Steroids in brain arise from the peripheral endocrine glands and from local synthesis. In traumatic brain injury (TBI), the endogenous circulating hormones at the time of injury are important for neuroprotection. In particular, pseudopregnant females recover better than males from TBI. We investigated the effect of pseudopregnancy and TBI on steroid levels in plasma and in three brain regions (within, adjacent and distal to the lesion site), 6 and 24 hours after prefrontal cortex injury. The following steroids were analysed by gas chromatography/mass spectrometry: pregnenolone, progesterone, 5-dihydroprogesterone, 3,5-tetrahydroprogesterone, 3,5-tetrahydroprogesterone, dehydroepiandrosterone, ⁴-androstenedione, testosterone, 5-dihydrotestosterone, 3,5-tetrahydrotestosterone, 3,5-tetrahydrotestosterone and 17-estradiol. Corticosterone was assayed in plasma to account for stress in the rats.

We found different steroid profiles in brain and plasma of male and pseudopregnant female rats and specific profile changes after TBI. In sham-operated pseudopregnant females, much higher levels of progesterone, 5-dihydroprogesterone, 3,5-tetrahydroprogesterone and 3,5-tetrahydroprogesterone were measured in both brain and plasma, compared to sham-operated males. Plasma levels of corticosterone were high in all groups indicating that the surgeries induced acute stress. Six hours after TBI, the levels of pregnenolone, progesterone and 5-dihydroprogesterone increased and those of testosterone decreased in male brain, while levels of 5-dihydroprogesterone and 3,5-tetrahydroprogesterone increased in brain of pseudopregnant female rats. Plasma levels of 5-dihydroprogesterone did not change after TBI, suggesting a local activation of the 5-reduction pathway of progesterone in both male and pseudopregnant female brain. The significant increase in neurosteroid levels in the male brain after TBI is consistent with their role in neuroprotection. In pseudopregnant females, high levels of circulating progestagens may provide protection against TBI.