The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia

Brain Res. 2015 Jan 21:1595:143-55. doi: 10.1016/j.brainres.2014.11.024. Epub 2014 Nov 15.

Abstract

Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia.

Keywords: Apoptosis signal-regulating kinase 1 (ASK1); Aquaporin-1 (AQP-1); Blood–brain barrier (BBB); Cerebral ischemia; Edema; Vascular endothelial growth factor (VEGF); Vascular permeability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 1 / metabolism
  • Blood-Brain Barrier / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain Edema / drug therapy
  • Brain Edema / etiology*
  • Brain Ischemia / complications*
  • Brain Ischemia / pathology
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology*
  • Cell Hypoxia / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Glucose / deficiency
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering / pharmacology
  • Time Factors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • Aquaporin 1
  • Glucose