Sex hormones modulate pathogenic processes in experimental traumatic brain injury

Area of Science:

• Neuroscience
• Endocrinology
• Pathology

Background:

• Traumatic brain injury (TBI) exhibits sex-specific differences in histopathological and neurological outcomes.
• The effects of perioperative sex steroid inhibitors on TBI are not well understood.

Purpose of the Study:

• To investigate the impact of inhibiting estradiol and dihydrotestosterone synthesis on TBI outcomes in male and female mice.
• To explore sex-specific molecular and neurological changes following TBI and pharmacological intervention.

Main Methods:

• Male and female C57Bl/6N mice underwent controlled cortical impact (CCI) TBI.
• Mice received letrozole (LET) or finasteride (FIN) starting 72 hours before CCI and continuing for 48 hours post-CCI.
• Gene expression, lesion size, neurological deficits, and protein levels of key molecular markers were analyzed.

Main Results:

• Larger brain lesions were observed in males than females, unaffected by FIN or LET.
• LET exacerbated neurological deficits in both sexes, while FIN reduced markers of excitotoxicity in males.
• LET increased reactive astrocyte markers in females, and both FIN and LET modulated neurotrophin and receptor expression in a sex-specific manner.

Conclusions:

• Sex hormones significantly modulate pathogenic processes in the injured brain after TBI.
• Pharmacological inhibition of steroid synthesis reveals distinct sex-specific responses to TBI.
• Findings highlight the importance of considering sex as a biological variable in TBI research and treatment.