Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone

• Published in: The European journal of neuroscience 2007-05, Vol.25 (10), p.3039-3046
• Main Authors: Barreto, George, Veiga, Sergio, Azcoitia, Iñigo, Garcia-Segura, Luis M., Garcia-Ovejero, Daniel
• Format: Article
• Language: English
• Subjects: androgen receptors; Animals; Astrocytes - drug effects; Astrocytes - metabolism; Biomarkers - metabolism; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - physiopathology; Dihydrotestosterone - pharmacology; Dihydrotestosterone - therapeutic use; Drug Administration Schedule; Estradiol - pharmacology; Estradiol - therapeutic use; gliosis; Gliosis - drug therapy; Gliosis - physiopathology; Gliosis - prevention & control; hippocampus; Histocompatibility Antigens Class II - metabolism; Immunohistochemistry; major histocompatability complex-II; Male; Microglia - drug effects; Microglia - metabolism; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Rats; Rats, Wistar; stab wound injury; Testosterone - pharmacology; Testosterone - therapeutic use; vimentin; Vimentin - metabolism; Wistar rats
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2007.05563.x

Previous studies have shown that the neuroprotective hormone, testosterone, administered immediately after neural injury, reduces reactive astrogliosis. In this study we have assessed the effect of early and late therapy with testosterone or its metabolites, oestradiol and dihydrotestosterone, on reactive astroglia and reactive microglia after a stab wound brain injury in orchidectomized Wistar rats. Animals received daily s.c. injections of testosterone, oestradiol or dihydrotestosterone on days 0–2 or on days 5–7 after injury. The number of vimentin immunoreactive astrocytes and the volume fraction of major histocompatibility complex‐II (MHC‐II) immunoreactive microglia were estimated in the hippocampus in the lateral border of the wound. Both early and delayed administration of testosterone or oestradiol, but not dihydrotestosterone, resulted in a significant decrease in the number of vimentin‐immunoreactive astrocytes. The volume fraction of MHC‐II immunoreactive microglia was significantly decreased in the animals that received testosterone or oestradiol in both early and delayed treatments and in animals that received early dihydrotestosterone administration. Thus, both early and delayed administration of testosterone reduces reactive astroglia and reactive microglia and these effects may be at least in part mediated by oestradiol, while dihydrotestosterone may mediate part of the early effects of testosterone on reactive microglia. In conclusion, testosterone controls reactive gliosis and its metabolites, oestradiol and dihydrotestosterone, may be involved in this hormonal effect. The regulation of gliosis may be part of the neuroprotective mechanism of testosterone.