Prostacyclin prevents pericyte loss and demyelination induced by lysophosphatidylcholine in the central nervous system

J Biol Chem. 2015 May 1;290(18):11515-25. doi: 10.1074/jbc.M114.587253. Epub 2015 Mar 20.


Pericytes play pivotal roles in physiological and pathophysiological conditions in the central nervous system. As pericytes prevent vascular leakage, they can halt neuronal damage stemming from a compromised blood-brain barrier. Therefore, pericytes may be a good target for the treatment of neurodegenerative disorders, although evidence is lacking. In this study, we show that prostacyclin attenuates lysophosphatidylcholine (LPC)-mediated vascular dysfunction through pericyte protection in the adult mouse spinal cord. LPC decreased the number of pericytes in an in vitro blood-brain barrier model, and this decrease was prevented by iloprost treatment, a prostacyclin analog. Intrathecal administration of iloprost attenuated vascular barrier disruption after LPC injection in the mouse spinal cord. Furthermore, iloprost treatment diminished demyelination and motor function deficits in mice injected with LPC. These results support the notion that prostacyclin acts on pericytes to maintain vascular barrier integrity.

Keywords: Axon; Blood-Brain Barrier; Mouse; Multiple Sclerosis; Neurite Outgrowth; Neurodegeneration; Oligodendrocyte; Spinal Cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Cell Count
  • Demyelinating Diseases / chemically induced*
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / physiopathology
  • Demyelinating Diseases / prevention & control*
  • Disease Progression
  • Epoprostenol / metabolism*
  • Female
  • Iloprost / pharmacology
  • Lysophosphatidylcholines / pharmacology*
  • Mice
  • Motor Activity / drug effects
  • Pericytes / cytology*
  • Pericytes / drug effects*
  • Proteolysis / drug effects
  • Rats
  • Signal Transduction / drug effects
  • Spinal Cord / pathology*
  • Tight Junction Proteins / metabolism


  • Lysophosphatidylcholines
  • Tight Junction Proteins
  • Epoprostenol
  • Iloprost