Prostacyclin Prevents Pericyte Loss and Demyelination Induced by Lysophosphatidylcholine in the Central Nervous System

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. Background: Pericyte damage is closely associated with the progression of neurodegeneration and neuronal dysfunction in the central nervous system (CNS). Results: Prostacyclin attenuates pericyte damage following vascular barrier dysfunction in the adult CNS. Conclusion: Prostacyclin therapy diminishes demyelination and neuronal deficits in pathophysiological conditions. Significance: This study provides the first evidence that pericyte protection contributes to attenuate disease progression in adult CNS.