Mechanism of Progesterone Neuroprotection of Rat Cerebellar Purkinje Cells Following Oxygen-Glucose Deprivation

The study investigated the neuroprotective effects of progesterone on rat cerebellar Purkinje cells during oxygen-glucose deprivation, hypothesizing that the protection was mediated through the potentiation of GABA A receptor activity. It was found that progesterone provided concentration-dependent protection, effective at physiological levels as low as 10 nM. The neuroprotection was nullified by the GABA A receptor antagonist picrotoxin, suggesting that progesterone's protective effects were mediated through GABA A receptors. Progesterone's metabolite, allopregnanolone (ALLO), also offered significant protection across various concentrations. Inhibition of progesterone metabolism with finasteride removed the protective effect of progesterone but did not affect ALLO's neuroprotection, indicating that progesterone's protective mechanism involved its conversion to a GABA-active metabolite.