The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in the Cerebral Cortex of Female Mice After a Stab Wound Injury

  • Andrea Crespo-Castrillo
  • Natalia Yanguas-Casás
  • Maria Angeles Arevalo
  • Iñigo Azcoitia
  • George E. Barreto
  • Luis M. Garcia-Segura


Previous studies have shown that estradiol reduces reactive gliosis after a stab wound injury in the cerebral cortex. Since the therapeutic use of estradiol is limited by its peripheral hormonal effects, it is of interest to determine whether synthetic estrogenic compounds with tissue-specific actions regulate reactive gliosis. Tibolone is a synthetic steroid that is widely used for the treatment of climacteric symptoms and/or the prevention of osteoporosis. In this study, we have assessed the effect of tibolone on reactive gliosis in the cerebral cortex after a stab wound brain injury in ovariectomized adult female mice. By 7 days after brain injury, tibolone reduced the number of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, the number of ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive microglia, and the number of microglial cells with a reactive phenotype in comparison to vehicle-injected animals. These effects on gliosis were associated with a reduction in neuronal loss in the proximity to the wound, suggesting that tibolone exerts beneficial homeostatic actions in the cerebral cortex after an acute brain injury.


Astrocytes Microglia Neuroinflammation Neuroprotection Steroid receptors Brain trauma 



We thank Elisa Baides Rosell for excellent technical assistance.


This work was supported by grants from Ministerio de Economía, Industria y Competitividad (MINECO), Spain (grant numbers BFU2014–51836-C2-1-R and BFU2017-82754-R), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), and Instituto de Salud Carlos III, Madrid, Spain and Fondos Feder.

Compliance with Ethical Standards

All procedures involving animals were approved by the CSIC institutional animal use and care committee and by the Comunidad de Madrid (PROEX 134/17) and followed the European Parliament and Council Directive (2010/63/EU) and the Spanish regulation (Ley 6/2013, 11th June) on the protection of animals for experimental use.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Consejo Superior de Investigaciones Científicas (CSIC)Instituto CajalMadridSpain
  2. 2.Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES)Instituto de Salud Carlos IIIMadridSpain
  3. 3.Department of Cell Biology, Faculty of BiologyUniversidad ComplutenseMadridSpain
  4. 4.Departamento de Nutrición y Bioquímica, Facultad de CienciasPontificia Universidad JaverianaBogotá D.C.Colombia

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