis, apoptosis, calpain activation, and cytokine secretion. Moreover, ischemic stroke proteins were related to cell death, ischemia, inflammation, oxidative stress, caspase activation and apoptotic injury. In conclusion, the proteomic responses identified in this study provide key information about target proteins involved in specific pathological pathways.
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Ren
authors.affiliation: Banyan Labs, Banyan Biomarkers Inc., Alachua, FL, USA; Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China.
authors.forename: Joy
authors.initials: J
authors.lastname: Guingab-Cagmat
authors.affiliation: Department of Psychiatry, Center for Neuroproteomics and Biomarkers Research, University of Florida, Gainesville, FL, USA.
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.affiliation: Banyan Labs, Banyan Biomarkers Inc., Alachua, FL, USA; Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China.
authors.forename: Susie
authors.initials: S
authors.lastname: Zoltewicz
authors.affiliation: Banyan Labs, Banyan Biomarkers Inc., Alachua, FL, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Hafeez
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Geng
authors.affiliation: Banyan Labs, Banyan Biomarkers Inc., Alachua, FL, USA; Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Larner
authors.affiliation: Banyan Labs, Banyan Biomarkers Inc., Alachua, FL, USA.
authors.forename: John
authors.initials: J
authors.lastname: Anagli
authors.affiliation: Banyan Labs, Banyan Biomarkers Inc., Alachua, FL, USA; Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.affiliation: Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China; Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Electronic address: jixm@ccmu.edu.cn.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Xuanwu-Banyan Biomarker Research and Assay Center, Beijing 100053, China; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D015398:Signal Transduction; D020521:Stroke / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D049490:Systems Biology / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: Intracerebral hemorrhage; Ischemia; Neuroproteomics; Stroke; System biology