Sildenafil-Mediated Neuroprotection from Adult to Neonatal Brain Injury: Evidence, Mechanisms, and Future Translation

Cells. 2021 Oct 15;10(10):2766. doi: 10.3390/cells10102766.

Abstract

Cerebral stroke, traumatic brain injury, and hypoxic ischemic encephalopathy are among the most frequently occurring brain injuries. A complex pathogenesis, characterized by a synergistic interaction between alterations of the cerebrovascular system, cell death, and inflammation, is at the basis of the brain damage that leads to behavioral and neurodevelopmental disabilities in affected subjects. Sildenafil is a selective inhibitor of the enzyme phosphodiesterase 5 (PDE5) that is able to cross the blood-brain barrier. Preclinical data suggest that sildenafil may be a good candidate for the prevention or repair of brain injury in both adults and neonates. The aim of this review is to summarize the evidence supporting the neuroprotective action of sildenafil and discuss the possible benefits of the association of sildenafil with current therapeutic strategies.

Keywords: brain injury; neuroprotection; sildenafil.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Brain Injuries / drug therapy*
  • Humans
  • Infant, Newborn
  • Neuroprotection* / drug effects
  • Nitric Oxide / metabolism
  • Sex Characteristics
  • Sildenafil Citrate / pharmacology
  • Sildenafil Citrate / therapeutic use*
  • Translational Research, Biomedical*

Substances

  • Nitric Oxide
  • Sildenafil Citrate