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

• Published in: Molecular neurobiology Vol. 55; no. 11; pp. 8651 - 8667
• Main Authors: Crespo-Castrillo, Andrea, Yanguas-Casás, Natalia, Arevalo, Maria Angeles, Azcoitia, Iñigo, Barreto, George E., Garcia-Segura, Luis M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2018; Springer Nature B.V
• Subjects: 17β-Estradiol; Animals; Astrocytes; Astrocytes - drug effects; Astrocytes - pathology; Biomedical and Life Sciences; Biomedicine; Brain; Brain Injuries - complications; Brain Injuries - drug therapy; Brain Injuries - pathology; Brain injury; Calcium; Calcium-Binding Proteins - metabolism; Cell Biology; Cell Count; Cell Death - drug effects; Cerebral cortex; Cerebral Cortex - pathology; Estrogens; Female; Females; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Gliosis; Gliosis - drug therapy; Gliosis - etiology; Gliosis - pathology; Hormonal effects; Image Processing, Computer-Assisted; Injuries; Macrophages - drug effects; Macrophages - metabolism; Menopause; Mice, Inbred C57BL; Microfilament Proteins - metabolism; Microglia; Microglia - drug effects; Microglia - pathology; Microglial cells; Nerve Tissue Proteins - metabolism; Neurobiology; Neurology; Neurons; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neurosciences; Norpregnenes - pharmacology; Norpregnenes - therapeutic use; Nuclear Proteins - metabolism; Osteoporosis; Ovariectomy; Phenotype; Phenotypes; Rodents; Stabbings; Steroids; Tibolone; Traumatic brain injury; Wounds; Wounds, Stab - complications; Wounds, Stab - drug therapy; Wounds, Stab - pathology; Xenoestrogens; Brain trauma; Neuroprotection; Neuroinflammation; Astrocytes; Steroid receptors; Microglia
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-018-1008-x

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.