Treating neonatal hypoxic-ischemic encephal opathy with substances that exist in the placenta and cord blood

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Progesterone and its metabolite, allopregnanolone, are neurosteroids that are present at high concentrations in fetal brains. Allopregnanolone is a potent positive modulator ofγ-aminobutyric acid A(GABA_A) receptor function. We examined the effect of exogenous administration of these steroids on hypoxic-ischemic encephalopathy in immature rats. Both progesterone and allopregnanolone significantly exacerbated brain injury in P7(postnatal day 7) and P14 rats, but not in P21 rats. Co-administration of the GABA receptor antagonist, bicuculline, partially A mitigated the exacerbating effect of allopregnanolone. This is in line with the notion that GABA is excitatory for immature neurons, while it is inhibitory for mature neurons.