On the crucial cerebellar wound healing-related pathways and their cross-talks after traumatic brain injury in Danio rerio

PLoS One. 2014 Jun 13;9(6):e97902. doi: 10.1371/journal.pone.0097902. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / metabolism*
  • Brain Injuries / physiopathology
  • Cerebellum / metabolism
  • Cerebellum / physiopathology*
  • Disease Models, Animal
  • Humans
  • Models, Neurological
  • Neurogenesis
  • Phosphatidylinositol 3-Kinase / metabolism
  • Protein Array Analysis
  • Protein Interaction Maps
  • Proteomics / methods*
  • Signal Transduction
  • Wound Healing*
  • Zebrafish
  • Zebrafish Proteins / metabolism*


  • Zebrafish Proteins
  • Phosphatidylinositol 3-Kinase

Grant support

The work was supported by the National Science Council of Taiwan, R.O.C. [NSC 102-2745-E-007-001-ASP]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.