Sexual Dimorphism Following In Vitro Ischemia in the Response to Neurosteroids and Mechanisms of Injury

The study explored the differences between male and female tissue responses to neurosteroids following in vitro ischemia, particularly in terms of cell death and injury mechanisms. It was found that male-derived tissue experienced higher levels of cell death post-ischemia compared to female-derived tissue. Neurosteroids like progesterone, allopregnanolone, and estradiol were effective in reducing cell death in both sexes, but medroxyprogesterone acetate (MPA) only provided protection in female tissue. The protective effect of progesterone was linked to its conversion to allopregnanolone, which was blocked by the 5α-reductase inhibitor finasteride. Additionally, caspase inhibition only reduced cell death in female tissue, while PARP inhibition was protective solely in male tissue. The study, which used 8 independent wells for data collection, concluded that there are significant sex differences in cell death and the pathways activated following ischemic injury, which should be considered when developing treatments for central nervous system disorders like stroke.