title: Characterization of the Molecular Mechanisms Underlying the Chronic Phase of Stroke in a Cynomolgus Monkey Model of Induced Cerebral Ischemia.
abstract: Stroke is one of the main causes of mortality and long-term disability worldwide. The pathophysiological mechanisms underlying this disease are not well understood, particularly in the chronic phase after the initial ischemic episode. In this study, a Macaca fascicularis stroke model consisting of two sample groups, as determined by MRI-quantified infarct volumes as a measure of the stroke severity 28 days after the ischemic episode, was evaluated using qualitative and quantitative proteomics analyses. By using multiple online multidimensional liquid chromatography platforms, 8790 nonredundant proteins were identified that condensed to 5223 protein groups at 1% global false discovery rate (FDR). After the application of a conservative criterion (5% local FDR), 4906 protein groups were identified from the analysis of cerebral cortex. Of the 2068 quantified proteins, differential proteomic analyses revealed that 31 and 23 were dysregulated in the elevated- and low-infarct-volume groups, respectively. Neurogenesis, synaptogenesis, and inflammation featured prominently as the cellular processes associated with these dysregulated proteins. Protein interaction network analysis revealed that the dysregulated proteins for inflammation and neurogenesis were highly connected, suggesting potential cross-talk between these processes in modulating the cytoskeletal structure and dynamics in the chronic phase poststroke. Elucidating the long-term consequences of brain tissue injuries from a cellular prospective, as well as the molecular mechanisms that are involved, would provide a basis for the development of new potentially neurorestorative therapies.
authors.affiliation: Department of Chemistry, The University of Hong Kong , Hong Kong, China.
authors.forename: Henry C H
authors.initials: HC
authors.lastname: Law
authors.affiliation: Department of Chemistry, The University of Hong Kong , Hong Kong, China.
authors.forename: Samuel S W
authors.initials: SS
authors.lastname: Szeto
authors.affiliation: Department of Chemistry, The University of Hong Kong , Hong Kong, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Quan
authors.affiliation: Department of Chemistry, The University of Hong Kong , Hong Kong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Centre for Research in Mass Spectrometry, York University , Toronto, Ontario M3J 1P3, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Krakovska
authors.affiliation: Department of Chemistry, The University of Hong Kong , Hong Kong, China.
authors.forename: Leong Ting
authors.initials: LT
authors.lastname: Lui
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Chengyou
authors.initials: C
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Avenue Padre Tomás Pereira S.J., Taipa, Macau 999078, China.
authors.forename: Simon M-Y
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Centre for Research in Mass Spectrometry, York University , Toronto, Ontario M3J 1P3, Canada.|Department of Chemistry and Biochemistry, University of Windsor , Windsor, Ontario N9B 3P4, Canada.
authors.forename: K W Michael
authors.initials: KW
authors.lastname: Siu
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University , Guangzhou 510632, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, The University of Hong Kong , Hong Kong, China.
authors.forename: Ivan K
authors.identifier: 0000-0003-0652-975X
authors.initials: IK
authors.lastname: Chu
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D055495:Neurogenesis / Q000235:genetics; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D020521:Stroke / Q000378:metabolism*
keywords: brain proteome; chronic phase; cynomolgus monkey; iTRAQ; ischemia; stroke biology