title: On the crucial cerebellar wound healing-related pathways and their cross-talks after traumatic brain injury in Danio rerio.
abstract: Upon injury, the direct damage and the subsequent secondary injury in the brain often result in chronic neurological disorders. Due to multifactorial nature of secondary injury and subsequent complex cellular responses, much of the underlying mechanisms are unclear. This study used an adult zebrafish cerebellum injury model to investigate the phenotypes and the secondary injury responses for recovery mechanisms of injured brain. Using the time course microarray analysis, a candidate protein-protein interaction (PPI) network was refined as cerebellar wound healing PPI network by dynamic modeling and big data mining. Pathway enrichment and ontological analysis were incorporated into the refined network to highlight the main molecular scheme of cerebellar wound healing. Several significant pathways, including chemokine, Phosphatidylinositide 3-kinases, and axon guidance signaling pathway and their cross-talks through PI3K, PAK2, and PLXNA3 were identified to coordinate for neurogenesis and angiogenesis, which are essential for the restoration of the injured brain. Our finding provides an insight into the molecular restoration mechanisms after traumatic brain injury, and open up new opportunity to devise the treatment for traumatic brain injury in human.
authors.affiliation: Deptartment of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chia-Chou
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Deptartment of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Tsai
authors.affiliation: Deptartment of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chieh
authors.initials: C
authors.lastname: Chang
authors.affiliation: Deptartment of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Tian-Thai
authors.initials: TT
authors.lastname: Lee
authors.affiliation: Deptartment of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Che
authors.initials: C
authors.lastname: Lin
authors.affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Irene Han-Juo
authors.initials: IH
authors.lastname: Cheng
authors.affiliation: Stroke Center and Deptartment of Neurology, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Mu-Chien
authors.initials: MC
authors.lastname: Sun
authors.affiliation: Deptartment of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
authors.affiliation: Deptartment of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Bor-Sen
authors.initials: BS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D002531:Cerebellum / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D008959:Models, Neurological; D055495:Neurogenesis; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D040081:Protein Array Analysis; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D014945:Wound Healing; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D058539:Phosphatidylinositol 3-Kinase