Acta Neuropathologica

, Volume 121, Issue 4, pp 499–508

Sildenafil (Viagra) ameliorates clinical symptoms and neuropathology in a mouse model of multiple sclerosis

  • Paula Pifarre
  • Judith Prado
  • María Antonia Baltrons
  • Merce Giralt
  • Pere Gabarro
  • Douglas L. Feinstein
  • Juan Hidalgo
  • Agustina Garcia
Original paper

DOI: 10.1007/s00401-010-0795-6

Cite this article as:
Pifarre, P., Prado, J., Baltrons, M.A. et al. Acta Neuropathol (2011) 121: 499. doi:10.1007/s00401-010-0795-6

Abstract

Cyclic GMP (cGMP)-mediated pathways regulate inflammatory responses in immune and CNS cells. Recently, cGMP phosphodiesterase inhibitors such as sildenafil, commonly used to treat sexual dysfunction in humans including multiple sclerosis (MS) patients, have been reported to be neuroprotective in animal models of stroke, Alzheimer’s disease, and focal brain lesion. In this work, we have examined if sildenafil ameliorates myelin oligodendrocyte glycoprotein peptide (MOG35–55)-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show for the first time that treatment with sildenafil after disease onset markedly reduces the clinical signs of EAE by preventing axonal loss and promoting remyelination. Furthermore, sildenafil decreases CD3+ leukocyte infiltration and microglial/macrophage activation in the spinal cord, while increasing forkhead box transcription factor 3-expressing T regulatory cells (Foxp3 Tregs). However, sildenafil treatment did not significantly affect MOG35–55-stimulated proliferation or release of Th1/Th2 cytokines in splenocytes but decreased ICAM-1 in spinal cord infiltrated cells. The presence of reactive astrocytes forming scar-like structures around infiltrates was enhanced by sildenafil suggesting a possible mechanism for restriction of leukocyte spread into healthy parenchyma. These results highlight novel actions of sildenafil that may contribute to its beneficial effects in EAE and suggest that treatment with this widely used and well-tolerated drug may be a useful therapeutic intervention to ameliorate MS neuropathology.

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Paula Pifarre
    • 1
  • Judith Prado
    • 1
  • María Antonia Baltrons
    • 1
    • 2
  • Merce Giralt
    • 3
  • Pere Gabarro
    • 1
  • Douglas L. Feinstein
    • 4
  • Juan Hidalgo
    • 3
  • Agustina Garcia
    • 1
    • 2
  1. 1.Institute of Biotechnology and BiomedicineUniversitat Autonoma de BarcelonaBellaterraSpain
  2. 2.Department of Biochemistry and Molecular BiologyUniversitat Autonoma de BarcelonaBellaterraSpain
  3. 3.Institute of Neurosciences and Department of Cellular Biology, Physiology and ImmunologyUniversitat Autonoma de BarcelonaBellaterraSpain
  4. 4.Department of AnesthesiologyUniversity of IllinoisChicagoUSA