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

Abstract

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.

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Acknowledgements

We thank Elisa Baides Rosell for excellent technical assistance.

Funding

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.

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Correspondence to George E. Barreto or Luis M. Garcia-Segura.

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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.

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The authors declare that they have no conflict of interest.

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Crespo-Castrillo, A., Yanguas-Casás, N., Arevalo, M.A. et al. The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in the Cerebral Cortex of Female Mice After a Stab Wound Injury. Mol Neurobiol 55, 8651–8667 (2018). https://doi.org/10.1007/s12035-018-1008-x

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Keywords

  • Astrocytes
  • Microglia
  • Neuroinflammation
  • Neuroprotection
  • Steroid receptors
  • Brain trauma